Pinocembrin suppresses oxidized low-density lipoprotein-triggered NLRP3 inflammasome/GSDMD-mediated endothelial cell pyroptosis through an Nrf2-dependent signaling pathway.

Pinocembrin (Pin) has been confirmed to exert anti-inflammatory and antiatherosclerotic effects. Here we have explored whether and how Pin would protect vascular endothelial cells against pyroptosis elicited by the exposure to oxidized low density lipoprotein (oxLDL). Our results showed that Pin preconditioning dose-dependently suppressed oxLDL-stimulated HUVEC injury and pyroptosis, which were manifested by improved cell viability, lower lactate dehydrogenase (LDH) levels and DNA damage as well as decreased expression of pyroptosis-related markers, such as NOD-like receptor pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), pro-Caspase-1, cleaved Caspase-1, N-terminus of Gasdermin D-N (GSDMD-N), pro-interleukins-1β (pro-IL-1β), IL-1β and inflammatory cytokines (IL-18 and IL-1β).

Astragaloside IV protects against C/EBP homologous protein-mediated apoptosis in oxidized low-density lipoprotein-treated macrophages by promoting autophagy.

Astragaloside Ⅳ (AS-Ⅳ) is one of the main active components extracted from Astragalus membranaceus that exerts an antiatherosclerotic effect. Our study explored the underlying anti-apoptotic effects and the mechanisms of action of AS-Ⅳ in oxidized low-density lipoprotein (oxLDL)-stimulated macrophages and in vulnerable plaques. The results showed that AS-Ⅳ lowered the oxLDL-induced lipid content and reversed the oxLDL-induced reduction in cell viability and elevation in lactate dehydrogenase (LDH) leakage and apoptosis in RAW264.

microelectrode monitoring of real-time hydrogen concentration in different tissues of rats after inhaling hydrogen gas.

Medical effects of hydrogen have been reported in many studies. Due to difficulties in measuring hydrogen concentration in vivo after intake and high explosive risks of hydrogen, studies about dose-response relationships and tissue concentrations of hydrogen are few. Here, for the first time, we monitored real-time hydrogen concentrations in different tissues in rats including brain, liver, spleen, kidney, thigh muscle, inguinal white adipose tissue, and gonadal white adipose tissue after inhaling different concentrations of hydrogen (4%, 42%, and 67%) using an electrochemical sensor.

D4F alleviates the C/EBP homologous protein-mediated apoptosis in glycated high-density lipoprotein-treated macrophages by facilitating autophagy.

The present study aimed to investigate the role of D4F, an apolipoprotein A-I mimetic peptide, in macrophage apoptosis induced by the glycated high-density lipoprotein (gly-HDL)-induced endoplasmic reticulum (ER) stress C/EBP homologous protein (CHOP) pathway, and unravel the regulatory role of autophagy in this process. Our results revealed that except for suppressing the accumulation of lipids within RAW264.7 macrophages caused by gly-HDL, D4F inhibited gly-HDL-induced decrease in the cell viability and increase in lactate dehydrogenase leakage and cell apoptosis, which were similar to 4-phenylbutyric acid (PBA, an ER stress inhibitor).

Human cholesteryl ester transport protein transgene promotes macrophage reverse cholesterol transport in C57BL/6 mice and phospholipid transfer protein gene knockout mice.

Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) belong to the same gene family. Liver-specific expression of CETP improves reverse cholesterol transport (RCT) and PLTP knockout (KO) decreases RCT in mice. In this study, we investigate the effect of CETP transgene (CETP-tg) on RCT and whether CETP-tg can partially restore RCT efficiency in PLTP KO mice.

Effects of hydrogen as adjuvant treatment for unstable angina.

Oxidative stress and inflammation are closely related to atherosclerotic cardiovascular disease. It is established that hydrogen has significant protective effects on many diseases as a potential antioxidative and anti-inflammatory agent. The purpose of this study is to evaluate the effect of hydrogen on unstable angina An atherosclerosis model was constructed by ox-LDL-induced injury of human umbilical vein endothelial cells and testing indicated hydrogen inhibited ox-LDL-induced oxidative stress and inflammatory response by down-regulating LOX-1/NF-kB signaling pathway.

Roles and mechanisms of phospholipid transfer protein in the development of Alzheimer's disease.

