A “press” disturbance was considered a chronic environmental stress on all organisms in an ecological community
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Efficient Strategies of Avoiding Whiteheads on Face - 0 views
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shared by Nathan Goodyear on 09 Jul 17
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Press-pulse: a novel therapeutic strategy for the metabolic management of cancer | Nutr... - 0 views
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ketogenic diet ketogenic press-pulse hyperbaric oxygen therapy HBOTnutrition diet cancer HBOT IVC IV vitamin C DCA dichloracetic acid cancer therapy cancer treatment alternative cancer treatment
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“pulse” disturbances were considered acute events that disrupted biological communities to produce high mortality
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Data from the American Cancer Society show that the rate of increase in cancer deaths/year (3.4%) was two-fold greater than the rate of increase in new cases/year (1.7%) from 2013 to 2017
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glucose is first split into two molecules of pyruvate through the Embden–Meyerhof–Parnas glycolytic pathway in the cytosol
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Aerobic fermentation, on the other hand, involves the production of lactic acid under normoxic conditions
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persistent lactic acid production in the presence of adequate oxygen is indicative of abnormal respiration
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The Crabtree effect is an artifact of the in vitro environment and involves the glucose-induced suppression of respiration with a corresponding elevation of lactic acid production even under hyperoxic (pO2 = 120–160 mmHg) conditions associated with cell culture
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the Warburg theory of insufficient aerobic respiration remains as the most credible explanation for the origin of tumor cells [2, 37, 51, 52, 53, 54, 55, 56, 57].
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The main points of Warburg’s theory are; 1) insufficient respiration is the predisposing initiator of tumorigenesis and ultimately cancer, 2) energy through glycolysis gradually compensates for insufficient energy through respiration, 3) cancer cells continue to produce lactic acid in the presence of oxygen, and 4) respiratory insufficiency eventually becomes irreversible
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Efraim Racker coined the term “Warburg effect”, which refers to the aerobic glycolysis that occurs in cancer cells
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Warburg clearly demonstrated that aerobic fermentation (aerobic glycolysis) is an effect, and not the cause, of insufficient respiration
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all tumor cells that have been examined to date contain abnormalities in the content or composition of cardiolipin
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The evidence supporting Warburg’s original theory comes from a broad range of cancers and is now overwhelming
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respiratory insufficiency, arising from any number mitochondrial defects, can contribute to the fermentation metabolism seen in tumor cells.
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data from the nuclear and mitochondrial transfer experiments suggest that oncogene changes are effects, rather than causes, of tumorigenesis
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Normal mitochondria can suppress tumorigenesis, whereas abnormal mitochondria can enhance tumorigenesis
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Glutamine is anapleurotic and can be rapidly metabolized to glutamate and then to α-ketoglutarate for entry into the TCA cycle
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Amino acid fermentation can generate energy through TCA cycle substrate level phosphorylation under hypoxic conditions
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Although Warburg’s hypothesis on the origin of cancer has created confusion and controversy [37, 38, 39, 40], his hypothesis has never been disproved
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Warburg referred to the phenomenon of enhanced glycolysis in cancer cells as “aerobic fermentation” to highlight the abnormal production of lactic acid in the presence of oxygen
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Emerging evidence indicates that macrophages, or their fusion hybridization with neoplastic stem cells, are the origin of metastatic cancer cells
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Radiation therapy can enhance fusion hybridization that could increase risk for invasive and metastatic tumor cells
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Kamphorst et al. in showing that pancreatic ductal adenocarcinoma cells could obtain glutamine under nutrient poor conditions through lysosomal digestion of extracellular proteins
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It will therefore become necessary to also target lysosomal digestion, under reduced glucose and glutamine conditions, to effectively manage those invasive and metastatic cancers that express cannibalism and phagocytosis.
