Weight gain has been associated with a higher gut permeability
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shared by Nathan Goodyear on 04 Aug 14
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Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk - 0 views
jme.endocrinology-journals.org/...R51.full
metabolic endotoxemia obesity insulin resistance cardiovascular disease LPS inflammation
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The starting point for innate immunity activation is the recognition of conserved structures of bacteria, viruses, and fungal components through pattern-recognition receptors
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TLRs are transmembrane proteins containing extracellular domains rich in leucine repeat sequences and a cytosolic domain homologous to the IL1 receptor intracellular domain
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The major proinflammatory mediators produced by the TLR4 activation in response to endotoxin (LPS) are TNFα, IL1β and IL6, which are also elevated in obese and insulin-resistant patients
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Obesity, high-fat diet, diabetes, and NAFLD are associated with higher gut permeability leading to metabolic endotoxemia.
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LPS promotes hepatic insulin resistance, hypertriglyceridemia, hepatic triglyceride accumulation, and secretion of pro-inflammatory cytokines promoting the progression of fatty liver disease.
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In the endothelium, LPS induces the expression of pro-inflammatory, chemotactic, and adhesion molecules, which promotes atherosclerosis development and progression.
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In the adipose tissue, LPS induces adipogenesis, insulin resistance, macrophage infiltration, oxidative stress, and release of pro-inflammatory cytokines and chemokines.
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the gut microbiota has been recently proposed to be an environmental factor involved in the control of body weight and energy homeostasis by modulating plasma LPS levels
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dietary fats alone might not be sufficient to cause overweight and obesity, suggesting that a bacterially related factor might be responsible for high-fat diet-induced obesity.
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This was accompanied in high-fat-fed mice by a change in gut microbiota composition, with reduction in Bifidobacterium and Eubacterium spp.
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n humans, it was also shown that meals with high-fat and high-carbohydrate content (fast-food style western diet) were able to decrease bifidobacteria levels and increase intestinal permeability and LPS concentrations
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it was demonstrated that, more than the fat amount, its composition was a critical modulator of ME (Laugerette et al. 2012). Very recently, Mani et al. (2013) demonstrated that LPS concentration was increased by a meal rich in saturated fatty acids (SFA), while decreased after a meal rich in n-3 polyunsaturated fatty acids (n-3 PUFA).
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this effect seems to be due to the fact that some SFA (e.g., lauric and mystiric acids) are part of the lipid-A component of LPS and also to n-3 PUFA's role on reducing LPS potency when substituting SFA in lipid-A
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these experimental results suggest a pivotal role of CD14-mediated TLR4 activation in the development of LPS-mediated nutritional changes.
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This suggests a link between gut microbiota, western diet, and obesity and indicates that gut microbiota manipulation can beneficially affect the host's weight and adiposity.
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endotoxemia was independently associated with energy intake but not fat intake in a multivariate analysis
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in vitro that endotoxemia activates pro-inflammatory cytokine/chemokine production via NFκB and MAPK signaling in preadipocytes and decreased peroxisome proliferator-activated receptor γ activity and insulin responsiveness in adipocytes.
