Aging is a phenomena in which the functions, applicability and
resistance of an organism reduces over time. With the globally aging at an accelerating pace, delaying the negative aspects of aging is vital for advancing the human life span and quality of life. The aging of multiple organs can lead to a lot of disease and no exception for cardiovascular system. Actually, one of the primary risk factors for cardiovascular diseases is aging because of altered cardiovascular metabolism resulting in metabolic disorders and inflammation. In this review, we discuss about the relationship of oxidative stress with aging and FoxO proteins, which is essential factor for anti-aging of cardiovascular systems.
Neurodegeneration: Factors Involved and Therapeutic Strategiesinventionjournals
Neurodegenerative disorders are disorders of the nervous system which are characterized by a loss of neuronal structure and function. These changes lead to a loss of several abilities that include cognition and movement as observed in Alzheimer’s and Parkinson’s. Several factors like oxidative stress and protein misfolding have been found to play a vital role in the etiology of common neurological disorders. Whether these factors contribute to the progression of the disorders or are a consequence still remains elusive. Inspite of attempts to elucidate the molecular and pathological mechanisms of these pathways, many aspects still remain unclear. However, newer areas of therapeutic interventions like stem cell therapy and anti-oxidant therapy are now being explored as potential treatments. The aim of this review is to study the various factors that are associated with neurodegeneration along with recent therapeutic strategies that are being employed in an attempt to treat neurodegenerative disorders.
This document reviews the role of reactive oxygen species (ROS) in muscle function and how they may contribute to age-related sarcopenia. ROS are produced in muscles through various pathways including the mitochondrial electron transport chain and NADPH oxidase enzymes. At low levels, ROS play a role in muscle force production and exercise adaptation, but high levels can damage muscles. In aging muscles, ROS levels increase due to reduced antioxidant defenses and may cause cumulative oxidative damage, contributing to sarcopenia through impaired muscle mass, strength, and function.
Protein glycation occurs spontaneously when sugars attach to proteins or lipids, forming advanced glycation end products (AGEs) that accumulate over time and contribute to aging and disease pathology. AGEs form through reactions like the Maillard reaction and can crosslink or modify proteins, DNA and lipids. They are implicated in diseases associated with aging like diabetes, where hyperglycemia overwhelms the body's ability to break down AGEs. AGEs bind receptors on macrophages, stimulating inflammation and complications in diabetes such as nephropathy, neuropathy and retinopathy. The accumulation of AGEs over a lifetime may accelerate aging through molecular damage and chronic inflammation.
This document summarizes the causes and consequences of oxidative stress in spermatozoa. It discusses how spermatozoa are vulnerable to oxidative attack due to their lack of antioxidant protection and high levels of polyunsaturated fatty acids. Oxidative stress can damage sperm membranes through lipid peroxidation, suppressing motility. It also causes DNA damage that is associated with miscarriage and developmental abnormalities. While reactive oxygen species are important for sperm capacitation, excessive levels can overwhelm antioxidant defenses and induce apoptosis. The main source of oxidative stress in spermatozoa is mitochondrial reactive oxygen species generation.
This document discusses the biology of healthy aging and longevity. It covers several topics:
1) Molecular mechanisms of aging including genome integrity, telomeres, epigenetics, protein stability, and pathways like mTOR, IIS, AMPK, and sirtuins that modify aging.
2) Biological models like yeast, worms, flies and mice that are used to study aging mechanisms.
3) Calorie restriction which increases longevity across species by reversing signs of aging.
4) Maintaining genome, telomere and epigenome integrity is important for healthy aging and preventing diseases.
5) Environmental factors and nutrition influence aging through epigenetic changes.
ATP (adenosine triphosphate) production declines with age due to mitochondrial dysfunction. Mitochondria are the primary producers of cellular energy in the form of ATP through oxidative phosphorylation. As we age, mitochondrial DNA mutations accumulate, impairing ATP production. This summary discusses strategies to increase ATP levels topically and through supplementation to enhance mitochondrial function and combat signs of aging. These include vitamins B1-B6, biotin, B12, folic acid, magnesium, alpha lipoic acid, carnitine, NADH, coenzyme Q10, creatine, and LED or microcurrent therapy. Maintaining optimal mitochondrial and ATP levels may help slow the visible signs of skin aging.
Mechanisms involved in Reactive oxygen species induced sperm damages and thei...rahulvet27
1) Reactive oxygen species (ROS) are produced in greater quantities during sperm cryopreservation and can cause oxidative stress-related damage through lipid peroxidation, DNA damage, apoptosis, motility impairment, and protein damage.
2) Common sources of ROS include immature sperm cells, leukocytes, semen processing techniques, and dissolved oxygen.
3) Amelioration of ROS-induced damage can be achieved through the use of enzymatic antioxidants like catalase and glutathione peroxidase, non-enzymatic antioxidants like vitamin C and E, biological ROS inhibitors from oviductal fluid and seminal plasma, and reducing dissolved oxygen levels in cryopreservation extenders.
Oxidative Stress in Health & Disease: The therapeutic potential of Nrf2 acti...LifeVantage
1. Oxidative stress is an imbalance between oxidants produced by cells and the antioxidant defenses needed to maintain balance. It has been linked to aging and many diseases. While initially seen as primarily involving superoxide, oxidative stress is now viewed more broadly.
2. The transcription factor Nrf2 is the "master regulator" of the antioxidant response, modulating hundreds of genes involved in antioxidant defenses as well as unrelated processes like inflammation. Maintaining balance through Nrf2 activation is a promising alternative to administering individual antioxidants.
3. Certain phytochemicals have been found to strongly activate Nrf2 in a synergistic manner. One such composition, Protandim, was shown to significantly increase
Neurodegeneration: Factors Involved and Therapeutic Strategiesinventionjournals
Neurodegenerative disorders are disorders of the nervous system which are characterized by a loss of neuronal structure and function. These changes lead to a loss of several abilities that include cognition and movement as observed in Alzheimer’s and Parkinson’s. Several factors like oxidative stress and protein misfolding have been found to play a vital role in the etiology of common neurological disorders. Whether these factors contribute to the progression of the disorders or are a consequence still remains elusive. Inspite of attempts to elucidate the molecular and pathological mechanisms of these pathways, many aspects still remain unclear. However, newer areas of therapeutic interventions like stem cell therapy and anti-oxidant therapy are now being explored as potential treatments. The aim of this review is to study the various factors that are associated with neurodegeneration along with recent therapeutic strategies that are being employed in an attempt to treat neurodegenerative disorders.
This document reviews the role of reactive oxygen species (ROS) in muscle function and how they may contribute to age-related sarcopenia. ROS are produced in muscles through various pathways including the mitochondrial electron transport chain and NADPH oxidase enzymes. At low levels, ROS play a role in muscle force production and exercise adaptation, but high levels can damage muscles. In aging muscles, ROS levels increase due to reduced antioxidant defenses and may cause cumulative oxidative damage, contributing to sarcopenia through impaired muscle mass, strength, and function.
Protein glycation occurs spontaneously when sugars attach to proteins or lipids, forming advanced glycation end products (AGEs) that accumulate over time and contribute to aging and disease pathology. AGEs form through reactions like the Maillard reaction and can crosslink or modify proteins, DNA and lipids. They are implicated in diseases associated with aging like diabetes, where hyperglycemia overwhelms the body's ability to break down AGEs. AGEs bind receptors on macrophages, stimulating inflammation and complications in diabetes such as nephropathy, neuropathy and retinopathy. The accumulation of AGEs over a lifetime may accelerate aging through molecular damage and chronic inflammation.
This document summarizes the causes and consequences of oxidative stress in spermatozoa. It discusses how spermatozoa are vulnerable to oxidative attack due to their lack of antioxidant protection and high levels of polyunsaturated fatty acids. Oxidative stress can damage sperm membranes through lipid peroxidation, suppressing motility. It also causes DNA damage that is associated with miscarriage and developmental abnormalities. While reactive oxygen species are important for sperm capacitation, excessive levels can overwhelm antioxidant defenses and induce apoptosis. The main source of oxidative stress in spermatozoa is mitochondrial reactive oxygen species generation.
This document discusses the biology of healthy aging and longevity. It covers several topics:
1) Molecular mechanisms of aging including genome integrity, telomeres, epigenetics, protein stability, and pathways like mTOR, IIS, AMPK, and sirtuins that modify aging.
