Brain repair diet

Do follow the anti-parasitic diet, eat whole foods rich in Vitamin C , A and E and get sufficient night time sleep. Avoid and run away from toxic people. Stay with nature and meet new friends. Make someone happy.  In nursing facilities, some seniors are suffering from sundowning syndrome, a state of acute mental confusion and behavioral change that takes place at the end of the day and into the night.  Since we synthesize cholesterol at night, eat a healthy fat food at night and use ways to calm the body for a good night sleep (dim the lights , except for a hallway night light) and stay with the seniors until he goes to sleep.

Connie

Omega-3 Fatty Acids, Vitamin E, Curcumin, and Caffeine

A number of studies point to the healthy effects of dietary factors on the brain. For example, fish-derived omega-3 fatty acids have been shown to improve cognition, plasticity, and recovery of neurons after traumatic brain injury. One of the most important forms of omega-3 fatty acids, docosahexaenoic acid (DHA), has been found to be a key component of neuronal membranes at sites of signal transduction at the synapse, suggesting that its action is vital to brain structure and function []. Evidence suggests that DHA serves to improve neuronal function by supporting synaptic membrane fluidity and function, and regulating gene expression and cell signaling []. Because the human body is not capable of producing its own DHA, supplementation of diet with foods rich in DHA is important in insuring proper function of neurons and in facilitating neuronal recovery after injury []. An additional benefit of omega-3 fatty acids which we observed in our studies is that they appear to reduce oxidative stress damage that results from trauma, indicating at the possibility of their application in assisting the recovery process [].

Another dietary supplement that has shown promise in protecting neurons is Vitamin E, found in certain oils, nuts, and spinach. Vitamin E functions as an antioxidant, reducing free radicals in the brain which would otherwise impede optimal function of neurons. Vitamin E has shown positive effects on memory performance in older people [], indicating its ability to maintain neuronal health. A different study similarly revealed the benefits of Vitamin E by showing a correlation between the amount of ingested Vitamin E and improved neurological performance, survival, and brain mitochondrial function in aging mice [].

Curcumin, a yellow curry spice, has also been suggested to enhance recovery events after brain trauma, displaying particular potency in preserving cognition. Curcumin was found to improve neuronal function in individuals afflicted with Alzheimer’s disease by reducing oxidative stress and amyloid pathology []. In addition, it was found to protect the brain from lipid peroxidation [] and nitric oxide-based radicals []. In accordance with these observations, our own studies have showed that the supplementation of curcumin into the diets of rats reduced the effects of experimental concussive injury on cognitive function tasks [].

Studies observing the effects of caffeine on neuronal regeneration and function are recently emerging. A new study shows that chronic, but not acute, treatment with caffeine protects the brain against injury in animal models of Parkinson’s disease and stroke by increasing glutamate release and inflammatory cytokine production [].

Caloric Intake

Cognition and plasticity of the brain have also been shown to be affected by caloric intake and the frequency of food consumption. Restriction of calories seems to increase levels of BDNF, resulting in improved neuronal function. Fasting every other day has been shown to protect neurons in the hippocampus against excitotoxicity-induced death []. In the study, rats put on an every-other-day-fasting diet for 2-4 months had hippocampus neurons that were much more resistant to degeneration induced by kainic acid, and greater preserved memory than rats fed ad lib.

Saturated-Fat Diet

While certain foods seem to contribute positively to neuronal health, diets that are rich in saturated fats appear to decrease levels of BDNF in the brain and lead in poorer neuronal performance. Molteni and colleagues have shown that rats fed a diet high in saturated fats and refined sugars (similar in content to the “junk food” that has become popular today) for a period of 1-2 months, performed significantly worse on the spatial learning mater maze test than rats fed a healthier diet that was low in fat and contained complex carbohydrates [].


 

CRISPR-Cas9 Allows Further Genetic Manipulation By Exploiting Endogenous DNA Repair Mechanisms

Thymosin beta 4 and Skin Repair

 Thymosin beta 4 and Skin Repair

By Carmia Borek, Ph.D.