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LPS-induced release of glucagon, GH and cortisol, which inhibit glucose uptake, both peripheral and hepatic
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Recent evidence has been linking ME with dyslipidemia, increased intrahepatic triglycerides, development, and progression of alcoholic and nonalcoholic fatty liver disease
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The hepatocytes, rather than hepatic macrophages, are the cells responsible for its clearance, being ultimately excreted in bile
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All the subclasses of plasma lipoproteins can bind and neutralize the toxic effects of LPS, both in vitro (Eichbaum et al. 1991) and in vivo (Harris et al. 1990), and this phenomenon seems to be dependent on the number of phospholipids in the lipoprotein surface (Levels et al. 2001). LDL seems to be involved in LPS clearance, but this antiatherogenic effect is outweighed by its proatherogenic features
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LPS produces hypertriglyceridemia by several mechanisms, depending on LPS concentration. In animal models, low-dose LPS increases hepatic lipoprotein (such as VLDL) synthesis, whereas high-dose LPS decreases lipoprotein catabolism
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When a dose of LPS similar to that observed in ME was infused in humans, a 2.5-fold increase in endothelial lipase was observed, with consequent reduction in total and HDL. This mechanism may explain low HDL levels in ‘ME’ and other inflammatory conditions such as obesity and metabolic syndrome
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It is known that the high-fat diet and the ‘ME’ increase intrahepatic triglyceride accumulation, thus synergistically contributing to the development and progression of alcoholic and NAFLD, from the initial stages characterized by intrahepatic triglyceride accumulation up to chronic inflammation (nonalcoholic steatohepatitis), fibrosis, and cirrhosis
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On the other hand, LPS activates Kupffer cells leading to an increased production of ROS and pro-inflammatory cytokines like TNFα
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high-fat diet mice presented with ME, which positively and significantly correlated with plasminogen activator inhibitor (PAI-1), IL1, TNFα, STAMP2, NADPHox, MCP-1, and F4/80 (a specific marker of mature macrophages) mRNAs
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prebiotic administration reduces intestinal permeability to LPS in obese mice and is associated with decreased systemic inflammation when compared with controls
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Cani et al. also found that high-fat diet mice presented with not only ME but also higher levels of inflammatory markers, oxidative stress, and macrophage infiltration markers
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This suggests that important links between gut microbiota, ME, inflammation, and oxidative stress are implicated in a high-fat diet situation
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high-fat feeding is associated with adipose tissue macrophage infiltration (F4/80-positive cells) and increased levels of chemokine MCP-1, suggesting a strong link between ME, proinflammatory status, oxidative stress, and, lately, increased CV risk
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markers of systemic inflammation such as circulating bacterial endotoxin were elevated in patients with chronic infections and were strong predictors of increased atherosclerotic risk
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As a TLR4 ligand, LPS has been suggested to induce atherosclerosis development and progression, via a TLR4-mediated inflammatory state.
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shared by Nathan Goodyear on 18 Nov 14
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AMA Journals - The Perils of Marketing Weight Management Remedies and the Role of Healt... - 0 views
journals.ama.org/...jppm.13.031
obese obesity weight loss drugs weight loss weight management health
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Do weight loss drugs reduce obesity or could they actually increase obesity rates? The search for gimmicks has created a dependance on weight-loss drug falsehoods that don't work long term. Life style has been and continues to be the long term answer. Weight-loss drugs actually are fueling the obesity trend due to a lack of metabolic solutions. They work for the health of pharma profits, just not for the health of the patient.
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shared by Nathan Goodyear on 19 Nov 14
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Differential Effects of Dehydroepiandrosterone and Testosterone in Prostate and Colon C... - 0 views
press.endocrine.org/...en.2012-2249
testosterone prostate colon colon cancer cancer NGF nerve growth factor dhea dehydroepiandrosterone
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Several studies indicate that DHEA may enhance cancer-promoting activities in several prostate cancer cell lines acting as agonist or antagonist for the intracellular AR
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the estrogenic metabolites of DHEA, 5a-androstane-3b, 17b-diol (3b-Adiol) and E2 bind to estrogen receptors but not to AR