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Previous studies in yeast and mammalian cells show that disruption of aerobic respiration can cause mutations (loss of heterozygosity, chromosome instability, and epigenetic modifications etc.) in the nuclear genome
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The somatic mutations and genomic instability seen in tumor cells thus arise from a protracted reliance on fermentation energy metabolism and a disruption of redox balance through excess oxidative stress.
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According to the mitochondrial metabolic theory of cancer, the large genomic heterogeneity seen in tumor cells arises as a consequence, rather than as a cause, of mitochondrial dysfunction
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A therapeutic strategy targeting the metabolic abnormality common to most tumor cells should therefore be more effective in managing cancer than would a strategy targeting genetic mutations that vary widely between tumors of the same histological grade and even within the same tumor
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Tumor cells are more fit than normal cells to survive in the hypoxic niche of the tumor microenvironment
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Hypoxic adaptation of tumor cells allows for them to avoid apoptosis due to their metabolic reprograming following a gradual loss of respiratory function
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The high rates of tumor cell glycolysis and glutaminolysis will also make them resistant to apoptosis, ROS, and chemotherapy drugs
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Despite having high levels of ROS, glutamate-derived from glutamine contributes to glutathione production that can protect tumor cells from ROS
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It is clear that adaptability to environmental stress is greater in normal cells than in tumor cells, as normal cells can transition from the metabolism of glucose to the metabolism of ketone bodies when glucose becomes limiting
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Mitochondrial respiratory chain defects will prevent tumor cells from using ketone bodies for energy
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glycolysis-dependent tumor cells are less adaptable to metabolic stress than are the normal cells. This vulnerability can be exploited for targeting tumor cell energy metabolism
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In contrast to dietary energy reduction, radiation and toxic drugs can damage the microenvironment and transform normal cells into tumor cells while also creating tumor cells that become highly resistant to drugs and radiation
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Drug-resistant tumor cells arise in large part from the damage to respiration in bystander pre-cancerous cells
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Because energy generated through substrate level phosphorylation is greater in tumor cells than in normal cells, tumor cells are more dependent than normal cells on the availability of fermentable fuels (glucose and glutamine)
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Although some tumor cells might appear to oxidize ketone bodies by the presence of ketolytic enzymes [181], it is not clear if ketone bodies and fats can provide sufficient energy for cell viability in the absence of glucose and glutamine
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A calorie restricted ketogenic diet or dietary energy reduction creates chronic metabolic stress in the body
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The KD can more effectively reduce glucose and elevate blood ketone bodies than can CR alone making the KD potentially more therapeutic against tumors than CR
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Campbell showed that tumor growth in rats is greater under high protein (>20%) than under low protein content (<10%) in the diet
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Calorie restriction, fasting, and restricted KDs are anti-angiogenic, anti-inflammatory, and pro-apoptotic and thus can target and eliminate tumor cells through multiple mechanisms
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Ketogenic diets can also spare muscle protein, enhance immunity, and delay cancer cachexia, which is a major problem in managing metastatic cancer
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The GKI can therefore serve as a biomarker to assess the therapeutic efficacy of various diets in a broad range of cancers.
