This document discusses the role of the transcription factor Nrf2 in attenuating cardiovascular disease through regulating antioxidant defenses. It begins by explaining how oxidative stress contributes to cardiovascular diseases and how early trials of antioxidant supplements were disappointing. It then describes how Nrf2 is the master regulator of cellular antioxidant defenses, regulating over 200 genes. Nrf2 is normally bound by Keap1 in the cytoplasm and targeted for degradation, but oxidative stress or phytochemicals can activate Nrf2 by modifying Keap1 or through kinase signaling. Activated Nrf2 upregulates antioxidant enzymes and other genes to maintain redox homeostasis and protect against disease. Exercise and certain phytochemicals are highlighted as potential ways to activate Nrf2 and attenu
1) Oxidative stress activates the transcription factor sterol regulatory element-binding protein 2 (SREBP2) in vascular endothelial cells. 2) SREBP2 increases expression of microRNA-92a (miR-92a), which targets genes involved in endothelial homeostasis like sirtuin 1, Krüppel-like factor 2, and Krüppel-like factor 4. 3) This leads to activation of the NLRP3 inflammasome and reduced nitric oxide bioavailability, exacerbating endothelial dysfunction during oxidative stress.
Nitric oxide (NO) is produced in the body from L-arginine and plays important roles in regulating organs and blood flow. L-arginine and L-citrulline support NO production, while antioxidants like vitamins C and E help maintain NO levels. Dr Qs NitroMax contains these ingredients like L-arginine, L-citrulline, quercetin and folate to support healthy NO levels, which is important for circulation, immune function and other bodily processes. The formula is designed to optimize blood flow, support male sexual function, lean body mass and brain health.
This study examined whether contractile activity in cardiomyocytes regulates inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production via focal adhesion kinase (FAK)-dependent signaling. The researchers treated spontaneously contracting neonatal rat ventricular myocytes with inhibitors of contraction and found they reduced iNOS expression and NO production by inhibiting FAK and AKT phosphorylation. Inhibiting FAK or PI3K also eliminated contraction-induced iNOS expression. Knockdown of FAK reduced AKT phosphorylation and iNOS expression, whereas overexpression of constitutively active FAK or AKT reversed the inhibitory effect of contraction inhibitors. Thus, contraction induces iNOS expression and NO production via a FAK-PI3K-AK
Dr Qs NitroMax is a supplement that contains L-arginine, L-citrulline, quercetin, folic acid, and vitamins C and E. These ingredients work to support nitric oxide production and blood flow throughout the body. Nitric oxide is important for circulatory, immune, and nervous system functions. The key active ingredients, L-arginine and L-citrulline, are precursors the body uses to make nitric oxide. They may help optimize blood flow and oxygen delivery while supporting cardiovascular health, brain function, and male sexual function.
This document describes arylphthalazines as potent inhibitors of VEGFR-2 (Vascular Endothelial Growth Factor Receptor 2), an important target for inhibiting angiogenesis. A series of arylphthalazine derivatives were synthesized in two steps from commercially available starting materials. Compound IM-094482 57 was found to be a potent inhibitor of VEGFR-2 and VEGFR-1 in enzymatic, cellular, and mitogenic assays, comparable to ZD-6474. Compound 57 also showed good oral bioavailability in mice. Structure-activity relationship studies around the 1-anilino group and 4-aryl group of the arylphthalazine core identified substituents that improved inhibitory potency against VEGFR-2.
The document discusses DNA repair mechanisms in human lymphocytes. It describes how oxidized purines in DNA are repaired through the base excision repair pathway involving the OGG1 glycosylase. This repair requires activation by the transcription factor NF-YA, which upregulates OGG1 expression when DNA is at risk of oxidation. The repair of oxidized bases by OGG1 in human lymphocytes is slow but can be activated by phytohemagglutinin. Disruption of this global repair of oxidized purines may be due to downregulation of OGG1. A second document discusses how green tea acts as an antioxidant to protect against oxidative stress and influence DNA damage and repair through activation of the Nrf2 transcription factor and upreg
Indole-3-carbinol (I3C) is a compound found in cruciferous vegetables that may have anticancer properties. This document summarizes I3C's sources, chemical properties, metabolism, mechanisms of action, and clinical trial data. Key points:
1) I3C is produced from glucosinolates in cruciferous vegetables and may be converted to dimers and trimers in the stomach and intestines.
2) Preclinical studies suggest I3C has anti-inflammatory, antioxidant, and anticancer effects through multiple pathways like NF-kB and Akt.
3) Phase I/II clinical trials show I3C is well tolerated at doses of 200-
Nrf2: A Master Regulator of Detoxification and also Antioxidant, Anti-inflam...LifeVantage
Nrf2 is a transcription factor that activates over 500 genes involved in cytoprotection, including antioxidant, detoxification, anti-inflammatory, and mitochondrial functions. Raising Nrf2 activity through various health-promoting nutrients and factors has been shown to prevent and/or treat a wide range of chronic diseases in animal and human studies, including cardiovascular, neurodegenerative, cancer, kidney, metabolic, liver, lung, autoimmune, and inflammatory diseases. These diseases often involve oxidative stress, inflammation, and mitochondrial dysfunction, which Nrf2 is able to regulate through its effects on multiple cytoprotective genes.
1) Oxidative stress activates the transcription factor sterol regulatory element-binding protein 2 (SREBP2) in vascular endothelial cells. 2) SREBP2 increases expression of microRNA-92a (miR-92a), which targets genes involved in endothelial homeostasis like sirtuin 1, Krüppel-like factor 2, and Krüppel-like factor 4. 3) This leads to activation of the NLRP3 inflammasome and reduced nitric oxide bioavailability, exacerbating endothelial dysfunction during oxidative stress.