IMAGE TAG

The promise of repairing sun parched aging skin is alluring, especially if damage control may be attained by applying a substance that is abundant in our body. Thymosin beta 4 (Tb4), a molecule that accelerates wound healing in animals and cultured cells, “may be valuable in repairing skin damage caused by sun or even by the wear and tear of aging?”

This hopeful message of Tb4’s potential to restore damaged human skin was voiced at the 5th International Symposium on Aging Skin, in California (May 2001), by Dr. Allan Goldstein, Chairman of the Biochemistry Department at George Washington University and founder of RegeneRX Biopharmaceuticals. RegeneRX is carrying out preclinical research on Tb4 as a wound healer, in collaboration with scientists at the National Institutes of Health.

Skin is the largest organ of the body, which makes up 16% of total body weight. It is also the largest organ that provides immune protection and plays a role in inflammation. Composed of specialized epithelial and connective tissue cells, skin is our major interface with the environment, a shield from the outside world and a means of interacting with it. As such, the skin is subjected to insults and injuries: burns from the sun’s ultraviolet radiation that elicit inflammatory reactions, damage from environmental pollutants and wear and tear that comes with aging.

Image with Caption

An effective healer, Tb4 can be
administered topically on the
surface of cells and systemically,
through injection. Besides
healing skin wounds, Tb4 has
been shown to promote repair
in the cornea of the eye, in rats,
thus preventing loss of vision.

There are several layers in the skin; the outer epidermis and beneath it the dermis and the subcutaneous layer. Cells in the epidermis include keratinocytes, its major cell type, that move continuously from the lower basal layer where they are formed by cell division. Other cells in the epidermis are the melanocytes that synthesize pigment and transfer it to the keratinocytes, giving our skin its color, and a wide variety of immune cells that maintain immune surveillance and secrete substances called cytokines, like interleukin 1 and 2, which are active in inflammation. The dermis contains connective tissue, mainly collagen, blood vessels, various types of immune white cells and fibroblasts.

The structure that provides the cell with form is the cytoskeleton, whose protein actin, a housekeeping molecule in cells, comprises 10% of the cell protein. Actin is essential for cell division, cell movement, phagocytosis (engulfing foreign bodies in immunoprotection) and differentiation.

Cells on the surface of the skin are constantly being replaced by regeneration from below. The repair of a wound is a scaling up of this normal process, with additional complex interactions among cells, formation of new blood vessels, collagen, more extensive cell division and cell migration, as well as strict control of inflammatory cells and the cytokines they release to resolve the inflammation.

Skin damage and aging are induced to a large extent by free radicals from the sun and environmental pollutants and from oxidants produced during infection and inflammation. Lipid peroxidation of membranes and increased inflammatory substances, such as thromboxanes and leukotriens, add insult to injury. While skin damage accumulates with age, repair processes slow down. Thus, any boost by a molecule that would reduce free radicals and accelerate molecular events in healing has the potential to hasten skin repair. Tb4 has such healing qualities.

The nature of Tb4

Image with Caption

The promise of repairing sun
parched aging skin is alluring,
especially if damage control
may be attained by applying
a substance that is abundant
in our body.

Thymosin beta 4 is a small 43 amino acid protein (a peptide) that was originally identified in calf thymus, an organ that is central in the development of immunity. Tb4 was later found in all cells except red blood cells. It is highest in blood platelets that are the first to enter injured areas, in wound healing. Tb4 is also detected outside cells, in blood plasma and in wound and blister fluids.

Its unique potential as a healing substance lies in that it interacts with cellular actin and regulates its activity. Tb4 prevents actin from assembling (polymerizing) to form filaments but supplies a pool of actin monomers (unpolymerized actin) when a cell needs filaments for its activity. A cell cannot divide if actin is polymerized. Tb4 therefore serves in vivo to maintain a reservoir of unpolymerized actin that will be put to use when cells divide, move and differentiate.

Tb4 has other effects that are needed in healing and repair of damaged tissue. It is a chemo-attractant for cells, stimulates new blood vessel growth (angiogenesis), downregulates cytokines and reduces inflammation, thus protecting newly formed tissue from damaging inflammatory events. Tb4 has been shown to reduce free radical levels (with similar efficiency as superoxide dismutase), decrease lipid peroxidation, inhibit interleukin 1 and other cytokines, and decrease inflammatory thromboxane (TxB2) and prostaglandin (PGF2 alpha).

