STG Makise Lifeup USA

Year – end and New Year holidays

CustomerTeam — Tue, 26 Dec 2023 02:19:58 +0000

The post Year – end and New Year holidays appeared first on STG Makise Lifeup USA.

Perilla is The Fish of The Lands

CustomerTeam — Tue, 25 Jan 2022 00:56:32 +0000

If you have ever searched for supplements of omega-3 fatty acids, fish oil is definitely on the top list. No wonder fish oil offers the highest available dose of omega-3s, as it contains both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).

But, if you are looking for a plant-based source, things might get confusing. You can see other oilseeds such as flaxseed, sunflower, or pumpkin seed becoming popular exclusively because of their high-cost advertisements. If you are wise enough not to fall victim to such ads, looking out for the best source and ratios of omega-3s and omega-6s can become stressful.

The Japanese folklore about perilla

Perilla frutescens (Egoma Oil) is a herb belonging to the mint family Lamiaceae, native to Eastern Asia. It is often known as wild sesame, Shiso, Japanese mint, and Chinese basil. Perilla is used as a culinary and medicinal herb in many parts of Asia.

In Japan, there is a belief that eating perilla, traditionally known as egoma, will make you live ten years longer. Hence perilla is also called juunen, which literally means ten years. It is also one of the secret ingredients of centenarians.

Perilla seeds and their oils have been widely used traditionally and medicinally for thousands of years. The Asian herbalists have used it to treat various ailments, including cough and lung afflictions, asthma, seafood poisoning, and indigestion. Like other botanicals, this herb contains strong antibacterial and antioxidant properties.

The aromatic leaves of perilla are well-known in parts of the Far East. These leaves are typically eaten with grilled meat or added to kimchi in South Korea. In the Tohoku region and other areas, local cuisine uses perilla miso, a mix of ground-up perilla seeds, miso, and other ingredients, which has long been a staple. Also, in Vietnam, it is served as a fragrant garnish to noodle soups and spring rolls.

The Japanese folklore about perilla

Perilla seed oil is a good source of unsaturated, plant-based omega-3 fatty acids, which our bodies cannot synthesize. The essential fat acid, omega-3s, in foods include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as their essential precursor alpha-linolenic acid (ALA).
Diet high in omega-3s, specifically ALA, stimulates cardioprotective effects by prompting vascular anti-inflammatory effects. This fact highlights the potentially important role of ALA in cardiovascular disease risk reduction.

ALA has been shown to reduce inflammation and may help prevent chronic diseases, such as skin diseases and arthritis. It is also beneficial for brain health and development.

https://pubmed.ncbi.nlm.nih.gov/15330276/
https://academic.oup.com/jn/article/134/11/2991/4688439

The omega-3 fatty acid is not the only aspect to look for in oils

When choosing plant oils, you should not miss checking the balance between omega-3, omega-6, and omega-9 fatty acids. The oils containing the highest amount of omega-3s would be most likely to promote health. In modern diets, omega-6 fatty acids are present in excessive amounts, and omega-3 fatty acids are deficient.

Perilla and flaxseed oil fall under the highest sources in omega-3 fatty acids. Any amount of omega-9 is beneficial, but in balancing these fatty acids, the omega-3 component is the most important.

While omega-3s are beneficial for cardiovascular health, certain types of cancers, and the immune system, omega-6s have different roles. The omega-6s enter the cell membranes, where the cellular machinery converts them into substances that promote abnormal clotting and increase inflammation. In recent years, it has been reported that the imbalance between omega-6 and omega-3 is one of the causes of allergic and lifestyle-related diseases.

Omega−3 content as the percentage of ALA in the seed oil (Source: Wikipedia)

Among plant sources of oil, perilla contains the highest proportion of omega-3 fatty acids (as alpha-linolenic acid), being in the 54-65% range and omega-6 (as linoleic acid) being in the 14-20% range. This unusual n6:n3 ratio of perilla makes it potential for an alternative to seed oils.

Kurowska EM, et al. Bioavailability of omega-3 essential fatty acids from perilla seed oil. Prostaglandins Leukot Essent Fatty Acids. (2003)

Comparison of perilla seed oil with fish oil

Studies show that omega-3s, particularly EPA and DHA found in fish oil, prevent cardiovascular diseases. In contrast, perilla seed oil only contains ALA as omega-3 fatty acids. However, later on, it metabolizes to give EPA and DHA.

The oily fish can potentially contain heavy metals and fat-soluble pollutants like PCBs and dioxin, which might accumulate in the fat cells. Hence, consumers of fish and their oils should be aware of it. Perilla seed oil is free from these organic pollutants. The consumption of perilla seed oil is wholesome, not only because of its ALA content but also for its antioxidant level.

Perilla seed oil is the best substitute for fish oil and is viable for vegetarians and vegans. Moreover, those who dislike the taste of fish, have a fish allergy or are just unable to tolerate fish oil due to reflux, can preferably take perilla seed oil for an omega-3 alternative.

You should not heat Perilla seed oil

Oils high in essential fatty acids, such as perilla seed oil, should not be heated in high temperatures because heat can decrease the stability and quality. Exposure to high heat can also cause the formation of trans-fats. It is thus not recommended to cook with oil rich in omega-3 fatty acids.

Also, due to commercial processing, the essential fatty acids in perilla seed oil can get denatured as it is heated in high temperatures for the refining process.

The traditional methods for the extraction of perilla seed oil involve pressing the oil out of seeds by applying pressure without heating them up or at low temperatures, which does not affect the nutritional value.

Our Egoma Oil contains 100% pure cold-pressed perilla seed oil exclusively processed in Japan with no added antioxidant. Considering its heat stability and usage, we have made it even more convenient by packaging it in a single-use sachet.

You can now preserve the omega-3 fatty acids on perilla seed oil by consuming it fresh as a part of salads or adding it directly to your lunch or desserts!

The secret oil of the east

Perilla seed oil is truly the hidden ingredient of the east, and its pharmacological, nutritional, and health benefits are even less known. It contains a variety of beneficial phytochemicals, phytosterols, tocopherols, and compounds such as rosmarinic acid, caffeic acid, ferulic acid, and luteolin.

These compounds confer cardiovascular benefits, anticancer properties and support healthy immune function. Perilla seed oil also suppresses the production of chemical mediators in the allergy and inflammatory responses.

With costly advertisements, other oilseeds are becoming popular. It is no surprise that the world is missing the potential of the perilla seed oil for its sheer lack of popularity. With the increase in interest and exploration of plant alternatives for health benefits nowadays, the demand for perilla seed oil is likely to increase. Moreover, this will help the remarkable benefits of perilla seed oil come to light.

The post Perilla is The Fish of The Lands appeared first on STG Makise Lifeup USA.

Revolutionary Method of Early Prediction of Alzheimer’s Progression

CustomerTeam — Mon, 06 Jul 2020 06:45:43 +0000

Revolutionary method to predict Alzheimer's disease 20 ～ 30 years prior to the onset of clinical symptoms.

Until recently two methods were used for diagnosis of Alzheimer’s disease (AD): PET (Positron Emission Tomography) or CSF (Cerebrospinal Fluid). Both methods are aimed to find amyloid β (Aβ). However, amyloid PET costs about $ 4,000 and CSF testing is invasive. Both are burdensome for the patients.

New blood test method may able to predict Alzheimer's disease

The new revolutionary technology, “Immunoprecipitation and Mass Spectrometry (IP-MS)”, has made it possible to quantitatively measure a few Aβ-related peptides, such as Aβ1-42, Aβ1-40, and APP669-711 in plasma, even though their concentration in plasma is extremely low. Just 0.5 ml of blood is enough. This was invented by Japanese researchers led by Koichi Tanaka (https://en.wikipedia.org/wiki/Koichi_Tanaka) who was awarded the Nobel Prize in 2002 for developing a method for mass spectrometric analyses. And they found that the ratio of these peptides, APP669-711/Aβ1-42, Aβ1-40/Aβ1-42, were an accurate surrogate for the brain Aβ burden.

In February 2018, IP-MS method was published in the scientific magazine “Nature”: [High-Performance plasma amyloid-beta biomarkers for Alzheimer’s disease]
https://www.nature.com/articles/nature25456

AD is a very tough disease. Once fully advanced, it is difficult to cure it by any modern mainstream medicines. However, if it is predicted 20~30 years prior to the onset of clinical symptoms of dementia by the IP-MS method when the patients have still almost healthy brain function, it can be treatable. At such an early stage, if we begin the treatment, curing or at least delaying its progress should be possible by cheap natural herbs, vitamins/minerals, and by changing our lifestyle to healthier one, or even by acupuncture or cranial osteopathy.
: Effect of acupuncture on the ultrastructure of neurons and astrocytes in the hippocampal dentate gyrus in rats with Alzheimer’s disease induced by Aβ1-42
https://europepmc.org/abstract/med/30942016

: Osteopathic Cranial Manipulative Medicine and the Blood-Brain Barrier: A Mechanistic Approach to Alzheimer Prevention
https://jaoa.org/article.aspx?articleid=2733780

In Japan, IP-MS method is planned to be introduced within 10 years to a routine health checks for office workers, school teachers, factory workers, or any persons who wish to prevent AD. And the cost will be covered by national health insurance and it will be at most less than $10. So cheap and so safe, compared with $4,000 amyloid PET or invasive CSF testing. Surely, by 2050 it will be possible to eradicate AD from our society except vary rare cases.
(*Recently the researcher of Washington University succeeded in a similar method like IP-MS. So, US has hope, too.)
How quickly the eradication of AD is achieved depends upon how quickly we can introduce the IP-MS method (or the like) to our society. In other words, it’s a matter of politics, not medicine.

It is often said that AD is expected to affect more than 115 million people all over the world by 2050. But the innovative detection method of a very early stage of AD by only 0.5 cc (= 0.5 ml) blood can definitely deny this gloomy expect. On the contrary, by 2050, our world will be “AD-Zero Society”, www.adzerosociety.com. We do have hope to conquer AD!!

Natural Supplements to Improve Alzheimer's disease

“Amyloid Hypothesis”
In AD, an abnormal peptide called amyloid β (Aβ) deposits in the brain tissue and Aβ is considered to destroy nerve cells. But a lot of people die quite old with a large Aβ plaque load without showing symptoms of dementia. Therefore, the recently amyloid hypothesis is being questioned by many clinical doctors. But this hypothesis is supported by mainstream researchers.

“Tau Hypothesis”
Abnormal tau protein forms neurofibrillary tangles inside nerve cells, which leads to microtubules disintegrate and destroy the structure of the cell’s cytoskeleton. Consequently, it causes the death of the nerve cells. Hyperphosphorylation of tau produces abnormal tau.

“Cholinergic Hypothesis”
Another cause of dementia is the decrease of acetylcholine, a neurotransmitter in the brain. Therefore, supplements that inhibit the enzymes which break down acetylcholine and supplements that increase acetylcholine itself are also important.

However, regardless of the hypothesis, if AD is predicted at a very early stage, it should be possible to stop the progress of the disease by natural supplements, acupuncture, cranial osteopathy, and changing our lifestyle. We can save millions of life and minimize the cost of medical treatments.

It would take 10～20 years for IP-MS method (or the like) to widely prevail to our society, and we are now not sure whether we are on the early threshold of AD when we begin to experience very mild forgetfulness, memory impairment, olfactory dysfunction, disorientation, and etc. These subtle symptoms might be a sign of AD. Therefore, when we suffer from such symptoms or if our family members suffered from AD, it is advisable to take natural supplements to prevent the progress of AD. The most of natural supplements described below are free from side effects. There’s nothing to lose just because we took these supplements, even if we do not or wouldn’t suffer from AD. Rather, they improve our general health.

Numerous natural supplements help the brain work. But, since the complex brain of a person is quite different, it is not possible to know what supplement is most effective for the individuals without actually trying it.
Choose 3 or 4 of them and try for about 2 months. For example, combination of “Gotu Kola, Alpinia zerumbet, Propolis, Cordyceps”. This combination is much more effective in synergism than Gotu Kola alone, or Alpinia zerumbet alone, or Propolis alone. And this combination doesn’t cost more than $150~ $200 per month.
Try the different combinations for 2 months, and try other combinations, and try —. Eventually, you will find the best combination for you. You can get these supplements through the Internet as long as you are living in the United States or in Japan.

** If you are already taking any medications, or pregnant, or breastfeeding, or under 15 years old, be sure to consult your doctor before taking these supplements.

List of Supplements for Alzheimer's disease

Gotu Kola

Its scientific name is Centella Asiatica. A perennial plant of the family Apiaceae that grows in Madagascar, Sri Lanka, and India where this plant is often used as herbal ingredients. Gotu Kola from Madagascar is especially famous.

Gotu Kola is called “Brahmi”, too, which means wisdom in Sanskrit. It is one of the most important herbs in Ayurveda medicine. In ancient times, it was used for leprosy and syphilis. In addition, Gotu Kola is said to activate the 7th chakra (crown chakra), which exists at the top of the head. The chakra is said to improve memory and insight and deepens thinking ability. It also has a sedative effect, which eases anxiety.

Gotu Kola can reduce Aβ. The effects are due to functional phytochemical components such as Asiatic acid, asiaticoside, madecasic acid, and madecasoside, which have been confirmed in many experiments. These effective substances can get through the BBB (blood-brain barrier) and work in the brain.
: Structure-activity relationship study of asiatic acid derivatives against beta amyloid (Aβ)-induced neurotoxicity
(https://www.sciencedirect.com/science/article/pii/S0960894X99006587&)

Bacopa (Bacopa monnieri)

This is a perennial, creeping herb that grows in marshy areas in India, Sri Lanka, Pakistan, Vietnam, Taiwan, and China. It is also found in Florida, Hawaii. Bacopa has been traditionally used in Ayurveda medicine to improve memory and to treat various diseases just like above mentioned Gotu Kola.

Preliminary clinical research found that Bacopa improved cognition.The main component is bacoside, a type of terpenoid saponin, which is thought to cross the BBB (blood-brain barrier) and exerts various effects. Anti-anxiety effects and tranquilization effects are also found. Therefore, it is being researched as a safe herb in the treatment of ADHD (Attention Deficit Hyperactivity Disorder), too.

: Insights Into the Molecular Aspects of Neuroprotective Bacoside A and Bacopaside I
(https://www.ingentaconnect.com/contentone/ben/cn/2019/00000017/00000005/art00006)

Ashitaba

Ashitaba (alleviate AD, prolong lifespan, against Coronavirus)
Ashitaba (Angelica keiskei in Latin) is a perennial plant indigenous to the Izu island chain that is a group of volcanic islands stretching south and east from the Izu Peninsula, Japan. Now it belongs to Tokyo Prefecture, and there are flights between the islands and Tokyo. But until 150 years ago, the islands were very remote and two of them were used to place internal exiles. They were engaged in arduous compulsory labor. To support their never waning stamina they ate this plant daily because the local people and the exiles knew of Ashitaba’s powerful tonic effects. Traditionally they boiled this plant or added it to the soup. And the powder of Ashitaba is mixed with buckwheat powder to make nutritious soba noodles even nowadays.

The most distinctive effect of Ashitaba is to stimulate the production of adiponectin especially by three chalcones; xanthoangelol, 4-hydroxyderricin, and isobavachalcone.
Adiponectin is an adipocytokine released by the adipose tissue and has multiple roles in the immune system and in the metabolic syndromes such as cardiovascular disease, diabetes, obesity, and also in the neurodegenerative disorders including Alzheimer’s disease. Adiponectin modulates memory and cognitive impairment and contributes to the deregulated glucose metabolism and mitochondrial dysfunction observed in Alzheimer’s disease.

: : Adiponectin as a new paradigm for approaching Alzheimer’s disease
(https://synapse.koreamed.org/DOIx.php?id=10.5115/acb.2013.46.4.229)

And another flavonoid, 4,4′ -dimethoxychalcone in Ashitaba, increases CLS （chronological lifespan）of budding yeast and reduces the ROS (reactive oxygen species ) levels in the yeast cells by activating autophagy. Therefore, Ashitaba is expected to contribute to human longevity, too.
: The flavonoid 4,4′ -dimethoxychalcone promotes autophagy-dependent longevity across species
(https://www.sciencedirect.com/science/article/pii/S2468501119300379

CBD (Cannabidiol)

Endocannabinoids are molecules made by our bodies. They act as neuromodulators on vertebrate central and peripheral nerves. Endocannabinoid system (ECS) is a complex cell-signaling system and considered to play a pivotal role to contribute to homeostasis. The two important endocannabinoids of ECS are 2-arachidonoylglyerol and anandamide which are eicosanoids.

There are two endocannabinoid receptors: CB1 and CB2. CB1 is for anandamide, CB2 is for 2-arachidonoylglyerol. The former is predominantly found in the central nervous system, and the latter found in the peripheral nervous system and immune cells.

Cannabinol in hemp and marijuana are similar to endocannabinoids. Two major cannabinol, CBD (cannabidiol) and THC (tetrahydrocannabinol) exert various effects on ECS when these cannabinoids are administered to our body.

Because THC interacts with ECS by binding to the two receptors (CB1 and CB2) that are for endocannabinoids, THC brings about not only strong positive effects but also strong negative effects on body and mind. Sometimes it gets us “high” and causes paranoia and anxiety. Therefore, many countries and many states in the United States ban marijuana in which more THC is contained than in hemp. But CBD is different. Unlike THC, CBD doesn’t bind to CB1 or CB2 receptors, and CBD blocks an enzyme that breaks down anandamide which is one of the key endocannabinoids and is regarded as the ‘bliss molecule’. Then, CBD allows for more benign effects to be present in our bodies through ECS. The Endocannabinoid system (ECS) is considered to be involved with various diseases including dementia. The low endocannabinoids may cause migraine, fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome of which true etiology is still unknown. And disturbed ECS definitely worsens AD, because ECS facilitates the neurogenesis of hippocampal granule cells.
Probable Alzheimer’s disease and Dementia with Lewy bodies (DLB) can be categorized as “Low Endocannabinoids Syndrome”.
: In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer’s Disease
(https://www.frontiersin.org/articles/10.3389/fphar.2017.00020/full)
: The Role of Endocannabinoid Signaling in the Molecular Mechanisms of Neurodegeneration in Alzheimer’s Disease
(https://content.iospress.com/articles/journal-of-alzheimers-disease/jad141635)

Essential Oils

Since a long time ago, even in ancient Egypt and Persia, essential oils have been used to activate the brain function. They didn’t understand the mechanism, but they empirically knew the effectiveness and safety of aromatherapy.

In the nasal cavity, aromatic molecules of essential oils bind to olfactory epithelium acceptors (olfactory nerves) which are illustrated as fine yellow fiber bundles in the figure. The axons of olfactory nerves penetrate the small foramina in the cribriform plate of the ethmoid bone and enter the cranial cavity, reaching the olfactory bulb which relays sensory data to the various parts of the brain: amygdala, limbic system, hippocampus, hypothalamus with consequent release of neuromediators.