2) Biological models like yeast, worms, flies and mice that are used to study aging mechanisms.
3) Calorie restriction which increases longevity across species by reversing signs of aging.
4) Maintaining genome, telomere and epigenome integrity is important for healthy aging and preventing diseases.
5) Environmental factors and nutrition influence aging through epigenetic changes.
ATP (adenosine triphosphate) production declines with age due to mitochondrial dysfunction. Mitochondria are the primary producers of cellular energy in the form of ATP through oxidative phosphorylation. As we age, mitochondrial DNA mutations accumulate, impairing ATP production. This summary discusses strategies to increase ATP levels topically and through supplementation to enhance mitochondrial function and combat signs of aging. These include vitamins B1-B6, biotin, B12, folic acid, magnesium, alpha lipoic acid, carnitine, NADH, coenzyme Q10, creatine, and LED or microcurrent therapy. Maintaining optimal mitochondrial and ATP levels may help slow the visible signs of skin aging.
Mechanisms involved in Reactive oxygen species induced sperm damages and thei...rahulvet27
1) Reactive oxygen species (ROS) are produced in greater quantities during sperm cryopreservation and can cause oxidative stress-related damage through lipid peroxidation, DNA damage, apoptosis, motility impairment, and protein damage.
2) Common sources of ROS include immature sperm cells, leukocytes, semen processing techniques, and dissolved oxygen.
3) Amelioration of ROS-induced damage can be achieved through the use of enzymatic antioxidants like catalase and glutathione peroxidase, non-enzymatic antioxidants like vitamin C and E, biological ROS inhibitors from oviductal fluid and seminal plasma, and reducing dissolved oxygen levels in cryopreservation extenders.
Oxidative Stress in Health & Disease: The therapeutic potential of Nrf2 acti...LifeVantage
1. Oxidative stress is an imbalance between oxidants produced by cells and the antioxidant defenses needed to maintain balance. It has been linked to aging and many diseases. While initially seen as primarily involving superoxide, oxidative stress is now viewed more broadly.
2. The transcription factor Nrf2 is the "master regulator" of the antioxidant response, modulating hundreds of genes involved in antioxidant defenses as well as unrelated processes like inflammation. Maintaining balance through Nrf2 activation is a promising alternative to administering individual antioxidants.
3. Certain phytochemicals have been found to strongly activate Nrf2 in a synergistic manner. One such composition, Protandim, was shown to significantly increase
This presentation discusses a newer approach to treating vascular dysfunction diseases using apomimetic peptides that mimic apolipoproteins. It provides background on lipoproteins, HDL, and apolipoproteins before discussing how short synthetic peptides called apomimetic peptides can mimic apolipoprotein functions. Several apomimetic peptides are presented that show promise in reducing atherosclerosis and improving cholesterol efflux in animal models. The presentation concludes that apomimetic peptides may prove useful as diagnostic and therapeutic agents for vascular diseases.
This document discusses the mechanisms of cellular injury and death. It explains that cells can either adapt to injury, experience reversible injury, or die. Common causes of injury include hypoxia, chemicals, physical trauma, nutritional imbalances, genetics, infections, and immunological factors. Four intracellular systems are particularly vulnerable: aerobic respiration, cell membrane integrity, protein synthesis, and the genetic apparatus. Five biochemical systems mediate injury or death: ATP depletion, oxidative stress from reactive oxygen species, loss of calcium homeostasis, defects in membrane permeability, and irreversible mitochondrial damage. Reversible and irreversible injury processes are outlined for ischemia-reperfusion and from free radicals generated by radiation, enzymes, normal respiration, and transition metals.
Mitochondria are organelles found in cells that are involved in biochemical processes like respiration and energy production. Mitochondrial dysfunction increases during aging and age-related disorders. The crosstalk between mitochondrial biogenesis, which generates new mitochondria, and mitophagy, which eliminates damaged mitochondria, is important for maintaining mitochondrial health and cellular homeostasis in response to physiological and environmental cues. Exercise can stimulate mitochondrial biogenesis and mitophagy through activation of AMPK signaling pathways, and may help treat various diseases by modulating mitochondrial dynamics proteins.
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
This document discusses protein breakdown and the ubiquitin-proteasome pathway. It notes that all proteins continually turnover and are broken down and replaced. The ubiquitin-proteasome pathway is the main system for degrading intracellular proteins in cells. In this pathway, target proteins are tagged with ubiquitin molecules and then degraded by the 26S proteasome complex. This pathway is responsible for the normal turnover of long-lived proteins as well as the accelerated breakdown of proteins in disease states. It plays an important role in various cellular processes like quality control, adaptation to changes, and immune function.
Role of Oxidative stress in disease modificationSoobiya Majeed
This presentation discusses the role of oxidative stress in disease modification. It defines oxidative stress as an imbalance between reactive oxygen species and a biological system's ability to detoxify them or repair damage. It discusses how free radicals accumulate and damage cells, DNA, lipids, sugars, and proteins. This can lead to dysfunction, damage, enzyme reactivation, and protein re-modification, resulting in aging and diseases. It provides Parkinson's disease, cancer, and cardiac failure as examples of diseases related to oxidative stress and discusses antioxidants as a way to prevent, intercept, or repair damage from free radicals. The conclusion emphasizes that oxidative stress underlies many diseases by generating reactive metabolites that overwhelm antioxidant defenses.
This document discusses genetic factors involved in the aging process. It begins by defining aging as the accumulation of damage to molecules, cells, and tissues over time, which decreases the body's ability to maintain homeostasis and increases risk of disease. Aging is influenced by both genetic and environmental factors. Several genetic factors are then reviewed in detail, including genes involved in DNA repair and telomere maintenance, as well as genes in pathways like insulin/IGF signaling that affect lifespan when mutated in model organisms. Specific genetic disorders called progerias that cause premature aging in humans are also described. The document concludes by mentioning linkage and association studies examining genetic variants related to longevity in centenarians.
This document discusses the molecular basis of aging and longevity. It covers several topics: genes and aging pathways like DNA repair and insulin signaling; environmental and epigenetic factors such as oxidative damage, diet, and calorie restriction; and promoting longevity. Key points include conserved genetic pathways regulating aging across species, the role of genes encoding DNA repair enzymes and insulin signaling proteins, and how calorie restriction and reducing insulin/IGF-1 signaling can increase longevity in various organisms.
Genes that affect replicative life span in yeast also influence aging in other organisms. A comprehensive analysis of replicative life span was performed on 4,698 single-gene deletion yeast strains, demonstrating conservation of longevity pathways between yeast and nematodes. Specifically, deletion of the LOS1 gene, which encodes a tRNA exporter, extended yeast lifespan by 60% due to LOS1 being excluded from the nucleus under dietary restriction and mTOR inhibition.
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 research on the role of reactive oxygen species (ROS) in human fertility. It finds that ROS are produced naturally in the body but can also be generated by leukocytes, abnormal sperm, and other sources. While low levels play a role in fertilization, high levels of ROS can damage lipids, proteins, DNA and impair sperm motility and the ability of sperm to fuse with eggs. This leads to decreased sperm counts and quality, as well as DNA damage that may cause embryo death, miscarriage or birth defects. Antioxidants normally neutralize ROS, but when levels are too high it causes oxidative stress that contributes to infertility in both males and females.
Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including anaerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease and how autophagy process is activated will impact approaches to cancer management and prevention.
Lastly the question is Why some people have no cancer ? the answer is it is the life style and the diet rich in Healthy fat, Antioxidants, Vitamin C, Salvestrols and many natural remedies.
Antioxidant potentials of tannic acid on lipid peroxidation induced by severa...Premier Publishers
Various prospective studies have indicated the antioxidant potency of tannic acid in several models. However, there is no clear-cut evidence revealing that the reported antioxidant properties of tannic acid remains potent regardless of the lipid sources and pro-oxidants employed for the oxidative assault. Hence, this study sought to investigate the antioxidant properties of tannic acid against cerebral and hepatic lipid peroxidation induced by several pro-oxidants (Iron (II) sulfate, Sodium nitroprusside, cyclophosphamide and acetaminophen) in vitro. Rats were decapitated under mild ether anesthesia and the tissues were rapidly dissected, placed on ice, weighed and immediately homogenized in cold 50 mM Tris-HCl, pH 7.4 (1/10, w/v). The homogenates were centrifuged for 10 min at 4000 g to yield a pellet that was discarded and a low-speed supernatant (S1). Our results indicated that Fe (II) showed the highest pro-oxidative effects in both tissues lipids. Furthermore, tannic acid demonstrated potent inhibitory effects against lipid peroxidation in both tissues lipids regardless of the pro-oxidant employed. To this end, there is a dire need to exploit the protective benefits of tannic acid as a potential exogenous antioxidant against lipid peroxidation with a view to providing solution to the global oxidative stress menace.
