TLRs are functionally inducible and associated with downstream NF-B activation and proinflammatory cytokine production.
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Breast Cancer Research | Full text | The growth response to androgen receptor signaling... - 0 views
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shared by Nathan Goodyear on 20 Nov 12
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Medroxyprogesterone Acetate Induces Cell Proliferation through Up-Regulation ... - 0 views
endo.endojournals.org/...4917.long
medroxyprogesterone acetate progestin progestins breast cancer prover NF-kapppB
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shared by Nathan Goodyear on 28 Apr 12
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Statin-Associated Myopathy with Normal Creatine Kinase Levels - 0 views
www.annals.org/...581.full.pdf+html
statins statin muscle cells mitochondria CoQ10 energy myopathy necrosis
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Obesity - Inducible Toll-like Receptor and NF-[kappa]B Regulatory Pathway Expression in... - 0 views
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TLRs represent a family of receptors that are critical to the innate immune response against foreign pathogens and microorganisms
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LPS has been shown to induce proinflammatory chemokine gene expression in differentiated human adipocytes through TLR and NF-B action
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Stimulation of TLRs initiates intracellular signaling cascades resulting in downstream NF-B and mitogen-activated protein kinase activation and production of proinflammatory chemokines associated with mechanisms of metabolic dysfunction and cardiovascular disease progression.
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Elevated fatty acids levels associated with obesity activate TLR4 signaling in fat cells and macrophages, and induce insulin resistance in murine models
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Nuclear factor-kappaB and IkappaB kinase are constitu... [Cancer. 2004] - PubMed - NCBI - 0 views
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Phosphatidylinositol 3-kinase and ERK are required for NF-κB activation but n... - 0 views
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http://www.ccsenet.org/journal/index.php/cco/article/viewFile/26281/16499 - 0 views
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Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1 - 0 views
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Overactivation of S6 Kinase 1 as a Cause of Human Insulin Resistance During Increased A... - 0 views
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Branched-chain amino acids in liver diseases - 0 views
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Serum concentrations of BCAAs are decreased, while the concentrations of the aromatic amino acids (AAAs) phenylalanine and tyrosine are increased, in patients with advanced liver diseases, resulting in a low ratio of BCAAs to AAAs, a ratio called the Fischer ratio
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a simplified Fischer ratio, the BCAA to tyrosine ratio (BTR), has been reported useful for predicting serum albumin concentration one year later
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BCAA supplementation was shown to delay the progression of CCl4-induced chronic liver injury in a rat model by reducing hepatic apoptosis
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BCAA supplementation for advanced cirrhotic patients improves nutritional status and quality of life
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BCAAs activate mTOR and subsequently increase the production of eukaryotic initiation factor 4E-binding protein-1 and ribosomal protein S6 kinase, which upregulate the synthesis of albumin
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BCAAs were shown to improve homeostasis model assessment scores for insulin resistance (HOMA-IR) and beta cell function (HOMA-%B) in patients with chronic liver disease, indicating that BCAAs can ameliorate insulin resistance
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Several clinical trials have suggested that BCAA supplementation improves the prognosis of cirrhotic patients
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Treatment with BCAAs may therefore have a beneficial effect on patients with hepatic encephalopathy mainly by compensating decreased ratio of BCAAs to AAAs, but not by reducing serum ammonia levels
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Two randomized studies also showed that BCAAs did not clearly prevent HE in patients with advanced cirrhosis, although BCAAs prevented the progression of hepatic failure
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a systematic review with meta-analyses on the effect of oral BCAAs for the treatment of HE was published[66]. The review has revealed that supplementation of oral BCAAs in cirrhotic patients inhibits the manifestation of HE, especially in patients with overt HE rather than those with minimal HE, but showed no effect on the survival of those patients[66]. Thus, oral administration of BCAAs is the treatment of choice in cirrhotic patients with HE
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Mechanism of IL-1β-Induced Increase in Intestinal Epithelial Tight Junction P... - 0 views
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The IL-1β-induced increase in intestinal epithelial tight junction (TJ) permeability has been postulated to be an important mechanism contributing to intestinal inflammation of Crohn’s disease and other inflammatory conditions of the gut
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The IL-1β-induced increase in MLCK mRNA transcription and subsequent increase in MLCK protein expression and Caco-2 TJ permeability was mediated by activation of NF-κB
