Hartkragelund0331

Most endocrine disorders are chronic in nature, and thus even a minor effect to increase risk for cardiovascular disease can lead to a significant impact over prolonged duration. Although robust therapies exist for many endocrine disorders (eg suppression of excess hormone amounts, or replacement of hormone deficiencies), the therapies do not perfectly restore normal physiology. Thus, individuals with endocrine disorders are at potential increased cardiovascular disease risk, and maximizing strategies to reduce that risk are needed. This article reviews various endocrine conditions that can impact lipid levels and/or cardiovascular disease risk.Cardiovascular disease (CVD) is the leading cause of mortality in the United States. Universal screening in all children aged 9 to 11 years and 17 to 21 years, and targeted screening in children with high-risk factors, can help in early identification and treatment of dyslipidemia during the youth, significantly reducing clinical CVD risk in adult life. Lifestyle modifications with heart-healthy diet and moderate-vigorous activity are fundamental in the management of pediatric dyslipidemia. Pharmacotherapy has been evolving in children, and statins, bile acid sequestrants, ezetimibe and PCSK9 inhibitors, fibrates, niacin, and omega-3 fish oils are available for use in pediatric population.Decades of research have shown that high-density lipoprotein cholesterol (HDL-C) levels in humans are associated with atherosclerotic cardiovascular disease (ASCVD). This association is strong and coherent across populations and remains after the elimination of covariates. Animal studies show that increasing HDL particles prevent atherosclerosis, and basic work on the biology of HDL supports a strong biological plausibility for a therapeutic target. This enthusiasm is dampened by Mendelian randomization data showing that HDL-C may not be causal in ASCVD. Furthermore, drugs that increase HDL-C have largely failed to prevent or treat ASCVD.Mild to moderate hypertriglyceridemia usually results from multiple small-effect variants in genes that control triglyceride metabolism. Hypertriglyceridemia is a critical component of the metabolic syndrome but can also occur secondary to several other conditions or drugs. Hypertriglyceridemia frequently is associated with an increased risk of cardiovascular disease (CVD). Statins are the mainstay of CVD prevention in hypertriglyceridemia, but eicosapentaenoic ethyl esters should be added in very-high-risk individuals. Although fibrates lower triglyceride levels, their role in CVD prevention remains unclear. Familial partial lipodystrophy is another relatively rare cause, although its true incidence is unknown.Inherited hypercholesterolemias include monogenic and polygenic disorders, which can be very rare (eg, cerebrotendinous xanthomatosis (CTX)) or relatively common (eg, familial combined hyperlipidemia [FCH]). In this review, we discuss familial hypercholesterolemia (FH), FH-mimics (eg, polygenic hypercholesterolemia [PH], FCH, sitosterolemia), and other inherited forms of hypercholesterolemia (eg, hyper-lipoprotein(a) levels [hyper-Lp(a)]). The prevalence, genetics, and management of inherited hypercholesterolemias are described and selected guidelines summarized.Assessment of atherosclerotic cardiovascular disease (ASCVD) risk is the cornerstone of primary ASCVD prevention, enabling targeted use of the most aggressive therapies in those most likely to benefit, while guiding a conservative approach in those who are low risk. ASCVD risk assessment begins with the use of a traditional 10-year risk calculator, with further refinement through the consideration of risk-enhancing factors (particularly lipoprotein(a)) and subclinical atherosclerosis testing (particularly coronary artery calcium (CAC) testing). In this review, we summarize the current field of ASCVD risk assessment in primary prevention and highlight new guidelines from the Endocrine Society.Based on decades of both basic science and epidemiologic research, there is overwhelming evidence for the causal relationship between high levels of cholesterol, especially low-density lipoprotein cholesterol and cardiovascular disease. Risk evaluation and monitoring the response to lipid-lowering therapies are heavily dependent on the accurate assessment of plasma lipoproteins in the clinical laboratory. This article provides an update of lipoprotein metabolism as it relates to atherosclerosis and how diagnostic measures of lipids and lipoproteins can serve as markers of cardiovascular risk, with a focus on recent advances in cardiovascular risk marker testing.The exogenous lipoprotein pathway starts with the incorporation of dietary lipids into chylomicrons in the intestine. Chylomicron triglycerides are metabolized in muscle and adipose tissue and chylomicron remnants are formed, which are removed by the liver. The endogenous lipoprotein pathway begins in the liver with the formation of very low-density lipoprotein particles (VLDL). VLDL triglycerides are metabolized in muscle and adipose tissue forming intermediate-density lipoprotein (IDL), which may be taken up by the liver or further metabolized to low-density lipoprotein (LDL). Reverse cholesterol transport begins with the formation of nascent high-density lipoprotein (HDL) by the liver and intestine that acquire cholesterol from cells resulting in mature HDL. The HDL then transports the cholesterol to the liver either directly or indirectly by transferring the cholesterol to VLDL or LDL.Colon cancer (CC) is one of the most common gastrointestinal malignant tumors with a high mortality rate. Glycolysis is an important