Even in the early stages of AD, neurofibrillary tangles aggregated by intracellular hyperphosphorylated tau proteins are present in the entorhinal cortex, hippocampus, amygdala, and thalamus of the patients. This seems to cause the olfactory dysfunction of AD patients. Often AD begins with abnormal olfaction (dysosmia). Therefore, some researchers are trying to develop the early detection method to predict AD by checking the patient’s olfaction. If combined with IP-MS Method, the accuracy of the diagnosis of AD would be much more improved.
: Olfactory dysfunction as a predictor of neurodegenerative disease
(https://link.springer.com/article/10.1007/s11910-996-0018-7)

To improve mental problems, essential oils especially of Melissa officinalis (Lemon balm) and Lavandula officinalis (Lavender) have been used in traditional medicine for centuries. And Rosmarinus officinalis (Rosemary), Salvia lavandulifolia (Spanish sage), Persicaria hydropiper (water-pepper or marsh pepper knotweed) are also effective. Aromatic molecules of these plants are considered to promote neurogenesis in dentate gyrus of the hippocampus damaged by neurofibrillary tangles. The olfactory system has a unique capacity for neurogenesis. Aromatic molecules stimulate neuropoiesis there. Put hot water in a glass, drip a few drops of essential oils, and inhale the steam. Or you can drip 2～3 drops of oil on handkerchief and place it on your nose and inhale the aroma. Also, put a few drops in the bath. If the aroma is too strong, reduce the drop.
: Effect of aromatherapy on patients with Alzheimer’s disease
(https://onlinelibrary.wiley.com/doi/full/10.1111/j.1479-8301.2009.00299.x)

: Aromatherapy and Aromatic Plants for the Treatment of Behavioural and Psychological Symptoms of Dementia in Patients with Alzheimer’s Disease: Clinical Evidence and Possible Mechanisms
(https://www.hindawi.com/journals/ecam/2017/9416305/)

Ferulic Acid (FA)

The name of ferulic acid comes from its first discovery in 1866 from a plant with the scientific name Ferula assafoetida. FA is a kind of polyphenols present in cell walls of various plants and has strong antioxidant and anti-inflammatory effects. It has been demonstrated in animal experiments that FA can reduce the accumulation of Aβ by weakening the effect of β-secretase that is a proteolytic enzyme.
: Ferulic Acid Is a Nutraceutical β-Secretase Modulator That Improves Behavioral Impairment and Alzheimer-like Pathology in Transgenic Mice.
(https://www.ncbi.nlm.nih.gov/pubmed/23409038)

When amyloid precursor protein (APP) is cleaved by β-secretase, γ-secretase works to produce Aβ and may cause AD. (Aβ is not produced if cleaved with α-secretase). Therefore, inhibiting β-secretase is effective in the treatment of AD.
: Ferulic Acid: A Hope for Alzheimer ‘s Disease Therapy from Plants
(https://www.mdpi.com/2072-6643/7/7/5246)

Alpinia zerumbet (Shell Ginger)

This is a perennial plant of the ginger family. But Shell Ginger is not the same as ordinary ginger. Don’t confuse it with ordinary ginger. Very much different in health benefits. This plant is an amazingly promising plant to improve Alzheimer’s disease because it contains various phytochemicals such as Quercetin, Ferulic Acid, Kaempferol. DDK (dihydro-5,6-dehydrokawain), DK (5,6-dehydrokawain), etc.

Quercetin:
: Improvement of memory recall by quercetin in rodent contextual fear conditioning and human early-stage Alzheimer’s disease patients
(https://www.ncbi.nlm.nih.gov/pubmed/27145228)

Ferulic Acid: It weakens the action of β-secretase, which leads to a reduction of the accumulation of amyloid β as is written above.

Kaempferol: This polyphenol has various effects such as anti-inflammatory, antioxidant, anti-allergic, and blood vessel strengthening effect. Recently, it has been found that Kaempferol reduces a protein called MCP-1 (Monocyte Chemoattractant Protein-1) which consists of 76 amino acids. It causes arteriosclerosis and neurodegenerative diseases. Kaempferol reduces MCP-1.
: Effect of kaempferol on the production and gene expression of monocyte chemoattractant protein-1
(https://www.ncbi.nlm.nih.gov/pubmed/15849384)
And, Kaempferol has also been shown to destabilize amyloid fibrils and prevent neurofibrillary tangles.
: Protective Effect of Kaempferol on the Transgenic Drosophila Model of Alzheimer ‘s Disease
(https://www.ncbi.nlm.nih.gov/pubmed/29745345)
In addition, Kaempferol also inactivates β-secretase and thus reduces amyloid β production.
: Flavonols and flavones as BACE-1 inhibitors: Structure-activity relationship in cell-free, cell-based and in silico studies reveal novel pharmacophore features
(https://www.sciencedirect.com/science/article/pii/S0304416508000299#)

DDK (dihydro-5,6-dehydrokawain) , DK (5,6-dehydrokawain) :
PAK1 (p21-activated kinase 1) is involved to cause various diseases including AD. PAK1 is inhibited directly by DK and DDK that are abundant in Shell Ginger. Hesperidin, a metabolite of DK, strongly inhibited PAK1, too.
: Several herbal compounds in Okinawa plants directly inhibit the oncogenic/aging kinase PAK1
(https://www.jstage.jst.go.jp/article/ddt/8/6/8_2014.01045/_article/-char/ja/)

Propolis

Propolis (bee glue) is a resinous substance produced by bees. It has been used as a folk medicine for the treatment of periodontal diseases. At least 180 different compounds have been identified so far. Its antibacterial, antiseptic, anti-inflammatory, antifungal, anesthetic, and healing properties have been confirmed. And quite safe substance, as it has been used for ages – by ancient Egyptians, Persians, and Romans.

It is well known that chronic periodontitis is closely related to heart disease (100%), diabetes, osteoporosis, pneumonia, premature birth, etc. And periodontitis is being proven to be critically involved in the development of AD. There are several types of bacteria that cause periodontitis. Among them, Porphyromonas gingivalis is a keystone pathogen in the development of periodontitis.

P.gingivalis is a Gram-negative anaerobic bacterium that produces major virulence factors known as gingipains, which are cysteine proteases consisting of lysine-gingipain, arginine-gingipain A, and arginine-gingipain B. The researchers have found that these toxic proteases are essential for P.gingivalis to survive and they cleave tau protein in human, which leads abnormal hyperphosphorylation of tau.
And Aβ1-42 is produced probably to protect nerve cells against the infection of P.gingivalis. In other words, Aβ (amyloid β) is not the real cause of Alzheimer’s disease, but Aβ is the consequence of P.gingivalis infection. This theory is a Copernican innovative idea.
: Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors
(https://advances.sciencemag.org/content/5/1/eaau3333?intcmp=trendmd-adv)
And Japanese researchers have proved propolis is effective against P.gingivalis due to its ability to affect bacterial membrane potential with increased membrane permeability, thanks to its highly lipophilic nature as compared with other compounds. Propolis is cheap and available at any vitamin shop worldwide.
: Rapid Bactericidal Action of Propolis against Porphyromonas gingivalis
(https://journals.sagepub.com/doi/abs/10.1177/0022034518758034)
Perhaps, Alzheimer’s disease may be prevented simply and easily by cleaning the gums with propolis!! So simple, so cheap, so safe treatment!! We lose nothing just because we clean our gums by propolis, even if we do not or wouldn’t suffer from AD. Rather, most of us can prevent at least heart disease or improve diabetes that is deeply connected with periodontitis.

(The author, Dr. Tadahiro Makise, of this article, declares that this article is written in the absence of any commercial or financial relationship with any companies or any persons that produce/sell any kinds of propolis or any inhibitors of gingipains.)

Curcumin

It is often said that “Indians have less AD than any other nations because they eat a lot of curries.” How about the truth? Was it medically proven? Japanese also often eat curry, but they suffer from AD. But it looks pretty close to the truth. Curcumin, one of the ingredients in curry powder, has great medicinal properties. It has a strong antioxidant, anti-inflammatory, anti-cancer effect. It improves liver function and increases glutathione production.

Turmeric is a plant belonging to the ginger family. The scientific name is Curcuma longa L. Turmeric rhizome is powdered and dried and used as a spice. Turmeric contains curcuminoid which is a kind of yellow polyphenol. Curcuminoid is a general term for curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Curcumin is the most common, accounting for 75% of curcuminoids.

It is traditionally known that curcumin has a good effect especially on cognitive function, and it has often been used since ancient times in Ayurveda medicine. Therefore, a lot of researches has been done. In 2018, researchers at ‘Texas Tech University Health Sciences Center’ experimented with mice and humans, and proved its efficacy clearly. Curcumin crosses the BBB (blood-brain barrier) and reaches brain cells, where it acts to prevent amyloid β aggregation and degeneration from aging.
: Protective Effects of Indian Spice Curcumin Against Amyloid Beta in Alzheimer ‘s Disease
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796761/)
The absorption of curcumin from the intestine used to be difficult, but recently, nano-sized and cyclodextrin inclusion have been made and the absorption became very good. And if curcumin is taken together with piperine, the bioavailability of curcumin increases.

Caution: If you are taking medications such as phenytoin (Dilantin), propranolol (Inderal), or theophylline, do not take curcumin. Also, if you are taking anticoagulants or antiplatelet drugs such as aspirin, heparin, warfarin, curcumin may increase the risk of bleeding, so be sure to consult with your doctor.

Corn Silk

Corn silk is the white thread-like strand of plant material that grows underneath the husk of a fresh ear of corn. Traditional Chinese and Native American medicine have been using this natural material to treat various ailments. Especially traditional Chinese medicine employed it to alleviate dementia. Its mechanism has not yet been well understood. In 2016, however, the researchers of the University of Hawaii discovered how it did work to improve Alzheimer’s disease.

The keystone is GSK3β (glycogen synthase kinase-3β). Extracts of corn silks inhibit GSK3β. GSK3β is a multifunctional protein (serine/threonine kinase) which has very wide importance in biological processes such as cell differentiation, neuronal functions, embryonic development, apoptosis, and insulin response. It is involved with various diseases such as Alzheimer’s disease, diabetes, obesity, cardiovascular diseases, inflammation and pain, schizophrenia, bipolar disorders, and cancers.

Many recent studies have also shown the relation between GSK3β and ECS (endocannabinoid system) which is responsible for the regulation of many physiological effects in the central and peripheral nervous system and this may be a subject of further research and interests for many researchers.

Neurofibrillary tangles aggregated by intracellular hyperphosphorylated tau proteins lead to microtubule destruction and neuronal dysfunction, consequently to Alzheimer’s disease, “Tau Hypothesis”. Abnormal hyperphosphorylation of tau is caused by GSK3β. Therefore, the development of GSK3β inhibitors attenuating tau hyperphosphorylation is a promising therapeutic strategy for Alzheimer’s disease treatment. Here, corn silk plays an important role.
: C-Glycosylflavones Alleviate Tau Phosphorylation and Amyloid Neurotoxicity through GSK3β Inhibition
(https://pubs.acs.org/doi/10.1021/acschemneuro.6b00059)
Recently the researchers of Alzheimer’s disease are shifting their researches toward an investigation of the Tau Hypothesis from Amyloid Hypothesis. They begin to think that accumulation of amyloid β (Aβ) is not the true cause but the consequence of neurofibrillary tangles aggregation caused by abnormal hyperphosphorylation of tau protein or immune response against infection of bacteria (Porphyromonas gingivalis), because all attempts to develop Aβ-targeting drugs to treat Alzheimer’s disease have ended in failure. Literally all the drugs failed.
: Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer’s Disease
(https://www.frontiersin.org/articles/10.3389/fnins.2018.00025/full)Alzheimer’s disease

Astaxanthin

This is a red carotenoid that is abundant in the algae called Haematococcus and is taken in by the food chain as algae → plankton → krill, cherry shrimp → salmon, trout. Salmon and salmon roe are red. That redness is due to this carotenoid.

The antioxidant effect of astaxanthin is said to be 500 to 1000 times stronger than that of vitamin E. In particular, it has an excellent ability to remove “singlet oxygen: ¹O₂” which is very unstable ROS (Reactive Oxygen Radical). Of special note is that astaxanthin can pass through the BBB (blood-brain barrier) and the blood-retinal barrier and reach directly the nerves in the brain and retina. This is important to treat Alzheimer’s disease.
: On the Neuroprotective Role of Astaxanthin: New Perspectives?
(https://www.mdpi.com/1660-3397/16/8/247/htm)
Astaxanthin improves insulin resistance in the hippocampus.
: Neuroprotective role of astaxanthin in hippocampal insulin resistance induced by Aβ peptides in animal model of Alzheimer’s disease
(https://www.sciencedirect.com/science/article/pii/S0753332218343695)

Astaxanthin also facilitates the generation of NO (Nitric Oxide) in endothelial cells. Therefore, it dilates blood vessels and lowers blood pressure.
When taking DHA /EPA, which are omega-3 unsaturated fatty acids, it is recommended to take them together with astaxanthin to prevent oxidation of these omega-3 unsaturated fatty acids.

Astaxanthin has also been shown to increase good cholesterol (HDL). In the past, astaxanthin was extracted from krill, but since it became possible to artificially culture a large amount of Haematococcus, inexpensive astaxanthin supplements came to market. When I had a small research project with the University of Hawaii located in Honolulu (Oahu Island), I once visited a factory on Hawaii Island where dazzling UV rays shined down. It seems that ultraviolet rays are much harder on Hawaii Island (famous for triathlon) than on Oahu Island. The factory was producing astaxanthin from Hematococcus that contains a large amount of astaxanthin to eliminate singlet oxygen (¹O₂ ) induced by the strong ultraviolet rays.

Cordyceps --- The Emperor's Fungus for Health and Immortality

Cordyceps is a genus of parasitic fungi that grows on the living larvae of insects. In Japanese, it is called “” which means ‘in winter an insect, in summer a grass’, because Cordyceps is insect-like during the winter and grass-like during the summer. It grows mainly in the meadows above 3,000 to 4,000 meters in the Himalayan regions such as Tibetan Plateau, Nepal, Bhutan, and also in Sichuan, Yunnan of China.

The most important substance of Cordyceps is Cordycepin that is also called 3′-deoxyadenosine. It has a structure in which the hydroxyl group (OH group) has been deleted from the 3′ position of one of the adenosine nucleosides. Cordycepin has a protective effect on the CNS (central nervous system) against excitotoxicity neuronal damage by inhibiting the neuronal hyperexcitability. And a recent study has confirmed that Cordycepin exerts neuroprotective effects by inhibiting Aβ-induced hippocampal neuronal apoptosis via activating adenosine A1 receptors.
Although in vitro, methanol extract of Cordyceps militaris stimulates primary neurite sprouting and extension of Neuro2A cells in a dose-dependent manner. And it alleviates a decrease in cholinergic immunoreactivity in the hippocampus.

Cordyceps used to be worth more than 4 times its weight in silver. Because now (2020) 1 gram of Cordyceps costs more than $80, it is called ‘Soft Gold’. In addition, lots of fake and defective Cordyceps are on the market in China, making it difficult to get genuine ones. Therefore, in 1993 the team of Japanese and Chinese researchers succeeded in the artificial culture of Cordyceps militaris by using aseptically-cultured silkworms. This type of Cordyceps contains the highest amount of Cordycepin. But mycelia (root part) cultured in a synthetic medium, or fruiting bodies cultured in a medium such as cereals or grains don’t contain enough Cordycepin. Please be careful when you choose the supplement of Cordyceps.

＜Reference Link＞: Effects of cordycepin on spontaneous alternation behavior and adenosine receptors expression in the hippocampus
(https://www.sciencedirect.com/science/article/abs/pii/S0031938417304171)
＜Reference Link＞:Protective role of Cordyceps militaris in Aβ1–42-induced Alzheimer’s disease in vivo
(https://link.springer.com/article/10.1007/s10068-018-0521-z)
＜Reference Link＞:Cordyceps Militaris improves neurite outgrowth in Neuro2A cells and reverses memory impairment in rats
(https://link.springer.com/article/10.1007/s10068-011-0221-4

Hericium Erinaceus (Lion's Mane Mushroom or Yamabushitake)

This mushroom is an edible and medicinal mushroom belonging to the tooth fungus group. Native to North America, Europe, and Asia. In the wild, these mushrooms are common during late summer and fall on hardwoods, particularly American beech. In English, it is called Lion’s Mane Mushroom, in Japanese Yamabushitake which is called so because it resembles the decoration of a crown worn by Yamabushi (Japanese mountain ascetic hermits).

Generally speaking, the active ingredient in mushrooms is the polysaccharide β-glucan, which is especially evaluated to increase immunity. Hericium Erinaceus also contains five types of polysaccharides, which are alleged to have an anti-cancer effect. However, for the brain, the components such as Helicenone and Erinasin that are found only in this mushroom are important. These two substances promote the production of NGF (Nerve Cell Growth Factor), thus preventing the decrease of neurons and delaying the progression of dementia with AD.
: Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial.
(https://www.ncbi.nlm.nih.gov/pubmed/18844328)
It also lowers LDL cholesterol, preventing cerebrovascular disorders caused by arteriosclerosis and hyperlipidemia.
In addition, it is effective in allergic symptoms and infectious diseases such as influenza.

Chaga (Inonotus obliquus)

Mushrooms have a mysterious healing power that the above mentioned Lion’s Mane Mushroom shows. Chaga also does have an effect. Chaga is a parasitic fungus on birch, found in Siberia, Poland, Finland, Estonia, the northern part of China, and Japan. At first glance, it looks like a coal-like black lump that protrudes from the bark. The image is quite different from that of ordinary mushrooms. Siberian farmers have long drunk Chaga tea traditionally. Russian Nobel laureate Alexander Solzhenitsyn is credited with informing the West about the health benefits of Chaga in his book, “The Cancer Ward”. In Estonia, one of the three Baltic States, Chaga is by far the most used alternative therapy for cancer.
: Estonian folk traditional experiences on natural anticancer remedies: From past to the future
(https://www.tandfonline.com/doi/full/10.3109/13880209.2013.871641)
But Chaga is effective not only in the treatment/prevention of cancer but also of dementia. Because Chaga contains a number of health-promoting substances such as β-glucan, saponin, inositol, lignin, flavonoids, triterpenoids, and SOD. Synergistic effects of these various substances bring about alleviation of dementia.

Japanese researchers found Chaga decreased the effect of AChE (acetylcholinesterase) and restored the level of acetylcholine. This effect is the same as that of Huperzine A below mentioned.
: Amelioration of scopolamine induced cognitive dysfunction and oxidative stress by Inonotus obliquus – a medicinal mushroom.
(https://www.ncbi.nlm.nih.gov/pubmed/21779570)

Huperzine A

Huperzine A is a kind of alkaloid contained in fern plant (Huperzia Serrata). It has an AChE (acetylcholinesterase) inhibitory effect. Acetylcholine is an important transmitter in the brain, and the enzyme that breaks it down is acetylcholinesterase. Huperzine A inhibits the activity of that enzyme. Therefore, acetylcholine is not easily decomposed.
The famous AChE inhibitors are the pharmaceutical drugs donepezil hydrochloride (trade name: Aricept) and galantamine (trade name: Razadyne). Huperzine A has the same mechanism of action.
It also has an antagonistic action on the N-methyl D aspartate (NMDA) receptor, one of the receptors for glutamate, a neurotransmitter, and protects the brain from damage caused by glutamate. This action is the same as memantine hydrochloride, a pharmaceutical product. It is marketed under many brand names (more than 100) worldwide.
: Huperzine A: A promising anticonvulsant, disease modifying, and memory enhancing treatment option in Alzheimer’s disease
(https://www.sciencedirect.com/science/article/abs/pii/S0306987716306508#)

Eleutherococcus senticosus (Siberian Ginseng)

Eleutherococcus senticosus is a deciduous shrub that grows in the Far East region of Russia (Amur, Sakhalin), China (Heilongjiang, Jilin Provinces), and Japan (Hokkaido). The rhizomes and roots of E.senticosus are recorded in the Chinese and Japanese pharmacopeias as a treatment for various diseases. This herb became famous after extensive research by the former Soviet Academy of Sciences in the 1960s and it was used to strengthen the Russian athletes of the 1980 Moscow Olympic.