The Role of Nrf2 in the Attenuation of Cardiovascular DiseaseLifeVantage
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
This document is an undergraduate thesis that examines the effects of ethanol-induced oxidative stress on antioxidant enzyme expression levels in three tissues of the zebrafish Danio rerio. The student measured expression levels of the antioxidant enzymes CuZnSOD, MnSOD, and CAT in the brain, liver, and gonads of zebrafish after acute ethanol exposure. The results showed that different tissues exhibited distinct expression patterns, with the highest levels found in gonad tissue and no significant changes in brain tissue. The study provides insight into how antioxidant enzymes may protect against oxidative DNA damage caused by excess reactive oxygen species produced during ethanol metabolism.
The document describes a thesis submitted by TeQuion Brookins on March 26, 2012 about the influence of the protein cross-linker diethyl acetylenedicarboxylate (DAD) on degradation of proteins by the 20S core particle of the 26S proteasome. The thesis explores how DAD-mediated electrophilic modification can cross-link proteins like the peroxiredoxin Tsa1, inactivate them, and potentially inhibit their degradation by the proteasome. Experiments were conducted to detect increased accumulation of ubiquitin, known proteasomal substrates, and damaged proteins like Tsa1 when yeast cells were treated with DAD, which would indicate disturbance of the cellular protein degradation mechanism. P
Oakes et al 2017 TBK1 - a new player in ALS linking autophagy and neuroinflam...Maria Davies
TBK1 is a kinase involved in innate immunity and autophagy pathways. Recent human genetics studies have linked mutations in TBK1 to amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons. TBK1 plays a major role in autophagy by phosphorylating autophagy adaptor proteins, and several other ALS-linked genes are also involved in autophagy. Mutations in TBK1 may impair autophagy and contribute to the accumulation of protein aggregates, a hallmark of ALS pathology. The review discusses the role of TBK1 in autophagy and how disrupted autophagy may underlie the pathogenesis of ALS
Toward the Synthesis of a Stable Water-Soluble Manganese(II) PorphyrinNicholas Gober
Detailed report of the research project I undertook while employed as a Research Chemist at Georgia College & State University for three consecutive summers (2008-2010).
ABSTRACT:
Recent research conducted on manganese porphyrins (MnPs) has shown that these complexes have a wide array of prospective medicinal applications that extend far beyond original assertions. To date, however, only water-insoluble (i.e., non-employable in vivo) MnP derivatives have been synthesized. The central challenge with synthesizing a stable water-soluble MnP derivative like MnTMPyPCl85+, our target molecule, is halogenation of the porphyrin’s eight β-carbons—full β-chlorination must occur before insertion of the Mn2+ ion. Here, we describe attempts at β-chlorination of two pre-cursor metalloporphyrins, Cu(II) and Ni(II) complexes, using three separate chlorinating agents—NCS, SOCl2, and Cl2 (g)—by widely varying reaction conditions, with close monitoring of structural changes via ultraviolet-visible (UV-Vis) absorption spectroscopy. The largest Soret-band (λmax) shifts were exhibited by the Ni(II) complex, the most drastic of which occurred after refluxing NiTMPyP4+ (as PF6- salt) with SOCl2 (Δλmax = 26.5 nm). This result suggests that complete halogenation (i.e., λmax ≈ 456 nm) is likely feasible after few minor reaction-system modifications. The Cu(II) complex, nor either metallo-complex when Cl2 and NCS were employed as chlorinating agents, showed no significant Δλmax. Elemental analysis will be performed on the Ni(II) compound to determine its actual degree of chlorination; accordingly, to elucidate the optimum conditions under which full β-halogenation may be successfully achieved, future work will place concerted efforts on experimental designs in which the Ni(II) complex is allowed to react with SOCl2 under several varying conditions.
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
This document summarizes the key points from a meeting discussing the role of reactive oxygen species (ROS) in physiological processes. The meeting highlighted that ROS produced during moderate exercise are beneficial, not detrimental, as they promote muscle adaptation, endurance performance, and antioxidant defenses. However, excessive ROS from exhaustive exercise can damage cells. The discussion reconsidered definitions of oxidative stress and antioxidants, noting that ROS also have important signaling functions and that mild oxidative stress can trigger protective responses. More research is still needed to fully understand ROS regulation and when levels become harmful versus beneficial.
This presentation discusses a newer approach to treating vascular dysfunction diseases using apomimetic peptides that mimic apolipoproteins. It provides background on lipoproteins, HDL, and apolipoproteins before discussing how short synthetic peptides called apomimetic peptides can mimic apolipoprotein functions. Several apomimetic peptides are presented that show promise in reducing atherosclerosis and improving cholesterol efflux in animal models. The presentation concludes that apomimetic peptides may prove useful as diagnostic and therapeutic agents for vascular diseases.
This document discusses the mechanisms of cellular injury and death. It explains that cells can either adapt to injury, experience reversible injury, or die. Common causes of injury include hypoxia, chemicals, physical trauma, nutritional imbalances, genetics, infections, and immunological factors. Four intracellular systems are particularly vulnerable: aerobic respiration, cell membrane integrity, protein synthesis, and the genetic apparatus. Five biochemical systems mediate injury or death: ATP depletion, oxidative stress from reactive oxygen species, loss of calcium homeostasis, defects in membrane permeability, and irreversible mitochondrial damage. Reversible and irreversible injury processes are outlined for ischemia-reperfusion and from free radicals generated by radiation, enzymes, normal respiration, and transition metals.
Mitochondria are organelles found in cells that are involved in biochemical processes like respiration and energy production. Mitochondrial dysfunction increases during aging and age-related disorders. The crosstalk between mitochondrial biogenesis, which generates new mitochondria, and mitophagy, which eliminates damaged mitochondria, is important for maintaining mitochondrial health and cellular homeostasis in response to physiological and environmental cues. Exercise can stimulate mitochondrial biogenesis and mitophagy through activation of AMPK signaling pathways, and may help treat various diseases by modulating mitochondrial dynamics proteins.
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
This document discusses protein breakdown and the ubiquitin-proteasome pathway. It notes that all proteins continually turnover and are broken down and replaced. The ubiquitin-proteasome pathway is the main system for degrading intracellular proteins in cells. In this pathway, target proteins are tagged with ubiquitin molecules and then degraded by the 26S proteasome complex. This pathway is responsible for the normal turnover of long-lived proteins as well as the accelerated breakdown of proteins in disease states. It plays an important role in various cellular processes like quality control, adaptation to changes, and immune function.
Role of Oxidative stress in disease modificationSoobiya Majeed
This presentation discusses the role of oxidative stress in disease modification. It defines oxidative stress as an imbalance between reactive oxygen species and a biological system's ability to detoxify them or repair damage. It discusses how free radicals accumulate and damage cells, DNA, lipids, sugars, and proteins. This can lead to dysfunction, damage, enzyme reactivation, and protein re-modification, resulting in aging and diseases. It provides Parkinson's disease, cancer, and cardiac failure as examples of diseases related to oxidative stress and discusses antioxidants as a way to prevent, intercept, or repair damage from free radicals. The conclusion emphasizes that oxidative stress underlies many diseases by generating reactive metabolites that overwhelm antioxidant defenses.
This document discusses genetic factors involved in the aging process. It begins by defining aging as the accumulation of damage to molecules, cells, and tissues over time, which decreases the body's ability to maintain homeostasis and increases risk of disease. Aging is influenced by both genetic and environmental factors. Several genetic factors are then reviewed in detail, including genes involved in DNA repair and telomere maintenance, as well as genes in pathways like insulin/IGF signaling that affect lifespan when mutated in model organisms. Specific genetic disorders called progerias that cause premature aging in humans are also described. The document concludes by mentioning linkage and association studies examining genetic variants related to longevity in centenarians.
