Stiffening of conduit arteries is a risk factor for cardiovascular morbidity. Aortic wall stiffening increases pulsatile hemodynamic forces that are detrimental to the microcirculation in highly perfused organs, such as heart, brain, and kidney. Arterial stiffness associated with hypertension but presumed be due an adaptive response increased load. In contrast, recent clinical study found precedes may contribute development although mechanisms underlying unknown. Here, we report diet-induced...

Fibrosis is emerging as a hallmark of metabolically dysregulated white adipose tissue (WAT) in obesity. Although fibrosis impairs adipocyte plasticity, little known about how aberrant extracellular matrix (ECM) remodeling WAT initiated during the development Here we show that treatment with antidiabetic drug metformin inhibits excessive ECM deposition ob/ob mice and diet-induced obesity, evidenced by decreased collagen surrounding adipocytes expression fibrotic genes including cross-linking...

Arterial stiffness, a major cardiovascular risk factor, develops within 2 months in mice fed high-fat, high-sucrose (HFHS) diet, serving as model of human metabolic syndrome, and it is associated with activation proinflammatory oxidant pathways vascular smooth muscle (VSM) cells. Sirtuin-1 (SirT1) an NAD + -dependent deacetylase regulated by the cellular status. Our goal was to study effects VSM SirT1 on arterial stiffness context diet-induced syndrome. Overnight fasting acutely decreased...

Sirtuin-1 (SirT1), a member of the NAD+-dependent class III histone deacetylase family, is inactivated in vitro by oxidation critical cysteine thiols. In model metabolic syndrome, SirT1 activation attenuated apoptosis hepatocytes and improved liver function including lipid metabolism. We show SirT1-overexpressing HepG2 cells that oxidants (nitrosocysteine hydrogen peroxide) or stress (high palmitate high glucose) reversible oxidative post-translational modifications (OPTMs) on three...

Sirtuin-1 (SirT1), a nicotinamide adenine dinucleotide(+)-dependent deacetylase, is key enzyme in the cellular response to metabolic, inflammatory, and oxidative stresses; however, role of endogenous SirT1 vasculature has not been fully elucidated. Our goal was evaluate vascular smooth muscle physiological aortic wall angiotensin II, potent hypertrophic, oxidant, inflammatory stimulus.Mice lacking (ie, knockout) had drastically high mortality (70%) caused by dissection after II infusion (1...

Aims: Nonalcoholic fatty liver (NAFL) is a common disease associated with metabolic syndrome, obesity, and diabetes that rising in prevalence worldwide. Various molecular perturbations of key regulators enzymes hepatic lipid metabolism cause NAFL. However, redox regulation through glutathione (GSH) adducts NAFL remains largely elusive. Glutaredoxin-1 (Glrx) small thioltransferase removes protein GSH without having direct antioxidant properties. The contains abundant Glrx but its function...

Abstract We determined the effectiveness of low‐volume resistance exercise (EX) for attenuation loss muscle mass and strength during leg immobilization. Men ( N = 5) women 12, age 24 ± 5 years, body index 25.4 3.6 kg/m 2 ) were divided into two groups: (EX; n 12) control (CON; 5). Subjects wore a knee brace on one that prevented weight bearing 14 days. Resistance 80% maximal) was performed by immobilized limb every other day. Immobilization induced significant reduction P < 0.05) in fiber...

Abstract Tumor cell migration is mediated by cell-autonomous signaling mechanisms as well paracrine and autocrine factors secreted activated stromal cells in the tumor microenvironment. Like other members of ADAM (a disintegrin metalloproteinase) family, integrin-binding metalloproteinase ADAM9 modulates cell-cell cell-matrix interactions ectodomain shedding surface receptors ligands, thereby modifying intracellular extracellular signaling. transcripts are alternatively spliced to express a...

BACKGROUND: The use of premedication to prevent acute transfusion reactions has been estimated occur in 50% 80% transfusions. While this practice some biologic rationale, few clinical studies have performed assess the efficacy practice, and methodologic quality these is variable. primary objective study was describe current practices regarding febrile nonhemolytic reactions, mild allergic transfusion‐associated circulatory overload. STUDY DESIGN AND METHODS: We conducted an observational...

Sirtuin-1 (SirT1) catalyzes NAD+-dependent protein lysine deacetylation and is a critical regulator of energy lipid metabolism, mitochondrial biogenesis, apoptosis, senescence. Activation SirT1 mitigates metabolic perturbations associated with diabetes obesity. Pharmacologic molecules, cellular redox, nutritional states can regulate activity. Technical barriers against measuring endogenous activity have limited characterization in disease its activation by small molecules. Herein, we...