The leaves contain effective substances that reconstruct neuronal networks destroyed by amyloid β (Aβ). The researchers of the Institute of Natural Medicine, University of Toyama (Japan) proved that eleutheroside B, eleutheroside E, and isofraxidin of E.senticosus had protective effects against Aβ(25–35)-induced atrophies of axons and dendrites in the experiment of cultured cortical neurons of rat.
: Active components from Siberian ginseng (Eleutherococcus senticosus) for protection of amyloid β(25-35)-induced neuritic atrophy in cultured rat cortical neurons.

They confirmed eleutheroside B was effective for reconstruction of neuronal network reconstruction.
(https://www.ncbi.nlm.nih.gov/pubmed/21301979)
: New Age Therapy for Alzheimer’s Disease by Neuronal Network Reconstruction
(https://www.jstage.jst.go.jp/article/bpb/39/10/39_b16-00438/_html/-char/en)

Caution: Avoid this herb if you are taking antiepileptic drugs, warfarin and if you suffer from hypertension.

Dihydroquercetin (DHQ)

Also called taxifolin, it has a structure similar to quercetin and shows the same effect. However, quercetin does not dissolve in water, but DHQ dissolves quickly and reaches cells easily. Moreover, because it is stable, it has a long-lasting effect. The capillary protective effect is 3～5 times stronger than that of quercetin.

Siberian larch is its raw material.It detoxifies strong peroxide such as superoxide. And it reduces the action of cyclooxygenase-2 (COX-2), an enzyme that metabolizes unsaturated fatty acids into malignant inflammatory eicosanoids, and exhibits potent anti-inflammatory effect. DHQ was given as a supplement to Russian athletes for the 2008 Beijing Olympics.

(Above mentioned Eleutherococcus senticosus was used to strengthen the Russian athletes of the 1980 Moscow Olympic. Rhodiola Rosea also has been used traditionally in Russia and Eastern Europe. I call these three supplements — DHQ, E.senticosus, Rhodiola Rosea— “Russian Secret Trio” to fight against the Western athletes. )

DHQ stimulates the production of glutathione that has a strong detoxification effect and suppresses the accumulation of amyloid β. And it strengthens memory.
In addition, by suppressing the production of apolipoprotein B, it prevents the increase of LDL and makes the blood vessels strong.
It also has anti-allergic effects.
Especially good compatibility with vitamin C, double the antioxidant power. Take it together with DHQ.
: Taxifolin prevents β-amyloid-induced impairments of synaptic formation and deficits of memory via the inhibition of cytosolic phospholipase A2/prostaglandin E2content
(https://link.springer.com/article/10.1007/s11011-018-0207-5)

Guarana

Guarana is a climbing plant in the family Sapindaceae, native to the Amazon basin and especially common in Brazil. Guaraní people, indigenous peoples of South America, cultivated this plant and used its fruit traditionally. They are said to have carried around during the war against other tribes.

Brazil and Paraguay produce several soft drink brands from the crushed seeds of guarana. They drink them every day like coffee.
Brazilian researchers have found using nematodes that guarana blocks the toxicity of amyloid β.
: Guarana (Paullinia cupana Mart.) Protects against amyloid-β toxicity in Caenorhabditis elegans through heat shock protein response activation
(https://www.tandfonline.com/doi/abs/10.1080/1028415X.2018.1517473)

It improves long-term memory, too. Platelet aggregation inhibitory effect has also been confirmed, and it is effective for recovery from fatigue, stamina enhancement, blood purification, flatulence, obesity, indigestion, migraine, arteriosclerosis, etc., too. It is wise not to take this supplement at night, because the blood flow of the brain becomes too good and the brain gets up and someone cannot sleep.

Buckwheat Extract

With aging, cognitive function declines, and the feeling of happiness is likely to decline. This phenomenon is also associated with a decrease in dopamine, one of the neurotransmitters in the brain. After the age of 45, everyone is producing less dopamine, and at the same time, fun, happiness, healthy sexual desire in their youth gradually fade away.

And brain function ages. When it gets much worse, the balance function of the body weakens. In particular, monoamine oxidase-B (MAO-B), increased by 70% in the white matter of the brain of AD patients, and also increased by 20-50% in the gray matter. MAO-B expression is increased in astroglia adjacent to amyloid plaques in the brain with AD. Due to the increased MAO-B, dopamine gets more easily decomposed. By preventing the increase of MAO-B, the cognitive function could be restored, and the gorgeous and vibrant sensation of youth should be maintained.

Buckwheat extracts work effectively against various diseases of the nerve system by suppressing the enzyme phosphodiesterase-4. It is worth noting that buckwheat extracts improve the function of endothelial cells in the cardiovascular system, too. It is the extract of flavone isovitexin, etc. contained in the exposed parts of air such as leaves and stems of special types of buckwheat (Avena sativa) that really works, not oatmeal made by threshing ordinary buckwheat and often used for breakfast.

Caution: If you are diagnosed with Parkinson’s disease or Dementia with Lewy bodies (DLB) and are taking medications, be sure to consult your doctor before taking this supplement.

Vitamin K

There are five types of vitamin K, K1 to K5. The most important one is K2, which is further classified into 11 types, but collectively called menaquinone (MK). Abbreviated as MK-4 to MK-14, of which MK-4 and MK-7 are important. It is converted from vitamin K1 to MK-4 in the arterial walls, pancreas, and testis. It is also converted from K1 to MK-4 by intestinal bacteria that inhabit the large intestine.

K2 actually exerts a lot of effects. It prevents the development of arteriosclerosis caused by calcium deposition and is effective in improving peripheral arterial disease. It also acts on the pancreatic beta cells to stimulate insulin secretion. Recently, it has been found that Alzheimer’s disease is so closely related to glucose metabolism that Alzheimer’s disease can be considered as type 3 diabetes. Insulin is also secreted in the hippocampus of the brain, and the secretion is reduced in Alzheimer’s disease.

But vitamin K2 doesn’t bring about instant improvement of the brain function. Generally, you don’t feel any alleviation soon. Please take it as the basic supplement to support healthy blood vessels that are of the utmost importance for brain function.
: Increased dietary vitamin K intake is associated with less severe subjective memory complaint among older adults
(https://www.sciencedirect.com/science/article/abs/pii/S0378512216300196)
Caution: People taking warfarin should not take this vitamin.

Saffron

Saffron is a perennial that belongs to the genus Saffron, and it has long been famous in West Asia, especially Iran. About 90% of the world’s total saffron production is produced in Iran.

It has been used as a spice and herbal medicine since ancient Egypt and China to improve memory impairment, insomnia, and prevent gynecological problems such as irregular menstruation, menstrual pain, and menopause. The water-soluble carotenoid yellow component “Crocin”, contained in saffron pistils, acts on cerebral hippocampal neurons to improve memory. Crocin is derived from the scientific name of saffron, Crocus sativus.

In an experiment using a cerebral ischemic rat at a medical university in Mashhad, the second city of Iran that is the saffron production area, they proved the cognitive ability of the rats was improved by 250 mg/kg for saffron extract and by 25 mg/kg for Crocin,
: Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats.
(http://www.ncbi.nlm.nih.gov/pubmed/21774008)
It also works to increase blood flow in the retina and choroid, so it’s a very good supplement for older people whose eyes are easily more blurred. And for even young people who have engaged in the IT industry and look at the monitor screen for a long time. Because saffron has been used as a coloring agent for food since ancient times, it is considered very safe.

Krill Oil (omega-3 unsaturated fatty acid: DHA / EPA)

DHA (docosahexaenoic acid)/EPA (eicosapentaenoic acid), omega-3 unsaturated fatty acids, are abundant in Fish Oil and are essential for maintaining cerebrovascular elasticity. They also promote the production of benign eicosanoids and suppress the production of malignant eicosanoids, so they have a wonderful anti-inflammatory effect. EPA cannot pass through the BBB (blood-brain barrier), but DHA passes through it and is particularly contained in neurons in the hippocampal region that controls memory. However, DHA is significantly deficient in hippocampal neurons in patients with Alzheimer’s disease.

DHA has been shown to be effective in the treatment of cognitive impairment of Alzheimer’s disease and cerebrovascular disorders. Recently, I recommend Krill Oil instead of Fish Oil. Krill is a small crustacean with a length of 1.2～2.4 inches, a kind of shrimp. With regard to fish oil, it is often said that care should be taken not to use poor products because it contains marine pollutants, but especially in the case of Antarctic Krill, the cleanliness is excellent.

In addition, DHA and EPA in Krill Oil are bound to phospholipids, so they dissolve in water and are easily absorbed. And astaxanthin is included, making it even more effective.
Astaxanthin is a red substance that can be seen in the picture. However, if you are allergic to shrimp and crabs, fish oil is safer.
: The importance of fish and docosahexaenoic acid in Alzheimer disease
(https://academic.oup.com/ajcn/article/85/4/929/4649017)

Be sure to take DHA / EPA supplements immediately after meals, whether Krill Oil or Fish Oil. DHA and EPA degraded by cholesterol esterase, a type of pancreatic lipase secreted by dietary stimulation, are absorbed from the small intestine along with bile acids. In other words, if there is no stimulation from meals, DHA / EPA will not be sufficiently absorbed. And it is recommended to take omega-3 unsaturated fatty acids with astaxanthin.
: Astaxanthin limits fish oil-related oxidative insult in the anterior forebrain of Wistar rats: Putative anxiolytic effects?
(https://www.sciencedirect.com/science/article/pii/S0091305711001511#!)

Perilla Oil (Perilla Seed Oil)

Perilla is an annual plant native to Southeast Asia and is one of the 50 fundamental herbs in TCM (Traditional Chinese Medicine). It is rich in α-linolenic acid, an unsaturated fatty acid of the omega-3 family. As mentioned briefly in the page of Krill Oil, it promotes the production of benign eicosanoids and suppresses the production of malignant eicosanoids.

Flaxseed oil is often used as a source of α-linolenic acid, but perilla oil also contains a large amount of α-linolenic acid. 60-70% of the fatty acid of perilla oil is α-linolenic acid, while in the case of flaxseed oil it is 50 – 60%. In other words, perilla oil contains about 10% more α-linolenic acid than flaxseed oil.

In addition, perilla oil is rich in rosmarinic acid, luteolin, apigenin, and perillaldehyde. Therefore, perilla oil exerts really various health effects.

Rosmarinic Acid: prevents deterioration of brain function, reduces anxiety, alleviates allergic diseases, anti-viral, and improves diabetes.
This polyphenol downregulates dopamine-degrading enzymes, such as monoamine oxidase B (MAO-B) oxidase in the substantia nigra and ventral tegmental area, which inhibits Aβ aggregation. : Rosmarinic acid suppresses Alzheimer’s disease development by reducing amyloid β aggregation by increasing monoamine secretion
(https://www.nature.com/articles/s41598-019-45168-1)

: Effects of Vegetable Oils with Different Fatty Acid Compositions on Cognition and Memory Ability in Aβ25–35-Induced Alzheimer’s Disease Mouse Model
(https://www.liebertpub.com/doi/abs/10.1089/jmf.2016.3737)

Apigenin: This is a type of flavonoid, with a yellow crystalline appearance. Apigenin exerts neuroprotective effects.
: Neuroprotective effects of apigenin against inflammation, neuronal excitability and apoptosis in an induced pluripotent stem cell model of Alzheimer’s disease
(https://www.nature.com/articles/srep31450)

Luteolin: It reduces uric acid, improves fatty liver, prevents atherosclerosis, improves insulin resistance

Perillaldehyde: anti-inflammation, anti-parasite, vasodilative effect

Perilla has a long history, and it has been eaten in Japan since the Jomon period (14,000 – 300 BCE) and it has a history in Japan’s agricultural culture as one of Japan’s oldest crops. It is said that the oil extraction of perilla began in the early Heian period(794 – 1185). Since perilla seeds contain 35 to 40% of oily components, they have been used as coating oils in oil paper and paper lanterns as well as food. In addition to lights, Japanese paper was coated with perilla oil for waterproofing and was used for rain gear such as umbrellas and raincoats.
Perilla oil was widely used for about 800 years until the late Edo period (1603 – 1868) when rapeseed oil spreads nationwide. In the 1990s, perilla oil which is rich in α-linolenic acid became popular as a health supplement.

Although perilla oil is sold even in supermarkets in Japan, the oil may be difficult to obtain in your country as .the origin of perilla is Asia. However, because perilla oil is becoming popular worldwide, you may find it in your country by searching the Internet.

Black Cumin Oil

This oil is popular in the Middle East. Black Cumin (also known as Nigella sativa, or Black Caraway) is an annual herb that originates in Egypt and surrounding areas. It was said that this oil works for anything except death. It seems that it was used even during the Tutankhamen period in ancient Egypt (14th century BC).

“This oil stimulates the body’s energy, relieves fatigue, cleanses and detoxifies it” says Avicenna (Ibn Sina), an Islamic physician who wrote medical books called “The Canon of Medicine” and “The Book of Healing”, etc. about 1000 years ago. “It promotes healing of various diseases such as respiratory, skin, fever, wounds, parasites, headaches”. So to speak, it is a panacea for Arabian Nights.

The distinguishing feature of this oil is that it contains a substance called Thymoquinone (TQ). This makes black cumin oil different from omega-3 unsaturated fatty acid oils such as Fish Oil, Krill Oil, Flaxseed Oil, Perilla Oil, and Sacha Inch Oil. TQ has the effect of protecting brain nerve cells from neurocytotoxicity of amyloid β. Researchers at the Tokyo University of Technology have discovered that TQ is effective in AD.
: Thymoquinone protects cultured rat primary neurons against amyloid β-induced neurotoxicity.
(https://www.ncbi.nlm.nih.gov/pubmed/23537659)
This oil also contains THQ (Thymohydroquinone), which has an inhibitory action on acetylcholinesterase, which prevents dementia.

Phosphatidylserine

Phosphatidylserine is naturally produced in the body, and there is approximately 60 mg in adults, half of which is said to be in the brain nerve cell membrane. Myelin sheaths (phospholipid layers) that insulate around axons of nerves are also rich in phosphatidylserine.
As shown in the figure, it exists a lot inside the membrane and regulates the enzyme Na + / K + ATPase. This ensures that the balance between intracellular sodium and extracellular potassium is well maintained depending on the situation.

Phosphatidylserine helps the brain to have “long-term potentiation” of the hippocampus, which plays an important role in memory. This has been confirmed by experiments. “Long-term potentiation” is a neurological term that means long-term enhancement of synaptic connections between neurons and plays an important role in maintaining memory.
: Evidence of a protective effect of phosphatidylserine-containing liposomes on lipopolysaccharide-induced impairment of long-term potentiation in the rat hippocampus
(https://www.sciencedirect.com/science/article/abs/pii/S0165572804000529)

It also has an inhibitory action on acetylcholinesterase, preventing the decrease in the neurotransmitter acetylcholine. It also improves the metabolism of dopamine and serotonin that are the same neurotransmitters and activates brain function. Phosphatidylserine has a function of inhibiting lipid oxidation and protects nerve cells. There are also reports of improving ADHD (Attention Deficit Hyperactivity Disorder).

As described above, it has various effects and is indispensable for short-term memory, long-term memory, recall, and the ability to learn new things. But phosphatidylserine in the body decreases with age. Therefore, supplementing with phosphatidylserine is efficient to improve brain function. It passes through the BBB (blood-brain barrier).
: Phosphatidylserine and the human brain
(https://www.sciencedirect.com/science/article/pii/S0899900714004523)

A method of synthesizing Phosphatidylserine from lecithin of soybean has been established, and it is now a readily available supplement. Taken together with DHA / EPA, unsaturated fatty acids of the omega-3 family has a synergistic effect.

Silk protein

Did you know how many meters of silk yarn each small silkworm produces? 1.5 kilometers (≒0.93 miles) !! 70% of the yarn is composed of a long chain with a molecular weight of 350,000 to 370,000 Da called Fibroin, which is composed of 10 or more amino acids linked alternately. A sticky protein called Sericin covers Fibroin around the center of the silk thread.

Silk protein, which is hydrolyzed with a special enzyme, is called FPEH (Fibroin Protein Enzymatic Hydrolysate, also called Brain Factor-7). When taken 200～400mg/day of this, cognitive function improves in just 3 weeks. This has been confirmed in experiments with humans between the ages of 28 and 92 (average 55 years).
: Effect of a Fibroin Enzymatic Hydrolysate on Memory Improvement: A Placebo-Controlled, Double-Blind Study
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5852809/#B1-nutrients-10-00233)

The mechanism of FPEH cognitive improvement is as follows. Improves blood circulation in the brain. Promotes uptake of glucose in nerve cells.
Part of the structure of FPEH binds to part of amyloid β (Aβ) and inhibits Aβ accumulation. FPEH increases insulin sensitivity. As noted in Vitamin K, AD is so closely related to glucose metabolism that AD is even considered type 3 diabetes.

Magnesium L-Threonate

There are 325 enzymes that are directly dependent on magnesium in the body. Compared to about 200 enzymes that depend on zinc, about 20 enzymes depending on copper, and 10 enzymes depending on selenium, 325 is really a big number. Therefore, it is estimated that magnesium is involved with thousands of chemical reactions, including the metabolism involving magnesium indirectly. In other words, if this mineral is not enough, the physiological function is paralyzed.

You will find several magnesium supplements in any vitamin shops. Magnesium citrate, magnesium glycinate, magnesium malate, magnesium L-threonate, magnesium ascorbate, and magnesium aspartate. Among these, magnesium L-threonate works particularly well in the brain and nervous system. It has been shown to support brain synaptic density in brain areas related to memory. Although its price is three to four times more expensive than other types of magnesium, I would like to recommend it to prevent forgetfulness and dementia.
: Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer’s disease mouse model
(https://molecularbrain.biomedcentral.com/articles/10.1186/s13041-014-0065-y)

* Serum magnesium is not examined during regular medical examinations. However, ALP (alkaline phosphatase) is often examined. So if the ALP value is quite low, please suspect the possibility of magnesium shortage, because there is magnesium in the active site of ALP.

Ginkgo Biloba Extract

The flavonoids ginkgo-flavone glycosides and the terpene ginkgolide improve blood flow in the brain and prevent unnecessary platelet aggregation. Another terpene bilobalide is said to have the ability to repair damaged nerve cells and prevent AD. In animal experiments, it has been confirmed that levels of dopamine are raised by Ginkgo Biloba Extract (GBE). It also contains a lot of kaempferol, which is described in Shell Ginger.

Although the efficacy of GBE for AD treatment is still controversial, GBE alleviates at least aluminum-induced neurotoxicity in rats. Aluminum is considered to be one of the culprit metals that induce Aβ deposition in the human brain. The researchers observed a significant decline of Aβ aggregation in hippocampal and cortical regions of the rats’ brains with GBE supplementation. Of course, the human is different from a rat. But basic physiology is the same. Therefore, those who are engaged in any metal processing industry are recommended to take GBE for prevention.
It is safer not to use it together with aspirin. It has been reported in rare cases that blood flow becomes too good and causes cerebral hemorrhage and fundus bleeding.