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It is important to remember that insulin drives glycolysis through stimulation of the pyruvate dehydrogenase complex
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The water-soluble ketone bodies (D-β-hydroxybutyrate and acetoacetate) are produced largely in the liver from adipocyte-derived fatty acids and ketogenic dietary fat. Ketone bodies bypass glycolysis and directly enter the mitochondria for metabolism to acetyl-CoA
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Due to mitochondrial defects, tumor cells cannot exploit the therapeutic benefits of burning ketone bodies as normal cells would
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Therapeutic ketosis with racemic ketone esters can also make it feasible to safely sustain hypoglycemia for inducing metabolic stress on cancer cells
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ketone bodies can inhibit histone deacetylases (HDAC) [229]. HDAC inhibitors play a role in targeting the cancer epigenome
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Therapeutic ketosis reduces circulating inflammatory markers, and ketones directly inhibit the NLRP3 inflammasome, an important pro-inflammatory pathway linked to carcinogenesis and an important target for cancer treatment response
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Chronic psychological stress is known to promote tumorigenesis through elevations of blood glucose, glucocorticoids, catecholamines, and insulin-like growth factor (IGF-1)
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In addition to calorie-restricted ketogenic diets, psychological stress management involving exercise, yoga, music etc. also act as press disturbances that can help reduce fatigue, depression, and anxiety in cancer patients and in animal models
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This physiological state also enhances the efficacy of chemotherapy and radiation therapy, while reducing the side effects
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lower dosages of chemotherapeutic drugs can be used when administered together with calorie restriction or restricted ketogenic diets (KD-R)
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Besides 2-DG, a range of other glycolysis inhibitors might also produce similar therapeutic effects when combined with the KD-R including 3-bromopyruvate, oxaloacetate, and lonidamine
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It is important to recognize, however, that the radiotherapy used in glioma patients can damage the respiration of normal cells and increase availability of glutamine in the microenvironment, which can increase risk of tumor recurrence especially when used together with the steroid drug dexamethasone
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Poff and colleagues demonstrated that hyperbaric oxygen therapy (HBOT) enhanced the ability of the KD to reduce tumor growth and metastasis
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The effects of the KD and HBOT can be enhanced with administration of exogenous ketones, which further suppressed tumor growth and metastasis
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Besides HBOT, intravenous vitamin C and dichloroacetate (DCA) can also be used with the KD to selectively increase oxidative stress in tumor cells
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Recent evidence also shows that ketone supplementation may enhance or preserve overall physical and mental health
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Some tumors use glucose as a prime fuel for growth, whereas other tumors use glutamine as a prime fuel [102, 186, 262, 263, 264]. Glutamine-dependent tumors are generally less detectable than glucose-dependent under FDG-PET imaging, but could be detected under glutamine-based PET imaging
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Many of the current treatments used for cancer management are based on the view that cancer is a genetic disease
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Emerging evidence indicates that cancer is a mitochondrial metabolic disease that depends on availability of fermentable fuels for tumor cell growth and survival
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Glucose and glutamine are the most abundant fermentable fuels present in the circulation and in the tumor microenvironment
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Low-carbohydrate, high fat-ketogenic diets coupled with glycolysis inhibitors will reduce metabolic flux through the glycolytic and pentose phosphate pathways needed for synthesis of ATP, lipids, glutathione, and nucleotides
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Why Do GPs Need a Telemedicine Strategy to Sustain their Practice? - Zeboc - 0 views
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The #telemedicine market is projected to grow upto 35 billion USD by 2025 in the US alone. Your practice too can have a slice of the pie by implementing a telemedicine #strategy. So, what are you waiting for? Check out this blog to know about the benefits your practice is missing out without a #telemedicinesolution.
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Journal of Endocrinological Investigation - 0 views
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Running: the risk of coronary events † - 0 views
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shared by Nathan Goodyear on 30 Apr 13
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Regulation of muscle glycogen repletion, muscle, protein synthesis and repair following... - 0 views
www.jssm.org/...v3n3-3pdf.pdf
exercise training exercise recovery recovery glycogen muscle protein amino acids carbohydrates
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shared by Nathan Goodyear on 18 May 16
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Telomerase at the intersection of cancer and aging - 0 views
www.ncbi.nlm.nih.gov/...PMC3896987
telomere telomeres telomerase telomerase activator aging disease cancer
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The anti-aging role of telomerase has been demonstrated to be largely mediated by its canonical role in elongating telomeres, which prevents the accumulation of critically short telomeres and loss of tissue homeostasis
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increased abundance of short telomeres correlates with higher genomic instability and decreased longevity in various organisms, including mice, zebrafish, and yeast
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mice deficient for telomerase or for telomere binding proteins are characterized by accelerated age-related defects
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In humans, short telomeres are considered good indicators of an individual’s health status and correlate with both genetic and environmental factors
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Although recent findings strongly support the idea that short telomeres drive several age-related diseases 38 we cannot exclude the possibility that in some situations short telomeres may be a consequence of the disease itself.
