Skip to main content

Home/ Dr. Goodyear/ Group items tagged activity

Rss Feed Group items tagged

Filter: All | Bookmarks | Topics Simple Middle
Nathan Goodyear

Toxicity of the spike protein of COVID-19 is a redox shift phenomenon: A novel therapeu... - 0 views

www.sciencedirect.com/...S0891584923005014

COVID19 COVID-19 cancer inflammation SARS-CoV-2 spike proteins COVID spikeopathy

shared by Nathan Goodyear on 01 Sep 23 - No Cached
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • ...88 more annotations...
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • most diseases display a form of anabolism due to mitochondrial impairment
  • most diseases display a form of anabolism due to mitochondrial impairment
  • most diseases display a form of anabolism due to mitochondrial impairment
  • infection by Covid-19 follows a similar pattern
  • chronic inflammation
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • infection by Covid-19 follows a similar pattern
  • unrelenting anabolism leads to the cytokine storm,
  • unrelenting anabolism leads to the cytokine storm,
  • unrelenting anabolism leads to the cytokine storm,
  • chronic inflammation
  • chronic inflammation
  • infection by Covid-19 follows a similar pattern
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • direct consequence of redox iMeBalance, itself a consequence of decreased energy yield by the mitochondria
  • direct consequence of redox iMeBalance, itself a consequence of decreased energy yield by the mitochondria
  • mitochondrial dysfunction and increased levels of lactate, which are important characteristics of metabolic shift and Warburg effect in many diseases
  • mitochondrial dysfunction and increased levels of lactate, which are important characteristics of metabolic shift and Warburg effect in many diseases
  • increased lactate dehydrogenase activity (LDH) was observed in COVID-19 patients
  • increased lactate dehydrogenase activity (LDH) was observed in COVID-19 patients
  • almost every disease presents an increased anabolism
  • almost every disease presents an increased anabolism
  • cell division is the most sophisticated way to release entropy
  • cell division is the most sophisticated way to release entropy
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Wow
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Wow
  • transition from catabolism to anabolism is driven by a redox shift
  • transition from catabolism to anabolism is driven by a redox shift
  • viral spike protein binds to ACE2 receptor of the host cell [22,23].
  • redox signaling plays an important role in regulating immune function and inflammation, and disruptions in this signaling can lead to excessive cytokine production and immune system activation
  • Aging is associated with a poor control of the redox balance
  • thiol/disulfide homeostasis
  • reduced extracellular environment in the elderly and the increased susceptibility to Covid-19 infection
  • reduced extracellular environment in the elderly and the increased susceptibility to Covid-19 infection
  • Redox signaling tightly modulates the inflammatory response and oxidative stress has been reported in acute Covid-19
  • People at high risk are the elderly, patients suffering from metabolic syndrome such as obesity, or those suffering from chronic diseases such as cancer or inflammation
  • COVID-19 patients with severe disease have higher levels of oxidative stress markers and lower antioxidant levels
  • oxidative stress can activate the NLRP3 inflammasome, which is a protein complex that plays a key role in the cytokine storm
  • inflammation leads to the formation of ROS and RNS, while redox iMeBalance results in cellular damage, which in turn triggers an inflammatory response
  • persistently elevated mtROS triggers endothelial dysfunction and inflammation, which results in a vicious loop involving ROS, inflammation, and mitochondrial dysfunction
  • Damaged mitochondria releasing ROS induce inflammation via the NLRP3 inflammasome
  • Damaged mitochondria releasing ROS induce inflammation via the NLRP3 inflammasome
  • reduced environment during the cytokine storm
  • IL-2 is highly up-regulated in Covid-19 patients [37], and IL-2 is known to significantly stimulate the generation of NO in patients
  • Nitric acid is also the key mediator of IL-2-induced hypotension and vascular leak syndrome
  • mitochondrial dysfunction has been linked to the pathogenesis of Covid-19
  • mitochondrial dysfunction triggered by SARS-CoV-2 leads to damage to the mitochondria
  • mitochondrial dysfunction triggered by SARS-CoV-2 leads to damage to the mitochondria
  • As catabolism is decreased, entropy is released through anabolism
  • Elevated levels of lactate, a characteristic of the Warburg effect, were also reported in the high-risk Covid-19
  • elevated levels of ventricular lactic acid consistent with oxidative stress
  • A decrease of ΔΨm is implicated in several inflammation-related diseases
  • decrease in ΔΨm in leucocytes from Covid-19 patients
  • vaccinated with RNA or DNA vaccines triggering the synthesis of the viral spike protein in human cells
  • viral reactivation in varicella-zoster virus [55] or hepatitis [56], coagulopathy and resulting stroke and myocarditis following both DNA-based vaccines [57] and RNA-based vaccines
  • Covid-19, mitochondrial impairment
  • characteristic of the Warburg effect is present in almost every disease and appears to be a central feature in most of the hallmarks of cancer
  • inflammation, mitochondrial dysfunction and increased lactate concentrations in the extracellular fluid
  • In Covid-19, like any inflammation, there is a metabolic rewiring where cells rely on glycolysis
  • As the mitochondria are impaired, the infected cell cannot catabolize efficiently. It will release lactic acid in the blood stream
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Mitochondrial impairment
  • Striking similarities are seen between cancer, Alzheimer's disease and Covid-19, all related to the Warburg effect
  • Cancer, inflammation, Alzheimer's, and Parkinson's diseases share a common peculiarity, the inability of the cell to export entropy outside the body in the harmless form of heat
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Entropy: lack of order or predictability; gradual decline into disorder.
  • MEB relieves the Warburg effect [87], improves memory [77], is active in the treatment of depressive episodes [79,80] and reduces the importance of ischemic strokes
  • MEB relieves the Warburg effect [87], improves memory [77], is active in the treatment of depressive episodes [79,80] and reduces the importance of ischemic strokes
  • MEB has been shown to inhibit SARS-Cov-2 replication in vitro
  • MEB has been shown to inhibit SARS-Cov-2 replication in vitro
  • It has been shown that Covid-19-patients treated with MEB, have a significant reduction in hospital stay duration and mortality
  • MeB is an acceptor-donor molecule
  • MeB + can take a pair of electrons (of H atoms) and MeBH can release this pair easily, so that MeB is partially recycled like a catalyst
  • MeB acts as an electron bridge between a donor (FADH2, FMNH, NADH) and an acceptor (complex IV of ETC or oxygen itself)
  • As a coenzyme of pyruvate dehydrogenase (PDH), alpha-lipoic acid (ALA) initiates the formation of acetyl-CoA to feed the TCA cycle
  • ALA enhances the catabolism of carbon. cycle and therefore may reduce the Warburg effect and consequently, lactate production
  • Methylene Blue plays a similar role after the TCA cycle, by carrying electrons to complex IV of the electron transport chain
  • Drugs such as lipoic acid and MeB, which target the metabolism, decrease the redox shift by increasing catabolism
Nathan Goodyear