Phospholipid transfer protein (PLTP) is a complex glycosylated protein that mediates the transfer of phospholipids, unesterified cholesterol, diacylglycerides, specific apolipoproteins, and tocopherols between different classes of lipoproteins as well as between lipoproteins and cells. Many studies have associated PLTP with a variety of lipid metabolic diseases. However, recent studies have indicated that PLTP is highly expressed in the brain of vertebrate and may be related to many central nervous system diseases, such as Alzheimer's disease.

Hydrogen influences HDL-associated enzymes and reduces oxidized phospholipids levels in rats fed with a high-fat diet.

Aims: Oxidized phospholipids (OxPLs) are formed as a result of oxidative stress, which potentially mediate multiple pathological effects. We aimed to evaluate the effects of hydrogen (H) on OxPLs in vivo and the underlying mechanism.

Main Methods: Rats were randomly assigned to three groups: control group fed with a chow diet, model group fed with a high-fat diet, and H-treated group fed with a high-fat diet and treated by 4% H inhalation for ten weeks.

Physcion, a tetra-substituted 9,10-anthraquinone, prevents homocysteine-induced endothelial dysfunction by activating Ca- and Akt-eNOS-NO signaling pathways.

Background: Homocysteine (Hcy) induced vascular endothelial dysfunction is known to be closely associated with oxidative stress and impaired NO system. 1,8-Dihydroxy-3-methoxy-6-methylanthracene-9,10-dione (physcion) has been known to has antioxidative and anti-inflammatory properties.

Purpose: The purpose of the present study was to define the protective effect of physcion on Hcy-induced endothelial dysfunction and its mechanisms involved.

Neuroprotective Effects of Molecular Hydrogen: A Critical Review.

Molecular hydrogen (H) is a physiologically inert gas. However, during the last 10 years, increasing evidence has revealed its biological functions under pathological conditions. More specifically, H has protective effects against a variety of diseases, particularly nervous system disorders, which include ischemia/reperfusion injury, traumatic injury, subarachnoid hemorrhage, neuropathic pain, neurodegenerative diseases, cognitive dysfunction induced by surgery and anesthesia, anxiety, and depression.

Sphingomyelin Synthase 2 Inhibition Ameliorates Cerebral Ischemic Reperfusion Injury Through Reducing the Recruitment of Toll-Like Receptor 4 to Lipid Rafts.

Background Inflammation is recognized as an important contributor of ischemia/reperfusion (I/R) damage after ischemic stroke. Sphingomyelin synthase 2 (SMS2), the key enzyme for the biosynthesis of sphingomyelin, can function as a critical mediator of inflammation. In the present study, we investigated the role of SMS2 in a mouse model of cerebral I/R.

Protective effects of oxymatrine on homocysteine-induced endothelial injury: Involvement of mitochondria-dependent apoptosis and Akt-eNOS-NO signaling pathways.

Homocysteine (Hcy) is an independent risk factor in the development of cardiovascular diseases (CVD). Hyperhomocysteinemia (HHcy), induces the injury of vascular endothelial cells via oxidative stress. Oxymatrine (OMT), one of the main components of Sophora flavescens, has displayed anti-inflammatory, anti-oxidant and anti-apoptotic activity.

Inhibitory effects of hydrogen on in vitro platelet activation and in vivo prevention of thrombosis formation.

Aims: Hydrogen (H) has antioxidant effects. The pharmacologic function of H in platelets is not yet clear. Therefore, in this study we sought to investigate the inhibitory effects of H on in vitro platelet activation and in vivo prevention of thrombus formation.

Reverse-D-4F improves endothelial progenitor cell function and attenuates LPS-induced acute lung injury.

Background: Patients with acute lung injury (ALI) have increased levels of pro-inflammatory mediators, which impair endothelial progenitor cell (EPC) function. Increasing the number of EPC and alleviating EPC dysfunction induced by pro-inflammatory mediators play important roles in suppressing ALI development. Because the high density lipoprotein reverse-D-4F (Rev-D4F) improves EPC function, we hypothesized that it might repair lipopolysaccharide (LPS)-induced lung damage by improving EPC numbers and function in an LPS-induced ALI mouse model.

Phospholipid transfer protein (PLTP) deficiency attenuates high fat diet induced obesity and insulin resistance.

Increased phospholipid transfer protein (PLTP) activity has been found to be associated with obesity, and metabolic syndrome in humans. However, whether or not PLTP has a direct effect on insulin sensitivity and obesity is largely unknown. Here we analyzed the effect by using PLTP knockout (PLTP) mouse model.

[Different types of molecular hydrogen donors and their pharmacokinetics in vivo].

