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Mel’s Diner

Melatonin potentiates flavone-induced apoptosis in human colon cancer cells by increasing the level of glycolytic end products.

– Melatonin has been described to possess cell protecting activity in normal cells but was shown to induce apoptotic cell death in cancer cells. It potentiates apoptosis induced by the flavonoid flavone significantly. A combination of flavone and melatonin increased caspase-3-like activity 30-fold and 80% of cells exhibited fragmentation of DNA when compared to untreated controls. Melatonin caused an increase in cytosolic lactate levels that most likely allows the flavone-induced activation of the mitochondrial pyruvate/lactate importer to deliver more substrates to mitochondrial respiration.

Melatonin Enhances the Anti-Tumor Effect of Fisetin

– Melatonin is a hormone identified in plants and pineal glands of mammals and possesses diverse physiological functions. Fisetin is a bio-flavonoid widely found in plants and exerts antitumor activity in several types of human cancers. However, the combinational effect of melatonin and fisetin on antitumor activity, especially in melanoma treatment, remains unclear. Here, we tested the hypothesis that melatonin could enhance the antitumor activity of fisetin in melanoma cells and identified the underlying molecular mechanisms. The combinational treatment of melanoma cells with fisetin and melatonin significantly enhanced the inhibitions of cell viability, cell migration and clone formation, and the induction of apoptosis when compared with the treatment of fisetin alone. Moreover, such enhancement of antitumor effect by melatonin was found to be mediated through the modulation of the multiply signaling pathways in melanoma cells.

 

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Melatonin Enhances the Anti-Tumor Effect of Fisetin

An Association Map on the Effect of Flavonoids on the Signaling Pathways in Colorectal Cancer – Flavonoids, Flavonols, Quercetin, Kaempferol, Myricetin, Fisetin, Rutin, Flavanones, Hesperidin, Naringenin, Silibinin, Eriodictyol, Flavones, Acacetin, Apigenin, Chrysin, Tangeretin, Luteolin, Baicalein, Nobiletin, Flavan-3-ols (flavanols), Catechins, Proanthocyanidin, Flavanonols, Pelargonidin, Peonidin, Cyanidin, Delphinidin, Malvidin.

PDFAn Association Map on the Effect of Flavonoids on the Signaling Pathways in Colorectal Cancer

Medical and Dietary Uses of N-Acetylcysteine

Microbes in the Era of Circadian Medicine

Bacterial circadian rhythm | Circadian advantage

Your Body, Your System – Dr. Shiva

Escin induces caspase-dependent apoptosis and autophagy

How do anti-mitotic drugs kill cancer cells?

Anti-tubulin antibodies in autoimmune thyroid disorders.

Mitotic inhibitor

Hesperidin suppressed proliferations of both human breast cancer and androgen-dependent prostate cancer cells.

The Flavonoids Hesperidin and Rutin Promote Neural Crest Cell Survival

Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia.


The Flavonoids Hesperidin and Rutin Promote Neural Crest Cell Survival

The neural crest (NC) corresponds to a collection of multipotent and oligopotent progenitors endowed with both neural and mesenchymal potentials. The derivatives of the NC at trunk level include neurons and glial cells of the peripheral nervous system in addition to melanocytes, smooth muscle cells and some endocrine cells. Environmental factors control the fate decisions of NC cells. Despite the well-known influence of flavonoids on the central nervous system, the issue of whether they also influence NC cells has not been yet addressed. Flavonoids are polyphenolic compounds that are integral components of the human diet.

The biological activities of these compounds cover a very broad spectrum, from anticancer and antibacterial activities to inhibition of bone reabsorption and modulation of inflammatory response. In the present work, we have investigated the actions of the flavonoids hesperidin, rutin and quercetin on NC cells of quail, in vitro. We show for the first time, that hesperidin and rutin increase the viability of trunk NC cells in culture, without affecting cell differentiation and proliferation. The molecular mechanism of this action is dependent on ERK2 and PI3K pathways. Quercetin had no effect on NC progenitors. Taken together, these results suggest that flavonoids hesperidin and rutin increase NC cell survival, which may be useful against the toxicity of some chemicals during embryonic development.

Zzz Best Sleep EVER

Where do you place sleep in your life? For me I have learned to place it at the top of the pile of important things to do. A little over a year ago I really started focussing on sleep as thee most important 8-9 hours of my day. Everything else took a back seat. Boy what a trip it has been. Here’s a few things I’ve observed.

Sleep has 2 shifts or phases. Without fail I always wake up about 1/2 way through my full nights sleep. It’s not always a full 8 hours but I do allow for up to 9 hours and 36 minutes. I usually get up and use the restroom for good measure, make sure I drink a good amount of water and take my systemic enzymes. Always falling back to sleep immediately.