Nitric oxide (NO) is produced in the body from L-arginine and plays important roles in regulating organs and blood flow. L-arginine and L-citrulline support NO production, while antioxidants like vitamins C and E help maintain NO levels. Dr Qs NitroMax contains these ingredients like L-arginine, L-citrulline, quercetin and folate to support healthy NO levels, which is important for circulation, immune function and other bodily processes. The formula is designed to optimize blood flow, support male sexual function, lean body mass and brain health.
This study examined whether contractile activity in cardiomyocytes regulates inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production via focal adhesion kinase (FAK)-dependent signaling. The researchers treated spontaneously contracting neonatal rat ventricular myocytes with inhibitors of contraction and found they reduced iNOS expression and NO production by inhibiting FAK and AKT phosphorylation. Inhibiting FAK or PI3K also eliminated contraction-induced iNOS expression. Knockdown of FAK reduced AKT phosphorylation and iNOS expression, whereas overexpression of constitutively active FAK or AKT reversed the inhibitory effect of contraction inhibitors. Thus, contraction induces iNOS expression and NO production via a FAK-PI3K-AK
Dr Qs NitroMax is a supplement that contains L-arginine, L-citrulline, quercetin, folic acid, and vitamins C and E. These ingredients work to support nitric oxide production and blood flow throughout the body. Nitric oxide is important for circulatory, immune, and nervous system functions. The key active ingredients, L-arginine and L-citrulline, are precursors the body uses to make nitric oxide. They may help optimize blood flow and oxygen delivery while supporting cardiovascular health, brain function, and male sexual function.
This document describes arylphthalazines as potent inhibitors of VEGFR-2 (Vascular Endothelial Growth Factor Receptor 2), an important target for inhibiting angiogenesis. A series of arylphthalazine derivatives were synthesized in two steps from commercially available starting materials. Compound IM-094482 57 was found to be a potent inhibitor of VEGFR-2 and VEGFR-1 in enzymatic, cellular, and mitogenic assays, comparable to ZD-6474. Compound 57 also showed good oral bioavailability in mice. Structure-activity relationship studies around the 1-anilino group and 4-aryl group of the arylphthalazine core identified substituents that improved inhibitory potency against VEGFR-2.
The document discusses DNA repair mechanisms in human lymphocytes. It describes how oxidized purines in DNA are repaired through the base excision repair pathway involving the OGG1 glycosylase. This repair requires activation by the transcription factor NF-YA, which upregulates OGG1 expression when DNA is at risk of oxidation. The repair of oxidized bases by OGG1 in human lymphocytes is slow but can be activated by phytohemagglutinin. Disruption of this global repair of oxidized purines may be due to downregulation of OGG1. A second document discusses how green tea acts as an antioxidant to protect against oxidative stress and influence DNA damage and repair through activation of the Nrf2 transcription factor and upreg
Indole-3-carbinol (I3C) is a compound found in cruciferous vegetables that may have anticancer properties. This document summarizes I3C's sources, chemical properties, metabolism, mechanisms of action, and clinical trial data. Key points:
1) I3C is produced from glucosinolates in cruciferous vegetables and may be converted to dimers and trimers in the stomach and intestines.
2) Preclinical studies suggest I3C has anti-inflammatory, antioxidant, and anticancer effects through multiple pathways like NF-kB and Akt.
3) Phase I/II clinical trials show I3C is well tolerated at doses of 200-
Nrf2: A Master Regulator of Detoxification and also Antioxidant, Anti-inflam...LifeVantage
Nrf2 is a transcription factor that activates over 500 genes involved in cytoprotection, including antioxidant, detoxification, anti-inflammatory, and mitochondrial functions. Raising Nrf2 activity through various health-promoting nutrients and factors has been shown to prevent and/or treat a wide range of chronic diseases in animal and human studies, including cardiovascular, neurodegenerative, cancer, kidney, metabolic, liver, lung, autoimmune, and inflammatory diseases. These diseases often involve oxidative stress, inflammation, and mitochondrial dysfunction, which Nrf2 is able to regulate through its effects on multiple cytoprotective genes.
1) The study found that inhibiting HDAC3 with the selective inhibitor MI192 increased tubulin acetylation levels and disrupted microtubule dynamics in prostate cancer cells.
2) Knockdown of HDAC3 using siRNA also increased tubulin acetylation levels, while overexpression of HDAC3 reduced acetylation.
3) However, in vitro assays showed that the HDAC3-SMRT-DAD complex did not directly deacetylate tubulin, suggesting HDAC3 modulates tubulin acetylation indirectly.
This document summarizes research on the effects of exercise on gene expression of inflammatory markers in human peripheral blood cells. It reviews 37 studies that examined gene expression in white blood cells like lymphocytes and monocytes after acute and long-term exercise. The studies found that an acute bout of exercise can upregulate expression of some pro-inflammatory genes like IL-1β, IL-8 and CXCL16 in peripheral blood mononuclear cells. However, long-term regular exercise is associated with attenuated inflammatory response and upregulation of anti-inflammatory genes like IL-10 and IL-13. Gene expression changes depend on exercise duration and intensity. The immune system and inflammatory response play a role in diseases like cardiovascular disease and cancer, so understanding
This document summarizes research on eicosanoids, lipid mediators derived from arachidonic acid that play important roles in inflammation and immunity. It focuses on the roles of prostanoids and leukotrienes in organ transplantation. Prostanoids like prostaglandin E2 and prostacyclin generally have immunosuppressive effects, while thromboxane A2 enhances immune responses. Studies in animals and some human trials suggest these eicosanoids can influence transplant rejection and outcomes. Future research on specific receptors for these lipids may lead to new pharmacological approaches for controlling inflammation and promoting graft acceptance.
we are teleologically cardioprotected. we are already cardioprotected. nature has given us everything we need to be unbreakable.we just have to push the right buttons.
please, pay heed to the turtles! they know best!