Testosterone Treatment and Sexual Function in Older Men with Low Testosterone Levels: T... - 0 views

press.endocrine.org/...jc.2016-1645

low T low Testosterone Testosterone male hormones libido ED estradiol hormones

shared by Nathan Goodyear on 13 Jul 16 - No Cached
  • Nathan Goodyear on 13 Jul 16
     
    new study finds that men >65 with low libido and Testosterone levels < 275 increase sexual function with Testosterone therapy.  Only libido was improved; no benefit to erectile function was noted--note that is likely due to depleted NO.  Given time that should improve with he increase in NO synthase and thus NO.  I have a fault with on elf the comments on this study: they point out that increased free Testosterone and estradiol levels were associated with improved sexual activity.  This lacks an understanding of the physiology.  In men with low T > 65, the majority are dealing with inflammation and excess weight; all of which increase aromatase activity and thus estradiol activity.  This does not indicate that an increase in estradiol activity is associated with improved libido in men.  How can elevated estrogen levels lead to low T and then increase levels are associated with improved libido?  This is merely a reflection of the body's dysfunctional physiology.  This observation of increased estradiol by no means shows cause and effect.  Scientists need to due a better job in vetting what they write!
Nathan Goodyear

Fructose decreases physical activity and increases body fat without affecting hippocamp... - 0 views

www.nature.com/...srep09589.html

fructose obesity fat diet nutrition activity physical activity

shared by Nathan Goodyear on 03 Aug 15 - No Cached
  • the fructose animals gained significantly more weight than the glucose animals
  • The average liver mass of mice in the fructose treatment group was 20% heavier than for mice in the glucose group
  • The fat pads of mice consuming the fructose diet were 69% heavier than the fat pads of animals consuming the glucose diet
  • ...12 more annotations...
  • there are many studies showing that consumption of fructose in comparison to other monosaccharides results in increased de novo lipogenesis, dyslipidemia, insulin resistance, BW6, 7 and, most recently, impaired cognitive function
  • in the present study, the intake of fructose by mice was more similar to that of typical human consumption in comparison to previous studies
  • prolonged consumption of diets containing fructose (11 weeks) increased BW and body fat deposition
  • studies in humans confirm that fructose, but not glucose (when provided as 25% of energy requirements), in the context of an energy-balanced diet increases de novo lipogenesis and visceral adiposity along with dyslipidemia, decreases insulin sensitivity10, 12 and decreases in fat oxidation
  • we hypothesize that fructose may reduce voluntary energy expenditure in terms of physical activity.
  • significant reduction (~20%) in physical activity in the fructose-fed animals in comparison to glucose
  • a recent study reported that ingestion of fructose (25% energy intake, 10 weeks) in human volunteers also resulted in reduced energy expenditure in relation to a diet with the same glucose dose
  • There is certainly evidence to suggest that, for example, exercise is able to prevent dyslipidemia in healthy subjects fed a weight-maintenance high-fructose diet (30%)54, which strongly suggests a protective role of physical activity in metabolic regulation.
  • the potential negative effects of fructose in brain and cognitive function have been investigated, with a series of studies showing cognitive deficits in spatial memory and learning in adolescent and adult animals following access to a high fructose diet
  • access to both fructose and sucrose, but not glucose, results in a 40% reduction in hippocampal neurogenesis
  • Collectively these studies seem to suggest that fructose consumption can have a considerable impact on hippocampal function and learning, which is in direct contrast with what we observed.
  • the impact of fructose is apparent only in BW, liver mass and body fat, but not in cognitive measures or rates of neurogenesis
  • Nathan Goodyear on 03 Aug 15
     