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Different members of neurotrophins are expressed during cancer progression, suggesting their involvement in cell proliferation, anoikis protection, and malignancy
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Regulation of the apoptotic machinery in prostate and colon cancer cells by testosterone occurs rapidly and is initiated at the plasma membrane level through specific membrane-binding sites not involving the classical cytoplasmic AR
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testosterone antagonizes the prosurvival effects of DHEA in neuronal cells, blocking its binding to NGF receptors
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elevated levels of DHEA or its sulfate ester DHEA-sulfate in young adults are associated to low incidence of androgen-dependent tumors
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The decline of DHEA with aging may contribute to prostate cancer progression associated with advanced age
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DHEA is an effective antiapoptotic factor, reversing the serum deprivation-induced apoptosis in prostate cancer cells (DU145 and LNCaP cell lines) as well as in colon cancer cells
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exposure of prostate DU145 and colon Caco2 cancer cells to testosterone totally blocked the protective effects of both DHEA and NGF. These findings suggest that testosterone acts as an antagonist of DHEA and NGF
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These findings support the hypothesis that testosterone may inhibit cancer cell growth by antagonizing the proliferative, antiapoptotic effects of endogenous factors, such as DHEA or NGF, in the case of prostate and colon cancer cells
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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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shared by wheelchairindia9 on 07 Nov 15
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Power Standing Wheelchair Support Motor And Battery - 0 views
onlywheelchair.blogspot.in/...-wheelchair-support-motor.html
Power Standing Wheelchair Support Motor And Battery Karma KP 10.3 Variety of Power Wheelchairs Power Standing Wheelchair Power wheelchairs need strong frames Lightweight Power Wheelchair
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Power mobility allows people to move within their home and community and it can help maximize independence for those with limited mobility. The two main types of power mobility available are in the form of electric scooters or power wheelchairs. The choice to use either an electric scooter versus an electric wheelchair depends on the users' needs and abilities. Knowing some of the benefits of power wheelchairs can help in making the right decision. Power wheelchairs also can be classified on the basis of the location of the drive wheels. There are three types of power wheelchairs: front-wheel drive, mid- or centre-wheel drive, and rear-wheel drive. Traditionally, rear-wheel drive powerwheelchairs were preferred because of their similarity to manual wheelchairs in design and maneuverability. However, centre-wheel drive wheelchairs have gained popularity because they provide increased maneuverability. Variety of Power Wheelchairs: Karma KP 10-2 Power Wheelchair Karma KP 10-3 Power Wheelchair Karma KP 80 Power Wheelchair GM Lite Power Wheelchair Bronco Wheelchair Angel Wheelchair Karma KP 10.3 S Power Wheelchair Ergonomic seat system provides comfortable seating Tool-free disassembled into 3 parts for traveling and transportation Quick-release battery pack Washable upholstery Height adjustable and flip back armrest 2-level adjustable back angle KARMA KP 80 POWER WHEELCHAIR are propelled by a motor and battery. They are very sophisticated. They are operated with a joy stick or push buttons. Some power wheelchairs use advanced technology and can climb up stairs, move across gravel and even raise up to give access to high shelves. Power wheelchairs need strong frames to support the motor and battery so they are very heavy and also quite expensive. KARMA KP 80 POWER WHEELCHAIR Karma KP 80 POWER STANDING WHEELCHAIR Karma latest power standing wheelchair is now available in India. Power Standing wheelchair - Increase your freedom Stand up ag
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shared by wheelchairindia9 on 26 Oct 15
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Complete Flexibility KM 2500 Small Wheel Wheelchair - 0 views
onlywheelchair.blogspot.in/...flexibility-km-2500-small.html
Complete Flexibility KM 2500 Small Wheel Wheelchair Karma KM 2500 Wheelchair easier to transport and store Karma KM 2500 traveling up and down ramps or hills KM 2500 Wheelchair Attendant cable brake