It is better not to take it before bedtime. This is because the blood flow in the brain becomes too good to sleep well. * It improves blood circulation and improves blood flow in the penile arteries of the penis. Therefore, it is effective for ED (erectile dysfunction).
: Ginkgo biloba attenuates aluminum lactate-induced neurotoxicity in reproductive senescent female rats: behavioral, biochemical, and histopathological study
(https://link.springer.com/article/10.1007/s11356-019-05743-5)

Acetyl-L-Carnitine (ALC)

Acetyl-L-carnitine is a combination of L-carnitine and an acetyl group (CH3CO-) that promotes the production of acetylcholine in the brain. ALC gets through the BBB (blood-brain barrier). Acetylcholine is a neurotransmitter released from the terminals of parasympathetic and motor nerves and is essential for the normal functioning of the nervous system.

Also, it removes the waste accumulated in the mitochondria of the brain cells, so if this is insufficient, the brain cells will be fragile. L-carnitine is a vitamin-like substance that is synthesized in the liver from lysine and methionine and is extremely abundant in skeletal and cardiac muscles. It works as a cofactor in fat metabolism, burns fat, and is deeply involved in ATP production. About 10% of carnitine in the body is said to exist in the form of ALC.

However, L-carnitine decreases with age, and if you are in your 50s, it is better to supplement 100mg a day. It is abundant in beef, mutton, and red shellfish. When taken together with α-lipoic acid, the efficacy of ALC improves. This combination is recommended especially for diabetics.
: Long‐term acetyl‐L‐carnitine treatment in Alzheimer’s disease
(https://n.neurology.org/content/41/11/1726)

Citicoline

Citicoline, also called CDP-Choline, stimulates the production of acetylcholine and activates brain metabolism. It has been confirmed to improve memory and concentration. When taken orally as a supplement, citicoline is hydrolyzed into choline and cytidine in the intestine. Then, the two substances are re-synthesized into citicoline in the brain after passing through the BBB (blood-brain barrier).

In the hippocampal area that is responsible for the memory of rats with AD, citicoline has been confirmed to prevent neuronal degeneration. In mild ischemic brain disease, citicoline protects neurons. It is also effective for glaucoma and amblyopia. When taken with an acetylcholinesterase inhibitor, the brain function is improved compared to the administration of the acetylcholinesterase inhibitor alone. This is an Italian study of 448 AD patients over 65 years old.
: The Citicholinage Study: Citicoline Plus Cholinesterase Inhibitors in Aged Patients Affected with Alzheimer ‘s Disease Study
(https://www.ncbi.nlm.nih.gov/pubmed/28035929)

Therefore, it is recommended to take it with huperzine A which has the acetylcholinesterase inhibitory effect. Citicoline is a very safe substance and there is no problem up to 2000mg a day.

Vitamin B12

Most nerves are covered with sheath-like lipid called myelin. It acts as an insulator and speeds up the electrical impulses that travel through the nerve fibers. B12 is needed to make that myelin sheath. B12 is also required for the production of the neurotransmitter acetylcholine. In other words, B12 is a very important vitamin for the normal functioning of nerves. As shown in the figure, it has a very complex structure centered on cobalt.
: Vitamin B12 offers neuronal cell protection by inhibiting Aβ-42 amyloid fibrillation
(https://www.sciencedirect.com/science/article/pii/S0141813017305457#!)

And if vitamin B12 is deficient, too much homocysteine is produced. Homocysteine is a “bad” or “toxic” amino acid biosynthesized from methionine. If the level of homocysteine in the blood is high, it causes various problems — dementia, coronary artery diseases, osteoporosis, NAFLD (Nonalcoholic Fatty Liver Disease), and so on.

: Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer’s Disease
(https://www.nejm.org/doi/full/10.1056/nejmoa011613)

Vitamin B12, vitamin B6, and folate are essential to reduce homocysteine. Usually, two types of supplements of vitamin B12 are sold in vitamin shops, 1000μg or 5000μg tablets. 5000μg is necessary. Vegetarians often lack this vitamin.

B Vitamins

Acetylcholine is a very important neurotransmitter in both the peripheral and central nerves. In AD, this important acetylcholine is reduced, which is one of the causes of dementia. Acetylcholine is synthesized from acetyl-CoA that is a kind of vitamin B choline. Since acetylcholine is broken down by acetylcholine degrading enzyme, the decrease of acetylcholine can be stopped by inhibiting it, and donepezil hydrochloride (trade name: Aricept) was developed. It can be supplemented with choline, which is a biosynthetic material, by increasing the original amount of acetylcholine.

Vitamin B1 also helps acetylcholine synthesis. Nicotinamide, a type of vitamin B3, helps to improve AD. This vitamin B does not block the accumulation of amyloid β (Aβ) but reduces the abnormal accumulation of tau protein.
: Nicotinamide Restores Cognition in Alzheimer’s Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau
(https://www.ncbi.nlm.nih.gov/pubmed/18987186)

Tau protein is necessary for the stabilization of microtubules that work mainly when cells divide. If this protein is abnormally phosphorylated, it results in neurofibrillary degeneration, which in turn causes AD, (Tau hypothesis). Recently, researchers have focused more on Tau hypothesis than the accumulation of amyloid β, (Amyloid Hypothesis). Usually, vitamin B group supplements contain a series of vitamin B, such as vitamins B1, B2, B3, B5, B6, B12, folic acid, biotin, choline, and inositol.

The post Revolutionary Method of Early Prediction of Alzheimer’s Progression appeared first on STG Makise Lifeup USA.

Supplements, Medicine and Ointment for Psoriasis: Effective and Unique Treatment From Japan

CustomerTeam — Thu, 09 Apr 2020 08:05:35 +0000

With proper guidelines, supplements, ointments, and treatment, you can be free from psoriasis within four months.

I am not a dermatologist but a general physician. I see psoriasis as an inside-out disease which is a different view from the ordinary dermatologists. For years, I’ve been using our special ointments, oral medication, and supplements for the treatment of psoriasis.

Psoriasis is a non-contagious inflammatory skin disease associated with rapid skin cell multiplication. A variety of factors like hereditary, infection, environment, medications, stress, smoking, and genetics cause Psoriasis. The most common symptom of psoriasis is dry and itchy skin, formation of red patchy inflamed skin and stiff swollen joints.

It might sound strange to a dermatologist, but the actual cause of psoriasis is viruses. These two to three kinds of viruses attack the patient’s abnormal genes variants linked with the onset of psoriasis. Consequently, the immune system functions differently and causes inflammation. For this reason, immunosuppressant drugs such as methotrexate or cyclosporine help ease psoriasis significantly.

As the virus triggers psoriasis and alters the immune system, there must be a selection of holistic approaches for the effective treatment of psoriasis.

1. Use of ointments for psoriasis treatment

With more than 15 years of research, analysis, and completion, and treatment of more than 40,000 patients with varieties of skin diseases, we have created a unique formula for psoriasis treatment. With proven assurance, we have developed three special ointments – PS (1), MAS (1), and MA (1) to speed up the cure of psoriasis.

Not only this, but it also helps to cure varied forms of eczemas due to psoriasis, Pustulosis palmaris et plantaris (PPP), atopic dermatitis, nodular prurigo, and many other skin conditions. But, in cases like fungus or serious malignancy such as mycosis fungoides (cutaneous T-cell lymphoma), these ointments cannot cure eczema.

The psoriasis ointment list with its ingredients are as follows:

PS(1): difluprednate, clofibrate, jojoba oil, vegetable squalene, lanolin hydrous, macadamia nut oil, fermented extract of leaves of shell ginger, very fine powder of 5 kinds of mineral ores.

MAS(1): difluprednate and clobetasol propionate, licorice oil, moringa oil, macadamia nut oil, fermented extract of leaves of shell ginger, vitamin B1, B2, B12, alpha-lipoic acid, very fine powder of 5 kinds of mineral ores.

MA(1): triamcinolone acetonide and clobetasol propionate, moringa oil, macadamia nut oil, vitamin B1, B2, B12, alpha-lipoic acid, fermented extract of leaves of shell ginger, very fine powder of 5 kinds of mineral ores.

From the safety perspective, though these psoriasis ointments contain corticosteroid: a steroid hormone, the side effects are merely present. Unlike others, our ointments emit infrared rays from the fine powder of 5 stones. It leads to quick restoration of the skin.
PS (1) and MAS (1) are effective for the treatment of Psoriasis Vulgaris. Despite this, its efficacy seems to depend upon factors like race, climate, and food. For cases with fair and thin skin, MAS (1) is more potent. Hence, at first, I prescribe both PS (1) and MAS (1) to the patients and allow them to observe their efficacy for a week.

Here’s a case example: I recommend applying PS (1) on the lesion on the left side of the body and MAS (1) on the right side twice a day for a week to the patient. Later, the patient can identify the efficiency of ointment of psoriasis for his condition.
Also, for the treatment of Guttate psoriasis, MA (1) is recommended.

2. Two Important Oral Medication for Psoriasis

The first treatment step includes eradicating viruses that modulate the immune system using medications having insignificant side effects. The following two medicines have minimal side effects compared to immunosuppressant pills:

a. Erythromycin (Erythrocin® 200 mg)

Erythromycin is an antibiotic used in the treatment and prevention of several bacterial infections. Theoretically, antibiotics are only effective against bacteria, but realistically, Erythromycin seems to be effective against the virus as well. Therefore, I recommend this as good medicine for psoriasis.

As for myself, whenever I travel overseasthemin by long flights, I always take Erythromycin as prophylactic for two days before the flight. It works for the prevention of both bacterial and viral infections.

How to take: 4 tablets/day — Morning (2 tablets) and Evening (2 tablets). But the process of taking is unique. Please take the medication as follows:

As shown above, take the 4 tablets for four days and don’t take them for the following three days. For example, if you begin from Sunday, take 4 tablets/ day for Monday, Tuesday, Wednesday. And on Thursday, Friday, Saturday, you should discontinue the medication. You should again continue the same pattern by taking 4 tablets every day from the next Sunday to Wednesday and keeping a gap from Thursday to Saturday.

Repeat this cycle for 12 weeks (almost 3 months).

*If you are allergic to Macrolides, please don’t take this antibiotic.

b. Cepharanthine (Cepharanthin® 1 mg)

It is a naturally occurring alkaloid extracted from the plant Stephania cepharantha Hayata. In Japan, Cepharanthin® is a somewhat obscure medicine. As it is inexpensive, doctors are not interested in prescribing it (Doctors prefer costly drugs for business!!), and Cepharanthine is often underrated. Despite its value, it helps to cure diseases like Multiple Sclerosis, Ulcerative Colitis, and Hypothyroidism. Being able to modulate the immune system, Cepharanthin is beneficial in the cure of psoriasis.

Now, only one Japanese company manufactures Cepharanthin. I do hope the other companies continue the production of this notably potent psoriasis pill.

How to take: 3 to 4 tablets/day. Generally, you must continue it for 3 months.

It has few side effects in contrast to biologics such as Stelara or immunosuppressants such as MTX.

Q. How to take these two medicines for the treatment of psoriasis?

A. For the first month, use Cepharanthine only. In the following second and third months, take both Cepharanthine and Erythromycin. Finally, in the fourth month followed, take Erythromycin only. From the third month, you can also begin to take natural supplements. I especially prescribe this to undergo the best psoriasis treatment.

3. Supplements for Psoriasis

a. Natural supplement for psoriasis

Shell Ginger Supplement (JIPANG Ginger®) 1400 mg ~ 2000 mg/day

b. Vitamin and other supplements for psoriasis

1) Lipids
Psoriasis patients manifest significant lipid abnormalities. Though this might not apply to all cases, I have seen psoriasis patients with high blood cholesterol recover miraculously by cholesterol-lowering statin drugs. Dermatologists, however, disregard this fact as its efficacy is controversial.

If you search “statin psoriasis” you can find fascinating articles such as:(https://www.webmd.com/skin-problems-and-treatments/psoriasis/news/20100308/cholesterol-drugs-may-treat-psoriasis#1). There are opposing articles likewise, but I think it is worth trying. Although I am against statin drugs for lowering cholesterol, I still recommend them for psoriasis. Particularly Simvastatin, marketed under the trade name Zocor, shows effectiveness on psoriasis.

2) Biotin
Biotin (a kind of vitamin B-complex) falls among the essential vitamins that help cure psoriasis. This vitamin is required for fat metabolism and thus influences skin health.
Patients using antibiotics, intaking only α-lipoic acid, following dialysis, and consuming an excessive amount of egg white are likely to be deficient in this vitamin. Besides, people taking sleeping pills, antidepressants, and antiepileptic drugs for a longer duration also lack biotin. As some species of lactic acid bacteria feed on biotin, you must limit intake of yogurt cautiously.

Dosage of biotin for psoriasis: 10 mg to 15 mg/day. Please do not mistake the unit. It is 10 mg to 15 mg (10,000 mcg to 15,000 mcg), not 10 mcg to 15 mcg (10 μg to 15 μg). Many biotin supplements contain 5000 mcg of biotin per capsule, in such cases, 2-3 capsules per day are recommended.

You should continue biotin supplements for at least six months. You must discontinue smoking, as biotin does not work efficiently with smoking.

3) Omega 3 Unsaturated Fatty Acid: 3000 mg to 4000 mg /day

Omega-3-fatty acids are one of the best supplements for psoriasis as it plays a vital role in reducing inflammation. Harp Seal Oil is very stable, contains EPA, DHA, and DPA, and is the best source of omega-3 fatty acids. These essential fatty acids circulate in human blood and maintain soft, plaque-free arterial walls. They also reduce inflammation and produce a healing effect on the cells of the skin. Furthermore, from these unsaturated fatty acids, beneficial eicosanoids are metabolized, which facilitates the cure of psoriasis.

But, if you love such a cute animal as Harp Seal and would not like to sacrifice their lives, you can choose Sacha Inchi Oil. And if you would like to economize, Flaxseed Oil can be a good substitute for omega-3 fatty acids.

4) Inositol (750 mg to 1000 mg /day)
Inositol is a vitamin-like substance synthesized in small quantities in our bodies. Phytate, naturally present in cereals and grains, acts as a precursor of inositol. Phytin, phytic acid, and inositol have different functions, such as maintaining cholesterol levels and promoting skin health. In some cases, psoriasis patients suffer from hyperlipidemia. Hence, rectifying it reduces the severity of psoriasis and is a potent supplement for psoriasis.

5) Zinc (40 mg/day Zinc Monomethionate or Zinc Picolinate)
Zinc regenerates collagen and maintains skin composition, being a vital mineral supplement for psoriasis. It is readily available online or at any vitamin shop and is reasonably priced. However, like copper, if you take zinc supplements at a higher dose for a long time, side effects are anticipated. Therefore, a doctor’s consultation is necessary. Zinc supplement is not advisable for hepatitis patients or those who are the carrier of the hepatitis virus.

6) Copper (4 mg to 6 mg/day)
Viral infections lead to the onset of psoriasis. Although mainstream medicines disagree with this viewpoint, copper suppresses the growth of the virus, making it another effective psoriasis supplement. Besides, they are affordable and available easily.

You should not take copper supplements continuously for a longer duration. You can take it for no longer than 3 months. After a gap of a month, you can again take it for 3 months. You can continue the cycle in a similar pattern.

7) Selenium: 200 mcg/day
Another effective mineral supplement for psoriasis is selenium. It synthesizes the glutathione peroxidase enzyme. This enzyme protects the cell from oxidative damage by neutralizing free radicals.

Selenium forms selenocysteine, an enzyme required in the activation of the thyroid hormone. It helps to convert tetraiodothyronine (T4) to triiodothyronine (T3). The deficiency of active thyroid hormone T3 adversely affects psoriasis.

8) Magnesium (200 mg/day Magnesium Glycinate is recommended)
About 325 kinds of enzymes are directly dependent on magnesium for functioning. If our body lacks adequate magnesium, the physiological function and metabolism will paralyze. It has a detoxification effect on toxic substances, which helps expel heavy metals and their complexes outside the body quickly.

The nicotine of cigarettes or a large amount of alcohol (the moderate amount is not a problem) can drain magnesium. Also, the intake of magnesium can impair the action of hypothyroidism drugs like levothyroxine. A common side effect of intake of magnesium supplements is passing of soft stool and onset of diarrhea. Hence, take the supplement under supervision.

9) Vitamin K2 as Menatetrenone
Tumor necrosis factor α (TNFα) antagonists play an indispensable role in curing psoriasis. Due to this reason, biologics such as infliximab (Remicade®), etanercept (Enbrel®), and adalimumab (Humira®) are in use for treatment.

Yet, the approval of these biologics is contradictory in patients with diseases like chronic leg ulcers, chest infections, congestive cardiac failure, and malignancy. The reason behind this is their immunosuppressive nature and high cost.

Vitamin K2 is a bonus alternative as it can inhibit the production of TNFα, is safe and economical, making it the best choice for the treatment of psoriasis.

Psoriasis Frequently Asked Questions (FAQs)

I’ve been asking by many patients while treating psoriasis. So i write here frequently asked question by patients.

1) What is the success rate you’ve seen from this program in curing Psoriasis?

With the use of ointment, about more than 90% of the lesions disappeared. It is used for symptomatic treatment and cannot cure internal problems, but it improves social life significantly. Without the intake of medicines (Cepharanthine/ Erythrocin), and supplements (Shell Ginger/ other), the symptom might reappear anytime soon.

With Cepharanthine, Erythrocin, Shell Ginger, and other supplements, you can be free from psoriasis for a year or more. After that, we cannot predict the duration it takes to be free from psoriasis as it depends upon numerous factors, particularly mental stress. Proper diets, low-stress levels, and exercise reduces the recurrence rate by less than 30%.

2) How much does the psoriasis treatment cost?

PS(1) 50 g: ¥4200
PS(1) 100 g: ¥7140
MAS (1) 50 g: ¥4200
MAS (1) 100 g: ¥7140
MA(1) 50 g: ¥4200
Erythrocin (64 tablets for a month): ¥3520
Cepharanthin (120 tablets for a month): ¥3960
Oil Paper (100 sheets): ¥1600
Bio-Three (60 packs for a month): ¥1380
Minimum Shipping Cost: ¥1400 (to Asia), ¥2000 (North America, Australia, New Zealand), ¥2200 (Europe), ¥2400 (South America, Africa)
Consultation: Free, if on the Internet.

One US dollar ($) is 105 ～115 Japanese yens(¥). It depends on the exchange rate of the day. Therefore, for exmaple, PS(1) 50g costs $36.5 ～$40.

3) Do these pills and supplements have to be taken forever?

You don’t need to take them forever!

Erythromycin: Take for at least 12 weeks (about 3 months).
Cepharanthine: At least for 6 months. If possible, for 12 months.
But if recurrence occurs, for example, after one year, it is again recommended to take them for 3 more months.
Biotin: 6 months at least.
Probiotics: 6 months at least.
For Zinc, Copper, Selenium: For 3 to 6 months.
Take Omega-3 Unsaturated Fatty Acid, Inositol, Magnesium, Shell Ginger for at least half a year.

These natural supplements for psoriasis are effective for “Maintenance Therapy” of psoriasis. Moreover, it aids in preventing cancer, cardiovascular diseases, cerebrovascular diseases, rheumatoid arthritis, depression, etc.
I’ve been taking these supplements for more than ten years to maintain my general health. Hence, I recommend them for a longer duration.

4) Are there any of the small side effects I should be aware of with the two pills -- Cepharanthine and Erythrocin?