    animal study finds that fructose increased liver mass, abdominal fat and decreased physical activity when compared to glucose.  The study groups were iso caloric, but one group was fed 18% fructose and the other 18% glucose.
Nathan Goodyear

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

shared by Nathan Goodyear on 04 Aug 14 - No Cached
  • Weight gain has been associated with a higher gut permeability
  • a high-fat diet promotes LPS absorption
  • higher concentrations of fatty acids impair intestinal barrier integrity
  • ...37 more annotations...
  • The starting point for innate immunity activation is the recognition of conserved structures of bacteria, viruses, and fungal components through pattern-recognition receptors
  • TLRs are PRRs that recognize microbe-associated molecular patterns
  • TLRs are transmembrane proteins containing extracellular domains rich in leucine repeat sequences and a cytosolic domain homologous to the IL1 receptor intracellular domain
  • 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
  • Obesity, high-fat diet, diabetes, and NAFLD are associated with higher gut permeability leading to metabolic endotoxemia.
  • Probiotics, prebiotics, and antibiotic treatment can reduce LPS absorption
  • LPS promotes hepatic insulin resistance, hypertriglyceridemia, hepatic triglyceride accumulation, and secretion of pro-inflammatory cytokines promoting the progression of fatty liver disease.
  • In the endothelium, LPS induces the expression of pro-inflammatory, chemotactic, and adhesion molecules, which promotes atherosclerosis development and progression.
  • In the adipose tissue, LPS induces adipogenesis, insulin resistance, macrophage infiltration, oxidative stress, and release of pro-inflammatory cytokines and chemokines.
  • 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
  • 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.
  • This was accompanied in high-fat-fed mice by a change in gut microbiota composition, with reduction in Bifidobacterium and Eubacterium spp.
  • 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
  • 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).
  • 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
  • these experimental results suggest a pivotal role of CD14-mediated TLR4 activation in the development of LPS-mediated nutritional changes.
  • 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.
  • endotoxemia was independently associated with energy intake but not fat intake in a multivariate analysis
  • 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.
  • T2DM patients have mean values of LPS that are 76% higher than healthy controls
  • LPS-induced release of glucagon, GH and cortisol, which inhibit glucose uptake, both peripheral and hepatic
  • LPSs also seem to induce ROS-mediated apoptosis in pancreatic cells
  • Recent evidence has been linking ME with dyslipidemia, increased intrahepatic triglycerides, development, and progression of alcoholic and nonalcoholic fatty liver disease
  • The hepatocytes, rather than hepatic macrophages, are the cells responsible for its clearance, being ultimately excreted in bile
  • 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
  • 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
  • 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
  • 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
  • On the other hand, LPS activates Kupffer cells leading to an increased production of ROS and pro-inflammatory cytokines like TNFα
  • 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
  • prebiotic administration reduces intestinal permeability to LPS in obese mice and is associated with decreased systemic inflammation when compared with controls
  • 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
  • This suggests that important links between gut microbiota, ME, inflammation, and oxidative stress are implicated in a high-fat diet situation
  • 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
  • LPS has been shown to promote atherosclerosis
  • markers of systemic inflammation such as circulating bacterial endotoxin were elevated in patients with chronic infections and were strong predictors of increased atherosclerotic risk
  • As a TLR4 ligand, LPS has been suggested to induce atherosclerosis development and progression, via a TLR4-mediated inflammatory state.
  • Nathan Goodyear on 04 Aug 14
     