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Wheelchairs are easy to push, they fold to make them easier to store and simple for a friend or relative to load into a car. A wide selection of accessories too. So customise chair to give the performance, portability, comfort and style. Lightweight portable wheelchair are designed for ease of use and are made from durable material. These wheelchair are often foldable and are easier to store than conventional or custom. They are perfect for both manual and electric wheelchairs, as well as many walking aids such as a 4 wheel scooter. Lightweight portable wheelchair are extremely lightweight and for this reason they are easier to transport and store than many other types of wheelchair. Lightweight portable are made to be ultra lightweight, compact, and user friendly. They fold up in interesting ways to collapse to the size of a suitcase when not in use and are usually large enough to cover one or two stairs when extended. It is important to consider their weight and the person who would most often be carrying the ramp and setting it up. Karma KM 2500 Small Wheel Wheelchair: Karma KM 2500 Small Wheel Wheelchair Specifications: Width 18" Front/Rear Wheels 6" to 14" Seat Width 47cm Seat Depth 40cm Overall Width 66cm Overall Collapsed Width 36cm Armrest Height 21cm Overall Length 90cm Seat Height 47cm Backrest Height 38cm Overall Height 86cm Weight 9.2 k.g. Karma KM 2500 Small Wheel Wheelchair Seat and Back: AEGIS Microbe Shield Approved by the FDA, EPA, EU, etc., bonded anti-microbial barrier upholstery protects from odor, staining and deterioration from bacteria, fungus and other microorganisms. It is a shield for your health. Karma KM 2500 Small Wheel Wheelchair Extended Armrest: By simulating the natural position of arms, the extended armrest design is ergonomic and creates bigger seating space. An Ultra lightweight wheelchair (9.2 kg) with a compact design for either attendant assisted or self propelling users. The use
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shared by wheelchairindia9 on 04 Apr 16
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Wrist and Forearm Splints Causes and Recovery Period | Health | Article Point - 0 views
www.articlepoint.org/...auses-and-recovery-period.aspx
Wrist and Forearm Splints Causes and Recovery Period best orthopedic wrist braces comfortable support to hand muscular attachments to the bone hand side of the forearm Anatomical thumb opening
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Wrist and forearm splints may be suggested for people with weak wrists or for those that have been previously injured, for tendonitis wrist support and even as a preventative for those who awaken in the morning with pain or numbness after sleeping on their hands at night. The best orthopedic wrist braces for carpal tunnel syndrome, occupational stabilization and relief from the pain of wrist strains and sprains. This Right hand wrist and forearm splint from tynor is meant to be used among patients suffering from any injury or sprain in these regions. The splint is meant to provide controlled compression in various orthopaedic conditions. The splint immobilizes the area that helps in a speedier recovery. It has anatomical thumb opening that allows free movement of the thumb. It provides a lot of comfort and is easily breathable. Forearm splint is the term used to describe the forearm pain similarly the pain of lower leg over the shin is known as shin splints. Forearm splint describes the painful disease of elbow or wrist joint. Continuous pain in forearm is often caused by tendonitis, joint injury or hairline fracture of forearm bones (proximal radius or ulna near elbow joint). Overstretching of the elbow joint often causes forearm injury. Symptoms consist of a dull pain in the forearm. Pain is minor initially but increases as activity continues. Often pin-pointed to the dorsal or back of the hand side of the forearm, mid-way between the wrist and elbow. The patient may experience weakness in the wrist extensor muscles and tenderness deep in the forearm. Pain may be reproduced by attempting to bend the wrist backwards against resistance. They provided wrist splints are used in different medical institutions and hospitals for management of hand fractures. Our offered wrist splints are manufactured by skilled professionals using optimum quality basic material and advanced technology as per the set norms of market. As well, these wrist splints can be availed in v
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shared by Nathan Goodyear on 06 Oct 18
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Estrogen receptor transcription and transactivation: Estrogen receptor alpha and estrog... - 1 views
www.ncbi.nlm.nih.gov/...PMC138655
ER alpha ER beta estrogen receptors estrogen receptor alpha estrogen receptor beta estrogen cancer
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Searching For an Old New Cure: Ivermectin Deficiency Syndrome? « The Healthy ... - 0 views
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Ivermectin can inactivate the protein kinase PAK1 and blocks the PAK1-dependent growth of human ovarian cancer and NF2 tumor cell lines
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PAK proteins encoded by the PAK1 gene are critical for cytoskeleton reorganization and nuclear signaling.
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PAK-1 kinase is required for the growth of more than 70% of human cancers such as pancreatic, colon, breast and prostate cancers, and neurofibromatosis
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PAK1 has also been implicated for maintenance of glucose homeostasis in pancreatic beta cells and skeletal muscle
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Ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells (Blood, November 4, 2010, vol.115). The paper states Ivermectin synergizes with chemo agents cytarabine and daunorubicin to induce cell death in leukemia cells.