An effective healer, Tb4 can be administered topically on the surface of cells and systemically, through injection. Besides healing skin wounds, Tb4 has been shown to promote repair in the cornea of the eye, in rats, thus preventing loss of vision.

Wound healing

A critical step in wound healing is angiogenesis. New vessels are needed to supply nutrients and oxygen to the cells involved in repair, to remove toxic materials and debris of dead cells and generate optimal conditions for new tissue formation. Another important step is the directional migration of cells into the injured area, joining up to repair the wound. This requires an attractant that will direct the cells to the wound and propel them to the site. These critical steps in wound healing are regulated by beta 4, as seen in the following experiments.

Endothelial cells

Cells that line blood vessels (endothelial cells), taken from human umbilical chord veins, were grown in culture and the layer of cells subjected to a scratch wound. Cultures were then treated with Tb4 or kept in growth medium without Tb4. When examined four hours later, Tb4 treatment attracted cells to migrate into the wound and accelerated their movement, showing it is a chemoattractant. Cell migration was four to six times faster in the presence of Tb4 compared to the migration of untreated cells. Tb4 also hastened wound closure and increased the production of enzymes, called metalloproteases, that could pave the way for angiogenesis by breaking down barrier membranes and facilitating the invasion of new cells to the needy area, to form new vessels. Other experiments showed Tb4 acts in vivo. When endothelial cells were implanted under the skin in a gel supplemented with Tb4, the cells formed vessel-like structures containing red blood cells, indicating the ability to stimulate angiogenesis in the animals.

Skin repair

Thymosin beta 4 accelerated skin wound healing in a rat model of a full thickness wound where the epithelial layer was destroyed. When Tb4 was applied topically to the wound or injected into the animal, epithelial layer restoration in the wound was increased 42% by day four and 61% by day seven, after treatment, compared to untreated. Furthermore, Tb4 stimulated collagen deposition in the wound and angiogenesis. Tb4 accelerated keratinocyte migration, resulting in the wound contracting by more than 11%, compared to untreated wounds, to close the skin gap in the wound. An analysis of skin sections (histological observations) showed that the Tb4 treated wounds healed faster than the untreated. Proof of accelerated cell migration was also seen in vitro, where Tb4 increased keratinocyte migration two to three fold, within four to five hours after treatment, compared to untreated keratinocytes.

Repair of the cornea

IMAGE TAG

The cornea is the outer thin layer of epithelial cells protecting the eye. After wounding, timely resurfacing of the cornea with new cells is critical, to prevent loss of normal function and loss of vision. Corneal epithelial healing occurs in stages, with cells migrating, dividing and differentiating. Therapies for corneal injury are limited. Therefore, the recent finding that Tb4 promotes corneal wound repair in animal models offers hope for a therapeutic product that will improve the clinical outcome of patients with injured corneas.

In the experiments, an epithelial wound was made in the corneas of sedated rats. A Tb4 solution was applied at several concentrations to the injured eyes in one group of rats while another group was treated with a solution without Tb4. Following 12, 24 and 36 hours, the eyes were tested by microscopic observation for epithelial growth over the injured site. Investigators found the Tb4 accelerated corneal wound repair at doses of Tb4 similar to those found to repair skin wounds. When tested 24 hours after treatment, the rate of accelerated repair was proportional to the concentration of Tb4, with the highest dose (25 microgram) showing a threefold acceleration of epithelial cell migration, compared to untreated. Treatment with Tb4 showed anti-inflammatory effects, helping resolve the injury. An application to human cells in a model of human corneal cells in culture showed that Tb4 enhanced epithelial cell migration in vitro.

RegeRx and Tb4

Thymosin beta 4, developed by RegeneRx Biopharmaceuticals as a pharmaceutical for the healing of wounds, is a synthetic version of the natural peptide. As Dr. Allan Goldstein emphasizes, “Tb4 represents a new class of wound healing compounds. It is not a growth factor or cytokine, but rather exhibits a number of physiological properties which include the ability to sequester and regulate actin, its potent chemotactic properties. . . and its capability to downregulate a number of inflammatory cytokines that are present in chronic wounds.” When a wound heals there are many growth factors produced in the area so that additional factors, such as those currently on the market for wound healing, may help but are not necessarily lacking. Tb4 treatment, however, adds a new dimension to wound repair by providing cells with actin as needed, for cell migration, replication and differentiation.