Molecular hydrogen (H) has been shown to have diverse biomedical effects. As a small molecular gas, hydrogen can be diffused to the target without hindrance. A variety of related hydrogen products used in medical research and public health have been developed.

Endoplasmic reticulum stress-dependent autophagy inhibits glycated high-density lipoprotein-induced macrophage apoptosis by inhibiting CHOP pathway.

This study was designed to explore the inductive effect of glycated high-density lipoprotein (gly-HDL) on endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP)-mediated macrophage apoptosis and its relationship with autophagy. Our results showed that gly-HDL caused macrophage apoptosis with concomitant activation of ER stress pathway, including nuclear translocation of activating transcription factor 6, phosphorylation of protein kinase-like ER kinase (PERK) and eukaryotic translation initiation factor 2α, and CHOP up-regulation, which were inhibited by 4-phenylbutyric acid (PBA, an ER stress inhibitor) and the gene silencing of PERK and CHOP. Similar data were obtained from macrophages treated by HDL isolated from diabetic patients.

Hydrogen-rich water ameliorates rat placental stress induced by water restriction.

Dehydration is one of the intrauterine abnormalities that could lead to fetal growth retardation and to increase the risk of a variety of adult diseases later in life. This study were to determine the impact of hydrogen-rich water (HRW) supplementation on placental angiotensin II type 1 receptor and placental oxidative stress induced by water restriction. Pregnant Wistar rat were randomly assigned to one of the three groups ( =12 per group).

Irisin protects macrophages from oxidized low density lipoprotein-induced apoptosis by inhibiting the endoplasmic reticulum stress pathway.

Irisin is a newly discovered myokine which can relieve metabolic disorders and resist atherosclerosis. The effects of irisin on ox-LDL-induced macrophage apoptosis and endoplasmic reticulum stress-related pathways were observed . RAW264.

Ubiquitin ligase TRAF2 attenuates the transcriptional activity of the core clock protein BMAL1 and affects the maximal Per1 mRNA level of the circadian clock in cells.

The ubiquitin-proteasome system (UPS) modulates the ubiquitination and degradation of many proteins and thus alters their abundance and biological functions. The core clock protein, aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL or BMAL1), is the master regulator of the circadian clock and plays important roles in the regulation of many biological processes, such as protein synthesis, cell senescence, and circadian rhythms. However, the influence of the UPS on BMAL1 is not fully understood.

Prodomain of Furin Promotes Phospholipid Transfer Protein Proteasomal Degradation in Hepatocytes.

Background: Phospholipid transfer protein (PLTP) is one of the major modulators of lipoprotein metabolism and atherosclerosis development; however, little is known about the regulation of PLTP. The effect of hepatic prodomain of furin (profurin) expression on PLTP processing and function is investigated.

Methods And Results: We used adenovirus expressing profurin in mouse liver to evaluate PLTP activity, mass, and plasma lipid levels.

[Activating transcription factor 6-C/EBP homologous protein pathway mediates advanced glycated albumin-induced macrophage apoptosis].

The purpose of this study was to investigate whether activating transcription factor 6 (ATF6), a sensor to endoplasmic reticulum stress (ERS), would mediate advanced glycated albumin (AGE-alb)-induced macrophage apoptosis and to elucidate the possible molecular mechanisms. RAW264.7 macrophages were cultured in vitro and treated with AGE-alb (2, 4 and 6 g/L), normal control albumin or tunicamycin (TM, 4 mg/L) for 24 h.

Molecular hydrogen: a preventive and therapeutic medical gas for various diseases.

Since the 2007 discovery that molecular hydrogen (H) has selective antioxidant properties, multiple studies have shown that H has beneficial effects in diverse animal models and human disease. This review discusses H biological effects and potential mechanisms of action in various diseases, including metabolic syndrome, organ injury, and cancer; describes effective H delivery approaches; and summarizes recent progress toward H applications in human medicine. We also discuss remaining questions in H therapy, and conclude with an appeal for a greater role for H in the prevention and treatment of human ailments that are currently major global health burdens.

Mechanisms of vasorelaxation induced by total flavonoids of Euphorbia humifusa in rat aorta.

Euphorbia humifusa Willd. (EH), rich in flavonoids, has long been used for the treatment of bacillary dysentery and enteritis in China, and is known to have antioxidant, hypotensive and hypolipidemic properties. However, the vasorelaxant effect of total flavonoids of EH (TFEH) and action mechanisms are not clearly defined yet.