1:36 before sunrise. Through additional research I discovered some who believe that there is what is called a/the creators hour that starts 1 hour and 36 minutes before sunrise. I don’t personally know of any science behind it, but I have noticed that I am much more creative at that time in the morning and flow state is much easier to achieve at that time.

Bedtime…9:36 before sunrise. What I decided to do is put myself in bed at about this time every night. I’m not very precise because it is an ever moving target by about 6 minutes per day. This has been absolute magic for quality of sleep and it always provides for a solid 8 hours of darkness for sleep.

Sun down; fork down. If it were always possible I would only ever eat during daylight hours. When the sun goes down so does my fork, knife and spoon. This allows for your food to clear the stomach before bedtime. It will also allow for supplements you need to take on an empty stomach before bed.

Sleeping on the job. That is our job. On the other hand we have a whole legion of microbial life living in and on our body that have work to do. And they tend towards nocturnal behavior. In other words, they work the night shift. In contrast the human part of us tends toward life under the sun. All those other living things that make up our existence and wellbeing work while we sleep.

Shift work. It would seem that our best work as a human and legion of microbial life is done in shifts. And that when we observe this obediently our overall health and wealth in life is filled to the top and overflowing. Yup, that human aspect of us has a responsibility to the other 99% of the DNA on this body to simply get out of their way and let them to their job, on their shift.

A cocktail for the ageless. As a benefit our night shift, or microbial partners graciously provide us with a bio-chemical cocktail that helps us fall asleep quickly. It’s hard not to notice if you are observant. For years I just blew past all the signs while looking for my second wind. All the while ignoring my bodies cue’s. My feeling is that this is our body’s window for falling asleep that we have ignored since modern electric and artificial lighting. And that once we blow past that bio-chemical cocktails effects our ability to fall asleep is diminished. I’ve come to appreciate it and almost enjoy it.

These are just some of what I have observed I look forward to learning more over the years. I’ve found that my body repairs and heals at a much more advanced rate when I play by these rules. Once I started seeing the benefits of simply sleeping smarter it became much more difficult to find good reasons to stay awake much later than 8 or 9. I am personally convinced that there is magic to be found in a perfected sleep.

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Who Had Their Finger on the Magic of Life – Antoine Bechamp or Louis Pasteur?

PDF | CELLULAR SENESCENCE- AGING, CANCER, AND INJURY

Inducers of Senescence, Toxic Compounds, and Senolytics – We herein describe in vitro and in vivo effects of fifteen Nrf2-interacting natural compounds (tocotrienols, curcumin, epigallocatechin gallate, quercetin, genistein, resveratrol, silybin, phenethyl isothiocyanate, sulforaphane, triptolide, allicin, berberine, piperlongumine, fisetin, and phloretin) on cellular senescence and discuss their use in adjuvant cancer therapy.

Cancer, aging and cellular senescence – Normal cells do not Continue reading linkRoll_2020.04.13

Cancer, aging and cellular senescence.

Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy

~Content Source

Normal cells do not divide indefinitely due to a process termed cellular or replicative senescence. Several lines of evidence suggest that replicative senescence evolved to protect higher eukaryotes, particularly mammals, from developing cancer. Senescent cells differ from Continue reading Cancer, aging and cellular senescence.

Pellagra: Interesting Alert-NIH

WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Despite the treatable dementia and psychosis, pellagra is often under-diagnosed, especially in developed countries and alcoholic patients. Pellagra should be routinely suspected in alcoholic patients because the response to appropriate treatment is typically dramatic.


Alcoholic Pellagra as a Cause of Altered Mental Status in the Emergency Department ~ Source-NIH

BACKGROUND:

Pellagra, which is caused by a deficiency of niacin and tryptophan, the precursor of niacin, is a rare disease in developed countries where alcoholism is a major risk factor due to malnutrition and lack of B vitamins. Although pellagra involves treatable dementia and psychosis, it is often underdiagnosed, especially in developed countries.

CASE REPORT:

In Japan, a 37-year-old man presented to the emergency department with altered mental status and seizures. Wernicke encephalopathy and alcohol withdrawal were suspected. The patient was treated with multivitamins, which did not include nicotinic acid amide, and oral diazepam. Despite medical treatment, his cognitive impairment progressively worsened, and eventually, pellagra was suspected. His response to treatment with nicotinic acid amide was substantial, and he was discharged without any long-term sequelae. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Despite the treatable dementia and psychosis, pellagra is often underdiagnosed, especially in developed countries and alcoholic patients. Pellagra should be routinely suspected in alcoholic patients because the response to appropriate treatment is typically dramatic.

Respectin the Pectin

Respecting the pectin. Such a wonderfully powerful health resource.