RegeneRX Biopharmaceuticals is focusing on the commercialization of Tb4 “For the treatment of injured tissue and non-healing wounds, to enable more rapid repair and/or tissue regeneration.” Especially needy are diabetics who suffer from poor blood circulation and loss of sensation of pain that keeps their wounds unnoticed and unattended for days, leading to ulcers that may not heal. Other hard healing wounds are pressure ulcers in patients who are bed ridden and often receive skin grafts as treatment, or reconstructive surgery.

RegeneRx is continuing with pre-clinical research, in collaborative arrangements with the National Institutes of Health, accumulating data on the effects of Tb4 and aiming for an IND application (Investigational New drug App-lication) to proceed with clinical studies. Phase I clinical trials will determine the ability of Tb4 to repair ulcers in diabetic patients and to reduce inflammation and accelerate recovery from burns and abrasions to the cornea.

Aging skin

IMAGE TAG

The potential of Tb4 to repair sun damaged and aging skin is yet to be established by extensive studies. Many of the biological events that occur in wounding are involved in skin impaired by sun and aging. Ultraviolet radiation damage or other injuries to skin that are associated with aging may be in the future repairable with Tb4, similar to the success with wound repair. It is a hopeful prediction that this small anti-inflammatory molecule, which plays a vital role in regeneration, remodeling and healing of damaged tissues, would help rejuvenate aging skin. The effects of Tb4 in accelerating wound repair are important following surgery; Tb4 would then have practical applications following cosmetic surgery, a procedure growing in popularity in our society, in dealing with aging skin.

References

Goldstein AL. Thymosin In: McGraw Hill Yearbook of Science & Technology, McGraw Hill Publishers, New York PP371-373.

Low T, Goldstein AL. Chemical characterization of thymosin beta 4, J Biol Chem 1982; 257:1000-1006.

Malinda KM, Goldstein AL. Kleinman HK Thymosine beta 4 stimulates directional migration of human umbilical vein endothelial cells. FASEB J 1997; 11: 474-481.

Malinda M et al. Thymosin beta 4 accelerates wound healing J Inves Dermatol 1999; 113: 364-368.

Nachmias VT et al. Thymosin beta 4 (Tbeta4)in activated platelets Eur J. Cell Biol 1993; 61:314-320.

Sanders MC, Goldstein AL, Wang YL. Thymosin beta 4 (Fx peptide) is a potent regulator of actin polymerization in living cells Proc Nat Acad Sci 1992;89:4678-4682.

Sosne G et al. Thymosin beta 4 promotes wound healing and modulates inflammatory mediators in vivo Exp Eye Res 2001; 72:605-609.

Young JD et al. Thymosin beta 4 sulfoxide is an anti-inflammatory agent generated by monocytes in the presence of glucocorticoids Nat.Med 1999;5:1424-1427.

Brain’s immune cells key to maintaining blood-brain barrier

Brain’s immune cells key to maintaining blood-brain barrier

blood-brain barrier
A network of capillaries supply brain cells with nutrients. Tight seals in their walls keep blood toxins—and many beneficial drugs—out of the brain. Credit: From: Bridging the Blood-Brain Barrier: New Methods Improve the Odds of Getting …more

New research shows that the cells responsible for protecting the brain from infection and inflammation are also responsible for repairing the system of defenses that separates the brain from the rest of the body. These findings have significant clinical implications because certain cardiovascular drugs could possibly impede the brain’s ability to repair itself after a stroke or other injury.

“This study shows that the resident immune cells of the central nervous system play a critical and previously unappreciated role in maintaining the integrity of the blood- barrier,” said Maiken Nedergaard, M.D., D.M.Sc., co-director of the Center for Translational Neuromedicine at the University of Rochester Medical Center (URMC) and lead author of the study. “When this barrier is breached it must be rapidly repaired in order to maintain the health of the brain and aid in recovery after an injury – a process that could be impaired by drugs that are intended to prevent this damage in the first place.”

