Current and new pharmacotherapy options for non-alcoholic steatohepatitis.

Current and new pharmacotherapy options for non-alcoholic steatohepatitis. Expert Opin Pharmacother. 2020 Apr 01;:1-15 Authors: Sumida Y, Yoneda M, Ogawa Y, Yoneda M, Okanoue T, Nakajima A Abstract Introduction: There is an unmet medical need for an effective anti-fibrotic treatment for NASH with advanced fibrosis.Areas covered: The authors review the current and novel agents for the treatment of NASH with fibrosis. They also consider the potential future strategies of combination therapies.Expert opinion: Farnesoid X receptor (FXR) agonist (obeticholic acid [OCA]) significantly ameliorated hepatic fibrosis in NASH stage 2/3 fibrosis in an interim analysis of phase 3 trial. Because OCA has several drawbacks such as itching and elevated low-density lipoprotein-cholesterol (LDL-C), non-bile acid FXR agonists are now under development. Selonsertib (apoptosis signaling kinase 1 inhibitor), emricasan (an irreversible pan-caspase inhibitor), and simtsuzumab (a monoclonal antibody against lysyl oxidase-like 2) were discontinued because of no efficacy over placebo. Peroxisome proliferator-activator receptor α/δ agonists, C-C motif chemokine receptor-2/5 antagonists, and thyroid β receptor agonist are ongoing in phase 3 trials. A variety of agents including fibroblast growth factor (FGF)-21 and FGF-19 agonists, as well as acetyl-CoA carboxylase inhibitors, are also expected. Among antidiabetic agents, semaglutide, a novel GLP-1 RA, is ongoing for ...
Source: Expert Opinion on Pharmacotherapy - Category: Drugs & Pharmacology Tags: Expert Opin Pharmacother Source Type: research

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AbstractChanges in neurovascular coupling are associated with both Alzheimer ’s disease and vascular dementia in later life, but this may be confounded by cerebrovascular risk. We hypothesized that hemodynamic latency would be associated with reduced cognitive functioning across the lifespan, holding constant demographic and cerebrovascular risk. In 387 adults aged 18–85 (mean = 48.82), dynamic causal modeling was used to estimate the hemodynamic response function in the left and right V1 and V3-ventral regions of the visual cortex in response to a simple checkerboard block design stimulus with mi...
Source: Anatomy and Embryology - Category: Anatomy Source Type: research
Abstract Changes in neurovascular coupling are associated with both Alzheimer's disease and vascular dementia in later life, but this may be confounded by cerebrovascular risk. We hypothesized that hemodynamic latency would be associated with reduced cognitive functioning across the lifespan, holding constant demographic and cerebrovascular risk. In 387 adults aged 18-85 (mean = 48.82), dynamic causal modeling was used to estimate the hemodynamic response function in the left and right V1 and V3-ventral regions of the visual cortex in response to a simple checkerboard block design stimulus with minim...
Source: Brain Structure and Function - Category: Neuroscience Authors: Tags: Brain Struct Funct Source Type: research
Abstract Bile acids are produced in the liver by the cholesterol breakdown and further metabolized by the intestinal microbiota to generate a group of chemically heterogeneous steroids that bind and activate a family of cells surface and nuclear receptors, collectively known as the bile acid-activated receptors (BARs). The two best characterized members of this family are the farnesoid-x-receptor (FXR) and G protein Bile Acid Receptor (GPBAR1). Both receptors are expressed by cells of innate immunity including liver-resident and intestinal-resident macrophages and monocytes-derived macrophages. Because FXR and GPB...
Source: Current Opinion in Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Opin Pharmacol Source Type: research
In conclusion, FAR possesses a strong anti-hyperlipidemic/anti-hypercholesterolemic activity mediated through its ability to modulate hepatic FAS, ACC, and SREPB-1c. FAR prevented oxidative stress, inflammation, and liver injury induced by HCD. Thus, FAR may represent a promising lipid-lowering agent that can protect against dyslipidemia and its linked metabolic deregulations. PMID: 32449150 [PubMed - as supplied by publisher]
Source: Environmental Science and Pollution Research International - Category: Environmental Health Authors: Tags: Environ Sci Pollut Res Int Source Type: research
;mez-Huelgas María Rosa Bernal-López The aim of this study was to analyze the utility of liver function tests (LFT) and fatty liver index (FLI), a surrogate marker of non-alcoholic fatty liver disease, in the categorization of metabolic phenotypes in a Mediterranean population. A cross-sectional study was performed on a random representative sample of 2233 adults assigned to a health center in Málaga, Spain. The metabolic phenotypes were determined based on body mass index (BMI) categorization and the presence or absence of two or more cardiometabolic abnormalities (high blood pressure, low h...
Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Article Source Type: research
This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function. On Nutraceutical Senolytics https://www.fightaging.org/archives/2020/05/on-nutraceutical-senolytics/ Nutraceuticals are compounds derived from foods, usually plants. In principle one can find useful therapies in the natural world, taking the approach of identifying interesting molecules and refining them to a greater potency than naturally occurs in order to produce a usefully large therape...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
ConclusionsBesides diabetes, the increased risks of different grades of NAFLD were found for prediabetic individuals categorized by impaired fasting glucose without IGT, IGT and isolated HbA1c 5.7 –6.4%.
Source: Journal of Diabetes Investigation - Category: Endocrinology Authors: Tags: Original Article Source Type: research
Conclusions: Inconsistent outcomes have been reported in the literature when comparing TSPO ligand binding for imaging neuroinflammation. Our data are consistent with findings from several recent studies; i.e., reduced PBR28 binding was associated with disease state (e.g., in patients with PTSD or alcoholism). A notion that the reduced binding might reflect competition from endogenous TSPO ligands such as cholesterol can’t be excluded. The strategies described here will test the hypothesis that pharmacological antagonism of RAGE signal transduction in either initiation or progression phases of the ALS will prolong su...
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Basic Science - Inflammation and Dementia Source Type: research
This study aimed to investigate whether RBD leads to liver inflammatory changes and altered reverse cholesterol metabolism in C57BL6/J mice compared to the control group, receiving a standard chow diet. To evaluate liver inflammation, ionized calcium-binding adapter protein-1 (IBA-1) positive cell counting, interleukin (IL)-1β immunohistochemistry, and tumor necrosis factor (TNF)-α and IL-10 transcription levels were analyzed. In addition, we assessed reverse cholesterol transport by measuring liver apolipoprotein (Apo)E, ApoA-I, and lecithin-cholesterol acyltransferase (LCAT) by RT-PCR. Furthermore, serum alani...
Source: Braz J Med Biol Res - Category: Research Authors: Tags: Braz J Med Biol Res Source Type: research
Conclusions The factors affecting the treatment and control of hypertension differed between the two genders. Therefore, healthcare providers should consider the differences in the factors between the two genders in early adulthood. To improve the treatment and control of hypertension, the guidelines for treatment interventions and management should be gender-specific from early adulthood. Nurses should actively suggest health-related behavioral modifications such as performing aerobic exercise for young adult men and reducing alcohol consumption for women.
Source: Journal of Nursing Research - Category: Nursing Tags: ORIGINAL ARTICLES Source Type: research
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