    Very nice updated review on Metabolic endotoxemia
Nathan Goodyear

Broad targeting of angiogenesis for cancer prevention and therapy - 0 views

www.ncbi.nlm.nih.gov/...PMC4737670

cancer curcumin VEGF EGCG green tea melatonin quercetin Resveratrol silymarin flavonoids HIF-1alpha

shared by Nathan Goodyear on 01 Jun 18 - No Cached
  • vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), interleukin-8 (IL-8), placental growth factor (PlGF), transforming growth factor-beta (TGFbeta), platelet derived growth factor (PDGF), angiopoietins (Angs) and others (reviewed in [4])
  • The switch may also involve down-regulation of endogenous inhibitors of angiogenesis such as endostatin, angiostatin or thrombospondin (reviewed in [5]) and has thus been regarded as the result of tipping the net balance between positive and negative regulators
  • There is a complex interrelationship between tumor hypoxia and tumor angiogenesis
  • ...17 more annotations...
  • chronic hypoxia
  • acute hypoxia
  • Environmental stress as a result of low oxygen and proper nutrient deprivation, such as glucose deprivation, are capable of inducing VEGF mRNA stabilization resulting in increased levels of the secreted ligand and angiogenic growth
  • HIFalpha subunits accumulate in the cytoplasm where they bind HIFbeta to form a heterodimer that subsequently translocates to the nucleus to activate transcription of target genes, including genes important for various processes such as metabolism (glucose transporter (GLUT)-1, hexokinase (HK)-1), cell growth (cyclin (CCN)-D1 [23]) and also angiogenesis, such as erythropoietin, VEGF and PDGF [24] (summarized in Fig. 1)
  • When oxygen levels are low (hypoxia; red arrow) PHDs cannot hydroxylate HIFalphas thereby allowing them to escape pVHL-mediated degradation. HIFalpha subunits accumulate and bind to their heterodimeric partner, HIFbeta, translocate into the nucleus and activate a cascade of hypoxic signaling first by the transcription of various target genes including microRNAs that are important for tumor promoting pathways
  • c-Src is also capable of activating HIFs by indirectly inhibiting PHD activity via the NADPH oxidase/Rac pathway.
  • mTOR can also promote stabilization and HIF transcriptional activity
  • hypoxia inducible factors (HIFs), heterodimeric transcription factors composed from alpha and beta subunits, which can be rapidly stabilized to fluidly adapt to and overcome the effects of a hypoxic environment
  • Curcumin inhibits the expression of epidermal growth factor receptor (EGFR), VEGFR-1, VEGFR-2 and VEGFR-3, and the kinase activity of Src and FAK, which are responsible for the induction of angiogenic genes as well as endothelial cell polarity and migration
  • Curcumin also reduces the MMP-2 and MMP-9 expression, along with the suppression of growth and invasion potential of tumor cells in culture and xenograft experiments
  • The expression of angiogenic biomarkers COX-2 and serum levels of VEGF were significantly reduced in the curcumin-treated group
  • Resveratrol inhibits capillary endothelial cell growth and new blood vessel growth in animals
  • interrupting cell proliferation, inducing apoptosis
  • [155] and impeding angiogenesis by suppressing VEGF expression through down-regulation of HIF-1alpha
  • resveratrol was reported to inhibit cell proliferation of human ovarian cancer cells and human osteosarcoma cells by attenuating HIF-1alpha
  • prevents cytokine-induced vascular leakage and tumor metastasis
  • The underlying molecular mechanisms include: blocking VEGF- and FGF-receptor-mediated MAPK activation, inhibiting Akt- and MAPK-driven HIF-1alpha basal expression and its induction by IGF-1, stimulating the proteasomal degradation of HIF-1alpha, inhibiting phosphatidyl inositol (PI)-3K/Akt and Ras/mitogen/extracellular signal-regulated kinase (MEK)/ERK pathways, and activation of forkhead box (FOX)O transcription factors
  • Nathan Goodyear on 01 Jun 18
     