The brain is essentially an independent and separate ecosystem. It possesses a dedicated system of defenses against infection and recently Nedergaard and her colleagues demonstrated that the brain also maintains its own unique process of removing waste. Movement in and out of the brain is tightly controlled through a complex system of gateways and controls that are collectively referred to as the (BBB).

When the BBB is breached the brain becomes vulnerable to infection and injury. It is, therefore, imperative that the openings in the BBB are resealed, and quickly. This most frequently occurs during a stroke, which triggers inflammation that can cause the BBB to break down.

The new study, which was published today in the Proceedings of the National Academy of Sciences, reveals that the brain’s immune system, specifically cells called , play a central role in the process of repairing damage to the BBB.

Microglia serve as the brain’s “first responders” and are present throughout the brain and spinal cord. These cells are constantly monitoring their environment, and can be switched on or activated to perform different functions such as control inflammation, destroy pathogens, clean up the debris from dead or damaged cells, and seal off the site of an injury.

Performing experiments in mice, Nedergaard and her colleagues observed that when small holes where made in the BBB, nearby microglia were rapidly mobilized and set about repairing the breach. In most instances, the integrity of the BBB was restored within 10 to 30 minutes.

The team identified a receptor called P2RYX12 that was responsible for activating the microglia and directing them to the site of the damage. This finding is significant because the same receptor is also present on platelets and is one of the targets of blood thinning drugs such as Plavix.

These drugs are given to individuals at risk of heart attack and stroke and helps prevent platelets from binding together to form blood clots that, when they make their way to the brain, can block the flow of blood and trigger a stroke. However, because these drugs also suppress P2RYX12 receptors in microglia, they could potentially impair the ability of the brain to carry out repairs to the BBB once a  occurs.

Nedergaard and her team are currently investigating the impact of P2RYX12-blocking drugs on microglia function in the brain.

“Our concern is that while certain types of blood thinning drugs may do a great job preventing strokes, they could have the unintended consequence of making them worse or hindering recovery once they occur,” said Nedergaard.

 Explore further: Blood clotting protein triggers immune attack on the brain

More information: Purinergic receptor P2RY12-dependent microglial closure of the injured blood–brain barrier, Proceedings of the National Academy of Sciences,www.pnas.org/cgi/doi/10.1073/pnas.1520398113

Visceral fat, genes, heart disease and how the stomach talks to the brain

Who is prone to visceral fat?

The tendency to accumulate visceral fat is governed by genetic, ethnic, and gender differences. For example, people who inherit two copies (one from each parent) of a mutation in a gene involved in fat metabolism are more likely to have higher amounts of visceral fat than people with just one copy. Those without any copies of the gene mutation are less likely to develop heart disease — even if they become obese. Natives of India and South Asia have a higher-than-average propensity for abdominal obesity. And white men and black women tend to accumulate more visceral fat than black men and white women.

Fat and aging

With age, people tend to lose muscle tissue, especially the type of specialized muscle fibers that produce quick bursts of speed and power. Fat frequently accumulates within the remaining muscle tissue, causing your body fat percentage to increase even when your weight remains constant. This scenario is closely linked to bodywide inflammation and diabetes risk. It may also explain why your BMI measurement doesn’t provide a true reflection of your health risks.

Evidence suggests that waist circumference and waist-to-hip ratio are better indicators of metabolic health than BMI. Even among people with the same BMI, those who have a large waist (defined as more than 40 inches for men and 35 inches for women) have a significantly higher risk. In addition, people who tend to carry their weight in their hips and thighs (a “pear” shape) have lower waist-to-hip ratios and are less prone to heart disease than people with abdominal obesity (an “apple” shape); see “Measuring your midsection.”

Measuring your midsection

To measure your waist accurately, exhale and wrap a measuring tape around your bare abdomen just above your navel (belly button). Don’t suck in your gut or pull the tape tight enough to squeeze the area.

To compute your waist-to-hip ratio, first measure your hips by putting the tape measure around the widest part of your buttocks. Keep the tape measure level. Then, divide your waist size by your hip size.