This document discusses the potential immunomodulatory effects of statins in organ transplant recipients. It notes that while immunosuppressive drugs prevent acute rejection, they can cause hyperlipidemia which may promote chronic rejection. Studies have found statins improve outcomes when given to transplant recipients by lowering lipids. The document then explores the biological mechanisms of statins including inhibiting HMG-CoA reductase and isoprenoid production, which can suppress T-cell response and lower MHC expression on antigen presenting cells like endothelial cells. This may prevent rejection by inhibiting interactions between MHC, T-cell receptors, and adhesion molecules like LFA-1 and ICAM-1. Further research is still needed to better understand how cholesterol synthesis
The interaction of Nrf2 and Glyoxalase I in response to lipid loading in Hepa...Farya Mubarik
This document summarizes a study that examined the interaction between Nrf2 and glyoxalase I in response to lipid loading in hepatocytes. The study first optimized the dose and duration of MG132 treatment, a proteasomal inhibitor, to induce accumulation of Nrf2 protein in HepG2 cells. It then examined the effects of oleic acid and palmitic acid on cell viability and found no significant effects. The study aims to determine if inhibition of proteasomal degradation leads to accumulation of Nrf2 and subsequent upregulation of glyoxalase I expression in response to lipid accumulation.
This study shows that bile acids (BA) may contribute to an increase in alveolar epithelial permeability in a dose-dependent manner. The key findings are:
1) BA upregulates mitogen-activated protein kinase (MAPK), cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) generation.
2) This leads to a reduction in the tight junction proteins occludin, zonula occludens-1 (ZO-1), and E-cadherin, which are responsible for maintaining epithelial integrity.
3) The increase in alveolar permeability and
This document summarizes a study examining the role of platelet-derived growth factor (PDGF)-evoked calcium signaling in human pulmonary fibroblasts. The study found that both acute and overnight PDGF treatment evoked calcium waves in these cells. Blocking external calcium, internal calcium stores, or phospholipase C inhibited the PDGF-evoked calcium waves and PDGF-induced expression of fibronectin and collagen genes. The results indicate that in human pulmonary fibroblasts, PDGF acts through IP3-induced calcium release from internal stores to trigger calcium waves, which then modulate expression of extracellular matrix genes.
The document discusses a study investigating the effects of food restriction on gene expression. It was previously found that 15 genes were upregulated in the brain during food restriction, suggesting they are part of an ancient stress response pathway. The current study aims to test if these genes are also induced in other tissue types under food restriction. Mice were either food restricted or not for 5 days, then gene expression was analyzed using qPCR in various tissues including the kidney. It was found that Angptl4, Mertk, Arrdc2 and Cdkn1a were significantly upregulated in the kidney of food restricted mice compared to controls, providing further evidence they are part of a general stress response pathway activated by food restriction across multiple
Nutritional immunology is a fascinating but highly complex and conflicted subject area. With almost every nutrient we consume having the ability to affect our immune response in one way or another and the activation of the immune system dramatically increasing nutrient requirements, understanding the genetic, cellular and metabolic mechanisms that interact, control and conflict with the immune system and how to manipulate them to our advantage, is fundamental to optimal health.
We are thrilled to announce that we have linked up with Professor Phillip Calder, a world renowned and highly cited expert in nutritional immunology, with over 500 publications to his name. Professor Calder will be joining us as our guest speaker for our January Webinar to help us kick off what promises to be our most exciting year of clinical nutrition education yet.
In this detailed Q&A session Professor Calder will shed light on a whole host of fascinating topics from the latest research into nutrition immunology, his projects involving nutrigenomics, probiotics and omega-3s, the real science behind effective clinical omega-3 interventions, his thoughts on the best forms of lipid supplementation, and doing some serious nutrition science myth busting.
Acute and chronic hyperammonemia modulate antioxidantrkkoiri
1) The study examines the effects of acute and chronic hyperammonemia on antioxidant enzyme levels and oxidative damage in the cerebral cortex and cerebellum of rats.
2) Acute hyperammonemia decreased antioxidant enzyme levels in both brain regions but increased lipid peroxidation only in the cerebellum.
3) Chronic hyperammonemia increased antioxidant enzyme levels in the cerebral cortex but decreased levels in the cerebellum, suggesting the cerebellum is more susceptible to oxidative stress during chronic hyperammonemia.
This document discusses hypoxia-inducible factor 1 (HIF-1) and its role in cancer therapy. HIF-1 is a heterodimeric protein composed of HIF-1α and HIF-1β subunits. Under normal oxygen conditions, HIF-1α is hydroxylated and degraded by the von Hippel-Lindau tumor suppressor protein (VHL). Under hypoxic conditions, HIF-1α evades degradation, dimerizes with HIF-1β, and activates genes involved in oxygen homeostasis, angiogenesis, glucose metabolism, and cell proliferation. Targeting HIF-1α stabilization and activity is a potential strategy for cancer therapy. The document reviews the
Protective role of co q10 or l carnitine on the integrity of the myocardium i...Prof. Hesham N. Mustafa
Doxorubicin (DOX) is a chemotherapeutic agent used for treatment of different cancers and its clinical usage is hindered by the oxidative injury-related cardiotoxicity. This work aims to declare if the harmful effects of DOX on heart can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study was performed on seventy two female Wistar albino rats divided into six groups, 12 animals each: Control group; DOX group (10mg/kg); CoQ10 group (200mg/kg); L-carnitine group (100mg/kg); DOX+CoQ10 group; DOX+L-carnitine group. CoQ10 and L-carnitine treatment orally started 5days before a single dose of 10mg/kg DOX that injected intraperitoneally (IP) then the treatment continued for 10days. At the end of the study, serum biochemical parameters of cardiac damage, oxidative stress indices, and histopathological changes were investigated. CoQ10 or L-carnitine showed a noticeable effects in improving cardiac functions evidenced reducing serum enzymes as serum interleukin-1 beta (IL-1 β), tumor necrosis factor alpha (TNF-α), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1, Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced glutathione levels to normal levels. Both corrected the cardiac alterations histologically and ultrastructurally. With a visible improvements in α-SMA, vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine supplementation improves the functional and structural integrity of the myocardium.