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IN THIS ISSUE - The Journal of Immunology - 0 views
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t has been suggested that increased permeability of intestinal epithelial tight junctions (TJ) in these diseases is mediated by proinflammatory cytokines including IL-1β,
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Al-Sadi et al. (p. 5653 ) hypothesized that myosin light chain kinase (MLCK), which is known to be important for intestinal TJ permeability, could mediate IL-1β-induced disruption of the epithelial barrier
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α-Lipoic acid increases energy expenditure by enhancing adenosine monophospha... - 0 views
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Fructose: A Key Factor in the Development of Metabolic Syndrome and Hypertension - 0 views
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HFCS consists of fructose and glucose mixed in a variety of concentrations, but most commonly as 55% fructose and 45% glucose
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In the United States, HFCS and sucrose are the major sources of fructose in the diet, and HFCS is a major ingredient in soft drinks, pastries, desserts, and various processed foods
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fructose and glucose are metabolized in completely different ways and utilize different GLUT transporters
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In the liver, fructose bypasses the two highly regulated steps of glycolysis, catalyzed by glucokinase/hexokinase and phosphofructokinase both of which are inhibited by increasing concentrations of their byproducts. Instead, fructose enters the pathway at a level that is not regulated and is metabolized to fructose-1-phosphate primarily by fructokinase or ketohexokinase
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Fructokinase has no negative feedback system, and ATP is used for the phosphorylation process. As a result, continued fructose metabolism results in intracellular phosphate depletion, activation of AMP deaminase, and uric acid generation which is harmful at the cellular level
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Uric acid inhibits endothelial NO both in vivo and in vitro, [15] and directly induces adipocyte dysfunction
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Serum uric acid increases rapidly after ingestion of fructose, resulting in increases as high as 2 mg/dL within 1 hour
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Uncontrolled fructose metabolism leads to postprandial hypertriglyceridemia, which increases visceral adipose deposition. Visceral adiposity contributes to hepatic triglyceride accumulation, protein kinase C activation, and hepatic insulin resistance by increasing the portal delivery of free fatty acids to the liver
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Several reviews have concluded that intake of both fructose and HFCS by children and adults was associated with an increased risk of obesity and metabolic syndrome
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shared by Nathan Goodyear on 13 Jan 15
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Intravenous Fluid Use in Athletes - 0 views
www.ncbi.nlm.nih.gov/...PMC3435915
IV intravenous fluid nutrition athletes athlete sports medicine sports exercise
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Treatment of exercise-associated hyponatremia with hypertonic IV infusion to correct plasma sodium levels is also a standard and accepted use of IV fluid infusions
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athletes who present for medical care with hypernatremia who cannot tolerate oral fluids can benefit from IV fluids
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Vaporization of sweat accounts for 80% of heat loss in hot, dry atmospheric conditions. This mechanism of water loss is the major contributor for exercise-associated dehydration
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Pre- and postexercise body weight measurements are the most common means to estimate overall water loss but are condition specific
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In highly trained endurance athletes, plasma volume and sodium serum concentration were preserved despite a 5% body weight loss
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In Ironman triathletes, dehydration to 5% body weight loss did not correlate with occurrence of medical complications
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hydration should begin hours prior to exercise, especially if known deficits are present, and fluids should be consumed at a slow, steady rate, with 5 to 7 mL/kg taken 4 hours prior to exercise
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Sodium concentration did not produce significant changes in the rate of absorption but was primarily dependent on carbohydrate concentration
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IV treatment of severe dehydration (>7% body weight loss), exertional heat illness, nausea, emesis, or diarrhea, and in those who cannot ingest oral fluids for other reasons, is clinically indicated
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A recent survey of the National Football League teams revealed that 75% (24 of 32) of the teams utilized IV infusion of fluids for prehydration in at least some otherwise healthy individuals
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In the National Football League, an average of 1.5 L of normal saline was administered approximately 2.5 hours prior to competition
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after 2 hours of exercise, the rectal temperature was 0.6° higher in the group not receiving IV infusion. Also, stroke volume and cardiac output were 11% to 16% lower in the control group versus the IV infusion group.