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the current view is that telomerase deficiency may contribute to the early steps of cancer development by fueling chromosomal instability, while subsequent activation of telomerase may be necessary to allow tumor growth and tumor progression towards more malignant states
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telomerase can stimulate tumor progression by ensuring maintenance of telomeres above a critically short length, thus preventing induction of cellular senescence or apoptosis
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Almost all human cancers present activation of telomerase as a hallmark, most likely as a mechanism to allow unlimited cell proliferation of tumor cells
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recent evidence demonstrated that short telomeres alone could lead to genomic instability and cancer
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Getting rid of telomerase can also be problematic; the lack of telomerase could lead to increased chromosomal instability, which in turn could be at the basis for cancer initiation when tumor suppressor barriers are bypassed
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telomerase activation in adult or old mice by means of a gene therapy strategy was shown to be sufficient to improve metabolic fitness, neuromuscular capacity, and prevent bone loss, as well as significantly increase both median and maximum longevity, without increased cancer incidence
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These studies suggest that telomerase expression could be considered a feasible approach to reverse tissue dysfunction and extend healthy lifespan without increasing cancer incidence
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a change of paradigm seems to be occurring in telomerase biology, with a switch from viewing telomerase as fueling cancer to reversing aging
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Telomerase expression in a background of high levels of tumor suppressors or in aged organisms seems to prevent its expected pro-cancer activity and yet it still functions as an anti-aging factor
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Telomerase activity and longer telomere length is shown to correlated inversely with many chronic diseases of aging. In contrast, telomerase activity is found to be involved in carcinogenesis. Increased carcinogenic potential of telomerase activity has not borne out in studies. In addition, increased CD8 cell activity as a result of telomerase activation will actually decrease carcinogenic potential via NK activation.
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Leg vascular and skeletal muscle mitochondrial adaptations to aerobic high-intensity ex... - 0 views
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shared by Nathan Goodyear on 20 Dec 11
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Obesity - The Obesity Pandemic: Where Have We Been and Where Are We Going? - 0 views
www.nature.com/...oby2004273a.html
obesity pandemic inflammation inflammatory overweight weight-loss
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nice study on contributors to the obesity epidemic. Particularly inflammation. This article touches on the idea that fat acts as a hormone producing organ. Minus some of the treatment strategies, surgery and prescription drugs, this is a good article. This article also touches on the implications of the obesity Pandemic as they state.
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Arch Neurol -- Abstract: Mediterranean Diet and White Matter Hyperintensity Volume in t... - 0 views
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shared by Nathan Goodyear on 04 Feb 14
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Testosterone Replacement Therapy Improves Metabolic Parameters in Hypogonadal Men with ... - 0 views
onlinelibrary.wiley.com/...full
low T Testosterone Diabetes men male hormones HgbA1c TC total cholesterol cholesterol waist circumference
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Testosterone therapy lowered HgbA1c in poorly controlled Diabetics. These patients were followed out to 52 weeks. Testosterone therapy, as is lifestyle change, a long term strategy of Diabetes control. Studies in controlled Diabetics have not shown a reduction in HgbA1c consistently. Total cholesterol and waist circumference were also reduced.
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Dietary Strategy to Repair Plasma Membrane After Brain Trauma - 0 views
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strategies directed to preserve phospholipids in the plasma membrane such as the use of dietary docosahexaenoic acid (C22:6n-3; DHA)5 can have beneficial effects for post-TBI recovery
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Curcumin provided in the diet before TBI can reduce oxidative damage and counteract TBI-related cognitive dysfunction.