This document discusses the molecular basis of aging and longevity. It covers several topics: genes and aging pathways like DNA repair and insulin signaling; environmental and epigenetic factors such as oxidative damage, diet, and calorie restriction; and promoting longevity. Key points include conserved genetic pathways regulating aging across species, the role of genes encoding DNA repair enzymes and insulin signaling proteins, and how calorie restriction and reducing insulin/IGF-1 signaling can increase longevity in various organisms.
Genes that affect replicative life span in yeast also influence aging in other organisms. A comprehensive analysis of replicative life span was performed on 4,698 single-gene deletion yeast strains, demonstrating conservation of longevity pathways between yeast and nematodes. Specifically, deletion of the LOS1 gene, which encodes a tRNA exporter, extended yeast lifespan by 60% due to LOS1 being excluded from the nucleus under dietary restriction and mTOR inhibition.
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 research on the role of reactive oxygen species (ROS) in human fertility. It finds that ROS are produced naturally in the body but can also be generated by leukocytes, abnormal sperm, and other sources. While low levels play a role in fertilization, high levels of ROS can damage lipids, proteins, DNA and impair sperm motility and the ability of sperm to fuse with eggs. This leads to decreased sperm counts and quality, as well as DNA damage that may cause embryo death, miscarriage or birth defects. Antioxidants normally neutralize ROS, but when levels are too high it causes oxidative stress that contributes to infertility in both males and females.
Emerging evidence indicates that impaired cellular energy metabolism is the defining characteristic of nearly all cancers regardless of cellular or tissue origin. In contrast to normal cells, which derive most of their usable energy from oxidative phosphorylation, most cancer cells become heavily dependent on substrate level phosphorylation to meet energy demands. Evidence is reviewed supporting a general hypothesis that genomic instability and essentially all hallmarks of cancer, including anaerobic glycolysis (Warburg effect), can be linked to impaired mitochondrial function and energy metabolism. A view of cancer as primarily a metabolic disease and how autophagy process is activated will impact approaches to cancer management and prevention.
Lastly the question is Why some people have no cancer ? the answer is it is the life style and the diet rich in Healthy fat, Antioxidants, Vitamin C, Salvestrols and many natural remedies.
Antioxidant potentials of tannic acid on lipid peroxidation induced by severa...Premier Publishers
Various prospective studies have indicated the antioxidant potency of tannic acid in several models. However, there is no clear-cut evidence revealing that the reported antioxidant properties of tannic acid remains potent regardless of the lipid sources and pro-oxidants employed for the oxidative assault. Hence, this study sought to investigate the antioxidant properties of tannic acid against cerebral and hepatic lipid peroxidation induced by several pro-oxidants (Iron (II) sulfate, Sodium nitroprusside, cyclophosphamide and acetaminophen) in vitro. Rats were decapitated under mild ether anesthesia and the tissues were rapidly dissected, placed on ice, weighed and immediately homogenized in cold 50 mM Tris-HCl, pH 7.4 (1/10, w/v). The homogenates were centrifuged for 10 min at 4000 g to yield a pellet that was discarded and a low-speed supernatant (S1). Our results indicated that Fe (II) showed the highest pro-oxidative effects in both tissues lipids. Furthermore, tannic acid demonstrated potent inhibitory effects against lipid peroxidation in both tissues lipids regardless of the pro-oxidant employed. To this end, there is a dire need to exploit the protective benefits of tannic acid as a potential exogenous antioxidant against lipid peroxidation with a view to providing solution to the global oxidative stress menace.
The Role of Nrf2 in the Attenuation of Cardiovascular DiseaseLifeVantage
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
This document is an undergraduate thesis that examines the effects of ethanol-induced oxidative stress on antioxidant enzyme expression levels in three tissues of the zebrafish Danio rerio. The student measured expression levels of the antioxidant enzymes CuZnSOD, MnSOD, and CAT in the brain, liver, and gonads of zebrafish after acute ethanol exposure. The results showed that different tissues exhibited distinct expression patterns, with the highest levels found in gonad tissue and no significant changes in brain tissue. The study provides insight into how antioxidant enzymes may protect against oxidative DNA damage caused by excess reactive oxygen species produced during ethanol metabolism.
The document describes a thesis submitted by TeQuion Brookins on March 26, 2012 about the influence of the protein cross-linker diethyl acetylenedicarboxylate (DAD) on degradation of proteins by the 20S core particle of the 26S proteasome. The thesis explores how DAD-mediated electrophilic modification can cross-link proteins like the peroxiredoxin Tsa1, inactivate them, and potentially inhibit their degradation by the proteasome. Experiments were conducted to detect increased accumulation of ubiquitin, known proteasomal substrates, and damaged proteins like Tsa1 when yeast cells were treated with DAD, which would indicate disturbance of the cellular protein degradation mechanism. P
Oakes et al 2017 TBK1 - a new player in ALS linking autophagy and neuroinflam...Maria Davies
TBK1 is a kinase involved in innate immunity and autophagy pathways. Recent human genetics studies have linked mutations in TBK1 to amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons. TBK1 plays a major role in autophagy by phosphorylating autophagy adaptor proteins, and several other ALS-linked genes are also involved in autophagy. Mutations in TBK1 may impair autophagy and contribute to the accumulation of protein aggregates, a hallmark of ALS pathology. The review discusses the role of TBK1 in autophagy and how disrupted autophagy may underlie the pathogenesis of ALS
Toward the Synthesis of a Stable Water-Soluble Manganese(II) PorphyrinNicholas Gober
Detailed report of the research project I undertook while employed as a Research Chemist at Georgia College & State University for three consecutive summers (2008-2010).
ABSTRACT:
Recent research conducted on manganese porphyrins (MnPs) has shown that these complexes have a wide array of prospective medicinal applications that extend far beyond original assertions. To date, however, only water-insoluble (i.e., non-employable in vivo) MnP derivatives have been synthesized. The central challenge with synthesizing a stable water-soluble MnP derivative like MnTMPyPCl85+, our target molecule, is halogenation of the porphyrin’s eight β-carbons—full β-chlorination must occur before insertion of the Mn2+ ion. Here, we describe attempts at β-chlorination of two pre-cursor metalloporphyrins, Cu(II) and Ni(II) complexes, using three separate chlorinating agents—NCS, SOCl2, and Cl2 (g)—by widely varying reaction conditions, with close monitoring of structural changes via ultraviolet-visible (UV-Vis) absorption spectroscopy. The largest Soret-band (λmax) shifts were exhibited by the Ni(II) complex, the most drastic of which occurred after refluxing NiTMPyP4+ (as PF6- salt) with SOCl2 (Δλmax = 26.5 nm). This result suggests that complete halogenation (i.e., λmax ≈ 456 nm) is likely feasible after few minor reaction-system modifications. The Cu(II) complex, nor either metallo-complex when Cl2 and NCS were employed as chlorinating agents, showed no significant Δλmax. Elemental analysis will be performed on the Ni(II) compound to determine its actual degree of chlorination; accordingly, to elucidate the optimum conditions under which full β-halogenation may be successfully achieved, future work will place concerted efforts on experimental designs in which the Ni(II) complex is allowed to react with SOCl2 under several varying conditions.
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
This document summarizes the key points from a meeting discussing the role of reactive oxygen species (ROS) in physiological processes. The meeting highlighted that ROS produced during moderate exercise are beneficial, not detrimental, as they promote muscle adaptation, endurance performance, and antioxidant defenses. However, excessive ROS from exhaustive exercise can damage cells. The discussion reconsidered definitions of oxidative stress and antioxidants, noting that ROS also have important signaling functions and that mild oxidative stress can trigger protective responses. More research is still needed to fully understand ROS regulation and when levels become harmful versus beneficial.
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.
1. The study examines how progesterone receptor activity is maintained in decidualizing human endometrial stromal cells exposed to oxidative stress.
2. It finds that modest oxidative stress activates the JNK pathway in stromal cells, leading to enhanced sumoylation and inhibition of the progesterone receptor.
3. However, JNK pathway signaling and its effects on sumoylation are disabled during decidualization, maintaining progesterone receptor activity even under oxidative stress. This is mediated by increased expression of the JNK pathway regulator MKP1 upon decidualization.