Potassium dysregulation can be life-threatening. Dietary potassium modification is a management strategy for hyperkalaemia. However, 2017 review clinical guidelines found no trials evaluating dietary restriction managing hyperkalaemia in chronic kidney disease (CKD). Evidence regarding was reviewed and practice recommendations disseminated. A literature search using terms potassium, hyperkalaemia, CKD undertaken from 2018 to October 2022. Researchers extracted data, discussed findings,...

Living Well during Pregnancy (LWdP) is a telephone-based antenatal health behavior intervention that has been shown to improve healthy eating behaviors and physical activity levels pregnancy. However, one-third of eligible, referred women did not engage with or dropped out the service. This study aimed explore experiences perceptions who were but attend complete LWdP program inform service improvements adaptations required for scale spread delivery patient-centered care. Semi-structured...

Dietary protein consumed in excess of requirements can be oxidized. We aimed to determine the dose that would maximize muscle anabolism yet minimize oxidative loss (OXID) after an acute bout resistance exercise. Six healthy males reported laboratory on five separate occasions perform intense leg exercise which they a drink containing 0, 5, 10, 20, or 40g (trials A-E, respectively) whole egg randomized order. Participants received primed constant infusion [1-13C]leucine over 4h for...

BACKGROUND Sirtuin‐1 (SIRT1), an NAD + ‐dependent deacetylase, is a key enzyme in the cellular response to metabolic, inflammatory, and oxidative stresses, however role of SIRT1 vascular smooth muscle (VSM) unclear. OBJECTIVE To study VSM physiological aortic wall angiotensin (Ang) II, potent oxidant inflammatory stimulus. METHODS We generated cell specific knock out mouse (SMKO) infused AngII (1 mg/kg/d) by osmotic minipump evaluated endpoints after 14 days. RESULTS SMKO mice had...

Arterial stiffness (AS), a major cardiovascular risk factor, develops within two months in mice fed high fat, sucrose diet (HFHS), serving as model of human metabolic syndrome, and is associated with functional impairment vascular smooth muscle (VSM) cells. Sirtuin1 (SirT1) NAD + -dependent deacetylase induced response to cellular stresses. Our goal was study the effects VSM SirT1 on AS context diet-induced syndrome. specific genetic over-expression (SMTG) prevented by HFHS, measured vivo...

Objective Oxidants can contribute to cellular signaling via glutathione‐(GSH) adducts, which are reversible post‐translational modifications of proteins that alter their function. Glutaredoxin‐1 (Glrx) is an enzyme specifically removes these GSH‐adducts and modulates activity. We aimed study the physiological role Glrx protein in vivo Methods Whole body knockout mice (Glrx ‐/‐ ) were created a C57BL/6J strain metabolic alterations monitored over eight months Results Chow fed developed...

BACKGROUND. Aortic stiffness (AS) is an independent predictor of cardiovascular events and associated with hypertension (HTN) in aging obesity however it unclear whether HTN causes AS or could develop advance HTN. C57Bl/6J mice fed a diet rich fat sucrose (HFHS) mimicking the metabolic syndrome. AIMS. We sought to determine: 1) occurs HFHS-fed mice; 2) relation between such model weight loss improve obese mice. METHODS. Pulse wave velocity (PWV) was measured by ultrasound as vivo index...

Sirtuin 1 (SirT1) is a NAD + ‐dependent class III histone deacetylase that orchestrates cell cycle progression, energy metabolism and aging. SirT1 activity modulated by [NAD ]/[NADH] ratio post translational modifications. Oxidative stress hallmark of metabolic disease inflammation contributes to the progression pathology in part through oxidative post‐translational modification (OPTM) proteins. HepG2 (liver carcinoma) HEK293 (transformed embryonic kidney) cells were treated with increasing...

BACKGROUND We previously showed that C57Bl/6J male mice fed a diet rich in fat (35%) and sucrose (16.5%) (HFHS) develop obesity, glucose intolerance, insulin resistance, chronic inflammation, cardiac diastolic kidney dysfunctions compared to normal (ND). also HFHS‐fed arterial stiffness (AS), measured vivo by pulse wave velocity (PWV), within 2 mos systolic hypertension, radiotelemetry, after 6 ND. AIM sought test the hypothesis AS hypertension would normalize obese reversal METHODS AND...