Keywords: Cardiotoxicity; CoQ10 and L-carnitine; Dox; Vimentin; eNOS.
Intermittent fasting had a strong anti inflammatory effect beside the many other benefits. Intermittent fasting is an eating pattern and Interventional strategy where in individuals are subjected to varying periods of fasting. It doesn’t specify which foods you should eat but rather when you should eat them. Intermittent fasting (IF) is an eating pattern that cycles between periods of fasting and eating. It’s currently very popular in the health and fitness community. Recently attracted attention because:
1- Its Evidence-Based Health Benefits
2- Its potential for correcting metabolic Abnormalities
3- Better adherence than other methods
New types of biomarkers in the cardiovascular sistem corectatFlorin George Frunza
PPT presentation from BIOMARKERS IN RESEARCH AND DEVELOPEMENT field.
From my course in CLINICAL AND FUNCTIONAL PROTEOMICS.
New dimentions in POSTTRANSLATIONAL MODIFICATIONS OF PROTEINS.
THE DARK FACE OF THE MOON for Third Millenium Medicine !!!
This study investigated whether supplementing glutathione (GSH) could attenuate lipopolysaccharide (LPS)-induced mitochondrial dysfunction and apoptosis in a mouse model of acute lung injury (ALI). The researchers found that LPS increased oxidative stress, mitochondrial dysfunction, and apoptosis in mouse lung tissue. However, pre-treating the mice with GSH-ethyl ester prevented the LPS-induced increases in oxidative stress, preserved mitochondrial function, and reduced apoptosis. Thus, GSH supplementation may protect against LPS-induced mitochondrial damage and cellular apoptosis in ALI.
The U.S. Patent Office issued patent #6630507 to the U.S.Health and Human Services filed on 2/2/2001. The patent lists the use of certain cannabinoids found within the cannabis sativa plant as useful in certain neurodegenerative diseases such as Alzheimer's, Parkinson's, and HIV dementia.
Since cannabis sativa (marijuana) contains compounds recognized and endorsed by an agency of the U.S. government- Why is it that marijuana remains on the Federal Schedule One list of drugs? The issuance of patent #6630507 is a direct contradiction of the governments own definition for classification of a Schedule 1 drug.
Vitamin C, glutathione, and various enzymes have radioprotective effects against cellular damage caused by ionizing radiation. Vitamin C is an antioxidant that can scavenge reactive oxygen species produced by radiation and protect DNA and membranes. Glutathione is also a free radical scavenger that protects against radiation damage. Various enzymes also help scavenge free radicals produced by radiation. The presentation concludes that vitamin C, glutathione, and enzymes play an important role in mitigating the effects of ionizing radiation exposure.
Aging is the progressive accumulation of damage to an organism over time leading to disease and death. Aging research has been very intensive in the last years aiming at characterizing the Pathophysiology of aging and finding possibilities to fight age-related diseases. Various theories of aging have been proposed. In the last years advanced glycation end products (AGEs) have received particular attention in this context. AGEs are formed in high amounts in diabetes but also in the physiological organism during aging. Higher levels of diabetic complications are due to poor glycemic control. The incidence and prevalence of diabetes mellitus is rising. About 50% of people with diabetes mellitus are unaware of their condition. Pharmacotherapy and Therapeutic lifestyle change (Diet, Regular exercises, Sunshine, Vitamin D and Calcium normal levels) should be the cornerstone of diabetes management.
Brian Covello: Diabetes Research Presentation Semester 2Brian Covello
This document summarizes previous research on the effects of 1,25-dihydroxyvitamin D3 and retinoic acid on PPARγ expression and insulin resistance in diabetes mellitus type 2. It was found that both metabolites inhibit PPARγ expression and adipocyte differentiation. However, past studies only tested the metabolites individually and on differentiated cells, not mixtures or on pre-adipocytes. The proposed research aims to test mixtures of the metabolites on pre-adipocytes and differentiated cells, as well as conduct transactivation studies to further understand how the metabolites modulate PPARγ and insulin resistance.
1) The study found that inhibiting HDAC3 with the selective inhibitor MI192 increased tubulin acetylation levels and disrupted microtubule dynamics in prostate cancer cells.
2) Knockdown of HDAC3 using siRNA also increased tubulin acetylation levels, while overexpression of HDAC3 reduced acetylation.
3) However, in vitro assays showed that the HDAC3-SMRT-DAD complex did not directly deacetylate tubulin, suggesting HDAC3 modulates tubulin acetylation indirectly.
This document summarizes research on the effects of exercise on gene expression of inflammatory markers in human peripheral blood cells. It reviews 37 studies that examined gene expression in white blood cells like lymphocytes and monocytes after acute and long-term exercise. The studies found that an acute bout of exercise can upregulate expression of some pro-inflammatory genes like IL-1β, IL-8 and CXCL16 in peripheral blood mononuclear cells. However, long-term regular exercise is associated with attenuated inflammatory response and upregulation of anti-inflammatory genes like IL-10 and IL-13. Gene expression changes depend on exercise duration and intensity. The immune system and inflammatory response play a role in diseases like cardiovascular disease and cancer, so understanding
This document summarizes research on eicosanoids, lipid mediators derived from arachidonic acid that play important roles in inflammation and immunity. It focuses on the roles of prostanoids and leukotrienes in organ transplantation. Prostanoids like prostaglandin E2 and prostacyclin generally have immunosuppressive effects, while thromboxane A2 enhances immune responses. Studies in animals and some human trials suggest these eicosanoids can influence transplant rejection and outcomes. Future research on specific receptors for these lipids may lead to new pharmacological approaches for controlling inflammation and promoting graft acceptance.
we are teleologically cardioprotected. we are already cardioprotected. nature has given us everything we need to be unbreakable.we just have to push the right buttons.
please, pay heed to the turtles! they know best!