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Praziquantel , my other favorite parasite medication for liver flukes, synergistically enhances Paclitaxel (Taxol) efficacy to inhibit cancer cell growth
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MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via ... - 0 views
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shared by Nathan Goodyear on 21 Mar 18
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Antineoplastic Mechanisms of Niclosamide in Acute Myelogenous Leukemia Stem C... - 0 views
cancerres.aacrjournals.org/...2516
Niclosamide cancer leukemia NF-kappaB ROS TNF tumor necrosis factor
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Here, we report on niclosamide as an antileukemic agent with two independent antineoplastic mechanisms: NF-κB pathway inactivation and ROS generation
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In this report, we validated the inhibitory action of niclosamide against tumor necrosis factor (TNF)–induced NF-κB activation in AML cells and identified its mechanism, together with generation of reactive oxygen species (ROS), as being responsible for induced apoptosis of AML cells
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niclosamide inhibiting TNF-induced IKK phosphorylation (Fig. 2A), niclosamide may exert its inhibitory effect at the TAK1 step
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Pretreatment with niclosamide completely blocked the time- and dose-dependent TNFα-induced alteration of the NF-κB–DNA complex
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Cancer Chemotherapy Via Drugs | Your Health Our Priority - 0 views
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Cortisol Exerts Bi-Phasic Regulation of Inflammation in Humans - 0 views
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GCs induce increased cellular expression of receptors for several pro-inflammatory cytokines including interleukin (IL)-1 (Spriggs et al. 1990), IL-2 (Wiegers et al. 1995), IL-4 (Paterson et al. 1994), IL-6 (Snyers et al. 1990), and IFN-g (Strickland et al. 1986), as well as GM-CSF
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GCs have also been shown to stimulate effector cell functions including phagocytosis by monocytes (van der Goes et al. 2000), effector cell proliferative responses (Spriggs et al. 1990), macrophage activation (Sorrells and Sapolsky 2010), and a delay of neutrophil apoptosis
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basal (diurnal) concentrations of cortisol do not exert an anti-inflammatory effect on several pro-and anti-inflammatory mediators of the human immune inflammatory response
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withdrawal of cortisol activity in vivo did not lead to increased inflammatory responsiveness of immune effector cells
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maximal suppression of inflammation was achieved by a stress-associated, but still physiologic, cortisol concentration. There was no greater anti-inflammatory effect at higher cortisol concentrations (Yeager et al. 2005) although IL-10 concentrations continued to increase with increasing cortisol concentrations as we and others have shown
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acutely, physiological cortisol concentrations are anti-inflammatory and, as proposed, act to limit over expression of an inflammatory response that could lead to tissue damage
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Acutely, cortisol has anti-inflammatory effects following a systemic inflammatory stimulus (Figure 4). However, a cortisol concentration that acts acutely to suppress systemic inflammation also has a delayed effect of augmenting the inflammatory response to subsequent, delayed stimulu
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1) GCs can exert pro-inflammatory effects on key inflammatory processes and, 2) GC regulation of inflammation can vary from anti- to a pro-inflammatory in a time-dependent manner
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The immediate in vivo effect of both stress-induced and pharmacological GC concentrations is to suppress concurrent inflammation and protect the organism from an excessive or prolonged inflammatory response
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GCs alone, in the absence of an inflammatory stimulus, up-regulate monocyte mRNA and/or receptors for several molecules that participate in pro-inflammatory signaling, as noted above and in the studies presented here.
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In humans, as shown here, if in vivo GC concentrations are elevated concurrent with an inflammatory stimulus, anti-inflammatory effects are observed
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In sharp contrast, with a time delay of 12 or more hours between an increased GC concentration and the onset of an inflammatory stimulus, enhancing effects on inflammation are observed. These effects have been shown to persist in humans for up to 6 days
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GC-induced enhancement of inflammatory responses is maximal at an intermediate concentration, in our studies at a concentration that approximates that observed in vivo following a major systemic inflammatory stimulus
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In addition to enhanced responses to LPS, recently identified pro-inflammatory effects of GCs also show enhanced localization of effector cells at inflammatory sites
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we hypothesize that pre-exposure to stress-associated cortisol concentrations “prime” effector cells of the monocyte/macrophage lineage for an augmented pro-inflammatory response by; a) inducing preparative changes in key regulators of LPS signal transduction, and b) enhancing localization of inflammatory effector cells at potential sites of injury
