Novel Therapeutic Potential of Retinoid-Related Orphan Receptor α in Cardiovascular Diseases.

The retinoid-related orphan receptor α (RORα) is one subfamily of nuclear hormone receptors (NRs). This review summarizes the understanding and potential effects of RORα in the cardiovascular system and then analyzes current advances, limitations and challenges, and further strategy for RORα-related drugs in cardiovascular diseases. Besides regulating circadian rhythm, RORα also influences a wide range of physiological and pathological processes in the cardiovascular system, including atherosclerosis, hypoxia or ischemia, myocardial ischemia/reperfusion injury, diabetic cardiomyopathy, hypertension, and myocardial hypertrophy. In terms of mechanism, RORα was involved in the regulation of inflammation, apoptosis, autophagy, oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial function. Besides natural ligands for RORα, several synthetic RORα agonists or antagonists have been developed. This review mainly summarizes protective roles and possible mechanisms of RORα against cardiovascular diseases. However, there are also several limitations and challenges of current research on RORα, especially the difficulties on the transformability from the bench to the bedside. By the aid of multidisciplinary research, breakthrough progress on RORα-related drugs to combat cardiovascular disorder may appear.

Dihydromyricetin Attenuates Diabetic Cardiomyopathy by Inhibiting Oxidative Stress, Inflammation and Necroptosis via Sirtuin 3 Activation.

Dihydromyricetin (DHY), the main flavonoid component in Ampelopsis grossedentata, has important benefits for health. The present study aimed to investigate the exact effects and possible mechanisms of DHY on diabetic cardiomyopathy (DCM). Male C57BL/6 mice and sirtuin 3 (SIRT3) knockout (SIRT3-KO) mice were injected with streptozotocin (STZ) to induce a diabetic model. Two weeks later, DHY (250 mg/kg) or carboxymethylcellulose (CMC) were administrated once daily by gavage for twelve weeks. We found that DHY alleviated fasting blood glucose (FBG) and triglyceride (TG) as well as glycosylated hemoglobin (HbA1c) levels; increased fasting insulin (FINS); improved cardiac dysfunction; ameliorated myocardial hypertrophy, fibrosis and injury; suppressed oxidative stress, inflammasome and necroptosis; but improved SIRT3 expression in STZ-induced mice. Neonatal rat cardiomyocytes were pre-treated with DHY (80 µM) with or without high glucose (HG) stimulation. The results showed that DHY attenuated cell damage but improved SIRT3 expression and inhibited oxidative stress, inflammasome and necroptosis in cardiomyocytes with high glucose stimulation. Moreover, the above protective effects of DHY on DCM were unavailable in SIRT3-KO mice, implying a promising medical potential of DHY for DCM treatment. In sum, DHY improved cardiac dysfunction; ameliorated myocardial hypertrophy, fibrosis and injury; and suppressed oxidative stress, inflammation and necroptosis via SIRT3 activation in STZ-induced diabetic mice, suggesting DHY may serve as a candidate for an agent to attenuate diabetic cardiomyopathy.

Transition-metal-free Synthesis of tetra-substituted Vinyl Iodides by Cascade Sequential Reaction of α-Keto Acids, 1-Iodoalkynes, and Alkyl Halides.

The cascade sequential reaction of α-keto acids, 1-iodoalkynes, and alkyl halides are reported herein to synthesize tetra-substituted vinyl iodides. It represents an efficient protocol to access a diverse range of tetra-substituted vinyl iodides starting from simple materials in a one-pot fashion, featuring mild reaction conditions, ease of operation, and broad substrate scope.

Roles of the adaptor protein tumor necrosis factor receptor type 1-associated death domain protein (TRADD) in human diseases.

Cells communication in response to extracellular or biophysical stimulus relies on elaborated systems of signal transduction. In the course of most signal pathway, the cascades involve signal protein complexes, which are often assembled by adaptor proteins. Tumor necrosis factor receptor type 1-associated death domain protein (TRADD) is an adaptor molecule involved in various signal pathways and mediating multiple biological activities, including cell survival, cell proliferation, cell differentiation, apoptosis, necroptosis and inflammation. TRADD contains an N terminal tumor necrosis factor receptor-associated factor 2 (TRAF2) binding domain and a C terminal death domain (DD) for interacting with multiple DD-containing proteins. Following activation of specific receptors, such as tumor necrosis factor receptor 1 (TNFR1), death receptor 3 (DR3), tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAILR1, DR4), TRAILR1 (DR5), DR6 and p75 neurotrophin receptor (p75NTR)，TRADD can bind to the receptors, serving as a platform for the recruitment of the downstream molecules for signal propagating and thus mediating various physiological and pathological processes. In this review, we provide a brief overview of the current knowledge on TRADD and discuss the roles of TRADD in infectious and inflammatory diseases, cardiovascular diseases, central nervous system diseases, cancer, endometriosis, hepatocyte proliferation, preterm birth and perinatal development.

Occurrence and risk assessment of emerging contaminants in a water reclamation and ecological reuse project.

Water reclamation and ecological reuse is gradually becoming a popular solution to address the high pollutant loads and insufficient ecological flow of many urban rivers. However, emerging contaminants in water reuse system and associated human health and ecological risks need to be assessed. This study determined the occurrence and human health and ecological risk assessments of 35 emerging contaminants during one year, including 5 types of persistent organic pollutants (POPs), 5 pharmaceutical and personal care products (PPCPs), 7 endocrine disrupting chemicals (EDCs) and 18 disinfection by-products (DBPs), in a wastewater treatment plant (WWTP) and receiving rivers, as well as an unimpacted river for comparison. Results showed that most of PPCPs and EDCs, especially antibiotics, triclosan, estrogens and bisphenol A, occurred frequently at relatively high concentrations, and they were removed from 20.5% to 88.7% with a mean of 58.9% via WWTP. The highest potential noncarcinogenic and carcinogenic risks in different reuse scenarios were assessed using maximal detected concentrations, all below the acceptable risk limits, with the highest total combined risk value of 9.21 × 10-9 and 9.98 × 10-7, respectively. Ecological risk assessment was conducted using risk quotient (RQ) method and indicated that several PPCPs, EDCs and haloacetonitriles (HANs) pose high risk (RQ > 1) to aquatic ecology in the rivers, with the highest RQ up to 83.8. The study suggested that ecological risks need to be urgently addressed by updating and optimizing the process in WWTPs to strengthen the removal efficiencies of emerging contaminants. The study can serve as a reference for safer water reuse in the future, while further studies could be conducted on the health risk of specific groups of people, exposure parameters in water reuse, as well as more emerging contaminants.