This document discusses the potential immunomodulatory effects of statins in organ transplant recipients. It notes that while immunosuppressive drugs prevent acute rejection, they can cause hyperlipidemia which may promote chronic rejection. Studies have found statins improve outcomes when given to transplant recipients by lowering lipids. The document then explores the biological mechanisms of statins including inhibiting HMG-CoA reductase and isoprenoid production, which can suppress T-cell response and lower MHC expression on antigen presenting cells like endothelial cells. This may prevent rejection by inhibiting interactions between MHC, T-cell receptors, and adhesion molecules like LFA-1 and ICAM-1. Further research is still needed to better understand how cholesterol synthesis
The interaction of Nrf2 and Glyoxalase I in response to lipid loading in Hepa...Farya Mubarik
This document summarizes a study that examined the interaction between Nrf2 and glyoxalase I in response to lipid loading in hepatocytes. The study first optimized the dose and duration of MG132 treatment, a proteasomal inhibitor, to induce accumulation of Nrf2 protein in HepG2 cells. It then examined the effects of oleic acid and palmitic acid on cell viability and found no significant effects. The study aims to determine if inhibition of proteasomal degradation leads to accumulation of Nrf2 and subsequent upregulation of glyoxalase I expression in response to lipid accumulation.
This study shows that bile acids (BA) may contribute to an increase in alveolar epithelial permeability in a dose-dependent manner. The key findings are:
1) BA upregulates mitogen-activated protein kinase (MAPK), cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) generation.
2) This leads to a reduction in the tight junction proteins occludin, zonula occludens-1 (ZO-1), and E-cadherin, which are responsible for maintaining epithelial integrity.
3) The increase in alveolar permeability and
This document summarizes a study examining the role of platelet-derived growth factor (PDGF)-evoked calcium signaling in human pulmonary fibroblasts. The study found that both acute and overnight PDGF treatment evoked calcium waves in these cells. Blocking external calcium, internal calcium stores, or phospholipase C inhibited the PDGF-evoked calcium waves and PDGF-induced expression of fibronectin and collagen genes. The results indicate that in human pulmonary fibroblasts, PDGF acts through IP3-induced calcium release from internal stores to trigger calcium waves, which then modulate expression of extracellular matrix genes.
The document discusses a study investigating the effects of food restriction on gene expression. It was previously found that 15 genes were upregulated in the brain during food restriction, suggesting they are part of an ancient stress response pathway. The current study aims to test if these genes are also induced in other tissue types under food restriction. Mice were either food restricted or not for 5 days, then gene expression was analyzed using qPCR in various tissues including the kidney. It was found that Angptl4, Mertk, Arrdc2 and Cdkn1a were significantly upregulated in the kidney of food restricted mice compared to controls, providing further evidence they are part of a general stress response pathway activated by food restriction across multiple
Nutritional immunology is a fascinating but highly complex and conflicted subject area. With almost every nutrient we consume having the ability to affect our immune response in one way or another and the activation of the immune system dramatically increasing nutrient requirements, understanding the genetic, cellular and metabolic mechanisms that interact, control and conflict with the immune system and how to manipulate them to our advantage, is fundamental to optimal health.
We are thrilled to announce that we have linked up with Professor Phillip Calder, a world renowned and highly cited expert in nutritional immunology, with over 500 publications to his name. Professor Calder will be joining us as our guest speaker for our January Webinar to help us kick off what promises to be our most exciting year of clinical nutrition education yet.
In this detailed Q&A session Professor Calder will shed light on a whole host of fascinating topics from the latest research into nutrition immunology, his projects involving nutrigenomics, probiotics and omega-3s, the real science behind effective clinical omega-3 interventions, his thoughts on the best forms of lipid supplementation, and doing some serious nutrition science myth busting.
Acute and chronic hyperammonemia modulate antioxidantrkkoiri
1) The study examines the effects of acute and chronic hyperammonemia on antioxidant enzyme levels and oxidative damage in the cerebral cortex and cerebellum of rats.
2) Acute hyperammonemia decreased antioxidant enzyme levels in both brain regions but increased lipid peroxidation only in the cerebellum.
3) Chronic hyperammonemia increased antioxidant enzyme levels in the cerebral cortex but decreased levels in the cerebellum, suggesting the cerebellum is more susceptible to oxidative stress during chronic hyperammonemia.
This document discusses hypoxia-inducible factor 1 (HIF-1) and its role in cancer therapy. HIF-1 is a heterodimeric protein composed of HIF-1α and HIF-1β subunits. Under normal oxygen conditions, HIF-1α is hydroxylated and degraded by the von Hippel-Lindau tumor suppressor protein (VHL). Under hypoxic conditions, HIF-1α evades degradation, dimerizes with HIF-1β, and activates genes involved in oxygen homeostasis, angiogenesis, glucose metabolism, and cell proliferation. Targeting HIF-1α stabilization and activity is a potential strategy for cancer therapy. The document reviews the
Protective role of co q10 or l carnitine on the integrity of the myocardium i...Prof. Hesham N. Mustafa
Doxorubicin (DOX) is a chemotherapeutic agent used for treatment of different cancers and its clinical usage is hindered by the oxidative injury-related cardiotoxicity. This work aims to declare if the harmful effects of DOX on heart can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study was performed on seventy two female Wistar albino rats divided into six groups, 12 animals each: Control group; DOX group (10mg/kg); CoQ10 group (200mg/kg); L-carnitine group (100mg/kg); DOX+CoQ10 group; DOX+L-carnitine group. CoQ10 and L-carnitine treatment orally started 5days before a single dose of 10mg/kg DOX that injected intraperitoneally (IP) then the treatment continued for 10days. At the end of the study, serum biochemical parameters of cardiac damage, oxidative stress indices, and histopathological changes were investigated. CoQ10 or L-carnitine showed a noticeable effects in improving cardiac functions evidenced reducing serum enzymes as serum interleukin-1 beta (IL-1 β), tumor necrosis factor alpha (TNF-α), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1, Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced glutathione levels to normal levels. Both corrected the cardiac alterations histologically and ultrastructurally. With a visible improvements in α-SMA, vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine supplementation improves the functional and structural integrity of the myocardium.