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Cancers | Free Full-Text | A Second WNT for Old Drugs: Drug Repositioning against WNT-D... - 0 views
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It should be also noted that the WNT pathway is not exclusively employed during development or overactivated in cancer. In adults many healthy tissues rely on it for renewal and homeostasis maintenance, most notably the intestine, haematopoietic system, hair, bones and skin. Therefore one might expect adverse reactions in all these organ systems, which has indeed been observed for many WNT-targeting compounds upon attempts to push them into the clinics
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Ivermectin inhibits proliferation of human colon cancer and lung cancer cells both in vitro and in vivo
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The anti-proliferative action, affecting both the bulk tumor cells and CSCs, was linked in this study to inhibition of WNT signaling
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the anti-WNT IC50 of ivermectin is 5–10 times (~1–2 µM vs. 10 µM) lower than that of its toxic effect against chloride channels
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oral bioavailability of the drug, as for other antiparasitic drugs discussed in this section, is very low
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Its anti-proliferative activity has been demonstrated in a wide array of cancer cell lines representative of WNT-dependent cancers: non-small lung carcinoma [96], multiple myeloma [97], hepatoma [98], adrenocortical carcinoma [99], ovarian cancer [100] and glioblastoma
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In addition to inhibiting the canonical WNT pathway, niclosamide may mediate its anticancer activities through several other signaling pathways such as NOTCH [107], MTOR [108], NF-κB [97] and STAT3 [96]
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Ascorbic acid: Chemistry, biology and the treatment of cancer - 0 views
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iron and ascorbate has long been used as an oxidizing system; the combination of these two reagents is referred to as the Udenfriend system
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pharmacokinetic data indicate that intravenous administration of ascorbate can bypass this tight control resulting in highly elevated plasma levels
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ascorbate readily oxidizes to produce H2O2, pharmacological ascorbate has been proposed as a prodrug for the delivery of H2O2 to tumors
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Ascorbate is an excellent reducing agent and readily undergoes two consecutive, one-electron oxidations to form ascorbate radical (Asc•−) and dehydroascorbic acid (DHA)
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Ascorbate oxidizes readily. The rate of oxidation is dependent on pH and is accelerated by catalytic metals
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In near-neutral buffers with contaminating metals, the oxidation and subsequent loss of ascorbate can be very rapid
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Ascorbate is an excellent one-electron reducing agent that can reduce ferric (Fe3+) to ferrous (Fe2+) iron, while being oxidized to ascorbate radical
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In a classic Fenton reaction, Fe2+ reacts with H2O2 to generate Fe3+ and the very oxidizing hydroxyl radical
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e presence of ascorbate can allow the recycling of Fe3+ back to Fe2+, which in turn will catalyze the formation of highly reactive oxidants from H2O2
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Depending on concentrations, the effects of ascorbate on models of lipid peroxidation can be pro- or antioxidant
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shared by Nathan Goodyear on 04 Oct 17
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Purple Carrot Anthocyanins Decrease LPS Stimulated Nitric Oxide Production - 0 views
www.fasebj.org/...A731.4.short
anthocyanin NO iNOS LPS lipopolysaccharides nitric oxide inflammation
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Curcumin abrogates LPS-induced proinflammatory cytokines in RAW 264.7 macrophages. Evid... - 0 views
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shared by Nathan Goodyear on 08 Dec 17
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Oncotarget | NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Id... - 0 views
www.oncotarget.com/index.php
vitamin C IV vitamin C cancer cancer stem cells milk thistle silymarin ascorbic acid bee propolis CAPE glycolytic inhibitor natural
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Cancer stem-like cells (CSCs) are thought to be the root cause of chemotherapy-resistance and radio-resistance
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ultimately leading to treatment failure in patients with advanced disease [1-3]. They have been directly implicated mechanistically in tumor recurrence and metastasis, resulting in poor patient survival
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Our results indicate that increased mitochondrial oxidative stress and high NADH levels are both key characteristics of the CSC metabolic phenotype
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high levels of NAD(P)H auto-fluorescence are known to be a surrogate marker for mitochondrial “power”, high OXPHOS capacity and increased ATP production
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an intact NAD+ salvage pathway is strictly required for mammosphere formation, supporting our results using NAD(P)H auto-fluorescence, which enriched CSC activity by more than 5-fold.