pathway for tumors to obtain energy. However, its role in CC remains largely unknown. In present study, we analyzed glycolysis-related gene expression to depict clinical characteristics and its relationship with tumor immunity in CC to find potential target treatments. A prognostic model based on 13 glycolysis-related genes was established by univariate and multivariate Cox regression analyses. The efficacy of the gene model was tested via survival analysis, receiver operating characteristic analysis, and principal component analysis. Furthermore, our findings revealed and validated 13 glycolysis-related genes (NUP107, SEC13, ALDH7A1, ALG1, CHPF, FAM162A, FBP2, GALK1, IDH1, TGFA, VLDLR, XYLT2, and OGDHL), which constituted a prognostic prediction model. The model exhibited clinical implication potential, had a relatively high accuracy, and was closely associated with the patients' clinical features. In particular, the tumor stage could be clearly distinguished by glycolysis-related gene signatures. Finally, a significant difference between glycolysis-related gene colon cancer immunity and sensitive immune drugs was observed. Our glycolysis-related gene model could provide the basis for potential early individualized treatment. The 13 glycolysis-related gene signature was a reliable predictive tool for the prognosis of colon cancer. Our findings could help patients select targets for individualized treatment and immunotherapy strategies. The study findings advance our understanding of the potential mechanism of glycolysis in colon cancer.Numerous neurochemical changes occur with aging and stroke mainly affects the elderly. Our previous study has found interferon regulatory factor 5 (IRF5) and 4 (IRF4) regulate neuroinflammation in young stroke mice. However, whether the IRF5-IRF4 regulatory axis has the same effect in aged brains is not known. In this study, aged (18-20-month-old), microglial IRF5 or IRF4 conditional knockout (CKO) mice were subjected to a 60-min middle cerebral artery occlusion (MCAO). Stroke outcomes were quantified at 3d after MCAO. Flow cytometry and ELISA were performed to evaluate microglial activation and immune responses. We found aged microglia express higher levels of IRF5 and lower levels of IRF4 than young microglia after stroke. IRF5 CKO aged mice had improved stroke outcomes; whereas worse outcomes were seen in IRF4 CKO vs. their flox controls. IRF5 CKO aged microglia had significantly lower levels of IL-1β and CD68 than controls; whereas significantly higher levels of IL-1β and TNF-α were seen in IRF4 CKO vs. control microglia. Plasma levels of TNF-α and MIP-1α were decreased in IRF5 CKO vs. flox aged mice, and IL-1β/IL-6 levels were increased in IRF4 CKO vs. controls. The anti-inflammatory cytokines (IL-4/IL-10) levels were higher in IRF5 CKO, and lower in IRF4 CKO aged mice vs. their flox controls. IRF5 and IRF4 signaling drives microglial pro- and anti-inflammatory response respectively; microglial IRF5 is detrimental and IRF4 beneficial for aged mice in stroke. IRF5-IRF4 axis is a promising target for developing new, effective therapeutic strategies for the cerebral ischemia.The current study outlines the toxicity-free green synthesis of reduced graphene oxide (GO) using Celosia argenta. The synthesized sample was characterized by UV-visible spectroscopy with a strong absorption peak at 260 nm due to redshift. The 2θ value around 24.1° by X-ray diffraction analysis and the functional groups like ─OH, ─CH2─, ─C═C─, and ─CHO by Fourier transmission infrared spectroscopy confirmed the reduction of GO. Field emission scanning electron microscopy-energy-dispersive X-ray spectroscopy reported stacked sheets with smooth edges with an atomic ratio of carbonoxygen (83.5616.44). The transmission electron microscope images proved the reduction of GO by folded thin sheets with the wrinkled appearance of our sample. This novel material showed antibacterial efficiency of 51.72-70.83% for both Gram-negative and Gram-positive organisms. 89.48% of antioxidant effect and potential anti-inflammatory property with the IC50 value of 86.04% was reported. RSM study proved the optimization of maximum yield and two-way analysis of variance reported the statistical significance (p value ≤ 0.05) for its anti-inflammatory effect. find more Bio-Gel formulated with a good spreadability rate and promising biocompatibility was proved with less hemolysis value of 2.74%. The genotoxicity study exposed the aberration-free active mitotic cell division in onion root tip cells. All these showcased that our biomaterial can find promising applications in biomedical and therapeutic fields.N-stearoylethanolamine (NSE), a lipid mediator that belongs to the N-acylethanolamine (NAE) family, has anti-inflammatory, antioxidant, and membranoprotective actions. In contrast to other NAEs, NSE does not interact with cannabinoid receptors. The exact mechanism of its action remains unclear. The aim of this study is to evaluate the action of NSE on activation, aggregation, and adhesion of platelets that were chosen as a model of cellular response. Aggregation of platelets was measured to analyze the action of NSE (10-6-10-10 M) on platelet reactivity. Changes in granularity and shape of resting platelets and platelets stimulated with ADP in the presence of NSE were monitored by flow cytometry, and platelet deganulation was monitored by spectrofluorimetry. In vivo studies were performed using obese insulin-resistant rats. Binding of fibrinogen to the GPIIb/IIIa receptor was estimated using indirect ELISA and a scanning electron microscopy (SEM). It was found that NSE inhibits the activation and aggregation of human platelets.