Search

Endothelial dysfunction is one of the main pathogenetic mechanisms of pulmonary hypertension (PH). In the pathological microenvironment, excess reactive oxygen species (ROS) further induce pulmonary microvascular endothelial cell (PMEC) dysfunction. Recently, there has been an extreme lack of drugs that specifically target and eliminate ROS within the microenvironment. Although some nanomaterials are known as effective ROS-scavenging agents and can further alleviate disease progression, few nanomaterials have been reported in the endothelial dysfunction of PH. Based on the above situation, we synthesized a kind of novel nanoclusters (cerium dioxide/bovine serum albumin, CeO2/BSA), which can not only effectively scavenge ROS but also inhibit hypoxia-induced PMEC overproliferation, migration, and apoptosis resistance. CeO2/BSA nanoclusters were proved to be enriched in the lung, which effectively relieved pulmonary vascular remodeling, reduced the pressure of the pulmonary artery, and finally significantly improved cardiac function. Through in-depth mechanism analysis, we found that CeO2/BSA nanoclusters may be involved in Th1 and Th2 differentiation pathways mainly by effectively scavenging high levels of ROS in the pulmonary artery. In addition, the good biocompatibility of CeO2/BSA nanoclusters increased the possibility of their clinical application in the treatment of PH. In conclusion, this work provides a novel and effective solution to improve the dilemma of the ROS target and elimination in the treatment of PH. [ABSTRACT FROM AUTHOR]

In order to improve the flame‐retardant performance of insulating paper and reduce the fire risk, hydroxyethyl diphosphate and dicyandiamide were used to modify starch to prepare a new starch‐based flame retardant (SHPD). The combustion, mechanical, and electrical properties of SHPD treated flame‐retardant insulating paper were investigated. The results showed that when the impregnation concentration of SHPD was 25.0%, the limiting oxygen index of the insulating paper was increased from 18.3% to 38.3% and reached the level of UL‐94 V‐0. The tensile index and burst index of the flame‐retardant insulating papers were only 10.17% and 12.5% lower than that of the control insulating paper. The ring crush strength and alternating current breakdown strength in air of the flame‐retardant insulating papers were 63.3% and 1.8% higher than that of the control insulating paper. The SHPD flame retardant has a good application prospect in insulating paper. [ABSTRACT FROM AUTHOR]

Background: While the GRIPHON study and others have confirmed the efficacy and safety of selexipag with single, dual, and initial triple combination therapy for patients with pulmonary arterial hypertension (PAH), multicenters studies concerning diverse triple oral combination therapies based on selexipag are limited. Hypothesis: This study was conducted to evaluate the effects of various sequential triple oral combination therapies on PAH outcomes. Methods: A retrospective study was carried out involving 192 patients from 10 centers, who were receiving sequential triple oral combination therapy consisting of an endothelin receptor antagonist (ERA), a phosphodiesterase 5 inhibitor (PDE5i)/riociguat and selexipag. Clinical parameters, event‐free survival, and all‐cause survival were assessed and analyzed at baseline and posttreatment. Results: Among the 192 patients, 37 were treated with ERA + riociguat + selexipag, and 155 patients received ERA + PDE5i + selexipag. Both sequential triple oral combination therapies improved the World Health Organization functional class and raised the count of low‐risk parameters. As a result of the larger patients' population in the ERA + PDE5i + selexipag group, these individuals exhibited significant increases in 6‐minute walking distance (6MWD), pulmonary arterial systolic pressure, pulmonary arterial pressure, right ventricle, and eccentricity index, and significant decreases in N‐terminal probrain natriuretic peptide after 6 months of treatment. Nevertheless, both sequential triple oral combination therapy groups demonstrated similar shifts in these clinical parameters between baseline and 6 months. Baseline 6MWD and mean pulmonary arterial pressure were independent predictors of survival in patients undergoing ERA + PDE5i + selexipag therapy. Importantly, no significant differences were found in 6‐month event‐free survival and all‐cause survival between two groups. Conclusions: Different oral sequential triple combination therapies based on selexipag could comparably improve outcomes in patients with PAH. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Ginkgo biloba extract (GBE) is an ancient Chinese phytomedicine which was used to treat various ailments including circulatory and demential disorders. Aim of the study: To study GBE''s protective effects on the glomerulosclerosis of diabetic nephropathy (DN) in rat mesangial cells by serum pharmacological methods. Materials and methods: The cultured mesangial cells were divided into seven groups: normal, solvent control, high glucose, low dose of GBE serum, moderate dose of GBE serum, high dose of GBE serum, and GBE. The activities of cell antioxidases, type IV collagen and laminin, Smad2/3 and Smad7, and TGF-β1 mRNA were measured by methods of spectrophotometry, radioimmunoassay, immunocytochemistry, and RT-PCR, respectively. Results: The intensity of oxidative stress decreased in the GBE serum-treated groups in comparison with the high glucose group. In addition, the expression of Smad2/3 was greatly reduced, whereas Smad7 expression increased; type IV collagen, laminin and TGF-β1 mRNA levels were also diminished. Conclusion: These results suggest that GBE is protective agent against glomerulosclerosis in diabetic nephropathy of mesangial cells. [Copyright &y& Elsevier]

Multitarget antidepressants selectively inhibiting monoaminergic transporters and 5-hydroxytryptamine (5-HT) 2A receptor have demonstrated higher efficacy and fewer side effects than selective serotonin reuptake inhibitors. In the present study, we synthesized a series of novel 3-(benzo[d][1,3]dioxol-4-yloxy)-3-arylpropyl amine derivatives, among which compound H05 was identified as a lead, exhibiting potent inhibitory effects on both serotonin ( K i = 4.81 nM) and norepinephrine (NE) ( K i = 6.72 nM) transporters and moderate 5-HT 2A antagonist activity (IC 50 = 60.37 nM). H05 was able to dose-dependently reduce the immobility duration in mouse forced swimming test and tail suspension test, with the minimal effective doses lower than those of duloxetine, and showed no stimulatory effect on locomotor activity. The administration of H05 (5, 10, and 20 mg/kg, by mouth) significantly shortened the immobility time of adrenocorticotropin-treated rats that serve as a model of treatment-resistant depression, whereas imipramine (30 mg/kg, by mouth) and duloxetine (30 mg/kg, by mouth) showed no obvious effects. Chronic treatment with H05 reversed the depressive-like behaviors in a rat model of chronic unpredictable mild stress and a mouse model of corticosterone-induced depression. Microdialysis analysis revealed that the administration of H05 at either 10 or 20 mg/kg increased the release of 5-HT and NE from the frontal cortex. The pharmacokinetic (PK) and brain penetration analyses suggest that H05 has favorable PK properties with good blood-brain penetration ability. Therefore, it can be concluded that H05, a novel serotonin and NE reuptake inhibitor with 5-HT 2A antagonist activity, possesses efficacious activity in the preclinical models of depression and treatment-resistant depression, and it may warrant further evaluation for clinical development., (Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.)