Abstract

A simple procedure for determining the galacturonic acid and methanol contents of soluble and insoluble pectins, relying on enzymatic pectin hydrolysis and colorimetric quantification, is described. Pectin samples are incubated with a commercial pectinase preparation, Viscozyme, then the galacturonic acid content of the hydrolyzed pectin is quantified colorimetrically using a modification of the Cu reduction procedure originally described by Avigad and Milner. This modification, substituting the commonly used Folin-Ciocalteau reagent for the arsenic containing Nelson reagent, gives a response that is linear, sensitive, and selective for uronic acids over neutral sugars. This method also avoids the use of concentrated acids needed for the commonly used m-phenylphenol method. Methanol, released by the action of the pectin methylesterase found in the Viscozyme, is quantified using alcohol oxidase and Purpald. This combined enzymatic and colorimetric procedure correctly determined the galacturonic acid and methanol content of purified, soluble citrus pectin. Application of the procedure to water insoluble pectins was evaluated with water insoluble material from apples and oranges. In both cases good agreement was obtained between this method and commonly used methods based on chemical pectin hydrolysis. Good agreement between these procedures was also found in the analysis of both soluble and insoluble pectins from several tomato products.

PDF | Combined enzymatic and colorimetric method for determining the uronic acid and methylester content of pectin- Application to tomato products


Glucuronic Acid, a Precursor of Ascorbic Acid in Aspergillus niger

Galacturonic acid prepared from pectin can be used to synthesize vitamin C.

Chemical Formula: C6H10O7
Layman’s explanation: Galacturonic acid is the monobasic acid resulting from oxidation of the primary alcohol group of D-galactose to carboxyl. It is widely distributed as a constituent of pectins (compounds with heterogeneous grouping of acidic structural polysaccharides, found in fruit and vegetables), many plant gums, and mucilages (gummy substances obtained from certain plants, which are used as food stabilizers). Gums tend to be used as thickening and bulking agents in pharmaceutics, and they play a less obvious part in most plants. Once swallowed, their actions are no different from those of the mucilages. D-Galacturonic acid prepared from pectin can be used to synthesize vitamin C. Native pectin is a mixture of polysaccharides, with the major component a polymer of -D-galacturonic acid. Pectin has numerous other medical and pharmaceutical uses, for example in combination with plant hemicelluloses and lignin, may be useful dietary constituents in preventing coronary heart disease, diverticular disease, ulcerative colitis, and a variety of other Western diseases.


Anti-cancer activities of pH- or heat-modified pectin

 

Senescent Cells

An Essential Role for Senescent Cells in Optimal Wound Healing through Secretion of PDGF-AA | PDF Source N.I.H.

Survey of senescent cell markers with age in human tissues

PDF Doc – Survey of senescent cell markers with age in human tissues

Telomeres: beacons of autocrine and paracrine DNA damage during skin aging.

Chronic inflammation induces telomere dysfunction and accelerates ageing… | PDF Doc – Chronic inflammation induces telomere dysfunction and accelerates ageing in mice

The Emerging Role of Senescence in Ocular Disease | PDF DocThe Emerging Role of Senescence in Ocular Disease

PDF | Targeting senescent cells in translational medicine Content Source[charts & diagrams]

 

Magic Beans – Lysine and Proline

L-Proline & L-Lysine supplement
L-Proline & L-Lysine supplement label

How it Works, from www.cancertutor.com

The Dr. Rath Cellular Solution is theorized to stop the spreading (i.e. metastasis) of cancer via stopping the destruction of the collagen matrix by enzymes secreted by cancerous cells, thus stopping the cancer from spreading. If the cancer is contained the body can usually deal with the cancer.

The Dr. Rath Cellular Solution

This quote explains how Dr. Rath felt cancer cells spread:

Cancer cells produce and secrete millions of enzyme molecules, which, like scissors [cancer scissors], cut collagen and tissue that surrounds cells. This picture shows how liver cancer cells use these enzymes to cut little holes in the blood vessel wall and get into the blood stream where they can travel to other organs, such as the lungs. Using the same mechanism, cancer cells can settle and start new tumor growth.

~Dr. Aleksandra Niedzwiecki, Rath Foundation

This quote explains more things about the importance of the connective tissue:

Connective tissue functions not only as a mechanical support for other tissues but also as an avenue for communication and transport among other tissues. Most significantly, connective tissue is the stage for inflammation. The principal cell types involved in immunological defense are found within connective tissue.

The Dr. Rath Cellular Solution consists of two amino acids, L-Lysine and L-Proline, plus Vitamin C, and a substance in Green Tea, the polyphenol catechin known as epigallocatechin gallate (EGCG). Laboratory trials and human trials have suggested the effectiveness of this combination.

It should be noted that Dr. Rath worked with two-time Nobel Prize winning chemist Linus Pauling on a heart disease prevention program. The three key elements of the heart prevention program are the same elements in the cancer solution (excluding the EGCG).


Additional Reading

Polyphenolic Profile and Biological Activity of Chinese Hawthorn (Crataegus pinnatifida BUNGE) Fruits