The document discusses how the SUMO E3-ligase PIAS1 couples reactive oxygen species (ROS)-dependent JNK activation to oxidative cell death in human endometrial stromal cells (HESCs). It finds that ROS-dependent JNK activation converges on the SUMO pathway via PIAS1. Knockdown of PIAS1 prevents ROS-dependent hypersumoylation but enhances JNK signaling in HESCs. PIAS1 determines the level of JNK activity, couples ROS signaling to the SUMO pathway, and promotes oxidative cell death. PIAS1 knockdown attenuates ROS-dependent caspase activation and apoptosis.
1) The study evaluated changes in the expression of hypoxia-associated genes in mouse lung tissue at various time points after radiation exposure. A microarray analysis found that 44 genes related to metabolism, growth, apoptosis, inflammation, oxidative stress, and fibrosis were upregulated after radiation.
2) Treatment with the antioxidant AEOL10150 after radiation exposure attenuated the elevated expression of 31 of these hypoxia-associated genes. This suggests that expression of many hypoxia genes is regulated by early oxidative stress following radiation.
3) The hypoxia-associated genes identified provide insight into how hypoxic signaling may contribute to radiation-induced lung injury. The study also provides clues about how AEOL10150's antioxidant properties confer radi
This document discusses inflammation and inflammatory diseases. It begins by describing the classic signs of inflammation - swelling, redness, heat and pain. A normal inflammatory response is important for fighting infection and tissue repair. However, inflammation can also cause harm if the response is excessive or prolonged. Many chronic diseases have an inflammatory component, such as atherosclerosis. The inflammatory response involves the migration of leukocytes to the injured tissue where they release inflammatory mediators like cytokines and eicosanoids. Nonsteroidal anti-inflammatory drugs (NSAIDs) work by inhibiting the cyclooxygenase enzymes and thereby reducing the production of prostaglandins, which mediate inflammation. Selective COX-2 inhibitors avoid the side effects of traditional NSA
A current genetic and epigenetic view on humanmariannajd
This document provides an overview of genetic and epigenetic factors that influence the aging process in humans and animal models. It discusses several key theories of aging, including the free radical theory of oxidative damage accumulation over time. Genetic studies in model organisms like yeast, worms, flies and mice have identified pathways like insulin/IGF-1 signaling and calorie restriction that affect longevity when manipulated. These pathways regulate processes like metabolism, stress resistance and reproduction that influence aging. The document concludes that while aging is genetically regulated, no single gene or theory fully explains the complex mechanisms involved, which are influenced by an interaction of genetic, environmental and lifestyle factors.
Neuroendocrine response In trauma and sepsis.pptxBiniam24
The document discusses mitochondrial function and dysfunction. It states that mitochondria generate ATP through oxidative phosphorylation, which can become less efficient and produce reactive oxygen species under stress. This can damage mitochondria and cells. The document also describes how trauma and infection lead to metabolic changes, especially increased breakdown of proteins in muscles, to provide substrates like glutamine to other organs. Hormones and cytokines interact to regulate these metabolic responses.
Nrf2: A Guardian of Healthspan and Gatekeeper of Species LongevityLifeVantage
This document summarizes a symposium discussing the role of the transcription factor Nrf2 in aging and longevity. Nrf2 regulates over 200 genes involved in cytoprotection, metabolism of toxins, oxidative stress response, and protein stability/degradation. Constitutively high expression and activation of Nrf2 and its downstream targets are observed in long-lived species and models of extended lifespan, suggesting Nrf2 plays a critical role in determining species longevity and regulating the aging process by protecting against age-related diseases and stressors. The document hypothesizes that Nrf2 is a "master regulator" of aging.
The paper proposes 9 hallmarks of aging based on accumulated cellular damage over time: 1) genomic instability, 2) telomere attrition, 3) epigenetic alterations, 4) loss of proteostasis, 5) deregulated nutrient sensing, 6) mitochondrial dysfunction, 7) cellular senescence, 8) stem cell exhaustion, and 9) altered intercellular communication. Some hallmarks like cellular senescence are beneficial at low levels but harmful in excess. The hallmarks represent primary damage, compensatory responses turned pathological over time, and integration of various damage types systemically.
Oxidative Stress, Inflammation & Cancer - How are they linked? LifeVantage
Oxidative stress can activate transcription factors like NF-κB, AP-1, p53, HIF-1α, PPAR-γ, β-catenin/Wnt, and Nrf2, leading to expression of over 500 genes involved in growth, inflammation, and cell cycle regulation. Chronic inflammation induced by oxidative stress is closely linked to cancer development by causing DNA damage and mutations, increased cell proliferation, and inhibiting apoptosis. The review discusses how oxidative stress activates inflammatory pathways contributing to cancer initiation, progression, survival, proliferation, resistance, invasion, angiogenesis and stem cell maintenance.
This document discusses phenolic Michael reaction acceptors that can act as both direct and indirect antioxidants. Specifically:
1) Phenolic Michael acceptors like chalcones and bis(benzylidene)acetone analogues can directly scavenge two types of radicals - the nitrogen-centered ABTS+ radical cation and the oxygen-centered galvinoxyl radical.
2) These same phenolic Michael acceptors can also indirectly increase antioxidant defenses by inducing phase 2 cytoprotective enzymes like glutathione, glutathione reductase, and thioredoxin reductase in human keratinocyte cells.
3) Therefore, phenolic Michael acceptors that are both direct
Artemisinin relieves osteoarthritis by activating mitochondrial autophagy through reducing TNFSF11 expression and inhibiting PI3K/AKT/mTOR signaling in cartilage. The study found that artemisinin treatment downregulated cartilage degradation proteins and inflammatory factors in IL-1β-stimulated chondrocytes. Gene sequencing revealed that artemisinin treatment significantly downregulated TNFSF11 expression, which encodes RANKL, a factor involved in osteoclast formation. The study also showed that artemisinin activated autophagy and relieved cartilage damage by inhibiting the PI3K/AKT/mTOR signaling pathway in IL-1β-induced chondrocytes.
L'idrossitirosolo è in grado di proteggere e aumentare l'attività dei mitocon...CreAgri Europe
L'idrossitirosolo, un polifenolo estratto dalle olive, attraverso una protezione dei mitocondri, le centrali energetiche della cellula, è in grado di aumentare la resistenza muscolare negli animali da esperimento
This presentation introduces a brief and rapid review for an important research area (oxidative stress) and its relation to liver fibrosis.
Liver fibrosis is very important for us as we are facing a very dangerous and continuously growing problem in Egypt, HEPATIC PATIENTS COMPLICATIONS.
This document summarizes the emerging roles of autophagy in cellular metabolism and metabolic disorders. It discusses how autophagy breaks down macromolecules and organelles to generate nutrients and energy during periods of starvation or stress. Defects in autophagy are associated with dysfunction in metabolic tissues like pancreas, liver, fat and muscle, and linked to diseases like obesity and diabetes. The document reviews different types of selective autophagy (like lipophagy, glycophagy and mitophagy) and their roles in metabolizing lipids, glycogen and mitochondria during nutrient deprivation.
Role of FOXO1 in Cardiomyopathy: ReviewSardar Alam
FOXO1 plays an important role in the development of diabetic cardiomyopathy (DCM). FOXO1 activation alters cardiac metabolism, promotes lipid accumulation, causes endothelial dysfunction, increases inflammation and apoptosis, and disrupts mitochondrial function - all of which contribute to the progression of DCM. While FOXO1 has been identified as a central player in the metabolic abnormalities associated with DCM, questions remain about the causes of persistent FOXO1 activation in the diabetic heart and the potential role of FOXO1 gene polymorphisms in susceptibility to DCM.
This document discusses genetic factors involved in the aging process. It begins by defining aging as the accumulation of damage to molecules, cells, and tissues over time, which decreases the body's ability to maintain homeostasis and increases risk of disease. Aging is influenced by both genetic and environmental factors. Several genetic factors are then reviewed in detail, including genes involved in DNA repair and telomere maintenance, as well as genes in pathways like insulin/IGF signaling that affect lifespan when mutated in model organisms. Specific genetic conditions associated with premature aging, called progeroid syndromes, are also discussed as they provide insights into aging mechanisms. In summary, this document examines the role of genetics in regulating the aging process at the molecular, cellular, and
Similar to International Journal of Cardiovascular Diseases & Diagnosis (20)
A 5-year old boy, with an established diagnosis of a topic
dermatitis, previously treated by topical corticosteroids and emollient cream with a good improvement, developed widespread papules on his legs, hands and forearm that appeared 5 months ago.