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Since glycolysis is especially critical for maintaining the TCA cycle, OXPHOS and overall mitochondrial function, we next assessed the effects of known glycolytic inhibitors
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we show that two other natural products that function as effective glycolysis inhibitors, also inhibited mammosphere formation. More specifically, vitamin C (ascorbic acid), which induces oxidative stress and inhibits the activity of GAPDH (a key glycolytic enzyme) [17], also inhibited mammosphere formation, with an IC-50 of 1 mM (Figure 7B). Therefore, vitamin C was ~10 times more potent than 2-DG at targeting CSC propagation
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silibinin (the major active constituent of silymarin, an extract of milk thistle seeds) [18], which specifically functions as an inhibitor of glucose uptake, blocked mammosphere formation, with an IC-50 between 200 and 400 µM
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caffeic acid phenyl ester (CAPE), a key component of honey-bee propolis, has potent anti-cancer properties
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Because of it aromatic ring structure (Figure 8), we speculated that CAPE might function as a potent inhibitor of oxidative mitochondrial metabolism
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CAPE quantitatively inhibits the mitochondrial oxygen consumption rate (OCR) and, in turn, induces the onset of aerobic glycolysis (ECAR)
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CAPE shows a clear selectivity for targeting CSCs and adherent cancer cells, relative to normal fibroblasts.
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CAPE functions as a “natural” mitochondrial OXPHOS inhibitor, that preferentially targets the CSC sub-population. This could explain CAPE’s known anti-cancer properties
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Our data directly shows that a small fraction of the total cell population, characterized by increased PGC1α activity, high mitochondrial ROS/H2O2 and high NADH levels, has the ability to survive and grow under anchorage-independent conditions, driving mammosphere formation
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We highlight the utility of certain natural products, such as Silibinin, Vitamin C and CAPE, that could be used to therapeutically target CSCs. Silibinin is the major active component of silymarin, which is an extract prepared from milk thistle seeds.
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Previous studies have also shown that when non-CSCs and CSCs are both fed mitochondrial fuels (such as L-lactate or ketone bodies), that CSCs quantitatively produce more NADH in response to this stimulus
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The Noble Prize winner, Linus Pauling, was among the first to describe and clinically test the efficacy of Vitamin C, as a relatively non-toxic anti-cancer agent
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Vitamin C has two mechanisms of action. First, it is a potent pro-oxidant, that actively depletes the reduced glutathione pool, leading to cellular oxidative stress and apoptosis in cancer cells. Moreover, it also behaves as an inhibitor of glycolysis, by targeting the activity of GAPDH, a key glycolytic enzyme.
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Here, we show that Vitamin C can also be used to target the CSC population, as it is an inhibitor of energy metabolism that feeds into the mitochondrial TCA cycle and OXPHOS
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Vitamin C may prove to be promising agent for new clinical trials, aimed at testing its ability to reduce CSC activity in cancer patients, as an add-on to more conventional therapies, to prevent tumor recurrence, further disease progression and metastasis
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Interestingly, a breast cancer based clinical study has already shown that the use of Vitamin C, concurrent with or within 6 months of chemotherapy, significantly reduces both tumor recurrence and patient mortality
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CAPE quantitatively reduces mitochondrial oxygen consumption (OCR), while inducing a reactive increase in glycolysis (ECAR). As such, it potently inhibits mammosphere formation with an IC-50 of ~2.5 µM. Similarly, it also significantly inhibits cell migration
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we also demonstrate that 7 different inhibitors of key energetic pathways can be used to effectively block CSC propagation, including three natural products (silibinin, ascorbic acid and CAPE). Future studies will be necessary to test their potential for clinical benefit in cancer patients.
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The future of cancer therapy is cancer stem cells. Study finds that Vitamin C, silymarin, and bee propolis blocks mitochondrial energy pathways in cancer stem cells. Vitamin C is a known glycolytic inhbitor. Vitamin C was found to inhibit glycolysis via GAPDH targeting to inhibit the energy pathways of the mitochondria in CSCs. The authors propse that Vitamin C can be used as add on therapies for conventional therapies to specifically attack the CSCs and their contribution to recrurence, treatment resistance, and metastasis potential all in addition to the ability of vitamin C to reduce the side effects of chemotherapy.
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The 3 Keys To Overcome Anxiety - Trina Blum - Medium - 0 views
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Hypnosis Therapy for Anxiety is very varied depending on the type of disorder being treated. But these three keys are usually present in one way or another in all treatments. Exposure is a fundamental part of overcoming anxiety, because only when you demonstrate to yourself that you are capable of facing situations, can you have the confidence and confidence to feel good. It is necessary to insist in the expositions the time that is necessary until the levels of anxiety are nonexistent and the negative thoughts of threat and danger are not generated.