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Our previous study indicated that n-3 fatty acids supplemented in the diet counteracted learning disability after TBI
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There was a significant group effect on BDNF (F 4,25 = 5.229, P < .01 by ANOVA), and FPI reduced BDNF levels (50% of CTL, P < .01; Figure 1C), which was counteracted by DHA supplementation (90% of CTL, P < .05; Figure 1C). Curcumin also counteracted this reduction of BDNF
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The combination of curcumin and DHA had a trend of greater effects in BDNF (117% of CTL; Figure 1C) compared with DHA or curcumin alone.
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curcumin contributed to enhance the action of DHA, protecting against cognitive impairment, and these effects were associated with elevations in the BDNF receptor signaling
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Our current results show that curcumin contributes to enhance the effects of DHA on TBI by promoting phosphorylation of the BDNF receptor TrkB in the hippocampus.
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previous evidence indicates that curcumin10 and DHA5 counteract TBI-related learning disability by involving BDNF
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The effects of the DHA diet and curcumin on cognitive enhancement were consistent with enhanced elevations in BDNF receptor signaling
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effects of DHA and curcumin up to 2 weeks after TBI because this is the most critical period for the course of injury recovery because the brain is metabolically dysfunctional during this time
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Salivary cortisol as a tool for physiological stud... [Braz J Med Biol Res. 2000] - Pub... - 0 views
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The measurement of salivary cortisol is a useful tool for physiological studies and for the diagnosis of CS in children and adults on an outpatient basis
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ScienceDirect - Free Radical Biology and Medicine : Neuroprotection by the Me... - 0 views
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preliminary human studies indicate that α-lipoate may be effective in numerous neurodegenerative disorders
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Focus on metabolic and nutritional corre... [Arch Gynecol Obstet. 2014] - PubMed - NCBI - 0 views
www.ncbi.nlm.nih.gov/...25200687
PCOS polycystic ovarian syndrome polycystic ovary syndrome nutrition diet lifestyle women female hormone hormones
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Testosterone in Men with Advanced Li... [J Gastroenterol Hepatol. 2014] - PubMed - NCBI - 0 views
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published ahead of print. The authors conclude that the Testosterone therapy in hypogonadal men with cirrhosis requires further study. They, the authors, state that the risk of Testosterone and hepatocellular carcinoma is overstated. This risk is associated with oral Testosterone replacement and thus in that light is not overstated. The majority of treatment strategies today employ none oral routes of administration which would support their statement.
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shared by Nathan Goodyear on 10 Feb 16
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The Role of Post-Exercise Nutrient Administration on Muscle Protein Synthesis and Glyco... - 0 views
www.ncbi.nlm.nih.gov/...PMC3761704
exercise athlete athletes recovery exercise recovery training protein carbohydrates glycogen muscle
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Free form amino acid ingestion acts similarly to whey by displaying a rapid and strong increase in aminoacidemia
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it appears that protein synthesis rapidly increases for up to two hours after amino acid administration
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The intervention of dietary protein or amino acid supplementation in conjunction with resistance training has proven to effectively increase protein synthesis rates
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291% increase in protein synthesis following the exercise bout, while protein degradation remained unchanged from baseline quantities
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it has been established that post-exercise EAA supplementation stimulates protein synthesis, in conjunction with a positive protein balance, comparable to that of intravenous infusion of amino acids
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Casein and whey protein ingestion yielded similar values of net positive protein balance, and thus an overall increase in protein synthesis
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A later analysis revealed that soy protein increased protein synthesis in rats similar to that of whey after a treadmill exercise protocol
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A human trial, however, concluded that milk proteins (caseins and whey) in comparison to soy promoted greater muscle protein accretion when they were ingested after regular resistance training
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Whey hydrolysate ingested after a resistance exercise bout acutely stimulated mixed muscle protein synthesis 31% greater than soy
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adequate amount of protein (20 g) is ingested (Tipton et al., 2009) immediately before or after a resistance exercise bout
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slow phase, which can last up to several hours if carbohydrate availability is high and insulin levels remain elevated