    natural compounds to attach cancer explained.
Nathan Goodyear

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

shared by Nathan Goodyear on 08 Dec 17 - No Cached
  • Vitamin C was ~10 times more potent than 2-DG for the targeting of CSCs
  • Cancer stem-like cells (CSCs) are thought to be the root cause of chemotherapy-resistance and radio-resistance
  • 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
  • ...26 more annotations...
  • mitochondrial biogenesis may be a key driver of the CSC phenotype
  • Our results indicate that increased mitochondrial oxidative stress and high NADH levels are both key characteristics of the CSC metabolic phenotype
  • 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
  • CSCs may be strictly dependent on NAD(P)H to maintain their enhanced mitochondrial function
  • 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.
  • Since glycolysis is especially critical for maintaining the TCA cycle, OXPHOS and overall mitochondrial function, we next assessed the effects of known glycolytic inhibitors
  • 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
  • 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
  • caffeic acid phenyl ester (CAPE), a key component of honey-bee propolis, has potent anti-cancer properties
  • Propolis has a strong history of medicinal use, dating back more than 2,000 years
  • Because of it aromatic ring structure (Figure 8), we speculated that CAPE might function as a potent inhibitor of oxidative mitochondrial metabolism
  • CAPE quantitatively inhibits the mitochondrial oxygen consumption rate (OCR) and, in turn, induces the onset of aerobic glycolysis (ECAR)
  • CAPE shows a clear selectivity for targeting CSCs and adherent cancer cells, relative to normal fibroblasts.
  • CAPE functions as a “natural” mitochondrial OXPHOS inhibitor, that preferentially targets the CSC sub-population. This could explain CAPE’s known anti-cancer properties
  • 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
  • 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.
  • high NADH is a property that is conserved between normal and cancerous stem cells
  • 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
  • CSCs may be strictly dependent on NADH to maintain their enhanced mitochondrial function
  • 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
  • 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.
  • 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
  • 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
  • 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
  • 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
  • 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.
  • Nathan Goodyear on 08 Dec 17
     
    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.
Nathan Goodyear

Cancer Chemopreventive Activity of Xanthohumol, a Natural Product Derived fro... - 0 views

mct.aacrjournals.org/...959.long

xanthohumol antioxidant hops flavonoid cancer

shared by Nathan Goodyear on 03 Jan 13 - No Cached
  • Nathan Goodyear on 03 Jan 13
     
    Xanthohumol, a relatively newly discovered flavonoid from Hops. Xanthohumol has been show to possess anti-tumor activity: anti-inflammatory activity , antioxidant, anti-proliferative activity.
Nathan Goodyear

Effects of androgens on telomerase activity in normal and malignant prostate cells in v... - 0 views

onlinelibrary.wiley.com/...AC2C88175F4E55359BA67DC.f03t03

androgen deprivation therapy Prostate cancer androgen deprivation therapy Testosterone Telomerase Telomere length

shared by Nathan Goodyear on 10 Jan 14 - No Cached
  • Nathan Goodyear on 10 Jan 14
     
    Androgen deprivation therapy reduces Telomerase activity in androgen dependent prostate cancer cell lines.  Conversely, Testosterone increases Telomerase activity.  In these cell lines Telomerase activity is positively associated with prostate cancer.
Nathan Goodyear

Aromatase and regulation of the estrogen-to... [Ann N Y Acad Sci. 2014] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24684533

aromatase aromatase activity vitamin D estrone E1 inflammation RA rheumatoid arthritis

shared by Nathan Goodyear on 07 Apr 14 - No Cached
  • Nathan Goodyear on 07 Apr 14
     
    Study looked at inflammatory markers in RA.  The authors point to high aromatase activity, low androgens, and elevated estrone in synovial fluid as an indicator of a link between aromatase activity and inflammation production through E1 production.  The authors also point to the 16 alpha metabolite pathway as pro-inflammatory as well.  One very interesting point made by the authors is that vitamin D down regulates aromatase activity.  In addition to NK-kappaB inhibition, this may be another mechanism by which vitamin D reduces inflammation.
Nathan Goodyear