Methods: Retrospectively, the file records of the patients who underwent sleeve gastrectomy were examined. Demographic features, Body Mass Index (BMI), the mouth opening, Mallampati score, thyromental distance, sternomental distance, neck circumference measurements and videolaryngoscopic examination results were recorded Results: In a total of 140 consecutive patients (58 male, 82 female) were included in the study. The mean age of the study participants was 35.40 ± 9.78 and the mean BMI of the patients was 44.33 ± 7.52 kg/m2
. The mean mouth opening of the patients was 4.82 ± 0.54 cm
and the mean neck circumference was 43.52 ± 4.66 cm. The mean thyromental distance was 8.02 ± 1.00 cm and the mean sternomental distance was16.58 ± 1.53 cm. Difficult intubation was determined in 8 (5.7%) patients. In logistic regression analysis, age (p : 0.446), gender (p : 0.371), BMI (p : 0.947), snoring (p : 0.567), sleep apnea (p : 0.218), mouth opening (p : 0.687), thyromental distance (p :0.557), sternomental (p : 0.596) and neck circumference (p : 0.838) were not the independent predictors of difficult intubation. However, Mallampati score (p : 0.001) and preoperative direct laryngoscopy findings (p : 0.037) performed in outpatient clinic were the significant
predictors of difficult intubation. Interestingly, all patients with grade 4 laryngoscopy findings had difficult intubation.
Introduction: Laparoscopic surgery has been performed in Mexico since 1989, but no reports about training tendencies exist. We conducted a national survey in 2015, and here we report the results concerning training characteristics during the surgical residence of the respondents. Materials and Methods: A prospective study was conducted through a survey questioning demographic data, laparoscopic training during pre and post surgical residency and other of areas of laparoscopic practice. The sample was calculated and survey piloted before
application. Special interest in this report was placed on type and quality of training received. Data are reported in percentages.
Heterotopic Ossification (HO) is defined as pathological bone formation at locations where bone normally does not exist. The
presence of HO has been found to be a rare complication after stroke in several studies, whereas there are only sporadic references relating HO to Cerebral Palsy (CP) and few for CP and stroke. No effective treatment for HO has yet been found, whereas the cellular and molecular mechanisms have not been completely understood. Therefore, increased awareness among physicians is required, as a challenge for early diagnosis and treatment. A case of a male patient with CP, who developed HO on the paretichip joint following an ischemic stroke is presented.
Objectives: To assess the practice of food hygiene and safety, and its associated factors among street food vendors in urban areas of Shashemane, West Arsi Zone, Oromia Ethiopia, 2019.
Methods: Cross-sectional study design was applied from December 28, 2019 to January 27, 2020. Data was collected from 120 food handlers, which were selected by purposive sampling techniques. Information was gathered from interview and field observation by conducting food safety survey and using questionnaires via face to face interview. The collected data was entered using Epi Data 3.1 and finally, it was analyzed using SPSS VERSION 20.
A Division I football player experienced acute posterior leg pain while playing. An ultrasound examination revealed an unusual injury - a complete rupture of the plantaris tendon mid-substance. This type of isolated plantaris tendon injury has rarely been reported. Ultrasound was useful for diagnosis and guided rehabilitation by monitoring healing over time. The athlete was able to return to full competition within 3 weeks through a progressive rehabilitation program focused on restoring range of motion and strength. This case suggests isolated plantaris tendon injuries may allow for faster return to play than other potential causes of posterior leg pain.
Type 1 Diabetes (T1D), is a severe disease, representing 5-10% of all reported cases of diabetes worldwide. Fulminant Type 1 Diabetes Mellitus (FT1D) is a subtype of type 1 diabetes mellitus that is largely characterized by the abrupt onset of Diabetic Ketoacidosis (DKA) and severe hyperglycemia without insulin defi ciency. Viral infections have been hypothesized to play a major role in the pathogenesis of Fulminant Type 1 Diabetes Mellitus (FT1D) through the complete and rapid destruction of pancreatic beta cells. Coxsackie viral infection has been detected in islets of 50% of the pancreatic tissue recovered from recent-onset Type 1 Diabetes (T1D) patients. In this report we have highlighted a case where the patient developed a Group B Coxsackie virus infection culminating in the development of Fulminant Type 1 Diabetes Mellitus (FT1D).
Methods: Cercariae are released by infected water snails. To determine the occurrence of cercariae-emitting snails in SchleswigHolstein, 155 public bathing places were visited and searched for fresh water snails. Family and genus of the collected snails were determined and the snails were examined for the shedding of cercariae, using a standard method and a newly developed method.
Objective: To generate preliminary information about of enteroviruses and Enterovirus 71 (EV71) in patients with aseptic meningitis in Khartoum State, Sudan.
Method: Cerebrospinal fluid specimens were collected from 89 aseptic meningitis patients from different Khartoum Hospitals
(Mohammed Alamin Hamid Hospital, Soba Teaching Hospital, Omdurman Military Hospital, Alban Gadeed Teaching Hospital and Police Hospital) within February to May 2015. Among these 89 patients, 43 (48%) were males and 46 (52%) were females. The patient’s age ranged between 1 day and 30 years old. The collected specimens were assayed to detect enteroviruses and EV71 RNA using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) technique
Femoral hernias, comprise 2% to 4% of all hernias in the inguinal region, and occur most commonly in women. Th ey present typically with a mass below the level of the inguinal ligament. The sac may contain preperitoneal fat, omentum, small bowel, or other structures and have a high rate of incarceration and strangulation due to the small size of the hernia neck orifice, requiring emergency surgery. We present the case of a 54-year-old female patient with intestinal occlusion due to incarcerated femoral hernia, repaired by laparoscopic approach, that gave the patient the opportunity to attend her daughter’s wedding the same day.
Small Supernumerary Marker Chromosome (sSMC) is a rare genetic condition marked by the presence of an extra chromosome to the 46 human chromosomes. This case report describes a 4 year old child with SSMC on the 46th chromosome. The child presented with delayed speech and language development, seizures and mild developmental delay. Speech and Language evaluation was carried out and management options are discussed.
A catheter is a thin tube made from medical grade materials that serve a broad range of functions, but mainly catheters are medical devices that can be inserted in the body to treat disease or perform surgical procedures. Catheters have been inserted into body cavities, ducts, or vessels to allow for drainage, administration of therapeutic fluids or gases, operational access for surgery. Catheters help perform tasks in various systems such as cardiovascular, urological, gastrointestinal, neurovascular, and ophthalmic systems. A dataset of 12 patients with varying “weights” and “heights” was recorded along with the lengths of their catheter tubes. This data set was found from two revered statistical textbooks on linear regression and the Department of Scientific Computing at Florida State University. This data set was not able to be linked to any particular clinical or experimental research studies, but the data set can be used to help catheter manufacturers and medical professionals better decide on what particular catheter lengths to use for patients knowing only their height & weight. These research insights could be helpful to healthcare professionals that have patients with incomplete or no healthcare records
to decide what catheter length to use. The main investigative inquiry that needed to be answered was how does patient weight & height influence catheter length together and separately? We conducted linear regression and other statistical analysis procedures in R program & Microsoft Excel and discovered that this data exhibited a quality called multi collinearity. With multi collinearity, all predictors (2 or more
independent variables) are not significant in an all encompassing linear aggression, but the predictors might be significant in their own individual linear regressions. Individual linear regression analyses were conducted for both patient height & weight to see how much they both contribute to varying catheter length. Patient weight was found to be more impatful than patient height in relationship to catheter length, even though height and weight are a classical example of multi collinearity predictors.
Bovine mastitis has a negative impact through economic losses in the dairy sector across the globe. A cross sectional study was carried out from September 2015 to July 2016 to determine the prevalence of bovine mastitis, associated risk factors and isolation of major causative bacteria in lactating dairy cows in selected districts of central highland of Ethiopia. A total of 304 lactating cows selected randomly from five districts were screened by California Mastitis Test (CMT) for subclinical mastitis. Based on CMT result and clinical examination, over all prevalence of mastitis at cow level was 70.62% (214/304).