I’ve not witnessed any adverse side effects caused by these two medicines. Except one of my patients complained of abdominal bloating after taking Cepharanthine. I advised him to discontinue the medication. If any symptom appears after taking medicine, please consult your doctor.
Erythromycin (Erythrocin®)
Contraindications: If you are taking the following drugs, please don’t take Erythromycin.
Ergotamine tartrate / anhydrous caffeine / isopropylantipyrine / dihydroergotamine mesylate / Pimozide / Asunaprevir

Attention: If you are on one of the following medications, please consult your doctor before using Erythromycin along with the medicines.
Antiarrhythmic drug/Warfarin potassium/Theophylline/Aminophylline hydrate/Cyclosporine/Crolimus hydrate/Digoxin (Lanoxin)/Felodipine (Plendil,Renedil)/Valproate (VPA) (to treat epilepsy)/Midazolam/Carbamazepine(Tegretol)/Colchicine/Simvastatin/Atorvastatin(Lipitor)/Pitavastatin/Blonanserin/Ebastine/Edoxaban/Zafirlukast/Ritonavir/Cimetidine(Tagamet)/any anti-cancer drugs.

Caution: If you are on Calcium Channel Blocker (such as Amlodipine) for lowering your blood pressure, please avoid taking Erythromycin. It is because the combination of Amlodipine and Erythromycin may lead to hypotension.
Azithromycin is a macrolide antibiotic and is safe with Amlodipine. Also, macrolides are very important in the treatment of psoriasis. Thus, if you are currently under the medication of CCB, Azithromycin is the most suitable choice. But its potency is less than that of Erythromycin.

Patients often ask, “If I have been taking Erythrocin, an antibiotic for three months, are the side effects unsafe?”. The answer is that it is generally not dangerous unless you have severe disease. For example, Erythrocin is prescribed in cases like COPD (Chronic Obstructive Pulmonary Disease) continuously for one year. If we compare the side effects, the side effects of erythromycin are pretty minimal as compared to steroid pill/immunosuppressants such as Methotrexate, biologics such as ustekinumab (Stelara).

Even so, if any symptoms appear with Erythrocin (or Azithromycin), you should immediately stop it and consult your doctor.

Cepharanthine (Cepharanthin®)

There are no contraindications observed with Cepharanthine yet.

5) How much do I need the ointment?

It depends upon the size and number of plaques or eczema. So, it is not possible to say how much you need it. But for mild cases, usually, 50 g/month is enough. After the lesion disappeared, you don’t need it till relapse.

6) What dietary recommendations and foods to avoid with psoriasis?

There are certain foods to avoid with psoriasis, but the one-word answer for this question is becoming a vegetarian!! I can understand that for many, this diet is hard to adopt. Still and all, try to avoid animal products such as meat, milk and cheese, and whey as much as possible.

Looking through history, about 150 years ago, when western civilization was unknown in the east, people did not consume meat as Buddhism prohibited meat-eating and the killing of animals. Psoriasis was foreign in the east at that period. After the influence of Western culture, psoriasis began to emerge in Japan but, it is not as prevalent as in the US and Europe. The prevalence of psoriasis in Japan is 2 to 3 of 1000 people and 2 to 3 out of 100 people in the US. The prevalence rate is ten times higher in the United States. It is not due to genetics but rather because of diets.

Since the diet plays a vital role in curing several ailments, it is necessary to find out what kind of food triggers psoriasis in your case. As psoriasis rarely occurs in strict vegetarians., the best and cheap treatment of psoriasis is to become a vegetarian.

Adopting a vegetarian diet can reduce the symptoms in three years. Some patients try a low carbohydrate diet. But a low carbohydrate diet contains excess lipids and protein, which worsen psoriasis.

Q. If a high carbohydrate diet is unhealthy for psoriasis, why do the Americans suffer more than the Japanese?

A. Rice, a rich source of carbohydrates, is the staple food of Japan. Undoubtedly, an excess amount of carbohydrates is harmful to psoriasis, but excess lipid is even worse. By seeking a proper diagnosis of your condition, you can find the best psoriasis treatment.

* Periodic Fasting: You can practice it even once in a half year. It can give a good rest to your intestine, helps for detoxification, and improve the condition of psoriasis soundly. You can either visit a clinic offering a fasting course or can easily find it on the internet. Please do not practice it without consultation.

Additional Notes for Psoriasis Treatment Guidelines

Iron
There is an association between the metabolism of iron and psoriasis. When anemic patients with psoriasis take iron supplements, their condition deteriorates, as red blood cells contains iron. You must stop taking unnecessary iron supplements in such cases. It also explains why the symptoms ease when a psoriasis patient gets phlebotomy (bloodletting).

Please don’t take excess vitamin C supplements, as it stimulates the absorption of iron.

Probiotics
Probiotics improve digestion by increasing good bacterias and crowding out harmful bacterias in our gut.

Intestines are the largest immune system organ in the human body. Here, many hair-like villi occupy the small intestine with Payer’s patches. These patches have a crucial role in monitoring the immune system. Besides, our gut is known as the second brain due to its connection with the brain. Together, the brain and the intestine control our emotions, stress, cravings, and sleep.

It explains the importance of maintaining the intestinal environment to maintain a healthy state. The severe symptoms of psoriasis, caused by extreme stress and anxiety, can only be resolved by ensuring the good health and functioning of the intestine.

We use a preparation called Bio-Three. It is the trade name of a probiotic product, which contains three active strains of host-friendly bacteria, E.faecalis T-110, C.butyricum TO-A, and B.mesentericus TO-A. Research has shown that the combination of these three bacteria provides optimal synergistic effects.

For more details, please open http://www.bio-three.com/. It is the website of the manufacturer, but it might not be available in your country. If so, please find any suitable probiotics on the internet. You may have to try three or four different probiotics until you find the best one that suits your intestine.

* Also, try to eat one apple a day. The pectin of the apple has dietary fiber and helps in maintaining a healthy environment in the intestine.
* Ayurvedic medicine recommends cleaning our tongue because it helps to improve your gut flora. Please clean your tongue with a tongue cleaner twice a day. You can find a tongue cleaner easily on the internet or in a general store.

Detoxification
Detoxification is necessary to eliminate substances like heavy metals, toxic chemicals, artificial food additives, fragments of medicines, viruses, bacteria, etc., that cause psoriasis.

It is a great traditional system of medicine, including classical Chinese, Ayurvedic, and Tibetan medicine. According to the conventional method, toxins collected in the body undergo detoxification before prescribing therapeutic medication. In contrast, the modern practice provides prescriptions to patients with no prior detoxification.

One of the best ways of detoxification is taking a sauna (thermal bath), especially one using far-infrared rays. In this method, toxic substances excrete through sweat. Yet, one should not take saunas more than three times a week.

Bloodletting (phlebotomy) is also an effective way of detoxification. A warning, which may seem obvious, but is critical anyway, is never to undertake phlebotomy on your own. Only trust experienced health professionals to carry out the process. Please have a look at this: https://en.drmakise.com/shaketsu/.

* Drink plenty of water: You should drink at least 1- 2 liters of water per day, preferably in the morning. Water detoxifies many toxic matters that intensify psoriasis. But if you have a kidney problem, please consult your doctor about the safe level of water intake.

Ultraviolet (UV) Light
Solar UV light stimulates the production of vitamin D, which is necessary for the cure of psoriasis. Vitamin D minimizes the scaling of the skin by decreasing the overproduction of skin cells. Still, sunbathing near the window is not an effective method. The best way is to stay under the natural rays of the sun. It may take several weeks to see an improvement in your psoriatic lesions. Some people even travel to a tropical zone, an approach worth trying.

UV blood irradiation therapy also uses UV light, today commonly known as photoluminescence. It is a modern technique to treat diseases, including psoriasis, and is safe from adverse side effects.

Go to bed early
Sleep is one of the overlooked aspects of maintaining good health. You should go to bed at least by 11 pm, and if you go to bed later than midnight, your psoriasis can never get cured.

The growth hormone secretes from the pituitary gland between 11 pm to 3 am (3 hours after you fall asleep). Late sleeping habits can hinder the release of the growth hormone and impact skin damage. You know well that the human growth hormone is flaunted very much as an anti-aging supplement. Some anti-aging clinics offer injections of growth hormones, but the best way is to go to bed earlier. Note that the growth hormone gets secreted even if you are 80 years old or more.

When the blood glucose level is high, the pituitary gland cannot secret growth hormones sufficiently. Thus, do not go to bed at least 2 hours after dinner.

Caution
If you feel joint pain, stiffness, or swelling along with the skin symptoms of psoriasis, please consult your doctor first. You might be suffering from Psoriatic Arthritis, and you may have to take immunosuppressants such as Methotrexate immediately to avoid deformation of joints.

Concluding remarks

I have treated many people in Japan with this approach for the treatment of psoriasis. Even though psoriasis is a chronic skin disease, its symptoms can be alleviated and even cured by proper care and supervision. Using ointments for psoriasis is one of the best ways to relieve the symptoms of psoriasis. The origin of this disease is due to viruses that infect skin cells and affects the immune system.

Hence, the inactivation of viruses with oral medications, use of ointments, and maintenance therapy of minerals and vitamins can treat psoriasis efficiently and effectively. If you practice proper care, guidance, medicines, and diet, you can even prevent relapse of this disease.

The post Supplements, Medicine and Ointment for Psoriasis: Effective and Unique Treatment From Japan appeared first on STG Makise Lifeup USA.

The Emperor’s Fungus for Health and Immortality

CustomerTeam — Fri, 27 Mar 2020 03:15:58 +0000

If I were an emperor in ancient China and faced against pandemic of Flu-like disease from Wuhan, immediately I would send thousands of soldiers to Tibet to exploit hundreds of tons of Cordyceps there. The soldiers should bring back them all to China. And I gave Cordyceps to my people, because Cordyceps has strong effect to empower immune system and also to improve lung function. These two effects are essential to conquer any types of “Flu”, including COVID-19.

Cordyceps has been shown to increase the activity of natural killer cells and the ability to produce IL-2, and to increase the nonspecific immunity by activating the phagocytic ability of macrophages. Therefore, Cordyceps has devastating effects against any viruses.

Cordyceps is a genus of parasitic fungi that grows on the living larvae of insects. In Japanese it is called “” which means ‘in winter insect, in summer grass’, because Cordyceps is insect-like during the winter and grass-like during the summer. Usually two Cordyceps, “Cordyceps sinensis” and “Cordyceps militaris”, are used to improve our health in Oriental medicine. (Cordyceps sinensis is called now Ophiocordyceps sinensis). Both Cordyceps exert wonderful health effects and have been loved by a lot of people since more than 2000 years ago in Asia.

It grows mainly in the meadows above 3,000 to 4,000 meters in the Himalayan regions such as Tibetan Plateau, Nepal, Bhutan, and also in Sichuan, Yunnan of China. But if you were very lucky, you could find Cordyceps like the picture in your country, too. The photo was taken in Shirakami-Sanchi that is a mountainous area located in northern part of Japan.

I’ve been studying mushrooms for medical use since more than 25 years ago, and have come to the conclusion that this fungus has the most versatile health effects clinically for humans and brings about the quickest effects among so called medicinal mushrooms. Due to its excellent effects for health, in TM (Tibetan Medicine) and in TCM (Traditional Chinese Medicine), doctors have been prescribing Cordyceps. And nowadays even in mainstream medicine doctors began to use Cordyceps as safe adjuvant treatments for cancer, Alzheimer’s disease, diabetes, and cardiovascular problems, etc. Therefore, the demand for Cordyceps is increasing every year, and the natural Cordyceps in Qinghai-Tibetan Plateau, Bhutan, Sichuan, Yunnan are over-collected. Consequently, the prices have skyrocketed.

15 years ago I went to Tibet and bought Cordyceps. I don’t remember exactly the price, but I got surprised at the expensiveness compared with the prices of daily commodities. And when I flew back to Japan from Lhasa via Beijing, my precious Cordyceps were all stolen at Beijing Airport!! Cordyceps used to be worth more than 4 times its weight in silver. Now (2020) 1 gram of Cordyceps costs more than $80. It is called ‘Soft Gold’. In addition, lots of fake or very poor quality Cordyceps are on the market in China, making it difficult to get genuine ones. Therefore, various efforts have been done to develop technique for artificial culture of Cordyceps. Finally, in 1993 the team of Japanese and Chinese researchers succeeded in the artificial culture of Cordyceps militaris by using aseptically-cultured silkworms.

In the United States, too, supplements of Cordyceps are sold. But the most of them are mycelia (root part) cultured in a synthetic medium, or fruiting bodies cultured in a medium such as cereals or grains. The mediums are not larvae of insects. However, if the medium is not a living creature, the most important components of Cordyceps for health are missing.

The Japanese new method is infecting living silkworm pupae with fungi of Cordyceps militaris and growing it using the pupae as a medium, similar to the mechanism by which natural Cordyceps grow.

A) Anti-Cancer Effects

Cordyceps has been shown to increase the activity of natural killer cells and the ability to produce IL-2, and to increase the nonspecific immunity by activating the phagocytic ability of macrophages. In addition, antioxidant and anti-inflammatory effects, angiogenesis inhibitory effects, and direct suppression of cancer cell growth have been reported.

The main substance that exerts anti-cancer effect is Cordycepin.(see Fgure) that is contained much more in Cordyceps militaris than in Cordyceps sinensis.

Although in vitro, Cordycepin is proved significantly inhibits cell proliferation in almost all the cancer cell lines such as human lung cancer cell, breast cancer, ovarian cancer, gastric cancer, colon cancer, hepatocellular cancer, brain cancer, leukemia, etc.

The mechanism of antitumor effects has been reported to include DNA and RNA synthesis inhibition, apoptosis induction, inhibition of transcription factor NF-κB activity, and inhibition of cancer cell proliferation signaling. The effect of suppressing metastasis of cancer cells has also been reported. Since Cordycepin is an adenosine derivative, it has been reported that adenosine A3 receptor stimulation may suppress cancer cell growth.
Cordycepin has also been reported to activate AMP-activated protein kinase (AMPK), which is activated by adenosine-1-phosphate (AMP). AMPK plays an important role in intracellular signaling that suppresses the growth of cancer cells.

B) Anti -Alzheimer's disease

Cordycepin has a protective effect on the CNS (central nervous system) against excitotoxicity neuronal damage by inhibiting the neuronal hyperexcitability. And a recent study has confirmed that Cordycepin exerts neuroprotective effects by inhibiting Aβ-induced hippocampal neuronal apoptosis via activating adenosine A1 receptor.

Although in vitro, methanol extract of Cordyceps militaris stimulates primary neurite sprouting and extension of Neuro2A cells in a dose-dependent manner. And it alleviates decrease in cholinergic immunoreactivity in the hippocampus.
Cordycepin (3′-deoxyadenosine) is an adenosine analog. The structure of Cordycepin comprises a purine (adenine) nucleoside molecule attached to a ribose sugar (ribofuranose) moiety via a β-N9-glycosidic bond. These characteristics indicate that the protective effect of Cordycepin on the CNS may be closely associated with A1R.

C) Improve Cardiovascular Health

a) Better Cholesterol Profile

Cordiceps has effects to reduce serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C).
Cordyceps militaris cultured in the body of living pupae usually contains β-glucan 8.04g/100g, ergosterol 757mg/100g. Both substances attribute to reduce cholesterol absorption from the intestine.

b) Anti-Hypertension

Although in rats, Japanese researchers proved that Cordyceps militaris improves the survival of Dahl salt-sensitive hypertensive rats possibly via influences of mitochondria and autophagy functions.
Excessive salt intake causes high blood pressure. This is scientifically well proved, But we are consuming too much salt without even realizing it, because salt is hidden in instant foods and junk foods in particular. Many restaurants also use excess salt to stimulate palatability to attract more customers. We are living in too much ‘Salted Life’. Therefore, Cordyceps can help us from our unhealthy meal environment.

c) Prevent Cardiac Hypertrophy

Cordycepin which is the main ingredient of Cordyceps militalis ameliorates cardiac hypertrophy via activating the AMPKα pathway and attenuates oxidative stress both in vivo in Cordycepin‐treated mice and in vitro in Cordycepin treated cardiomyocytes.
Nowadays heart failure is increasing with aging. To prevent it taking Cordyceps prophylactically is much recommended.

D) Anti-Diabetic Effects

Water extract of Cordyceps militaris improves insulin resistance by enhancing glucose utilization in skeletal muscles such as soleus and quadriceps muscles.

Cordyceps polysaccharide can enhance insulin signaling transduction and glucose metabolism resulting in reducing insulin resistance and hyperglycemia symptom.

Chinese classical Materia Medica, “Ben Cao Bei Yao ” by Wang Ang , published in 1694 wrote that Cordyceps could strengthen the kidney function. In the experiment of rats, extract of fruiting body of Cordyceps militaris was found to reduce membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway. Diabetics often suffer from renal function and may have to undergo dialysis. Therefore, Cordyceps is very much recommended to prevent the progress of diabetes.

E) Reduce Inflammation

A characteristic of blood components common to centenarians is that their CRP (C-reactive protein) value which indicates the degree of inflammation in the body is very low. Its normal range is below 0.3mg/dl, and the lower the better for longevity. When chronic inflammation lasts, it gradually induces deterioration of many organs, causing premature aging. I once saw a woman with 0.03 mg/dl CRP that is only one tenth of the normal level. She was 101 years old and very healthy, working in her shop every day.

Cordycerebroside A, the new cerebroside, along with soyacerebroside I and glucocerebroside inhibited the accumulation of pro-inflammatory iNOS protein and reduced the expression of COX-2 protein in LPS-stimulated RAW264.7 macrophages.

Cordycepin that is the most important substance contained in Cordyceps militaris is reported to suppresses the NF-κB (nuclear factor-kappaB), Akt, and MAPK (mitogen-activated protein kinases) signaling pathways that induces inflammation.
In addition, Cordycepin functions as a polyadenylation inhibitor to reduce inflammation.

F) Improve Exercise and Sexual Performance

Since hundreds of years ago Cordyceps has been used as an excellent remedy for weakness and fatigue by the residents in Tibetan Plateau, Nepal, and Bhutan to give them energy. The people know empirically its energy enhancing effects of Cordyceps. The key substance for energy production is Cordycepin. It is also called 3′-deoxyadenosine, and has a structure in which the hydroxyl group (OH group) has been deleted from the 3 ‘position of adenosine.

Adenosine is one of the nucleosides consisting of adenine and ribose, and is involved in energy transport as part of ATP and ADP, and in signaling as cyclic AMP. Therefore, one of the mechanisms of action of Cordycepin has an effect on the function of adenosine. So, Cordycepin is said to increase ATP by 30%, and athletes often take Cordyceps to enhance their endurance during exercise.

During convalescence of diseases, patients are recommended to take Cordyceps to recover from exhaustion of physical strength.
In both TM (Tibetan Medicine) and TCM (Traditional Chinese Medicine), Cordyceps has been used to improve fertility treatment in men. Cordyceps exerts the positive effect on sperm productivity, motility, kinematics, morphology, and enhancement of sexual activity. It contains various spermatogenic factors. Therefore, Cordyceps is called Himalayan aphrodisiac.

In addition, Cordyceps improves kidney function due to its capability to elevate 17-ketosteroid and 17-hydroxycorticosteroid levels, and protects sodium pump activity of tubular cells, accelerates tubular cells regeneration. Strong kidney function is one of the most important factors that improve sexual performance. Decreased renal function often results in ED (erectile dysfunction) and reduced fertility.