Plant-Based Nutritional Supplementation Attenuates LPS-Induced Low-Grade Systemic Activ... - 0 views

www.ncbi.nlm.nih.gov/...PMC7826722

TLR4 inflammation LPS metabolic endotoxemia plant-based nutrition plant-based diet plant-based

shared by Nathan Goodyear on 03 Sep 21 - No Cached
  • consumption of this particular diet for at least a 2-month period helped to reduce the outcomes of both acute and chronic inflammation induced by LPS.
  • chronic inflammation compromised both glucose and insulin tolerance, which is normally seen in certain chronic metabolic diseases
  • LPS resulted in an increase in neopterin levels, which is a marker for immune system activation
  • ...6 more annotations...
  • diet enriched in fruits and vegetables (and consequently phytochemicals) was able to reverse the process and maintain and even elevate insulin sensitivity and glucose tolerance
  • LPS-mediated effects are related to an increase in TLR4 levels that triggers the activation of nuclear factor-kB (NF-kB), a transcription factor that activates a cascade of inflammatory mediators [41]. These factors control the transcription of inflammatory mediators, such as IL-1β, IL-6, TNF-α, TNF-β, INF-α, INFβ, INF-γ
  • Inflammation can alter insulin action and give rise to diabetes and obesity by blocking insulin receptor downstream events, impairing insulin receptor substrate 1 (IRS-1) activation and phosphatidylinositol 3-kinase-dependent (PI3K) pathways, therefore compromising insulin signaling
  • systemic inflammation (generated by LPS) also increased neopterin levels in the urine and resulted in altered neuronal activity by decreasing dopamine (DA) metabolism
  • an increase in neopterin levels has been recognized a sensitive biomarker for immune system activation
  • Our experiments denoted that these diets were able to diminish inflammatory mediators and oxidative damage
Nathan Goodyear

Toll-like receptor signaling links dietary fatty acids to the metabolic syndrome - 0 views

www.ncbi.nlm.nih.gov/...PMC3099529

TLR toll-like receptors toll-like receptors fatty acids fat metabolic syndrome obesity overweight inflammation dietary

shared by Nathan Goodyear on 08 Oct 12 - No Cached
  • Activation of the innate immune system controls macronutrient metabolism
  • the innate immune response is the first line of defense against invading pathogens, wherein highly conserved pathogen-associated molecular patterns (PAMPs) are recognized by cognate pattern recognition receptors (PRRs
  • many studies have supported the idea that cytokine signaling directly promotes insulin resistance
  • ...10 more annotations...
  • innate immune system may be causally linked to obesity
  • adipose tissue contains a substantial population of macrophages, and macrophage-driven adipose inflammation contributes significantly to the pathogenesis of obesity
  • Collectively, activation of the innate immune system is strongly associated with ASCVD, insulin resistance, and obesity, and recent evidence suggests that much of this association can be traced to a unique family of PRRs known as TLRs
  • TLRs are a family of type I transmembrane receptors, currently thought to comprise at least 13 members in mammals, that specifically recognize a variety of microbial PAMPs and trigger host cellular responses
  • Free SFAs have indeed been demonstrated to elicit TLR4-dependent and TLR2-dependent responses in several cell types.
  • Endogenous SFAs released from adipocytes activate cocultured macrophages via TLR4 [18], indicating the potential for cellular crosstalk in adipose tissue. Collectively, there is a growing body of evidence that SFAs promote, whereas long chain PUFA antagonize, TLR4-dependent and TLR2-dependent signaling in multiple cell models
  • In an elegant study, Shi et al. [16] demonstrated that SFAs activate TLR4-dependent signaling in both macrophages and adipocytes, and mice lacking TLR4 are protected against insulin resistance driven by intravenous lipid infusion
  • In addition to effects in macrophages and adipocytes, SFAs can activate TLR4 in the hypothalamus, which triggers a central inflammatory response that results in resistance to anorexigenic signals
  • endogenous SFAs can indeed promote innate immunity and inflammatory disease
  • This finding strongly supports the work of Hwang and coworkers [19–22] demonstrating that ω-3 PUFAs can effectively counteract SFA-induced TLR4 activation in cultured macrophages and dendritic cells.
  • Nathan Goodyear on 08 Oct 12
     
    high dietary fatty acids linked to metabolic syndrome through TLR.
Nathan Goodyear

