Repressing cytokine storm-like response in macrophages by targeting the eIF2α-integrated stress response pathway.

Cytokine storm is a life-threatening systemic hyper-inflammatory state caused by different etiologies, in which the bulk production of pro-inflammatory cytokines from activated macrophages has a central role. Integrated stress response (ISR) comprises several protective signaling pathways, leading to phosphorylation of eukaryotic initiation factor 2α (eIF2α) and repression of protein translation. Emerging evidence suggests that ISR induction may elicit anti-inflammatory effects.

Alizarin attenuates oxidative stress-induced mitochondrial damage in vascular dementia rats by promoting TRPM2 ubiquitination and proteasomal degradation via Smurf2.

Background: Alizarin (AZ) is a natural anthraquinone with anti-inflammatory and moderate antioxidant properties.

Purpose: In this study, we characterized the role of AZ in a rat model of vascular dementia (VaD) and explored its underlying mechanisms.

Methods: VaD was induced by bilateral common carotid artery occlusion.

Puerarin inhibits NHE1 activity by interfering with the p38 pathway and attenuates mitochondrial damage induced by myocardial calcium overload in heart failure rats.

Previous studies have shown that puerarin plays a key role in protecting humans and animals from cardiovascular diseases. The exact mechanism of the therapeutic effect of puerarin on various cardiovascular diseases (protective effect on cardiomyocytes) is still unclear. In the present study, we identify the role of puerarin in an animal model of experimental heart failure (HF) and explore its underlying mechanisms.

CX-5461 is a potent immunosuppressant which inhibits T cell-mediated alloimmunity via p53-DUSP5.

CX-5461 is a first-in-class selective RNA polymerase I inhibitor. Previously we found that CX-5461 had anti-inflammatory activities. In this study we characterized potential immunosuppressive effects of CX-5461 and explored the underlying mechanisms.

Amino acid starvation-induced LDLR trafficking accelerates lipoprotein endocytosis and LDL clearance.

Mammalian cells utilize Akt-dependent signaling to deploy intracellular Glut4 toward cell surface to facilitate glucose uptake. Low-density lipoprotein receptor (LDLR) is the cargo receptor mediating endocytosis of apolipoprotein B-containing lipoproteins. However, signaling-controlled regulation of intracellular LDLR trafficking remains elusive.

The p53 pathway in vasculature revisited: A therapeutic target for pathological vascular remodeling?

Pathological vascular remodeling contributes to the development of restenosis following intraluminal interventions, transplant vasculopathy, and pulmonary arterial hypertension. Activation of the tumor suppressor p53 may counteract vascular remodeling by inhibiting aberrant proliferation of vascular smooth muscle cells and repressing vascular inflammation. In particular, the development of different lines of small-molecule p53 activators ignites the hope of treating remodeling-associated vascular diseases by targeting p53 pharmacologically.

Angiotensin II type 1 receptor blockers prevent aortic arterial stiffness in elderly patients with hypertension.

: Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blockers (ARBs) are potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of ARBs in aged patients with essential hypertension are not entirely investigated. : The carotid-femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension.

S-Nitrosylation of Prostacyclin Synthase Instigates Nitrate Cross-Tolerance In Vivo.

Development of nitrate tolerance is a major drawback to nitrate therapy. Prostacyclin (PGI2) is a powerful vasodilator produced from prostaglandin (PGH2) by prostacyclin synthase (PGIS) in endothelial cells. This study aimed to determine the role of PGIS S-nitrosylation in nitrate tolerance induced by nitroglycerin (GTN).

Traditional Chinese medicine Ka-Sai-Ping suppresses the growths of gastric cancers via induction of autophagy.

Traditional Chinese medication is increasingly used to treat a wide range of human chronic diseases like cardiovascular diseases and cancers. This study was designed to explore whether ka-sai-ping (KSP), a novel traditional Chinese medicine developed by us, prevents gastric cancer growths and to investigate the underlying mechanism. The xenograft model of mouse gastric cancer was established by injecting MFCs into nude mouse subcutaneously.