References

Anti-Cancer Effects : 1)~8)

Specific antiproliferative activity against human cancer cells with metabolites from several species related to the genus Cordyceps
http://www.tochukaso.co.jp/Yukiko_Ogawa_et_al_IJCMAS.pdf
Cordycepin inhibits breast cancer migration and invasion by targeting epithelial to mesenchymal transition-inducing transcription factors (EMT-TFs)
https://cancerres.aacrjournals.org/content/78/13_Supplement/2039.short
Cordycepin induces human lung cancer cell apoptosis by inhibiting nitric oxide mediated ERK/Slug signaling pathway
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385633/
Cordycepin induces apoptosis of human ovarian cancer cells by inhibiting CCL5-mediated Akt/NF-κB signaling pathway
https://cancerres.aacrjournals.org/content/79/13_Supplement/709.short
Preclinical study of the fungal derivative cordycepin as an anti-cancer agent
https://mct.aacrjournals.org/content/18/12_Supplement/A062.abstract
Cordycepin induces apoptotic cell death of human brain cancer through the modulation of autophagy
https://www.sciencedirect.com/science/article/abs/pii/S0887233317302849#
Mushroom consumption and incident risk of prostate cancer in Japan: A pooled analysis of the Miyagi Cohort Study and the Ohsaki Cohort Study
https://onlinelibrary.wiley.com/doi/full/10.1002/ijc.32591
Cordycepin, a Natural Antineoplastic Agent, Induces Apoptosis of Breast Cancer Cells via Caspase-dependent Pathways
https://journals.sagepub.com/doi/abs/10.1177/1934578X1601100119

Anti -Alzheimer’s disease:1)~5)

Effects of cordycepin on spontaneous alternation behavior and adenosine receptors expression in hippocampus
https://www.sciencedirect.com/science/article/abs/pii/S0031938417304171
Protective role of Cordyceps militaris in Aβ1–42-induced Alzheimer’s disease in vivo
https://link.springer.com/article/10.1007/s10068-018-0521-z
Cordycepin protects against β-amyloid and ibotenic acid-induced hippocampal CA1 pyramidal neuronal hyperactivity
https://synapse.koreamed.org/DOIx.php?id=10.4196/kjpp.2019.23.6.483
Cordyceps Militaris improves neurite outgrowth in Neuro2A cells and reverses memory impairment in rats
https://link.springer.com/article/10.1007/s10068-011-0221-4
Neuroprotective and therapeutic effect of Cordyceps militaris on ischemia-induced neuronal death and cognitive impairments
https://www.sciencedirect.com/science/article/pii/S1319562X1830192X

Improve Cardiovascular Health :1)~3)

Cordycepin prevents hyperlipidemia in hamsters fed a high-fat diet via activation of AMP-activated protein kinase.
https://www.ncbi.nlm.nih.gov/pubmed/20724804
Lipid-lowering effect of cordycepin (3′-deoxyadenosine) from Cordyceps militaris on hyperlipidemic hamsters and rats.
https://www.ncbi.nlm.nih.gov/pubmed/21882527
Cordycepin ameliorates cardiac hypertrophy via activating the AMPKα pathway
https://onlinelibrary.wiley.com/doi/full/10.1111/jcmm.14485

Anti-Diabetic Effects:1)~6)

Improvement of Insulin Resistance and Insulin Secretion by Water Extracts of Cordyceps militaris, Phellinus linteus, and Paecilomyces tenuipes in 90% Pancreatectomized Rats
https://www.tandfonline.com/doi/abs/10.1271/bbb.68.2257
The anti-hyperglycemic activity of the fruiting body of Cordyceps in diabetic rats induced by nicotinamide and streptozotocin.
https://www.ncbi.nlm.nih.gov/pubmed/15050427
Effects of Cordyceps Polysaccharide on InsR/IRS-1 Pathway and Glucose Metabolism in Type 2 Diabetic Mice
http://en.cnki.com.cn/Article_en/CJFDTotal-ZYSG201102007.htm
Hypoglycemic Activity through a Novel Combination of Fruiting Body and Mycelia of Cordyceps militaris in High-Fat Diet-Induced Type 2 Diabetes Mellitus Mice
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519550/
Cordyceps militaris Treatment Preserves Renal Function in Type 2 Diabetic Nephropathy Mice
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104498/
Extracts of Cordyceps militaris Lower Blood Glucose via the Stimulation of Cholinergic Activation and Insulin Secretion in Normal Rats
https://onlinelibrary.wiley.com/doi/abs/10.1002/ptr.3709

Reduce Inflammation:1)~5)

Anti-inflammatory Cerebrosides from Cultivated Cordyceps militaris
https://pubs.acs.org/doi/abs/10.1021/acs.jafc.5b05931
Effects of the Immunomodulatory Agent Cordyceps militaris on Airway Inflammation in a Mouse Asthma Model
https://www.sciencedirect.com/science/article/pii/S1875957209600048
Ergosterol of Cordyceps militaris Attenuates LPS Induced Inflammation in BV2 Microglia Cells
https://journals.sagepub.com/doi/abs/10.1177/1934578X1501000623
Regulation of human cytokines by Cordyceps militaris
https://www.sciencedirect.com/science/article/pii/S1021949814000301#!
The polyadenylation inhibitor cordycepin reduces pain, inflammation and joint pathology in rodent models of osteoarthritis
https://www.nature.com/articles/s41598-019-41140-1

Improve Exercise Performance:1) ～3)

Cordyceps militaris Improves Tolerance to High-Intensity Exercise After Acute and Chronic Supplementation
https://www.tandfonline.com/doi/abs/10.1080/19390211.2016.1203386
Studies on the Antifatigue Activities of Cordyceps militaris Fruit Body Extract in Mouse Model
https://www.hindawi.com/journals/ecam/2015/174616/
Aphrodisiac Effect of Cultured Cordyceps militaris in Aged Male Rats
https://www.tci-thaijo.org/index.php/TJP/article/view/222801

The post The Emperor’s Fungus for Health and Immortality appeared first on STG Makise Lifeup USA.

11 Effective Natural Supplements for Prostate Cancer Prevention

CustomerTeam — Thu, 26 Mar 2020 06:01:00 +0000

Natural Prostate Cancer Supplements that Prevent Prostate Cancer

Prostate cancer supplements are recommended for those who are suspected of having prostate cancer but whose PSA is still less than 10ng/ml and are in doubt about whether or not to undergo a biopsy, or who are on “watchful waiting/active surveillance” or his family member has a history of prostate cancer, ovarian cancer, breast cancer. A current estimate is that one in every six men in the United States will be diagnosed with prostate cancer.

The most important and basic prostate cancer supplements are :

Alpinia zerumbet (Shell Ginger) 2000 ～3000mg /day
Vitamin K2 100 mcg/day
IP6 1000 mg/day
Zinc 20 ～30 mg/day
Selenium 200 mcg/day
Fish Oil 2000～3000 mg/day

These prostate supplements are effective not only to make your prostate healthy but also to keep your cerebrovascular system young. Therefore even if you don’t suffer from any prostate problems or if you are a woman, these supplements are recommended.

If your PSA is higher than 10ng/ml, or if your PSA is increasing after 3-month-take of these supplements, please add one or two of the followings. Or if affordable, from the beginning, you can take one of them below together with above supplements for prostate cancer.

Pomegranate
Saw palmetto
Epilobium
Green tea extract (epigallocatechin gallate)
Pygeum

If your Gleason score is high, please don’t rely on alternative natural supplements alone. Surgery, or radiation, or hormone therapy is imperative. Otherwise metastasis would take place. Natural supplements have their own limit. They are not a panacea.

If metastasis already occurred, immediately undergo modern mainstream medicine. Please trust it, too. And in any cases, when you take the natural supplements, please talk to your doctor.

1) Alpinia zerumbet (Shell Ginger : JIPANG Ginger®)

Alpinia zerumbet is its scientific name, and Shell Ginger is the common name. This is a perennial plant of the ginger family. But Shell Ginger is not the same as ordinary ginger. Don’t confuse it with ordinary ginger. Very much different in health benefits. It contains various phytochemicals such as followings.

Polyphenols

Ferulic acid: It acts on the cell cycle of prostate cancer cells and promotes apoptosis of cancer cells.
(https://link.springer.com/article/10.1007/s13277-015-3689-3)
Quercetin: It suppresses androgen receptor function of prostate cancer cells.
(https://academic.oup.com/carcin/article/22/3/409/2733786)
Kaempferol stimulates the macrophage colony-stimulating factor of cancer cells.
(https://www.sciencedirect.com/science/article/pii/S0303720708000245#!)

These 3 polyphenols are just typical examples. Shell Ginger contains much more polyphenols. Therefore it shows very strong antioxidant effect synergistically.

ORAC (Oxygen Radical Absorbance Capacity) FAZM (Fermented Powder of Leaves of Alpinia zerumbet-MAKISES: JIPANG Ginger®)
Lactones : DDK (dihydro-5,6-dehydrokawain) & DK (5,6-dehydrokawain)
The most characteristic of Shell Ginger is that it contains DDK and DK very much.
- DDK and DK have the interleukin-12 (IL-12) inhibitory activity.
  Selective neutralization of IL-12 p40 monomer induces death in prostate cancer cells via IL-12–IFN-γ.
  (https://www.pnas.org/content/114/43/11482.short)
- DDK and DK inhibit directly PAK1 (RAC/CDC42-activated kinase 1) which is the major oncogenic kinase that is responsible for a wide variety of diseases such as cancers.

2) Vitamin K2

When varicocele occurs, free testosterone flows in the veins near the prostate 130 times more than usual. Testosterone itself does not cause prostate cancer, but dihydrotestosterone (DHT), which is metabolized from it, is produced in large quantities. The prostate has an enzyme called 5-α-reductase that converts testosterone to DHT. DHT is the culprit that causes hyperplasia or cancer of the prostate. It is necessary to prevent thickening and calcification of smooth muscles in the venous wall media that cause varicocele. That requires vitamin K2.

Caution: People taking warfarin should not take vitamin K2.

3) IP6

This is an abbreviation for inositol hexaphosphate, also called phytic acid. A type of phosphoric acid compound in which inositol is bound to phosphoric acid.
About 60 years ago, research began when applied to the prevention and treatment of kidney stones. Since then, it has been found that IP6 has many beneficial effects such as reducing the risk of coronary heart disease, thrombosis, embolism, etc. by improving platelet aggregation, improving lipids such as cholesterol, and preventing anemia. Of particular interest is its anticancer effect. It is effective against colorectal cancer, breast cancer, lung cancer, leukemia, and malignant melanoma. It is also effective against prostate cancer.

Prostate Cancer and Inositol Hexaphosphate: Efficacy and Mechanisms (http://ar.iiarjournals.org/content/25/4/2891.short)

4) Zinc

Zinc can also be used as supplements for prostate cancer. Prostate cells usually contain a lot of zinc, but when prostate cancer develops, zinc gets significantly reduced. In order to suppress the growth of cancer cells, a large amount of zinc is required to block the expression of androgen receptor in prostate cells.
Zinc Inhibits Expression of Androgen Receptor to Suppress Growth of Prostate Cancer Cells（https://www.mdpi.com/1422-0067/19/10/3062）

5) Selenium

Selenium is another thing that is usually recommended when it comes to prostate cancer supplements. Selenium is an essential component mineral of an enzyme called glutathione peroxidase, a high molecular weight antioxidant. Therefore a shortage of selenium brings about greatly reduced ability to scavenge oxygen radicals.

The selenium content of the toenails is accurate indicator of how much selenium has been consumed over time. The amount of selenium in the toenails of 58279 men (55-69 years old) in the Netherlands and the incidence of prostate cancer were followed up for 6.3 years. The smaller the amount of selenium, the higher the incidence of prostate cancer. (Similar results for lung cancer).
After 6.3 years of follow-up Toenail Selenium Levels and the Subsequent Risk of Prostate Cancer (http://cebp.aacrjournals.org/content/12/9/866.short)

6) Fish Oil : EPA (eicosapentaenoic acid) & DHA (docosahexaenoic acid)

This is a study in Auckland, New Zealand. They compared EPA and DHA-derived phosphatidylcholine levels in red blood cells of 317 prostate cancer patients and 480 non-prostate cancer patients. Those who consumed a lot of EPA and DHA had a lower incidence of prostate cancer.
Prostate cancer risk and consumption of fish oils: A dietary biomarker-based case–control study
(https://www.nature.com/articles/6690835）

EPA and DHA are abundant in fish oil. These two omega-3 unsaturated fatty acids are thought to act on the metabolic pathway of arachidonic acid. The presence of excess arachidonic acid increases the enzyme 5-LOX (5-lipoxygenase). This enzyme stimulates the growth of prostate cancer. This enzyme also converts arachidonic acid into a fatty acid called 5-HETE (5-hydroxyeicosatetraenoic acid). This fatty acid inhibits cancer cell apoptosis. Prostate cancer tissue contains 6-times more 5-LOX than normal prostate tissue, and 5-HETE is 2.2 times more.
Arachidonic acid is abundant in red meat. It is also metabolized from vegetable oils such as safflower oil, sunflower oil and rapeseed oil, which contain a large amount of unsaturated fatty acids of omega-6.

Therefore, to prevent prostate cancer, avoid eating meat and don’t use vegetable oils. And eat fish that is high in EPA and DHA.
*If Krill Oil is available, it is more recommended than Fish Oil because Krill Oil contains Astaxanthin, too

7) Pomegranate

Combinations of ellagic acid, luteolin, punicic acid, etc., abundant in pomegranate, have proven to be particularly effective for prostate cancers that are prone to metastasis.

Luteolin, ellagic acid and punicic acid are natural products that inhibit prostate cancer metastasis
(https://academic.oup.com/carcin/article/35/10/2321/323353)

And urolithin A, which is metabolized from ellagic acid by intestinal bacteria, promotes prostate cancer apoptosis.
Urolithin A induces prostate cancer cell death in p53-dependent and in p53-independent manner.
(https://www.ncbi.nlm.nih.gov/pubmed/31177307)

In addition, urolithin A does not only bring about good effects for prostate health but also activates mitochondria and prevents muscle weakness. It is also effective against muscle loss due to aging, so-called “sarcopenia”.

The prevalence of prostate cancer increases with age. In other words, it is often at the age of sarcopenia. Therefore, it should be very reasonable to supplement phytochemicals such as ellagic acid with pomegranate since when you are still robust late 40s. Pomegranate also has a blood pressure lowering effect and LDL cholesterol reducing effect, so it can be used as a supplement against metabolic syndrome. People with metabolic syndrome are more likely to have problems with the prostate. So this is also very effective for prostate cancer supplement.

8) Saw palmetto

This plant is a short palm native to North America. It is called so because the leaves are jagged like a “saw”. It has been used to reduce prostate enlargement all over the world.

Often people think testosterone causes prostate enlargement or prostate cancer. But that’s wrong. The villain is not testosterone. If testosterone is the cause, why does prostatic hyperplasia or prostate cancer rarely occur during the youngest period when testosterone level is the highest? The real cause is dihydrotestosterone (DHT). And with aging, testosterone is converted by aromatase into estrogen that proliferates prostate tissue.

Saw palmetto extract inhibits the activity of 5-α-reductase of the prostate and prevents testosterone from being converted into dihydrotestosterone (DHT). DHT not only proliferates prostate tissue and causes prostate enlargement, but also upregulates androgen and CXCR4 (a type of chemokine) receptor to promote prostate cancer metastasis. Therefore, this prostate supplement is recommended especially for the patients on “watchful waiting/active surveillance”. Fibroblast growth factor (b-FGF), which is produced from testicular stromal cells, also promotes prostate enlargement, while saw palmetto extract suppresses the production of this factor.

It also blocks the effect of two enzymes, cyclooxygenase and lipoxygenase, reducing the inflammatory eicosanoids produced by these two enzymes and improving prostatitis, urethritis, and cystitis. If you search for “saw palmetto prostate” on Google Scholar, more than 100 papers will appear in 2019 alone. In other words, saw palmetto has been studied so much.
(https://www.sciencedirect.com/science/article/pii/B978012811397400007X#!)

9) Epilobium (Fireweed)

This plant has various effects on anti-inflammatory, anti-proliferation, antioxidant, anti-bacterial and anti-aging. Epilobium flavonoids and ellagitannins are considered the main active ingredients. In particular, oenothein B, a macrocyclic ellagitannin, inhibits hormone-dependent prostate cancer growth and reduces PSA secretion.

It is also converted into urolithins A, B, and C by intestinal bacteria, and urolithin C shows the strongest anticancer effect.

Oenotein B inhibits 5-α-reductase and prevents testosterone from being converted to DHT (dihydrotestosterone). This is the same as the action of saw palmetto extract.
In addition, it has a strong antibacterial effect against H. pylori and S. aureus.
Therapeutic Potential of Polyphenols from Epilobium angustifolium (Fireweed) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045895/#R135)

10) Green tea extract (epigallocatechin gallate)

Japanese men have less prostate cancer than foreign men because they drink tea more often”. This is often said not only about prostate cancer but also about lung cancer and colon cancer.

The catechins that are abundant in green tea are classified into polyphenol flavonoid flavanols, and there are mainly four types such as epicatechin, epigallocatechin, epicatechin gallate, and epigallocatechin gallate. Among them, epigallocatechin gallate is the most effective. It is often called EGCG for short. It is an ester of epigallocatechin and gallic acid. Green tea extract contains the most EGCG (approximately 60%).

Epigallocatechin is about 20%, epicatechin gallate is about 14%, and epicatechin is about 6%. The anticancer effect of EGCG has been studied extensively all over the world, and it has a comprehensive function such as promoting apoptosis of prostate cancer, blocking metastasis by inhibiting angiogenesis, and blocking the androgen receptor.

11) Pygeum

The scientific name is Prunus africana, an evergreen tree that grows in an African mountain forest and reaches a height of 30-40m. Traditionally, in Africa, drugs are made from the bark of this tree and used for antipyretic, stomach pain, dysuria and malaria. In recent years, its effects on prostate enlargement and prostate cancer have attracted attention, and it has been used in many countries as prostate cancer supplement.

The mechanism of action is due to the inactivation of prostate androgen receptors by compound, N-butylbenzene-sulfonamide (NBBS) , contained in Pygeum. Pygeum also inhibits an enzyme called 5-LOX (5-lipoxygenase). This enzyme stimulates the growth of prostate cancer. This enzyme converts arachidonic acid into a fatty acid called 5-HETE (5-hydroxyeicosatetraenoic acid). And this fatty acid inhibits apoptosis of cancer cells. Prostate cancer tissue contains 6-fold more 5-LOX than normal prostate tissue, and 2.2-fold more 5-HETE.

NBBS isolated from Pygeum africanum bark exhibits androgen antagonistic activity, inhibits AR nuclear translocation and prostate cancer cell growth
(https://link.springer.com/article/10.1007/s10637-009-9304-y)

Phytosterol Pygeum africanum regulates prostate cancer in vitro and in vivo
(https://link.springer.com/article/10.1007/s12020-007-0014-y)

Prostate cancer is one of the easiest cancers to cure.

With the exception of rare variants, prostate cancer is one of the easiest cancers to cure. This success in treatment is largely due to advances in surgery, radiotherapy, brachytherapy, and cryotherapy. Despite these improvements, there is a risk, albeit minimal, of erectile dysfunction (impotence) and incontinence in the wake of surgery or radiation therapy.

If surgery and radiation don’t cause impotence, hormone therapy ultimately leads to erectile dysfunction, and eventually prostate cancer cells become hormone refractory. For men with preexisting heart problem, androgen-deprivation therapy (= hormone therapy) increases the possibility of developing vascular disorders. Patients receiving chemotherapy can have serious side effects, affecting healthy cells and the immune system. Watchful waiting, also known as expectant management, is a reasonable strategy for men in their 70s or older, but for those under 70, that approach may be less appropriate. What is needed is more efficacious, safer, and noninvasive therapy for prostate cancer. A barrier is the limitations of what we know about the underlying mechanisms that drive prostate cancer and, like all cancers, various signaling pathways, proteins and genetic aberrations are involved, a complex process at best.