Extranuclear Actions of the Androgen Receptor Enhance Glucose-Stimulated Insulin Secret... - 0 views

www.cell.com/...S1550-4131(16)30118-8

Testosterone low Testosterone low T hormones male hormones DHT dihydrotestosterone insulin AR androgen receptor Diabetes

shared by Nathan Goodyear on 18 May 16 - No Cached
  • Nathan Goodyear on 18 May 16
     
    only abstract available here. Mouse model finds possible explanation for low Testosterone and diabetes link.  Actually, the link is between the metabolite DHT and the AR. The activity of AR from DHT binding induces beta cell insulin secretion in the presence of glucose.  This is dependent on glucagon-like peptide 1 receptor activation also, which AR activation by DHT does in fact do.
wheelchairindia9

Best Tennis Elbow Support - 0 views

www.wheelchairindia.com/...Tynor-Tennis-Elbow-Support

Tennis Elbow Support Help Relief From Forearm porous and a comfortable material firm grip with silicon pad Custom compression and fit compressive strength and support free and natural movement

shared by wheelchairindia9 on 25 Mar 16 - No Cached
  • wheelchairindia9 on 25 Mar 16
     
    Tynor Wrist Brace with Thumb is created to reinforce, prevent and partially immobilize the wrist and the palm. This wrist brace allows natural and free activity of the fingers. It keeps the affected area compact and maintains the body heat to lessen the local pain inflammation. Its has high quality striped elastic webbing which provides high modulus of elasticity which gives the comfortable feel. It is made from the strong, durable, porous and a comfortable material which remains for a long time. This Wrist Brace provides excellent compressive strength and support to the wrist. Its Hook loop closures allow easy application and removal. It fits comfortably around the wrist and comes in universal sizing. It also has an anatomical thumb opening which fastens the healing process. It keeps the thumb in relaxed and comfortable position. Its extra porous material allows the proper ventilation to the affected skin. Wrist brace with thumb is designed to support, protect and partially immobilize the wrist and the palm while allowing free and natural movement of the fingers. It compresses the area and retains the body heat to allay local pain and inflammation. Extra grip. Extra porous Controlled compression. Anatomical thumb placement. Tynor Wrist Brace with Thumb Features High quality , striped elastic webbing Strong and durable Porous and comfortable High modulus of elasticity- Retains shape and size for a long time. Excellent compressive strength, better support Hook loop closures Easy to apply and remove Ensures optimal compression Better fitting and universal sizing. Anatomical thumb opening Better pain relief and healing. Thumb in abduction remains relaxed, no fatigue Improves comfort Allows free and natural movement of the thumb and fingers. Tynor tennis elbow support is specially crafted to aid and render relief from generalized pain and tenderness in the forearm and elbow caused by repetitive strain injury due to the firm grip or ac
Nathan Goodyear

Genomic agonism and phenotypic antagonism between estrogen and progesterone receptors i... - 0 views

advances.sciencemag.org/...e1501924.full

progesterone PR progesterone receptors progesterone receptor cancer breast cancer hormones

shared by Nathan Goodyear on 29 Jun 16 - No Cached
  • The presence and activity of PR significantly affect the prognostic value of ER.
  • The observed loss of PR protein expression in a subset of ER+/PR+ breast cancers, because of hypermethylation or deletion of the PR gene locus, results in the loss of ER prognostic value
  • These findings emphasize the clinical value of assessing both PR and ER expression in breast cancer samples
  • ...7 more annotations...
  • PR is an essential modulator of ER-regulated genes but also that it significantly contributes to the prognostic value of ER in ER+/PR+ breast cancers
  • PR-regulated genes have independent prognostic value, and the presence of PR correlates with favorable clinicopathological outcomes
  • this study demonstrates that progestin-activated PR redirects ER chromatin binding and functions as a genomic estrogen agonist and as a phenotypic estrogen antagonist in ER+/PR+ breast cancer cells and human tumors
  • Approximately 80% of ER+ breast cancers are also positive for PR,
  • In isolation, both hormones activate or inhibit cellular processes in similar directions, although the magnitude of these effects is less for progestin alone than for estrogen alone
  • PR-mediated antagonism of estrogenic phenotypes is well documented
  • joint activation of ER and PR antagonized ER-regulated oncogenic processes
  • Nathan Goodyear on 29 Jun 16
     