Vitamin B6 prevents isocarbophos-induced vascular dementia in rats through N-methyl-D-aspartate receptor signaling.

Background: We have previously reported that the long-term exposure of organophosphorus induces vascular dementia (VD) in rats. As a coenzyme, vitamin B6 is mainly involved in the regulation of metabolisms. Whether vitamin B6 improves VD remains unknown.

Traditional Chinese medicine xin-mai-jia recouples endothelial nitric oxide synthase to prevent atherosclerosis in vivo.

Endothelial dysfunction, which is caused by endothelial nitric oxide synthase (eNOS) uncoupling, is an initial step in atherosclerosis. This study was designed to explore whether Chinese medicine xin-mai-jia (XMJ) recouples eNOS to exert anti-atherosclerotic effects. Pretreatment of XMJ (25, 50, 100 μg/ml) for 30 minutes concentration-dependently activated eNOS, improved cell viabilities, increased NO generations, and reduced ROS productions in human umbilical vein endothelial cells incubated with HO for 2 hours, accompanied with restoration of BH4.

Chronic administration of isocarbophos induces vascular cognitive impairment in rats.

Vascular dementia, being the most severe form of vascular cognitive impairment (VCI), is caused by cerebrovascular disease. Whether organophosphorus causes VCI remains unknown. Isocarbophos (0.

Protective effect of Xin Mai Jia ultrafiltration extract on human umbilical vein endothelial cell injury induced by hydrogen peroxide and the effect on the NO-cGMP signaling pathway.

The aim of the present study was to evaluate the protective effect of the ultrafiltration extract of Xin Mai Jia (XMJ) on a human umbilical vein endothelial cell (HUVEC) injury model induced by hydrogen peroxide (HO), by providing experimental data to investigate the mechanism and efficacy underlying the therapeutic effects on atherosclerosis. HUVECs were first injured by HO and then varying final concentrations of the Chinese herb extract were added. Effects of the XMJ extract on morphology, activity, monolayer permeability, biochemical indicators, cytokines, endothelial nitric oxide synthase (eNOS) protein content and eNOS gene expression in the HUVECs were analyzed.

Protective effect of the ultra-filtration extract from Xin Mai Jia on human aortic smooth muscle cell injury induced by hydrogen peroxide.

The aim of the present study was to explore whether an ultra-filtration extract from Xin Mai Jia (XMJ), a Chinese medicinal formulation, has a protective effect on human aortic smooth muscle cell (HASMC) injury models induced by hydrogen peroxide (HO), and to consider the mechanism and efficacy of the therapeutic action of XMJ on atherosclerosis. HASMCs were injured by HO and then exposed to various concentrations of XMJ. The morphological changes, growth, proliferation, migration and cytokine release of HASMCs were detected using 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT), an enzyme-linked immunosorbent assay and a scratch adhesion test.

[Role of ventricular M3 receptor in arrhythmia resulted from cerebral-cardiac syndrome].

To detect the function and expression of ventricular M3 receptor (M3R) in cerebral-cardiac syndrome (CCS) model rats and to explore the relationship between the expression of M3R and the arrhythmia resulted from CCS, CCS model rats were induced by occluding right middle cerebral artery. ECG was monitored. Intracellular calcium ([Ca2+]i) changes after agitating M3R were recorded by laser scanning confocal microscope.

Aberration of L-type calcium channel in cardiac myocytes is one of the mechanisms of arrhythmia induced by cerebral ischemia.

We have examined whether there is a close link between cerebral ischemia and arrhythmogenesis in rats as well as its possible electrophysiological mechanisms. Cerebral ischemic model was made by middle cerebral artery occlusion (MCAO). The incidence of electrocardiographic (ECG) abnormality was as high as 75.