One theory is that prostate cancer is fueled by testosterone. However, very young men usually have a greater amount of free testosterone than older men, but rarely suffer from prostate cancer. Excess estradiol, converted from testosterone by aromatase, also plays a role in the development of prostate cancer. The hypothalamic-pituitary-gonadal axis, which controls embryonic development, reproduction and aging, is also involved. Gonadotropin-releasing hormone (GnRH) is produced by the hypothalamus, whereas luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are produced by the anterior part of the pituitary gland, and the gonads produce estrogen and testosterone. LH stimulates the production of testosterone and estrogen in testicular Leydig cells. The prostate cancer picture is further embellished by two enzymes, 5-lipoxygenase (5-LOX) and aromatase. 5-LOX is critical in the synthesis of leukotrienes from arachidonic acid, and exacerbates prostate cancer. 5-LOX converts arachidonic acid into 5-hydroperoxyeicosatetraenoic acid (5-HPETE), which is spontaneously reduced to 5-hydroxyeicosatetraenoic acid (5-HETE). 5-HETE is a fatty acid that abrogates apoptosis, or the death, of prostate cancer cells. Aromatase converts testosterone to estradiol, which in excess amounts is carcinogenic.

Thus, to tackle prostate cancer, novel therapies must fulfill various roles, including enhancing immunity, regulating hormone dysregulation and enzymatic activity. A supplement already exists that can address these mechanisms. Shell Ginger (Alpinia zerumbet) improves immunity and re-establishes hormonal and enzymatic homeostasis, or balance. The leaves of Shell Ginger have been long used to prepare a tea, which is commonly drunk by the people of Okinawa, who have one of the longest life spans in the world.

I discovered the medicinal properties and activities of Shell Ginger. For the past 30 years, I have traveled to more than 85 countries in my quest to discover natural substances that can improve human health. This effort led me to identify the most effective and safest herb for treating prostate cancer, JIPANG Ginger, whose main active ingredient is derived from the fermented leaves of Shell Ginger.

Plants get energy by photosynthesis, which releases reactive oxygen species. The stronger the sunlight is, the more free radicals are produced, requiring plants to adopt compensatory mechanisms for protecting their leaves and stalks. I and my research team discovered the fact that Shell Ginger grown in tropical soil is packed with dozens of polyphenols, such as ferulic acid, chlorogenic acid, quercetin, kaempferol, epicatechin, catechin, and others. These polyphenols act synergistically to become powerful natural antioxidants with the ability to protect normal human cells.

Caution

Other vitamins should NOT be taken with my anti-prostate cancer formula. Cancer cells are by nature fairly clever entities because of their ability to escape from capture and annihilation by the immune system and continue to propagate. They are so clever that when they become resistant to traditional therapies, which they almost always do when the patient lives long enough, they are able to spread cancer to other parts of the body, or transmutate into different types of tumors. Among their bag of clever tricks is their ability to use various vitamins and minerals that people take to destroy cancer cells or to allay their development in the first place, and instead paradoxically use the vitamins to grow and metastasize. Cancer cells are avaricious and opportunistic, so we must be very careful not to fuel them by taking too many different supplements.

For example, according to the study of Jane C. Figueiredo, PhD, of the University of Southern California, Los Angeles, “Folic Acid and Risk of Prostate Cancer: Results From a Randomized Clinical Trial”, folic acid supplementation was associated with an increased risk of prostate cancer. Vitamin C is no exception. The danger exists that cancer cells utilize vitamin C to grow. Thus, the commonly utilized mega dose vitamin C therapy is quite controversial and its benefits are moot.

Some people have asked why my prescription does not contain lycopene. Lycopene has long been touted as a natural and effective remedy for prostate cancer, and it is if it is ingested from whole tomatoes. The concentrated extract of lycopene, on the other hand, is dangerous, similar to β-carotene supplementation. Supplemental β-carotene has been associated with an increased risk of prostate cancer, cardiovascular disease and overall mortality in people who smoke cigarettes. The possibility exists that this danger extends to non-smokers. Lycopene is a carotenoid and too much of it is simply not safe, however, no one knows how much is too much.

Dr. Makise - After following your protocol of JIPANG Ginger and flax for 2 months, my PSA has fallen from 62 to 29. Hopefully, the next two months will have it down to 0. I'm down to my last bottle of JIPANG Ginger. I called your number and they said they were out of the product. Could you see that I get some more before I run out? Thank you. I used the JIPANG Ginger to help me survive prostate cancer. It worked very well. I am now cancer-free. I know of other people that are now contacting me with inoperable forms of terminal cancer. I was hoping they would be able to purchase the ginger to start taking and at least give them some hope. Please let me know if they will be able to purchase directly from you. Thank you.

Disclaimer The information about alternative natural medicine on this website Is intended only for educational purposes and reports Dr. Makise’s success in treating and, in some cases, curing prostate cancer. However, the statements made in this article have not been evaluated by the FDA. The information on this website is not intended to prevent, diagnose, treat, or cure any condition, including prostate cancer. This is an informational site only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay seeking it because of anything you have read on this website. This website and its contents are provided as is, with no warranties of any kind. We assume no liability or responsibility for any errors or omissions in the content of this website. Any losses or damages arising from the use of the content provided on Dr.Makise's website is solely the responsibility of the users of this website. Additionally, the information accessible via our site may not be entirely accurate, complete or up-to-date.

The post 11 Effective Natural Supplements for Prostate Cancer Prevention appeared first on STG Makise Lifeup USA.

Stem Cell

CustomerTeam — Wed, 25 Mar 2020 06:06:42 +0000

What is Stem Cell?

A Stem cell is an undifferentiated cell that differentiates to become any type of cell and from there further sub-divides. Scientists have recently utilized stem cells in regenerative and rejuvenative medicine. Stem cells transplanted into damaged human bodies will eventually contribute to a “De-Hospitalized Society”. The society has less drugs and less hospitals than now.

Stem cell Types:

ES Cell (embryonic stem cell)
iPS Cell (induced pluripotent stem cell)
Adult Stem Cell

Let’s survey historical aspects of stem cells.

I. Epigenetic Landscape

Cells develop from only one fertilized egg — zygote. A “Totipotent Cell” with the ability to differentiate into more than 220 cell types. except placenta. But its Totipotency, (which represents the cell with the greatest differentiation potential) is not retained during all the various stages of cell sub-division.

The first sub-division provides 2 Totipotent cells. The second 4 cells, retain Totipotency But the following 8 cells no longer retain the ability to differentiate into all types of cells. Further sub-divisions differentiate into specialized cells such as fibroblasts, erythrocytes, nerve cells, intestinal mucosal epithelial cells and pancreatic islet cells, etc. but following 6 to 7 full further cell sub-divisions (about 5 days after fertilization), the embryo becomes a “Blastocyst” and possesses “Inner Cell Mass (ICM) “

ICM cells can differentiate into any cell type, except placenta — pluripotency. 3 weeks after fertilization, the cells of the inner cell mass differentiate into ectoderm, mesoderm, and endoderm. In the 1950s, this differentiation was thought to be irreversible, being described as a ball rolling down a hill and technically known as ” Epigenetic Landscape”.

This was until 1962 when John Gurdon created clone frogs and then in 1996, Ian Wilmut created “Dolly ” the cloned sheep. Scientists had previously thought stem cells could not have pluripotency once dispersed into a specialized cell. however, in nature, even once differentiated, some cells can again differentiate and this phenomenon is known to science.

II. Cells of Planaria

The stem cells of humans have a limited ability to differentiate. But for example, Planaria that is a small flatworm living in rivers has an amazing ability to differentiate into any organs, even into itself. When it is chopped into 3 fragments like a picture, each fragment regenerates to a perfect Planaria. There is a record that 1/279 fragment of one Planaria regenerated to perfect Planaria. When Planaria grows to a certain size, it divides itself to two fragments. And each fragment grows to a perfect Planaria. For Planaria, division and regeneration are mechanisms for reproduction. But under some circumstances, Planaria chooses sexual reproduction.

III. Cells of Plant

A Plant can regenerate itself from one already differentiated cell. An Enzyme mixture of Cellulase Onozuka R-10 and Macerozyme R-10 dissolves tobacco plant (Nicotiana tabacum) leaf cell walls, and cells become leaf protoplasts (= cell without cell walls). When protoplasts are cultivated under appropriate condition, the protoplasts grow to a seedling plant through plant callus (= mass of unorganized parenchyma cells). When the seedling plant is planted in soil, it grows to a perfect tobacco plant.

Two British scientists proved biological technique could change Epigenetic Landscape.

IV. Frog of John Gurdon

Gurdon created cloned frogs.

He destroyed the nucleus of Frog A ovum by ultraviolet rays.
He removed the intestinal cell “tadpole nucleus” of Frog B which was transplanted into Frog A’s ovum, the nucleus of which was already destroyed by ultraviolet rays. This new ovum became Clone Embryo B which grew into Frog B’s tadpole was later to become cloned adult Frog B.

V. Ian Wilmut’s “Dolly” The Cloned Sheep

Wilmut used a cell nucleus which had been differentiated in the mammary gland.

He took out the ovum from Sheep A, and removed its nucleus.
From Sheep B he removed the mammary gland cell nucleus.
Into the ovum of Sheep A, he transplanted the nucleus of Sheep B.
The Sheep A ovum was then electrically stimulated.
The stimulated cell divided to became the cloned embryo of Sheep B.
The cloned Sheep B embryo was transplanted into the uterus of Sheep C.
Sheep C gave birth to Cloned Sheep B. This sheep was named “Dolly”.

VI. ES Cells(embryonic stem cells)

Human embryos reach “Blastocyst” about 5 days’ post-fertilization. The Blastocyst possesses an “Inner Cell Mass (ICM) ” In 1981 Martin Evans succeeded in culturing mouse ICM cells. These cells are capable of propagating themselves indefinitely in an undifferentiated state, and they can differentiate into any type of cell except placenta. These cells are pluripotent and known as Embryonic Stem Cell (ES Cells).
James Thomson created ES Cells from Monkey embryo in 1995 and later in 1998 created ES Cells from a human embryo. However, research into ES Cell needs further study due to an ethical dilemma, that in order to isolate inner cells from the blastocyst, the blastocyst is destroyed, so is the embryo at the pre-implantation stage to be considered human? and even if not, do we have the right to destroy human potential growth.

VII. iPS Cells (Shinya Yamanaka)

The ethical issue of ES Cells can be by-passed by using Induced pluripotent stem cells. The iPS cell is a pluripotent stem cell which can be generated directly from adult cells, not from human embryos, and in 2006, Shinya Yamanaka and his team in Kyoto University created iPS cells from mouse fibroblasts.

He hypothesized that the genes playing a pivotal role in the function of ES Cells could induce an embryonic state in adult cells. But how many are the genes? The human has 20 – 25 thousand genes. Yamanaka researched and found 24 genes which were important for the characteristic protein of human ES Cells, and then used retroviruses to deliver all 24 genes into mouse fibroblasts, and the fibroblasts were able to propagate indefinitely. These iPS Cells were pluripotent like ES Cells.

Yamanaka removed one factor at a time from the 24 factors to identify the necessary genes for reprogramming and by this process he identified 4 factors — Oct3/4, Sox2m Klf4, and c-Myc – named the “Yamanaka Factors”, and Later he found c-Myc was not needed for reprogramming, but without c-Myc the process took longer and was inefficient.

A strong concern of the iPS researchers was if iPS Cell differentiation caused cancerous cells. But this issue has almost been resolved completely through rigorous study. And many clinical human applications are now carried out in Japan. For example, in 2014 retina transplantation by iPS Cells was successfully carried out for age-related macular degeneration. And cells did not differentiate into cancer cells. In my next page, I write more about these applications.

iPS Cells are useful not just for regenerative medicine but for drug discoveries or development. Because it is very easy for researchers to recreate special cells which cause special diseases, in a petri dish — Alzheimer’s disease, Parkinson’s disease, ALS (Amyotrophic Lateral Sclerosis), Schizophrenia.

For example, “Achondroplasia” which is caused by a mutation in fibroblast growth factor receptor 3. This is a common cause of dwarfism. Researchers made iPS Cells from skin fibroblasts of 3 patients with achondroplasia then allowed the iPS Cells to differentiate into chondrocytes over 2 to 3 weeks. Chondrocytes in the petri dish secreted about themselves an extracellular matrix which is characteristic of chondrocytes and made a mass.
Compared to the chondrocytes of healthy people, these patient’s chondrocytes grew slowly, and the researchers tried thousands of drugs one by one to cure the abnormal chondrocytes of the petri dish specimens. Then finally, and with much surprise, they found the “Statin drug” was effective and able to cure the abnormal chondrocytes of achondroplasia patients. Why surprise? Because Statin drugs are for lowering cholesterol, and nobody expected cholesterol-lowering drugs to be effective against achondroplasia.

In the next pages, I explain in more detail about practical and clinical uses of iPS Cells.

The researchers of iPS Cells were most afraid of differentiation of iPS Cells into cancer cells. But now this problem has been almost solved by rigorous studies. And many clinical applications for humans are being done in Japan. For example, in 2014 transplantation of iPS Cells of retina was successfully done for age-related macular degeneration in Japan. The cells have not differentiated into cancer cells. In the next page, I write more about the applications.

iPS Cell is very useful not only for regeneration medicine but also for drug discovery or drug development. Because it is very easy for researchers to make the special cells that cause the special diseases — Alzheimer’s disease, Parkinson’s disease, ALS (Amyotrophic Lateral Sclerosis), Schizophrenia — in petri dish.

VIII. Adult Stem Cell (Somatic Stem Cells or Tissue Stem Cell)

Adult Stem Cells are undifferentiated cells found throughout the body such as in bone marrow, and umbilical cord blood, and the mammary gland, and the surface of the small and large intestines, the adipose tissue, the lining of the nose, the testicles, and the hair follicle, between the basement membrane and the sarcolemma of muscle fibers (Satellite Cells), etc.

These cells are multipotent cells that have less ability to differentiate into specialized cells than pluripotent cells. The adult stem cell from the bone marrow, called Hematopoietic Stem Cell (HSC), was discovered in the 1960s by two Canadian biologists, James Till, and Ernest McCulloch, and has been used clinically to cure various blood diseases, such as leukemia, malignant lymphoma, multiple myeloma, etc. Clinically a very important cell. But for regenerative medicine, it needs much practical work to obtain stem cells from bone marrow and requires general anesthesia, however, scientists recently have found it easier to obtain these cells.

This is by ASC (adipose-derived stem cell) from our fat. The first scientific reports on ASC were made by an American scientist, Patricia Zuk (UCLA), in 2001. She reported the presence of mesenchymal stem cells in the fat tissues, and as they have a faster growth rate, these cells are expected to be advantageous for regenerative medicine.

ASC can differentiate into muscle, bone, cartilage, liver, adipose cell (lipid cell). And besides the advantages as stem cell, ASC secrets exsosome (nano-size particles) that contain enzymes which dissolve beta-amyloid of Alzheimer’s disease. The efficacy is 8 times more potent than the enzymes secreted by the exssome of the bone marrow.

ASC is now aggressively researched in Japan for practical uses. It will be used to treat many diseases such as Alzheimer’s, Parkinson’s, and diseases of the liver and kidneys, and periodontal disease, and more. For example, please see the video:

In Japan, Tottori University Medical School researchers have established the technique of breast reconstruction by ASC after mastectomy due to cancer. They operate and inject ASC into the patient’s depressed breast. The breast recovers to the original shape within three months. This is not silicon, but the patient’s own cells. Quite natural. No rejection. The cost of this treatment will be covered by health insurance within three years in Japan.

Doctors at the Nagoya University Medical School use ASC against urinary incontinence stress. The sphincter function of the urethra often weakens due to aging, delivery, and some bladder diseases. ASC is injected around the patient’s urethra to strengthen the smooth muscle.

However, some side effects may occur by use of ASC. For example, male prostate hyperplasia and female endometriosis. Issues not studied in depth. So for now until the side effects have been dealt with, we should wait for general anti-aging treatments.

IX. Direct Reprogramming. “A Newer Approach”

Recently it was found possible to induce, directly from somatic cells, not only iPS but nerve cells, hepatocyte cells, myocardium cells, cartilage cells, and many varied cells by introducing the specific key transcription factors in cell differentiation, which means that through by-passing of pluripotent stem cells it is possible to induce differentiated specific cells from somatic cells. This is called “Direct Reprogramming”, and the most exciting research for example is: myocardial reprogramming in vivo, where Doctors inject patient’s fibroblasts with transcription factors to the infarcted lesion of the heart.
There the fibroblasts differentiate into myocardium (heart muscle). So, simple and quick. And this regenerative medical technique is under development mainly in Japan and the United States and as this technique is established, lots of heart surgeries will become obsolete and this is also true of brain surgery. The numbers of hospitals will eventually reduce and cost of time-consuming surgeries will lower and this will lead on to a “De-Hospitalized Society”.

Conclusion

For a basic understanding of stem cell mechanisms: ES Cell is studied along with iPS Cell and ASC. But ES Cell has an ethical dilemma and this issue shall not be overcome by science. So, it cannot be used for the treatment of human diseases. Direct Reprogramming: Wonderful technology. But it may take 10 or 20 years more to accomplish it. Therefore, at this moment, iPS Cell and ASC are most realistic medical tools for those who are suffering from degenerative diseases and wish rejuvenation.

PRACTICAL APPLICATIONS OF IPS CELLS

Stem cells and induced pluripotent stem cells (iPS or iPSCs) have found their usage in a large number of human welfare such as drug development, toxicity tests, organ/ tissue regeneration, and repair etc. Induced pluripotent stem cells (iPSCs) could also be of great use in studying molecular mechanism of many diseases. Many diseases have been modeled by using iPSCs for better understanding of their etiology which may be further utilized for developing putative treatments for these diseases. The use of iPSCs may eliminate the chances of immune rejection as patient-specific cells may be used for transplantation in various engraftment processes. Moreover, iPS technology has been employed in various diseases for disease modeling and gene therapy. The technique offers benefits over other similar techniques such as animal models. Many toxic compounds (different chemical compounds, pharmaceutical drugs, other hazardous chemicals, or environmental conditions) which are encountered by humans and newly designed drugs may be evaluated for toxicity and effects by using iPSCs. The applications of stem cells and especially iPSCs in regenerative medicine, disease modeling, and drug discovery are enormous and should be explored in a more comprehensive manner.

In this web presentation you read 6 major applications of Stem cells and IPS cells:

Uses in Regenerative medicine (tissue/organ regeneration)
Uses in Disease modeling
Uses in Drug Discovery / Development
Uses in Drug testing/ Toxicity Testing
Uses in Tissue repair
Uses in Gene Therapy

Advantages of iPS technology over other conventional therapies:

The ethical issues are avoided by the use of iPSCs
iPSCs have solved the controversy over the destruction of embryos associated with the use of ES Cells (embryonic stem cells).
Reduced chances of immunorejection
iPSCs are generated from the somatic cells of one’s own body and hence there is no risk of immunorejection of these autologous cells.
Throughput screening for predicting toxicity/therapeutic responses of newly developed drugs
The concept of using iPSCs to predict toxicology and therapeutic responses of drugs in based on the property of iPSCs to continuously self- renew which make it possible to generate libraries and their ability to give rise to all types of body cells.
Lowering the overall cost and risk of clinical trials
The cost used for the clinical trials could be reduced by using iPSCs to provide the toxicity details of the drug by different cytotoxicity assays. The use of iPSCs for these tests may cut the cost associated with providing animal models which will ultimately decrease the overall costs of the clinical trials.
Development of a personalized approach for administration of drugs
As, iPSCs are derived from individual patients, these offer scientists an opportunity for modeling diseases on a patient-by-patient basis. This enables screening the genomic differences between individuals that may help in the progression of disease, and the screening of pharmacological agents to find the ideal one for each individual.
Gene targeting and correction technologies (gene therapy)
Reprogramming of somatic cells from any genetic background to iPSCs has allowed the generation of cell lines possessing disease-causing mutations.