    WOW!!  study finds that progesterone through PR activity antagonizes ER protein expression by the cell.  This has huge implications in breast cancer and possible prostate cancer.  But then again, women don't need progesterone; only estrogen.  The presence of PR correlates with improved clinicopathological outcomes.  The authors do seem to get confused about progesterone and progestins.  They are not one in the same.
Nathan Goodyear

Stimulation of aromatase activity in bre... [Mol Cell Endocrinol. 1994] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...7895904

inflammatory cytokines inflammation TNF-alpha aromatase activity estrone testosterone adipose fat tissue breast men women hormones androstenedione

shared by Nathan Goodyear on 29 Apr 12 - No Cached
  • Nathan Goodyear on 29 Apr 12
     
    inflammatory cytokine, TNF-alpha, increases aromatase activity.  This article discusses the increased production of estrone from androstenedione from aromatase activity in fat tissue in the breast.
Nathan Goodyear

Sex hormones influence on the immune system: basic and clinical aspects in autoimmunity - 0 views

lup.sagepub.com/...635.short

aromatase testosterone estrogen estradiol IL-6 TNF-alpha IL-1 autoimmune disease inflammation inflammatory cytokines men hormones immune system

shared by Nathan Goodyear on 29 Apr 12 - No Cached
  • Nathan Goodyear on 29 Apr 12
     
    high conversion of testosterone to estrogen conversion in men is from increased aromatase activity.  Inflammatory cytokines, such as IL-6, TNF-alpha, has been shown to increase aromatase activity and at the same time increase IL-6 and other inflammatory cytokines is the result of increased aromatase activity.
Nathan Goodyear

Increased 5α-Reductase Activity and Adrenocortical Drive in Women with Polycy... - 0 views

jcem.endojournals.org/...3558.long

5-alpha reductase activity women PCOS PCO polycystic ovary ovarian syndrome 11-betaHSD

shared by Nathan Goodyear on 13 Mar 12 - No Cached
  • Nathan Goodyear on 13 Mar 12
     
    increased 5-alpha reductase activity found in women with PCOS. Weight showed no variance.  Additionally, no change in 11-betaHSD activity was found.
Nathan Goodyear

The endocabbinoid system and the treatment of obesity - 0 views

diabesity.eu/annals.pdf

endocannabinoid endocannabinoid-mediated adiponectin obesity overweight weight-loss CB1

shared by Nathan Goodyear on 19 Mar 12 - No Cached
  • Nathan Goodyear on 19 Mar 12
     
    nice review of CB1 receptors and the role they play in obesity. Endocabbinoid receptors play an important role in the hypothalamus control of metabolism and energy. CB1 is active both centrally and peripherally. Increased CB1 activity increases fat storage; decrease CB1 activity increases fatty acid oxidation through adiponectin.
Nathan Goodyear

Obesity - Inducible Toll-like Receptor and NF-[kappa]B Regulatory Pathway Expression in... - 0 views

www.nature.com/...oby200825a.html

TLR-4 TLR Toll-like receptors NF-kapppB inflammation obesity

shared by Nathan Goodyear on 19 Jan 12 - No Cached
  • TLRs are functionally inducible and associated with downstream NF-B activation and proinflammatory cytokine production.
  • TLRs represent a family of receptors that are critical to the innate immune response against foreign pathogens and microorganisms
  • LPS has been shown to induce proinflammatory chemokine gene expression in differentiated human adipocytes through TLR and NF-B action
  • ...2 more annotations...
  • 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.
  • Elevated fatty acids levels associated with obesity activate TLR4 signaling in fat cells and macrophages, and induce insulin resistance in murine models
  • Nathan Goodyear on 19 Jan 12
     
    TLR, especially TLR-4, is directly involved in NF-KappaB activation and release of inflammatory cytokines
Nathan Goodyear

Oestrogens and prostate cancer - 0 views

erc.endocrinology-journals.org/...187.full.pdf

aromatase activity aromatase activity prostate cancer disease Testosterone estradiol male hormone hormones

shared by Nathan Goodyear on 24 Sep 13 - No Cached
  • Nathan Goodyear on 24 Sep 13
     
    Study confirms aromatase activity in the prostate itself. Systemic Testosterone and Estradiol evaluation (ie blood) will not necessarily reflect endogenous prostate aromatase activity.
‹ Previous 21 - 40 of 1093 Next › Last »
Showing 20▼ items per page