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Doing something about physician burnout - The Lancet - 0 views
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Hyperthermia as an immunotherapy strategy for cancer - 1 views
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After antigen uptake at tumor sites, APCs have the ability to create a robust response by entering lymphoid compartments and programming lymphocytes
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Hyperthermia differs fundamentally from fever in that it elevates the core body temperature without changing the physiological set point
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mor cells [2]. Although significant cell killing could be achieved by heating cells or tissues to temperatures > 42°C for 1 or more hours, the application, measurement and consistency of this temperature range within the setting of cancer clinical trials
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mild temperature hyperthermia (ie, within the fever-range, 39–41°C)
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moderate hyperthermia (41°C)
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Hsps ensure appropriate post-translational protein folding, and are able to refold denatured proteins, or mark irreversibly damaged proteins for destruction
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the ability of fever-range hyperthermia to induce reactive immunity against tumor antigens through DCs and NK-cells is likely mediated by Hsps
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Hsps support the malignant phenotype of cancer cells by not only affecting the cells’ survival, but also participating in angiogenesis, invasion, metastasis and immortalization mechanisms
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Hsps released from stressed or dying cells activate dendritic cells (DCs), transforming them into mature APCs
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In theory, fever-range hyperthermia may take advantage of tumor cell Hsps by inducing their release from tumor cells and augmenting DC priming against tumor antigens
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In several models of hyperthermia, heat-treated tumors exhibited improved DC priming and generation of systemic immunity to tumor cell
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hyperthermia alone can enhance antigen display by tumor cells, thus rendering them even more susceptible to programmed immune clearance
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Hsps may exert an adjuvant effect by bolstering MHC class II and co-stimulatory molecule expression by DCs
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thermal ablation of liver tumors in particular has demonstrated an ability to potentiate immune responses [57, 58] and elicit robust T-cell infiltrates at ablation sites
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specific Hsp, Hsp70, directly inhibits apoptosis pathways in cancer cells, as demonstrated in human pancreatic, prostate and gastric cancer cells
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Cross-priming is the ability of extracellular Hsps complexed to tumor peptides to be internalized and presented in the context of MHC class I molecules on APCs, thus allowing potent priming of CTLs against tumor antigens
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It has been reported that Hsps are generated from necrotic tumor cell lysates, but not from tumor cells undergoing apoptosis
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tumor cells exposed to hyperthermia in the heat shock range (42°C for 4h) prior to lysing, DC activation and cross-priming were significantly enhanced with the application of heat
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Due to the ability of Hsps to activate DCs directly by chaperoning tumor antigens upon their release [28], it is possible that both local and regional immune stimulation can be achieved with hyperthermia.
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support the use of hyperthermia as an inducer of Hsps to serve as ‘danger signals’, activating antitumor immune responses
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whole-body hyperthermia not only augments immune responses, but also stimulates the migration of skin-derived DCs to draining lymph nodes
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In mice treated with fever-range whole-body hyperthermia, tumor growth was significantly inhibited and NK-cell infiltration increased
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exposure to fever-range hyperthermia resulted in improved endogenous NK-cell cytotoxicity to several cancer types
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The combined effects of hyperthermia on lymphoid tissue endothelium and lymphocytes can promote immune surveillance and increase the probability of naive lymphocytes leaving the circulation and encountering their cognate antigen displayed by DCs in lymphoid organs.
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In independent clinical studies, whole-body hyperthermia resulted in a transient decrease in circulating lymphocytes in patients with advanced cancer [12, 94, 99, 100], a finding which mirrored observations in animal models in which lymphocyte entry into lymph noeds was increased following hyperthermia treatment [93]. Enhanced recruitment of lymphocytes to lymphoid tissues may be exploited in the treatment of malignancies.
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The initial tumor antigen presentation and initiation of clonal expansion of CTLs transpires in the lymph nodes and cannot take place outside this specialized compartment
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the ability of DCs present in the lymph nodes to stimulate an anti-tumor immune response is critical