Circulating adiponectin concentrations are reduced in obese individuals, and this reduction has been proposed to have a crucial role in the pathogenesis of atherosclerosis and cardiovascular diseases ...associated with obesity and the metabolic syndrome. We focus on the effects of adiponectin on glucose and lipid metabolism and on the molecular anti-atherosclerotic properties of adiponectin and also discuss the factors that increase the circulating levels of adiponectin. Adiponectin reduces inflammatory cytokines and oxidative stress, which leads to an improvement of insulin resistance. Adiponectin-induced improvement of insulin resistance and adiponectin itself reduce hepatic glucose production and increase the utilization of glucose and fatty acids by skeletal muscles, lowering blood glucose levels. Adiponectin has also β cell protective effects and may prevent the development of diabetes. Adiponectin concentration has been found to be correlated with lipoprotein metabolism; especially, it is associated with the metabolism of high-density lipoprotein (HDL) and triglyceride (TG). Adiponectin appears to increase HDL and decrease TG. Adiponectin increases ATP-binding cassette transporter A1 and lipoprotein lipase (LPL) and decreases hepatic lipase, which may elevate HDL. Increased LPL mass/activity and very low density lipoprotein (VLDL) receptor and reduced apo-CIII may increase VLDL catabolism and result in the reduction of serum TG. Further, adiponectin has various molecular anti-atherosclerotic properties, such as reduction of scavenger receptors in macrophages and increase of cholesterol efflux. These findings suggest that high levels of circulating adiponectin can protect against atherosclerosis. Weight loss, exercise, nutritional factors, anti-diabetic drugs, lipid-lowering drugs, and anti-hypertensive drugs have been associated with an increase of serum adiponectin level.
Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of death worldwide. The risk of developing CVD is associated with an unhealthy lifestyle. A high level of low-density ...lipoprotein (LDL) cholesterol (LDL-C) is a primary risk factor for ASCVD. However, even if the LDL-C management target has been achieved, hypertriglyceridemia and a high level of total cholesterol minus high-density lipoprotein (HDL) cholesterol (non-HDL-C), which contains cholesterol concentrations of triglyceride-rich lipoproteins, are considered a significant residual risk factor for ASCVD and consequently the management of these conditions is important for controlling the residual risk for ASCVD.
See article vol. 28: 703-715 Many epidemiologic studies have reported an inverse relationship between coronary heart disease (CHD) events and high-density lipoprotein (HDL)-cholesterol (HDL-C) ...levels. However, the Copenhagen studies (City Heart Study and General Population Study) demonstrated U-shaped associations between HDL-C levels and cardiovascular mortality, and the Canadian CANHEART study also showed similar U-shaped associations between them. Namely, not only low HDL-C but also extremely high HDL-C may be associated with high CHD mortality.
Next‐generation sequencing (NGS) of tumor tissue (ie, clinical sequencing) can guide clinical management by providing information about actionable gene aberrations that have diagnostic and ...therapeutic significance. Here, we undertook a hospital‐based prospective study (TOP‐GEAR project, 2nd stage) to investigate the feasibility and utility of NGS‐based analysis of 114 cancer‐associated genes (the NCC Oncopanel test). We examined 230 cases (comprising more than 30 tumor types) of advanced solid tumors, all of which were matched with nontumor samples. Gene profiling data were obtained for 187 cases (81.3%), 111 (59.4%) of which harbored actionable gene aberrations according to the Clinical Practice Guidelines for Next Generation Sequencing in Cancer Diagnosis and Treatment (Edition 1.0) issued by 3 major Japanese cancer‐related societies. Twenty‐five (13.3%) cases have since received molecular‐targeted therapy according to their gene aberrations. These results indicate the utility of tumor‐profiling multiplex gene panel testing in a clinical setting in Japan. This study is registered with UMIN Clinical Trials Registry (UMIN 000011141).
The results of the TOP‐GEAR project (UMIN 000011141) indicate the utility of tumor‐profiling multiplex gene panel testing in a clinical setting in Japan.
Separation analysis of lipoprotein classes have various methods, including ultracentrifugation, electrophoresis, and gel permeation chromatography (GPC). All major lipoprotein classes can be ...separated via ultracentrifugation, but performing the analysis takes a long time. Low-density lipoprotein (LDL), intermediate-density lipoprotein (IDL), and very low-density lipoprotein (VLDL) in patient samples cannot be sufficiently separated via electrophoresis or GPC. Thus, we established a new method anion-exchange high-performance liquid chromatography (AEX-HPLC) by using HPLC with an AEX column containing nonporous gel and an eluent containing chaotropic ions. AEX-HPLC can separate five lipoprotein fractions of high-density lipoprotein (HDL), LDL, IDL, VLDL, and others in human serum, which can be used in substitution for ultracentrifugation method. The method was also approved for clinical use in the public health-care insurance in Japan in 2014. Furthermore, we developed an additional method to measure cholesterol levels of the four leading lipoprotein fractions and two subsequent fractions (i.e., chylomicron and lipoprotein(a)). We evaluated the clinical usefulness of AEX-HPLC in patients with coronary heart disease (CHD), diabetes, and kidney disease and in healthy volunteers. Results indicate that the cholesterol levels in IDL and VLDL measured by AEX-HPLC may be useful risk markers of CHD or diabetes. Furthermore, we developed another new method for the determination of alpha-tocopherol (AT) in lipoprotein classes, and this method is composed of AEX-HPLC for the separation of lipoprotein classes and reverse-phase chromatography to separate AT in each lipoprotein class. The AT levels in LDL were significantly correlated with the lag time to copper ion-induced LDL oxidation, which is an index of oxidation resistance. The application of AEX-HPLC to measure various substances in lipoproteins will be clinically expected in the future.
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