Two hundred fourteen milk samples collected from CMT positive cows were cultured for isolation of major causative bacteria. From 214 milk samples,187 were culture positive and the most prevalent isolates were Staphylococcus aureus 42.25% (79/187) followed by Streptococcus agalactiae 14.43%
(27/187). Other bacterial isolates were included Coagulase Negative Staphylococcus species 12.83% (24/187), Streptococcus dysgalactiae 5.88% (11/187), Escherichia coli 13.38% (25/187) and Entrococcus feacalis 11.23% (21/187) were also isolated. Moreover, age, parity number, visible teat abnormalities,husbandry practice, barn fl oor status and milking hygiene were considered as risk factors for the occurrence of bovine mastitis and they were found significantly associated with the occurrence of mastitis (p < 0.05). The findings of this study warrants the need for strategic approach including dairy extension that focus on enhancing dairy farmers’ awareness and practice of hygienic milking, regular screening for subclinical mastitis, dry cow therapy and culling of chronically infected cows.
A 36-year-old female developed right upper quadrant pain and nausea after taking the herbal supplement kratom for two weeks to manage back pain. Laboratory tests showed elevated liver enzymes. A liver biopsy ruled out other causes and determined she had drug-induced liver injury from kratom use. Her symptoms and liver enzymes gradually returned to normal over six weeks after stopping kratom. The case report discusses kratom's potential for hepatotoxicity and advises clinicians to consider its effects on patient health.
The assessment, diagnosis and treatment of critically ill patients is extremely challenging. Patients often deteriorate whilst being
reviewed and their rapidly changing pathophysiology barrages healthcare professionals with new data. Furthermore, comprehensive assessments must be postponed until the patient has been stabilised. So, important data and interventions are often missed in the heat of the moment. In emergency situations, suboptimal management decisions may cause signifi cant morbidity and mortality. Fortunately, standardisation and careful design of documentation (i.e. proformas and checklists) can enhance patient safety. So, I have developed a series of checklist proformas to guide the assessment of critically ill patients. These proformas also promote the systematic recording and presentation of information to facilitate the retrieval of the precise data required for the management for critically ill patients. The proformas have been modifi ed extensively over the last twenty years based on my personal experience and extensive consultation with colleagues in several world-renowned centres of excellence. The proformas were originally developed for use in the intensive therapy unit
or high dependency unit. However, they have been adapted for use by outreach teams reviewing patients admitted outside of critical care areas. The use of these tools can direct eff orts to provide appropriate organ support and provides a framework for diagnostic reasoning.
This review article discusses microvascular and macrovascular disease in systemic hypertension. It summarizes that:
1) Cardiac imaging plays a crucial role in risk stratifying hypertensive patients and identifying management strategies by properly diagnosing microvascular and coronary artery disease.
2) The nitric oxide synthase (eNOS) G298 gene allele may be a marker for microvascular angina in hypertensive patients, as studies have found it to be more prevalent in hypertensive patients with chest pain and reversible myocardial defects but normal coronary arteries.
3) Both structural changes like capillary rarefaction and functional changes like endothelial dysfunction can cause microvascular dysfunction and angina in hypertensive individuals in the absence of
This study characterized dengue infections in Pakistan by analyzing hematological and serological markers in 154 suspected dengue cases and 146 control patients with other febrile illnesses. NS1 antigen was detected in 55% of dengue cases, IgM antibodies in 30%, and both in 15%. Control groups primarily had malaria (71%) and enteric fever (20%). Hematological markers (platelet count, hematocrit, WBC) measured before and after treatment showed significant differences for platelet count and hematocrit but not WBC count between the groups. Analysis of clinical symptoms and serological/hematological markers helps diagnose dengue, assess prognosis, and inform prevention efforts to reduce morbidity, mortality and spread of the disease.
Researchers from Utrecht recently published yet another paper on the use of Magnetic Resonance Imaging (MRI)demonstrating an additional failed attempt to understand the importance of qualitative versus quantitative imaging, and anatomic versus physiologic imaging. Th e implications of this failure here cannot be overstated.
Introduction: Stroke is an even more dramatic major public health problem in young people. Goal of the study: Contribute to the knowledge of strokes in young people. Methodology: This was a retrospective study carried out over a period of 02 years (January 2017 to December 2018) including the files of patients aged 18 to 49 years hospitalized for any suspected case of stroke in the Neurology department of the University Hospital
Center of the Sino-Central African Friendship (CHUSCA) of Bangui.
Background: This report describes a unique case of a patient that developed psychotic symptoms believed to be secondary
to a tentorial meningioma with associated hydrocephalus. These psychotic symptoms subsequently abated with placement of a
ventriculoperitoneal shunt. Case description: 60-year-old female was admitted to an inpatient psychiatric facility on a psychiatric involuntary commitment petition due to progressive paranoia, homicidal ideation and psychosis. The work up showed a calcified six cm tentorial meningioma with associated hydrocephalus. The patient initially rejected treatment but later became amenable to placement of Ventriculoperitoneal Shunt
(VPS).
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Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
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Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
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Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
2. SRL Cardiovascular Diseases & Diagnosis
SCIRES Literature - Volume 1 Issue 1 - www.scireslit.com Page - 002
Keywords: Aging, Cardiovascular, FoxO transcription
factor, oxidative stress, reactive oxygen species
Aging is a phenomena in which the functions, applicability and
resistance of an organism reduces over time. With the globally aging
at an accelerating pace, delaying the negative aspects of aging is vital
for advancing the human life span and quality of life. The aging of
multiple organs can lead to a lot of disease and no exception for
cardiovascular system. Actually, one of the primary risk factors for
cardiovascular diseases is aging because of altered cardiovascular
metabolism resulting in metabolic disorders and inflammation. In
this review, we discuss about the relationship of oxidative stress with
aging and FoxO proteins, which is essential factor for anti-aging of
cardiovascular systems.
Oxidative stress and Aging
The free radical/oxidative stress theory of aging first proposed
by Harman (1953) suggested that the accumulation of irreversible
molecular damage caused by reactive oxygen species (ROS) is
one of the most significant factors in aging [1]. It is believed that
irreversibly oxidised biomolecules do not function properly and that
the accumulation of oxidised biomolecules accelerates aging. This
theory has been supported by a number of studies in various model
organisms demonstrating a correlation between aging and redox state
or demonstrating an increase in longevity associated with exogenous
treatment with various antioxidants [2-4]. Therefore, understanding
the aging-related alterations induced by changes in redox state will
provide a clue to anti-aging strategies that may be applied in complex
organisms.
Oxidative stress and FoxO
transcription factors
It has been reported that moderate oxidative stresses promote
the nuclear localization of FoxO, resulting in the expression of
target genes [5]. This process results in both lifespan extension and
metabolic changes in aging model organism nematode, C. elegans [6].
The relatively recent development of this more nuanced view presents
a challenge to the biomedical research community in terms of the
possible assessment of the significance of ROS and scavenging of
ROS in biological systems [5]. As many researches have shown [7-8],
FoxO plays a pivotal role in redox signaling, but it is unclear whether
and how redox signaling to and from FoxO contributes to its effects
on longevity. One emerging theme is that the consequences of FoxO
activation depend on the cellular environment and can produce a
switch in the FoxO-mediated gene expression profile. FoxO protein
expression, subcellular localization, and transcriptional activity
are regulated predominantly by two modes of signaling, namely,
antioxidant-induced PDK-1/SGK-1 signaling and oxidative stress-
induced JNK-1/MST-1 signaling. FoxO localization is regulated
differently by the PDK-1/SGK-1 and JNK-1/MST-1 signaling
pathways [5, 9]. In addition to this mechanism, a number of other
post-translational modifications control the activity of FoxO. Most
likely, the physiological response triggered by FoxO is determined
by cellular context as well as the cofactors involved, although the
mode of action through which cell context modifies FoxO is yet to
be fully determined. ROS are known to regulate FoxO transcriptional
activity through posttranscriptional modifications including
phosphorylation, which changes the ability of FoxO to transactivate
target-gene transcription. The effects of ROS on FoxO activity depend
on cellular context, duration, and possibly the intensity of ROS
accumulation.