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Recent evidence suggests the etiology of EAMC is related to muscle fatigue and neuronal excitability
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there may be a subset of muscle cramping that is associated with a loss of both body fluid and sodium
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elevation of plasma volume by 200 to 300 mL via dextran infusion resulted in 15% increase in stroke volume, 4% increase in VO2 max, and an increase in the exercise time to fatigue
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Neither the tonicity nor mode of hydration resulted in improved speed of rehydration, greater fluid retention, or improved performance
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There are beneficial anecdotal reports of EAMC treatment in elite and professional-level athletes with IV hydration during the course of an event
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Plasma volume was better restored during rehydration with IV fluids at preexercise and 5 minutes of exercise. At 15 minutes, there was no difference between IV and oral rehydration
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More rapid restoration of plasma volume was accomplished in the IV treatment group with no advantages over oral rehydration in physiological strain, heat tolerance, ratings of perceived effort, or thermal sensations
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No difference was found in exercise time to exhaustion. IV and oral rehydration methods were equally effective. Heart rates were statistically higher in the oral rehydration group through 75 minutes of exercise, and there were higher increases in norepinephrine plasma concentrations
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No significant differences between the groups were found for time to recovery, number of days with pain, number of days with stiffness, sleep disturbance, fatigue, rectal temperature, and loss of appetite
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There may be physiological benefits of decreased heart rate and norepinephrine in athletes rehydrated via IV route
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Postexercise blood 1 hour and 24 hours showed no differences in circulating myoglobin or creatine kinase
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this should be reserved for high-level athletes with strong histories of symptoms in well-monitored settings.
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Testosterone Supplementation Reverses Sarcopenia in Aging through Regulation of Myostat... - 0 views
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shared by Nathan Goodyear on 12 Nov 14
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BMC Cancer | Full text | A lactate shuttle system between tumour and stromal cells is a... - 0 views
www.biomedcentral.com/...352
cancer prostate cancer CAFs cancer associated fibroblasts mono-carboxylate transporters
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Under hypoxic conditions, tumour cells primarily use glycolysis for energy, producing lactate, which is expelled to the tumour microenvironment, allowing tumours to continue their glycolytic activity
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Sonveaux et al. showed that lactate, which is generally considered a waste product, is preferred over glucose by oxidative tumour cells as their primary energy source
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MCT4 is a low-affinity transporter, which is abundant in highly glycolytic muscle cells and is one of the many target genes of hypoxia-inducible factor 1 alpha (HIF-1α)
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Other targets of HIF-1α include glucose transporter-1 (GLUT-1), the main transporter involved in glucose uptake [9,10]; lactate dehydrogenase V (LDHV), which is responsible for the conversion of pyruvate into lactate; pyruvate dehydrogenase kinase isozyme 1 (PDK1), which is responsible for the phosphorylation and consequent inactivation of pyruvate dehydrogenase (PDH); and carbonic anhydrase IX (CAIX), a hypoxia-related protein involved in pH regulation [11]. Alpha-methylacyl-CoA racemase (AMACR), pristanoyl-CoA oxidase (ACOX-3) and D-bifunctional protein (DBP), are also important fatty acid oxidation-related proteins in prostate cancer
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the essential role played by the cross-talk between stroma and epithelium in carcinogenesis and prostate cancer progression has been increasingly recognised
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strong membranous expression of MCT1 was consistently observed in cancer cells, suggesting a role for MCT1 in the transport of lactate into tumour cells from the acidic extracellular matrix, suggesting that lactate might be used as a fuel by oxidative cancer cells.