Keywords: Cardiotoxicity; CoQ10 and L-carnitine; Dox; Vimentin; eNOS.
Intermittent fasting had a strong anti inflammatory effect beside the many other benefits. Intermittent fasting is an eating pattern and Interventional strategy where in individuals are subjected to varying periods of fasting. It doesn’t specify which foods you should eat but rather when you should eat them. Intermittent fasting (IF) is an eating pattern that cycles between periods of fasting and eating. It’s currently very popular in the health and fitness community. Recently attracted attention because:
1- Its Evidence-Based Health Benefits
2- Its potential for correcting metabolic Abnormalities
3- Better adherence than other methods
New types of biomarkers in the cardiovascular sistem corectatFlorin George Frunza
PPT presentation from BIOMARKERS IN RESEARCH AND DEVELOPEMENT field.
From my course in CLINICAL AND FUNCTIONAL PROTEOMICS.
New dimentions in POSTTRANSLATIONAL MODIFICATIONS OF PROTEINS.
THE DARK FACE OF THE MOON for Third Millenium Medicine !!!
This study investigated whether supplementing glutathione (GSH) could attenuate lipopolysaccharide (LPS)-induced mitochondrial dysfunction and apoptosis in a mouse model of acute lung injury (ALI). The researchers found that LPS increased oxidative stress, mitochondrial dysfunction, and apoptosis in mouse lung tissue. However, pre-treating the mice with GSH-ethyl ester prevented the LPS-induced increases in oxidative stress, preserved mitochondrial function, and reduced apoptosis. Thus, GSH supplementation may protect against LPS-induced mitochondrial damage and cellular apoptosis in ALI.
The U.S. Patent Office issued patent #6630507 to the U.S.Health and Human Services filed on 2/2/2001. The patent lists the use of certain cannabinoids found within the cannabis sativa plant as useful in certain neurodegenerative diseases such as Alzheimer's, Parkinson's, and HIV dementia.
Since cannabis sativa (marijuana) contains compounds recognized and endorsed by an agency of the U.S. government- Why is it that marijuana remains on the Federal Schedule One list of drugs? The issuance of patent #6630507 is a direct contradiction of the governments own definition for classification of a Schedule 1 drug.
Vitamin C, glutathione, and various enzymes have radioprotective effects against cellular damage caused by ionizing radiation. Vitamin C is an antioxidant that can scavenge reactive oxygen species produced by radiation and protect DNA and membranes. Glutathione is also a free radical scavenger that protects against radiation damage. Various enzymes also help scavenge free radicals produced by radiation. The presentation concludes that vitamin C, glutathione, and enzymes play an important role in mitigating the effects of ionizing radiation exposure.
Aging is the progressive accumulation of damage to an organism over time leading to disease and death. Aging research has been very intensive in the last years aiming at characterizing the Pathophysiology of aging and finding possibilities to fight age-related diseases. Various theories of aging have been proposed. In the last years advanced glycation end products (AGEs) have received particular attention in this context. AGEs are formed in high amounts in diabetes but also in the physiological organism during aging. Higher levels of diabetic complications are due to poor glycemic control. The incidence and prevalence of diabetes mellitus is rising. About 50% of people with diabetes mellitus are unaware of their condition. Pharmacotherapy and Therapeutic lifestyle change (Diet, Regular exercises, Sunshine, Vitamin D and Calcium normal levels) should be the cornerstone of diabetes management.
Brian Covello: Diabetes Research Presentation Semester 2Brian Covello
This document summarizes previous research on the effects of 1,25-dihydroxyvitamin D3 and retinoic acid on PPARγ expression and insulin resistance in diabetes mellitus type 2. It was found that both metabolites inhibit PPARγ expression and adipocyte differentiation. However, past studies only tested the metabolites individually and on differentiated cells, not mixtures or on pre-adipocytes. The proposed research aims to test mixtures of the metabolites on pre-adipocytes and differentiated cells, as well as conduct transactivation studies to further understand how the metabolites modulate PPARγ and insulin resistance.
This document appears to be a resume for Lea Mansour, who works as an art director. It lists her contact information and then provides descriptions of several projects she has worked on, including for McGraw Hill Construction, various logo and corporate identity work, the GradTrain website and app, a JH website and logo, and several other website and logo projects. For each project, it lists the design programs used, with Adobe Illustrator, Photoshop, and InDesign being commonly used.
A blind boy was sitting with a hat out seeking donations. A man changed the sign to emphasize that while others could see the day's beauty, the boy could not due to his blindness. This more emotionally impactful message led to more donations being given to the boy. The story suggests we should appreciate what we have and help others where possible, as well as think creatively about finding solutions.
The Partner ACS R8 processor provides 5 lines and 9 stations. It features caller ID, dual line ports, backup/restore capabilities, administration ports, and slots for add-ons like voicemail. The processor is compatible with a variety of phones, voicemail systems, and expansion modules. It offers numerous features including paging, contact closures, music on hold, and SMDR ports.