An effective redox strategy for
anti-aging by regulate cellular
redox state
FoxO activation can induce cell cycle arrest through the direct
induction of multiple changes in factors associated with the cell
cycle transition [10]. The cell cycle arrest induced by FoxO can
influence the eventual outcome in terms of cell fate and may also
promote DNA damage repair and stress resistance. In our previous
results [5], antioxidants appear to act as inducers of DNA repair. The
transcription levels of the cell cycle arrest- and DNA repair-related
genes were increased, but the transcription levels were decreased
in antioxidant-treated cells. Under low/moderate oxidative stress
conditions, GADD45 has been shown to be a downstream target of
FoxO that mediates DNA repair mechanisms and regulates growth
arrest at the G2-M checkpoint. Although oxidant treatment did not
affect these cell cycle arrest and DNA repair genes at our experimental
concentrations, higher concentrations of oxidants increased the
expression of these genes significantly. However, the oxidant
concentrations required to increase these genes are much higher than
the optimal concentration for FoxO nuclear translocation. FoxO
proteins also play a significant role in regulating whole-body energy
metabolism [11]. FoxO activation results in the repression of a large
number of nuclear-encoded genes with mitochondrial functions, a
process mediated by the FoxO-dependent inhibition of c-Myc. The
expression of the metabolism-related genes decreased under the
antioxidantcondition.Inaddition,theexpressionofthemitochondrial
gene decreased under antioxidant conditions. Antioxidant-mediated
FoxO activation may regulate mitochondrial activity through the
inhibition of c-Myc function. Moreover, the expression levels of
these genes were increased at oxidant concentrations higher than
our experimental concentration but decreased under severe oxidative
stress.
Our previous data suggest that antioxidants work as protectors,
maintaining cell integrity by DNA repair [5]. Antioxidants may also
exert calorie restriction-like effects by inhibiting the insulin pathway,
one of the major signaling pathways in calorie restriction-induced
longevity, possibly through c-Myc inhibition. Therefore, antioxidants
appear to act primarily by helping active cells maintain cell integrity
and attenuate any unnecessary hyperactivity. In contrast, oxidant
treatment can activate detoxification enzymes that are typically
reduced in aged cells, which could promote aged cell recovery and
revitalisation by inducing detoxification and energy hormesis. These
different mechanisms of action suggest that there may be a way to
maximise the positive effects of antioxidants and oxidants to achieve
lifespanextension.However,inhigheranimals,suchasmiceorhumans,
there may be much more variation in the optimal concentration of
FoxO nuclear translocation due to individual genetic backgrounds,
the physiological conditions of specific organs and tissues, and
specific cell types. The key might be in the fine tuning of FoxO activity
in response to certain ROS levels and cellular environments, leading
to the most appropriate cell fate decision (detoxify, arrest and repair
or initiate apoptosis or senescence) for whole-organism longevity like
as propose for proteostasis or mitohormesis. A personalised approach
may yield good results in humans if applied after thorough genetic,
physiological, and biochemical analyses of a patient’s organs, tissues,
and cells accompanied by the development of a local delivery system
that can deliver an antioxidant or an oxidant where they are needed.
3. SRL Cardiovascular Diseases & Diagnosis
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The critical role of FoxO in
cardiovascular function
FoxO stimulates cell growth and proliferation and also
decreases VEGF secretion and mediates eNOS phosphorylation,
vasorelaxation and angiogenesis by Akt kinase [12]. The action
of Akt on its downstream target FoxO determines a function in
cardiocascular physiology [13]. The alteration of FoxO signaling
plays an important role in many cardiovascular pathological
processes such as atherosclerosis, cardiac hypertrophy, and vascular
remodeling. FoxO induces pro-apoptotic Bcl-2 family of proteins or
stimulates expression of death receptor ligands such as Fas ligand
and tumor necrosis factor-related apoptosis-inducing ligand, TRAIL.
It can also enhance the levels of cyclin dependent kinase inhibitors.
Phosphorylation of FoxO by Akt inhibits the transcriptional functions
of FoxO and leads to decrease Bcl-2 and increased cell survival [14].
Furthermore, endothelial cell-directed deletion of FoxO1 in adult
mice induced overzealous proliferation along with reduced apoptosis
[15]. However, in endothelial cells, FoxO1 inhibits transcription of
endothelial nitric oxide synthase (eNOS) and accelerates inducible
NOS expression in response to oxidative stress, leading to generation
of peroxynitrite and endothelial dysfunction [16] which contributes
to atherogenesis. In addition, ablation of the three genes encoding
isoforms of FoxO in endothelial cells blocks atherosclerosis in low-
density lipoprotein receptor knockout mice [17]. Fine-tuning of
FoxO is essential to controlling cellular functions in cardiovascular
function.
Atherosclerosis
In atherosclerosis, lability and abolish of the plaque leads to
myocardial infarction, which could be caused by apoptosis of vascular
smooth muscle cells [18]. FoxO seems to have an action in smooth
muscle cell apoptosis through insulin/insulin-like growth factor 1
(IGF1) receptor signaling. Reduced IGF1R signaling and inhibition
of phosphorylation of Akt, FoxO3a and GSK3 induce apoptosis of
vascularsmoothmusclecells[19].InhibitionofAktinvascularsmooth
muscle cells can result in significant increase in phosphorylation of
JNK and c-jun, pro-apoptotic proteins, opposite manner in immune
cells [20]. In addition, FoxO1 regulates asymmetric dimethyl-
arginine through downregulation of dimethyl-aminohydrolase 1 in
endothelial cells and subjects with atherosclerosis [21]. These studies
strongly suggest that FoxO is a pivotal element in the regulation of
endothelial activation.
Vascular remodeling
Vascular remodeling process is composed of changes of
cell growth, death, migration and generation or degradation
of extracellular matrix [22]. FoxO proteins act a pivotal role in
pathogenesis of vascular remodeling. Akt substrate GSK3β has an
essential role in smooth muscle proliferation [23]. Recent study also
reveals that growth arrest-specific protein 6 delays senescence in
vascular smooth muscle cells through the FoxO signaling pathway
[24]. In restenosis and atherosclerosis, increased proliferation of
vascular smooth muscle cells contribute to medial thickening. FoxO
also affects the activity of adventitia in the vasculature. In case of
arterial injury, FoxO activity is remarkably lower in the adventitia and
attributes the increased proliferation of adventitial fibroblasts [25].
Cardiac hypertrophy
Cardiac hypertrophy can be defined at a cellular level as elevated
cardiomyocyte cell volume [26]. In normal growth, physical condition
and growth induced by pathologic stimulation are the major types of
cardiac hypertrophy [27]. Maladaptive hypertrophy could be caused
as a response to excessive hemodynamic workload or by genetic
mutations. Over-expression of Akt induces cardiac hypertrophy,
which may lead to heart failure. Preventing cardiac hypertrophy
by inhibiting mTOR failed to prevent the decline in mitochondrial
function, but glucose utilization was maintained [28]. Reducing
FoxO-mediated transcriptional activation of mitochondrion-targeted
nuclear genes results in repressed expression of mitochondrial
regulation. In myocytes, Akt activation abolished mitochondrial
bioenergetics, which could be partially reversed by maintaining
nuclear FoxO [29]. Constitutively activated Akt could raise the
angiogenesis in heart and contribute to adaptive cardiac hypertrophy.
Later stage of this can lead to heart failure [30]. There is a dilemma
cause exercise is known to increase the cardiovascular health by
raised Akt activity [31]. There must be a fine balance among with the
optimal and maladaptive FoxO activation levels and duration which
is yet to be investigated.
Summary and Perspectives
Aging is a phenomenon in which the functions, adaptability and
resistance of an organism decrease over time, which are triggered by
mainly accumulated oxidative stress. The aging of multiple organs
can ultimately lead to diseases and the cardiovascular system is no
exception. In fact, aging is primary risk factors for cardiovascular
diseases by altered cardiovascular metabolism, metabolic disorders
of the extracellular matrix, abnormal apoptosis, and inflammation.
Therefore, delaying many of the negative aspect of cardiovascular
aging is vitally important for improving the human healthy life span
and quality of life. Most of the studies on FOXO on cancer research,
there are some similarities between pathological conditions in
cardiovascular diseases and the hallmarks of cancer. Although, more
studies should be done to understand actions of ROS and FOXO in
cardiovascular diseases, there is a mandatory need to develop potent
tissue specific inhibitors or activators of the FOXO pathway for
cardiovascular research and therapeutic interests.
Acknowledgments
The authors are grateful to the Caenorhabditis Genetics Center
for the C. elegans strains.
Author Contributions
The author(s) have made the following declarations regarding
their contributions. JK and SC wrote and discussed the paper.
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