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Our hypothesis is in agreement with those of Fiaschi et al.[17], who describe the metabolic reprogramming of CAFs towards the Warburg phenotype as a result of contact with prostate cancer cells
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Using in vitro studies, they showed lactate production and efflux by de novo expressed MCT4 in CAFs and also demonstrated that, upon contact with CAFs, prostate cancer cells were reprogrammed towards aerobic metabolism, with an increase in lactate uptake via the lactate transporter MCT1.
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pharmacological inhibition of MCT1-mediated lactate uptake dramatically affected PCa cell survival and tumour outgrowth
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In this model, “energy transfer” or “metabolic coupling” between the tumour stroma and epithelial cancer cells fuels tumour growth and metastasis via oxidative mitochondrial metabolism in anabolic cancer cells
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the concomitant expression of MCT1 in tumour cells and MCT4 in fibroblasts in the same tissue is clinically significant, and associated with poor prognosis.
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Antitumor activity of dichloroacetate on C6 glioma cell: in vitro and in vivo evaluation - 0 views
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DCA can penetrate into the traditional chemotherapy sanctuary sites. Interestingly, it was reported that DCA could penetrate across the BBB,30 exhibiting the potential activity for brain therapy.
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It has been reported that DCA activates the PDH by inhibition of PDK in a dose-dependent manner, and results in increased delivery of pyruvate into the mitochondria
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The antitumor activity of DCA on nonsmall cell lung cancer, breast cancer, glioblastomas, and endometrial and prostate cancer cells has been demonstrated
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The most common metabolic hallmark of cancer cells is their propensity to metabolize glucose to lactic acid at a high rate even in the presence of oxygen
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Pyruvate dehydrogenase kinase (PDK) is a gate-keeping enzyme that regulates the flux of carbohydrates (pyruvate) into the mitochondria
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In the presence of activated PDK, pyruvate dehydrogenase (PDH), a critical enzyme that converts pyruvate to acetyl-CoA instead of lactate in glycolysis, is inhibited, limiting the entry of pyruvate into the mitochondria.
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It has been reported that DCA treatment resulted in an increase in the proportion of tumor cells in the S phase, showing a decrease in proliferation as well as the induction of apoptosis
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Heat shock proteins (HSPs) are involved in protein folding, aggregation, transport, and/or stabilization by acting as a molecular chaperone, leading to the inhibition of apoptosis by both caspase-dependent and/or independent pathways
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HSPs are overexpressed in a wide range of human cancers and are implicated in tumor cell proliferation, differentiation, invasion, and metastasis
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Considering the fact that high expression of HSPs is essential for cancer survival, the inhibition of HSPs is an important strategy of anticancer therapy.
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In addition, after 5 years of continued treatment with oral DCA at a dose of 25 mg/kg, the serum DCA levels are only slightly increased compared with the levels after the first several doses, also showing its safety for oral administration at this dose.
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DCA can enter the circulation rapidly after oral administration and then generate the stimulation of PDH activity generally within minutes.
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Our in vivo results in tumor tissues indicated that DCA significantly induced ROS production and decreased MMP in tumor tissues
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The numbers of microvessels in the DCA treatment groups were significantly decreased, suggesting the potential antiangiogenic effect of DCA
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The inhibition effect of DCA on HIF-1α would decrease vascular endothelial growth factor and inhibit angiogenesis
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the antiangiogenic effect in the 25 mg/kg treatment group was lower than that in 75 mg/kg or 125 mg/kg treatment groups
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In conclusion, DCA induces the apoptosis of C6 cells through the activation of the mitochondrial pathway, arresting the cell cycle of C6 cells in S phase and down-regulating Hsp70 expression.
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DCA significantly induced the ROS production and decreased the MMP in tumor tissues. Our in vivo antitumor activity results also indicated that DCA has an antiangiogenic effect
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