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive function. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
Canvas Orientation Video Script Final EditsMichelle Tovar
This video provides an overview of the Canvas learning management system used at American Institute. It demonstrates the key components of the Canvas dashboard including the dashboard, global navigation bar, sidebar, course cards, recent activity toggle, account settings, courses, calendar, inbox, and help options. It then shows how to access a course interface, which includes the course navigation links, content area that displays course material, and sidebar with upcoming assignments. The video highlights each area while explaining its purpose and navigation options to help orient students to using Canvas at American Institute.
The document summarizes the work of the Linus Pauling Institute at Oregon State University over the past 13 years. It discusses the Institute's focus on determining the roles of micronutrients, antioxidants, and other dietary factors in promoting optimal health and preventing disease. Key areas of research include cancer prevention, cardiovascular health, aging, and the protective effects of certain foods/compounds against oxidative stress and inflammation. The Institute has grown from half a researcher in 1996 to 12 full researchers and 4 research assistants currently. The work described emphasizes the important influence of diet and lifestyle on gene expression and chronic disease risk, beyond just genetic factors.
A perspective on dietary phytochemicals and cancerMonirg
This document discusses the role of oxidative stress and dietary phytochemicals in cancer prevention. It describes how oxidative stress causes an imbalance between reactive oxygen/nitrogen species and antioxidant defenses, potentially leading to DNA damage and cancer. The transcription factor Nrf2 plays a key role in activating antioxidant and detoxification genes. Many dietary phytochemicals have been shown to activate the Nrf2 pathway and protect against cancer by reducing oxidative stress. In addition, some phytochemicals can modify gene expression epigenetically by altering DNA methylation and histone modifications, including reactivating the Nrf2 pathway. Understanding these mechanisms may help develop new strategies for cancer prevention using phytochemicals.
Biogen Idec Study: BG-12 (Tecfidera) vs. ProtandimLifeVantage
This study investigated whether activating the Nrf2 pathway using different compounds could boost antioxidant enzyme expression in oligodendrocytes and protect them from reactive oxygen species (ROS)-mediated cell death. The researchers treated primary rat oligodendrocytes and rat and human oligodendrocyte cell lines with various Nrf2 activators including BG-12, tBHQ, SFN, and protandim. They found that all activators strongly induced antioxidant enzyme production, with protandim showing the most potent induction. The activators were also able to protect oligodendrocytes against ROS-induced cell death. Therefore, activating the Nrf2 pathway may be a novel therapeutic strategy to promote oligodendrocy
The document summarizes recent research on the transcription factor Nrf2, which regulates antioxidant and cytoprotective mechanisms in the cell. It finds that Nrf2 activation by health-promoting nutrients and other factors can prevent or treat many chronic inflammatory diseases. Specifically, it discusses how factors like antioxidants, omega-3 fatty acids, carotenoids, isothiocyanates, and caloric restriction increase Nrf2 activity. This reduces oxidative stress, inflammation, and improves mitochondrial function, thereby protecting against diseases like cancer, diabetes, and neurodegenerative disorders. Traditionally healthy diets are rich in Nrf2-activating nutrients, while modern diets are often deficient in these.
Role of antioxidants in neurologic diseasesNeurologyKota
This document discusses oxidative stress and various neurological conditions where free radicals may play a role, such as Alzheimer's disease, Parkinson's disease, and stroke. It then summarizes several antioxidants that have been studied for treating these conditions, including vitamin E, tirilazad, ebselen, coenzyme Q10, idebenone, and combinations of antioxidants for ALS and mitochondrial diseases. While some studies showed benefits, the evidence is limited and more research is still needed on dosing schedules. Cocktail antioxidant regimes may not be cost-effective options.
This document summarizes a study that evaluated the potential of an adeno-associated virus (AAV) vector delivering a peptide derived from the Nrf2 protein to target the Nrf2 signaling pathway in the retina. The Nrf2 peptide was fused to a cell-penetrating peptide sequence (Tat-peptide) and expressed from an AAV vector. In vitro, the TatNrf2mer peptide induced antioxidant gene expression, blocked IL-1β secretion, and protected cells from oxidative injury. In mouse models, TatNrf2mer expression partially protected photoreceptor function and decreased inflammatory cytokines and cells in models of retinal oxidative injury and uveitis. The results suggest this AAV-delivered TatNrf
The role of antioxidant supplement in immune system, neoplastic, and neurodegenerative disorders: a point of view for an assessment
of the risk/benefit profile. Nutritional Journal
Keto reductases (AKRs) are overexpressed in a large number of human tumors and mediate
resistance to cancer chemotherapeutics and antihormonal therapies. Existing drugs and new agents in development may surmount this resistance by acting as specific AKR isoforms or AKR
pan-inhibitors to improve clinical outcome.
Keto reductases (AKRs) are overexpressed in a large number of human tumors and mediate
resistance to cancer chemotherapeutics and antihormonal therapies. Existing drugs and new
agents in development may surmount this resistance by acting as specific AKR isoforms or AKR
pan-inhibitors to improve clinical outcome.
Keto reductases (AKRs) catalyze the NADPH-dependent reduction of carbonyl groups to
alcohols for conjugation reactions to proceed. They are implicated in resistance to cancer
chemotherapeutic agents either because they are directly involved in their metabolism or help
eradicate the cellular stress created by these agents (e.g., reactive oxygen species and lipid
peroxides). Furthermore, this cellular stress activates the nuclear factor-erythroid 2 p45-related
factor 2 (NRF2)-Kelch-like ECH-associated protein 1 pathway. As many human AKR genes are
upregulated by the NRF2 transcription factor, this leads to a feed-forward mechanism to enhance
drug resistance. Resistance to major classes of chemotherapeutic agents (anthracyclines,
mitomycin, cis-platin, antitubulin agents, vinca alkaloids, and cyclophosphamide) occurs by this
mechanism. Human AKRs also catalyze the synthesis of androgens and estrogens and the
elimination of progestogens and are involved in hormonal-dependent malignancies. They are
upregulated by antihormonal therapy providing a second mechanism for cancer drug resistance.