USES IN REGENERATIVE MEDICINE

The application of iPSCs for generating tissues and organ grafts can solve many problems in organ transplants and improve the quality of life for millions of patients. iPSCs can be directed to generate specific cell types and can be used to replace ailing or degenerating tissues. The greatest advantage of this technique is that it overcomes graft-to-host incompatibility. It is for this reason that graft rejection by the hosts immune system decrease significantly. There are about 90,000 patients in the US transplant-waiting list, who need medical assistance, which can be addressed by stem cell technologies.

Kidney Regeneration

iPSCs technology can be used to transform terminally differentiated skin cells into kidney organoids which are functionally and structurally similar to those of kidney tissue in vivo. During kidneys healing process, a progenitor stem cell needs to become 20 types of cells, required for waste excretion, pH regulation, and restoration of water and electrolytic ions. The ex vivo kidney organoids are similar to fetal first-trimester kidneys for their structure and physiology. They can also be served as model for nephrotoxicity screening of drugs, disease modelling, and organ transplantation. However, there are many hurdles coming to the point of generation of fully functional kidney that can be dreamed for the near future.

Liver Regeneration

iPSC-Liver buds have been developed from a mixture of three different kinds of stem cells, i.e., hepatocytes (for liver function) coaxed from iPSCs; endothelial stem cells (to form lining of blood vessels) from umbilical cord blood; and mesenchymal stem cells (to form connective tissue). This approach is like mimicking the fetal development and formation of a complex organ. In one experiment, after growing in vitro for a few days, the liver buds were transplanted into mice where the ‘liver’ quickly connected with the host blood vessels and continued to grow. It also performed regular liver functions including metabolizing drugs and producing liver-specific proteins. Further studies will monitor the longevity of the transplanted organ in the host body (ability to integrate or avoid rejection) and whether it will transform into tumors. Using this method, cells from one mouse could be used to test 1,000 drug compounds to treat liver disease and reduce animal use by up to 50,000.

Visual acuity Regeneration

Loss of neurons in age-related macular degeneration (ARMD) is the common cause of blindness. At preclinical level, transplantation of iPSCs derived neuronal progenitor cells (NPCs) in rat limits progression of disease through generation of 5-6 layers of photoreceptor nuclei, restoring visual acuity.

Y. Tsai, B. Lu, B. Bakondi et al., “Human iPSC-derived neural progenitors preserve vision in an AMD-like model,” STEM CELLS, vol. 33, no. 8, pp. 2537–2549, 2015.

Neurons Regeneration

The high order brain functions, like emotions, anxiety, sleep, depression, appetite, breathing heartbeats, and so forth, are regulated by serotonin neurons. Generation of serotonin neurons occurs prior to birth, which is post-mitotic in their nature. Any sort of developmental defect and degeneration of serotonin neurons might lead to neuronal disorders like bipolar disorder, depression, and schizophrenia-like psychiatric conditions. Manipulation of signaling in human iPSCs in defined culture conditions leads to an in vitro differentiation of iPSCs to serotonin-like neurons. These iPSCs-neurons primarily localize to rhombomere 2-3 segment of rostral raphe nucleus, exhibit electrophysiological properties similar to serotonin neurons, express hydroxylase 2, the developmental marker, and release serotonin in dose and time dependent manner. Transplantation of these neurons might cure from schizophrenia, bipolar disorder, and other neuropathological conditions.

J. Lu, X. Zhong, H. Liu et al., “Generation of serotonin neurons from human pluripotent stem cells,” Nature Biotechnology, vol. 34, no. 1, pp. 89–94, 2016.

Placenta Regeneration

Placenta, the cordial connection between mother and developing fetus, gets degenerated in certain pathophysiological conditions. Nuclear programming of OCT4 knock-out (KO) and wild type (WT) mice fibroblast through transient expression of GATA3, EOMES, TFAP2C, and +/− cMYC generates transgene independent trophoblast stem-like cells (iTSCs), which are highly similar to blastocyst derived TSCs for DNA methylation, H3K7ac, nucleosome deposition of H2A.X, and other epigenetic markings. Chimeric differentiation of iTSCs specifically gives rise to hemorrhagic lineages and placental tissue, bypassing pluripotency phase, opening an avenue for generation of fully functional placenta for human.

H. Benchetrit, S. Herman, N. Van Wietmarschen et al., “Extensive nuclear reprogramming underlies lineage conversion into functional trophoblast stem-like cells,” Cell Stem Cell, vol. 17, no. 5, pp. 543–556, 2015.

Lungs Regeneration

Degeneration of other organs and tissues also has been reported, like degeneration of lungs which might occur due to tuberculosis infection, fibrosis, and cancer. The underlying etiology for lung degeneration can be explained through organoid culture. Coaxing of iPSC into inert biomaterial and defined culture leads to the formation of lung organoids that consisted of epithelial and mesenchymal cells, which can survive in culture for months. These organoids are miniature lung, resemble tissues of large airways and alveoli, and can be used for lung developmental studies and screening of antituberculotic and anticancer drugs.

B. R. Dye, D. R. Hill, M. A. Ferguson et al., “In vitro generation of human pluripotent stem cell derived lung organoids,” eLife, vol. 4, Article ID e05098, pp. 1–25, 2015.

Chronic Wound Healing

Chronic wounds are rarely seen in otherwise healthy individuals; they are often associated with diabetes, obesity or old age. It has been estimated that 1-2% of people in developed countries suffer from chronic wounds in their lifetime [i].Current methods of wound management are palliative, but their ineffectiveness for complex wounds is an ongoing clinical problem. Healthcare systems are in desperate need of alternative therapies. Stem cells/ iPSCs are known to tremendously influence normal cell and tissue repair/regeneration, which is why a large proportion of research focuses on stem cells as the answer to treating chronic wounds. Self-renewing characteristics and multipotent differentiation potential of stem cells make them ideal candidates for the treatment of chronic wounds. Stem cell-based therapies bring about their effectiveness via a number of mechanisms. Stem cells can differentiate into new cells, secrete trophic factors, promote angiogenesis, modulate the immune system, improve wound closure, and also help in the development of new extracellular matrix (ECM).

F. Gottrup. A specialized wound-healing center concept: the importance of a multidisciplinary department structure and surgical treatment facilities in the treatment of chronic wounds. The American Journal of Surgery, vol. 187, no. 5, pp. S38– S43,2004.
http://www.fiercebiotech.com/r-d/researchers-repair-retinas-mice-virus-free-stem-cells

DISEASE MODELLING

The use of stem cells especially iPSCs for disease modeling is based on the fact that these cells are capable of self-renewing and that these cells can differentiate into all types of cells of the human body which can be utilized for the preparation of different disease models to study those diseases. Moreover, a patient-specific iPSC could be of enormous use as far as development of specific therapeutics regimen/drug is concerned. By combining 3D culture with extracellular matrix proteins, in-vivo microenvironment can be mimicked. iPSCs have helped out in studying various mechanisms that play role in different diseases, a few have been described below.

The following findings from modeling different diseases help out in knowing the molecular mechanisms underlying the disease better, which ultimately carries the work forward to knowing the disease better for the development of a treatment.

Neurogenerative diseases

Parkinson’s Disease (PD) is a very common neurodegenerative disease, in which, dopaminergic neurons of substantia nigra (a structure in midbrain) get lost and formation of Lewy’s bodies (inclusions in the cytoplasm of neurons all over the body) occurs. Treatment of this disease had not been possible due to the reason that by the time, Parkinson Disease gets clinically manifested, the neurons have already lost, which makes it very difficult to study the underlying mechanisms of Parkinson disease so as to develop a treatment of it. In such a situation, iPSCs can be used and experiments have also been carried out in this aspect. Devine et al. developed iPSCs from fibroblasts taken from a Parkinson disease affected person possessing triplication of Synuclein gene by the transduction of four basic transcription factors. These iPSCs were then directed to differentiate into dopaminergic neurons in vitro for the study of Parkinson Disease. Another research by Professor Atsushi Takahashi of Kyoto University iPS cell research institute transplanted nerve cells made from human iPS cells to Parkinson’s disease monkey on August 30, 2017, claimed to alleviate the Parkinson disease symptom (hand tremor). The research results were published in English Science Journal, Nature (electronic version). The research team created nerve cells that emitted dopamine from iPS cells based of Parkinson’s disease patients. This was transplanted into the brain of cynomolgus monkeys reproducing the symptoms of Parkinson’s disease. Observing the one year course after transplantation, the symptoms of Parkinson ‘s disease such as trembling and reduced exercise ability were alleviated over time.

Devine, Michael J., et al. “Parkinson’s disease induced pluripotent stem cells with triplication of the α-synuclein locus.” Nature Communications 2 (2011): 440

Alzheimer’s Disease

Recent preclinical evidence suggests that stem cells can be used to treat or model Alzheimer’s Disease. The mechanisms of stem cell-based therapies for Alzheimer’s Disease include stem cell-mediated neuroprotection and trophic actions, anti-amyloidogenesis, beneficial immune modulation, and the replacement of the lost neurons. iPSCs have been recently used to model investigate sporadic and familial Alzheimer’s Disease pathogenesis, and screen for anti- Alzheimer’s Disease, drugs.

Fan, Xiaotang, et al. “Stem‐Cell Challenges in the Treatment of Alzheimer’s Disease: A Long Way from Bench to Bedside.” Medicinal research reviews 34.5 (2014): 957-978.

Down’s syndrome

Briggs et al. used iPSCs for the identification of molecular networks that drive the different aspects related to pathogenesis in Down’s Syndrome. iPSCs in combination with microarray and RNA sequencing technology, can be used to generate phenotype-genotype maps of complex diseases by linking various defects with phenotypes, like in Down’s Syndrome using Chromosome engineering of Down Syndrome-iPSCs

Briggs, James A., et al. “Integration‐free induced pluripotent stem cells model genetic and neural developmental features of down syndrome etiology.” Stem Cells 31.3 (2013): 467-478.

Study of Prostate and Urinary Tract diseases

Moad et al. used human prostate and urinary tract cells for the formation of iPSCs and further for studying the mechanisms that regulate the differentiation of prostate and urinary tract cells. With their study, they reported the first successful reprogramming of bladder, prostate and ureter stromal fibroblasts into a pluripotent state and concluded that iPSCs generated from prostate and urinary tract had better efficiency of differentiation to cells of prostate and urinary tract as compared to iPSCs derived from skin fibroblasts which showed that organ of origin plays an important role in terms of efficiency of differentiation.

Moad, Mohammad, et al. “A novel model of urinary tract differentiation, tissue regeneration, and disease: reprogramming human prostate and bladder cells into induced pluripotent stem cells.” European urology 64.5 (2013): 753-761.

Other deficiency diseases – Various types of diseases which are caused by some deficiency have been studied by using iPSCs. Park et al. used iPSCs from patients of various diseases like Adenosine Deaminase Deficiency-related Severe Combined ImmunoDeficiency (ADA-SCID), Shwachman-Bodian-Diamond syndrome (SBDS), Gaucher disease (GD) type III for the study of disease models and drug discovery.


Disease/Syndrome	Becker type muscular dystrophy (BMD)
Causes	Mutation in dystrophin gene
Features	Loss of walking ability, but progression slower than DMD
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Downs syndrome/trisomy 21
Causes	Trisomy of chromosome 21
Features	Cardiac and cognitive defects, premature Alzheimers disease and aging, dysmorphic facial features
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Familial dysautonomia (FD) or Riley-Day syndrome
Causes	Autosomal recessive disorder caused by a single mutation in exon 20 in I-K-B kinase complex associated protein (IKBKAP) gene
Features	Dysfunction of small fiber sensory neurons
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Childhood cerebral adreno leuko dystrophy (CCALD)
Causes	Mutation in ABCD1 gene
Features	Adrenal cortex, nervous system and testes get affected, leading to rapid cerebral demyelination and adrenocortical atrophy.
Cells used for iPSC generation	Skin fibroblasts


Disease/Syndrome	Rett’s syndrome
Causes	Classic form caused by loss-of-function mutation in Methyl-CpG-binding protein 2 (MECP2) gene on the X – chromosome, variants caused by mutations in FOXG1 or CDKL1 on chromosome 14 and X-chromosome, respectively
Features	Neurocognitive regression and autistic behavior
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Duchenne type muscular dystrophy (DMD)
Causes	Biochemical and genetic defects in Dystrophin-glycoprotein complex
Features	Loss of walking ability
Cells used for iPSC generation	Tail tip fibroblasts (mouse)


Disease/Syndrome	Alzheimer disease
Causes	Duplication of amyloid β precursor protein (APP)
Features	Presence of neurofibrillary tangles and amyloid plaques in the brain
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	LEOPARD syndrome
Causes	Mutation in protein tyrosine phosphatase non-receptor type 11 (PTPN11) gene
Features	Increased failure of bone marrow, pulmonary fibrosis and cancer, oral leykoplakia, abnormal skin pigmentation and nail dystrophy
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	α1-antitrypsin deficiency
Causes	Mutation in α1-antitrypsin (A1AT) gene
Features	misfolded α1-antitrypsin gets aggregated in the endoplasmic reticulum
Cells used for iPSC generation	Dermal fibroblasts


Disease/Syndrome	Parkinson’s Disease (PD)
Causes	Familial forms caused by α-synuclein, ubiquitin carboxy terminal hydroxylase L1, parkin, DJ-1, putative serine threonine kinase 1 and leucine rich repeat kinase 2
Features	Loss in nigrostriated dopaminergic neurons in substantia nigra; presence of Lewy bodies
Cells used for iPSC generation	Dermal fibroblasts of patient with idiopathic PD


Disease/Syndrome	Huntington disease (HD)
Causes	CAG repeats (36 or more) in the first exon of htt gene gets expanded abnormally
Features	Degeneration in striatum and cerebral cortex
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	ALS or Lou Gehrig’s disease
Causes	Autosomal dominant mutation in superoxide demutase (SOD1)
Features	Death of motor neurons of the motor cortex, brain stem and spinal cord
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Friedreich’s ataxia (FRDA
Causes	GAA trinucleotide repeat in the first exon of the frataxin gene gets expanded
Features	Accumulation of mitochondrial iron, specific enzymes in mitochondria become defective, sensitivity to oxidative stress increases, cell death mediated by free radicals
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Lesch-Nhyan syndrome (carrier state)
Causes	Deficiency of hypoxanthine guanine phospho ribosyl transferase (HPRT)
Features	Over-production of uric acid, low or medium level of mental retardation, megaloblastic anemia is frequent
Cells used for iPSC generation	Dermal fibroblasts


Disease/Syndrome	Shwachman-Bodian-Diamond syndrome (SBDS)
Causes	Mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene
Features	Exocrine pancreatic insufficiency, predisposition to leukemia, hematopoietic dysfunction
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Gaucher’s type III
Causes	Deficiency of acid hydrolase, β-glucocerebrosidase, or glucosylceramidase
Features	Myoclonal epilepsy, nerve deafness
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Generation of human prostate and urinary tract cells
Causes	NA
Features	NA
Cells used for iPSC generation	Human prostate and urinary tract cells


Disease/Syndrome	Adenosine deaminase deficiency-related severe combined immunodeficiency (ADA-SCID)
Causes	Defects in Adenosine deaminase (AD) gene
Features	Impaired development and functioning of T, B, and NK cells; complete absence of humoral and cellular immunity; recurrence of infections.
Cells used for iPSC generation	Bone Marrow derived mesenchymal cells


Disease/Syndrome	Type 1 diabetes mellitus (DM)
Causes	Progressive β-cell destruction
Features	Long term micro and macro-vascular complications.
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Hemophilia A
Causes	Deficiency of factor VIII
Features	Decreased protein production, inefficient clotting of blood
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Familial hypercholestrolaemia
Causes	Mutation in low density lipoprotein receptor (LDLR) gene
Features	Deficiency of LDL-receptor mediated uptake of cholesterol
Cells used for iPSC generation	Dermal fibroblasts


Disease/Syndrome	Spinal muscular atrophy
Causes	Mutation in survival of motor neuron 1 (SMN1) gene
Features	Paralysis, muscle weakness and often death
Cells used for iPSC generation	Fibroblasts


Disease/Syndrome	Hutchinson-Gilford progeria syndrome
Causes	Point mutations in lamin A
Features	Premature atherosclerosis, vascular smooth muscles gets degraded
Cells used for iPSC generation	Fibroblasts

The post Stem Cell appeared first on STG Makise Lifeup USA.

STG Makise Lifeup USA

Year – end and New Year holidays

Perilla is The Fish of The Lands

The Japanese folklore about perilla

The Japanese folklore about perilla

The omega-3 fatty acid is not the only aspect to look for in oils

Comparison of perilla seed oil with fish oil

You should not heat Perilla seed oil

The secret oil of the east

Revolutionary Method of Early Prediction of Alzheimer’s Progression

Revolutionary method to predict Alzheimer's disease 20 ～ 30 years prior to the onset of clinical symptoms.

New blood test method may able to predict Alzheimer's disease

Natural Supplements to Improve Alzheimer's disease

List of Supplements for Alzheimer's disease

Gotu Kola

Bacopa (Bacopa monnieri)

CBD (Cannabidiol)

Essential Oils

Ferulic Acid (FA)

Propolis

Curcumin

Corn Silk

Astaxanthin

Hericium Erinaceus (Lion's Mane Mushroom or Yamabushitake)

Chaga (Inonotus obliquus)

Huperzine A

Eleutherococcus senticosus (Siberian Ginseng)

Dihydroquercetin (DHQ)

Guarana

Buckwheat Extract

Vitamin K

Saffron

Krill Oil (omega-3 unsaturated fatty acid: DHA / EPA)

Black Cumin Oil

Phosphatidylserine

Silk protein

Magnesium L-Threonate

Ginkgo Biloba Extract

Acetyl-L-Carnitine (ALC)

Citicoline

Vitamin B12

B Vitamins

Supplements, Medicine and Ointment for Psoriasis: Effective and Unique Treatment From Japan

1. Use of ointments for psoriasis treatment

2. Two Important Oral Medication for Psoriasis

3. Supplements for Psoriasis

a. Natural supplement for psoriasis

b. Vitamin and other supplements for psoriasis

Psoriasis Frequently Asked Questions (FAQs)

Additional Notes for Psoriasis Treatment Guidelines

The Emperor’s Fungus for Health and Immortality

11 Effective Natural Supplements for Prostate Cancer Prevention​

Natural Prostate Cancer Supplements that Prevent Prostate Cancer

1) Alpinia zerumbet (Shell Ginger : JIPANG Ginger®)

2) Vitamin K2

3) IP6

4) Zinc

5) Selenium

6) Fish Oil : EPA (eicosapentaenoic acid) & DHA (docosahexaenoic acid)

7) Pomegranate

8) Saw palmetto

9) Epilobium (Fireweed)

10) Green tea extract (epigallocatechin gallate)

11) Pygeum

Prostate cancer is one of the easiest cancers to cure.

Caution

Stem Cell

What is Stem Cell?

PRACTICAL APPLICATIONS OF IPS CELLS

11 Effective Natural Supplements for Prostate Cancer Prevention