Measurements that signal high risk Waist (inches) Waist-to-hip ratio
Women 35 or more 0.9 or more
Men 40 or more 1.0 or more

What should you do about visceral fat?

People with abdominal obesity — even if they’re not overweight — can lessen their heart disease risk with regular exercise and healthy eating habits. “Reducing the total amount of fat in your body frees up storage space for fat particles in places that are associated with less metabolic risk,” says Dr. Mantzoros. That’s why losing as little as 7% of your total weight helps lower heart disease risk: the most dangerous visceral fat disappears first.

 

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Connie’s comments:
  1. Get adequate sleep at night
  2. Do strength training
  3. Use music – toning relaxation music for brain health
  4. Eat colored whole food and get quality supplements at:

http://www.clubalthea.pxproducts.com

Resveratrol and calorie restriction activates SIRT1 , anti-aging gene

resveWhen the SIRT1 gene is activated, it produces proteins that protect cells from inflammation and oxidative stress, two of the primary causes of premature aging and many degenerative diseases. Almost all organisms have a gene that is equivalent to SIRT1. The gene is a defense mechanism, activated by low calorie consumption, that gives cells an extra level of protection during periods of time when they need it the most. The gene is believed to have a profound affect on lifespan, as studies have shown that animals on calorie-restricted diets live, on average, as much as 40 percent longer than those whose calories are not limited.

Several studies since 2003 have shown that resveratrol can mimic many of the positive effects of calorie restriction. High SIRT1 levels appear to be the key to slowing the aging process and living a healthier life, and calorie restriction and resveratrol are the two primary SIRT1 activators.

The Power of Resveratrol

Unlike pharmaceutical drugs that are specifically targeted to prevent or treat specific illnesses and symptoms, resveratrol can offer protection on a cellular level from two of the primary, underlying causes of premature aging and many age-related diseases. Inflammation and oxidative stress result from two natural body processes, the immune response and oxygen metabolism, but nonetheless are harmful and disruptive to healthy cellular activity. SIRT1 protects cells from free radical damage, inhibits inflammatory substances such as NF-kappa B, and lowers nitrotyrosine, tumor necrosis factor-alpha, and other measures of inflammation and oxidative stress. With its remarkable anti-inflammatory and anti-oxidative effects, SIRT1 can slow the aging process, extend lifespan, and reduce the risk of many degenerative diseases.

Diabetes

Resveratrol improves insulin sensitivity and lowers hepatic glucose production (HGP) in rat models of obesity and diabetes1, 2, 3, 4, 5, but the underlying mechanisms for these antidiabetic effects remain elusive. One process that is considered a key feature of resveratrol action is the activation of the nicotinamide adenine dinucleotide (NAD+)–dependent deacetylase sirtuin 1 (SIRT1) in various tissues1, 3, 6, 7, 8. However, the low bioavailability of resveratrol raises questions about whether the antidiabetic effects of oral resveratrol can act directly on these tissues9, 10. We show here that acute intraduodenal infusion of resveratrol reversed a 3 d high fat diet (HFD)–induced reduction in duodenal–mucosal Sirt1 protein levels while also enhancing insulin sensitivity and lowering HGP. Further, we found that duodenum-specific knockdown of Sirt1 expression for 14 d was sufficient to induce hepatic insulin resistance in rats fed normal chow. We also found that the glucoregulatory role of duodenally acting resveratrol required activation of Sirt1 and AMP-activated protein kinase (Ampk) in this tissue to initiate a gut–brain–liver neuronal axis that improved hypothalamic insulin sensitivity and in turn, reduced HGP. In addition to the effects of duodenally acting resveratrol in an acute 3 d HFD–fed model of insulin resistance, we also found that short-term infusion of resveratrol into the duodenum lowered HGP in two other rat models of insulin resistance—a 28 d HFD–induced model of obesity and a nicotinamide (NA)–streptozotocin (STZ)–HFD-induced model of mild type 2 diabetes. Together, these studies highlight the therapeutic relevance of targeting duodenal SIRT1 to reverse insulin resistance and improve glucose homeostasis in obesity and diabetes.

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