Inhibitors of the NRF2 system or pan-AKR1C inhibitors offer promise to surmount cancer drug
resistance and/or synergize the effects of existing drugs.
This document discusses reactive oxygen species (ROS), antioxidants, and their roles in various disorders. It begins by defining ROS as unstable molecules that can damage cells, and listing their sources. ROS are necessary in small amounts but can cause issues in excess. Antioxidants help neutralize ROS and prevent oxidative damage. The document then examines the roles of ROS and antioxidants in specific disorders like diabetes, cardiovascular disease, chronic fatigue, cancers, pregnancy complications, and male infertility. It provides treatment options like antioxidant supplementation to help control ROS levels and reduce related disease complications.
Eduardo Marbán, MD, PhD gives a deep dive into the complexities of regenerative cardiovascular medicine and the future directions for cell therapies.
Dr. Marbán’s lab has found several noncoding RNA (ncRNA) species, including short Y RNAs, which themselves have intriguing biological actions. The ncRNA within extracellular vesicles can either be used as they occur naturally or serve as bioinspiration for new chemical entities. The next generations of cell-free biologics (extracellular vesicles and noncoding RNAs) may provide, or even transcend, the benefits of cell therapy without the intrinsic limitations.
Key Topics Include:
- Understand the current status of cell therapy for heart disease
- Review the mechanisms whereby cells exert their therapeutic benefits
- Explore the future of RNA drugs inspired by the contents of extracellular vesicles
Oxidative Stress in Aging and Human Diseases - Exploring the MechanismsQIAGEN
Many modern diseases, including cancer, cardiovascular disease, diabetes, liver disease, arthritis and neurodegenerative disease are related to aging, and aging is closely linked to oxidative stress. Intensive research is being conducted to understand the antioxidant defense mechanism, the mechanisms of aging itself, as well as their roles in human diseases. This slidedeck provides an update on how oxidative stress is linked to aging and how inflammation leads to aging through DNA damage, telomere dysfunction, cellular senescence and oxidative stress. Recent progress on the health benefits of antioxidants and examination of their potential mechanisms in the prevention and treatment of chronic diseases are also covered. Various assay technologies to tackle the complex signaling pathways in this process will be introduced. Learn how you can apply these advanced tools to your research!
Drugs having Pleiotropic effects, Nutraceuticals and role of antioxidants ant...SwaroopaNallabariki
This document discusses several drugs that have pleiotropic effects beyond their primary mechanism of action, including statins, SGLT2 inhibitors, metformin, thiazolidinediones, cardiac glycosides, and antithrombotic drugs. It also discusses the role of antioxidants in disease prevention and treatment. Statins have beneficial effects including improving endothelial function, reducing inflammation and oxidative stress, stabilizing plaques, and inhibiting smooth muscle proliferation. SGLT2 inhibitors and thiazolidinediones improve glycemic control and have additional vascular benefits. Metformin reshapes the gut microbiota. Antioxidants help counteract free radical damage linked to diseases. Nutraceuticals and antioxidants’ properties influence their bioavailability
Deletion of TLR4 Ameliorates Inflammation Response and Apoptosis in Septic Ca...semualkaira
Septic cardiomyopathy (SCM) is featured by
severe myocardial dysfunction and remains one of the lethal complications in clinical sepsis. Toll-like receptor 4 (TLR4) signaling
is known as a classical innate pathway in heart diseases, whereas
the precise underlying mechanism of TLR4 in SCM remains elusive. This study was designed to examine the specific role of TLR4
in SCM with a focus on inflammation and apoptosis.
Deletion of TLR4 Ameliorates Inflammation Response and Apoptosis in Septic Ca...semualkaira
Septic cardiomyopathy (SCM) is featured by
severe myocardial dysfunction and remains one of the lethal complications in clinical sepsis. Toll-like receptor 4 (TLR4) signaling
is known as a classical innate pathway in heart diseases, whereas
the precise underlying mechanism of TLR4 in SCM remains elusive. This study was designed to examine the specific role of TLR4
in SCM with a focus on inflammation and apoptosis.
The imbalance between free radical production and endogenous antioxidant defence may result in cellular oxidative stress, causing oxidative damage to various cellular components, such as DNA, proteins and membrane lipids. The human system employs the use of endogenous enzymatic and non-enzymatic antioxidant defence systems against the onslaught of free radicals and oxidative stress.
Unsurprisingly, oxidative damage has been implicated in and is believed to be a key factor causing various pathological conditions, such as cardiovascular disease, neurodegenerative disease, diabetes and cancer. Free radicals can be quenched through a number of mechanisms. Antioxidants directly scavenge free radicals (e.g., via hydrogen atom transfer or electron transfer), prevent free radical formation by chelating metal ions and by interrupting the radical chain reactions of lipid peroxidation, thus retarding its progression. Enzymatic antioxidants include superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Non-enzymatic antioxidants include vitamins A, C, and E, glutathione, alpha-lipoic acid, carotenoids, and coenzyme Q10. Other antioxidants include polyphenols, minerals (copper, zinc, manganese, and selenium), and cofactors (B-vitamins). Together, antioxidants work synergistically with each other using different mechanisms against different free radicals and stages of oxidative stress.
The benefits associated with antioxidants are numerous and diverse but it can be a minefield when choosing the appropriate antioxidant support for clients. In this hour-long webinar, Dr Nina Bailey discusses the direct and indirect benefits and actions of key antioxidants including (but not limited to) astaxanthin, alpha lipoic acid, polyphenols and co-enzyme Q10, with a focus on:
-Antioxidant sources and benefits
-Mechanisms and actions
-When to combine antioxidants for synergistic effects
-Overcoming bioavailability issues
-Targeted intervention, which antioxidant(s) and why