Intermedin Alleviates Diabetic Cardiomyopathy by Up-Regulating CPT-1β through Activation of the Phosphatidyl Inositol 3 Kinase/Protein Kinase B Signaling Pathway.

Diabetic cardiomyopathy (DCM), one of the most serious long-term consequences of diabetes, is closely associated with myocardial fatty acid metabolism. Carnitine palmitoyltransferase-1β (CPT-1β) is the rate-limiting enzyme responsible for β-oxidation of long-chain fatty acids. Intermedin (IMD) is a pivotal bioactive small molecule peptide, participating in the protection of various cardiovascular diseases.

SIRT3 sulfhydration using hydrogen sulfide inhibited angiotensin II-induced atrial fibrosis and vulnerability to atrial fibrillation via suppression of the TGF-β1/smad2/3 signalling pathway.

Atrial fibrosis is associated with the occurrence of atrial fibrillation (AF) and regulated by the transforming growth factor-β1 (TGF-β1)/Smad2/3 signalling pathway. Unfortunately, the mechanisms of regulation of TGF-β1/Smad2/3-induced atrial fibrosis and vulnerability to AF remain still unknown. Previous studies have shown that sirtuin3 (SIRT3) sulfhydration has strong anti-fibrotic effects.

SIRT3/AMPK Signaling Pathway Regulates Lipid Metabolism and Improves Vulnerability to Atrial Fibrillation in Dahl Salt-Sensitive Rats.

Background: Hypertension may result in atrial fibrillation (AF) and lipid metabolism disorders. The Sirtuins3 (SIRT3)/AMP-activated protein kinase (AMPK) signaling pathway has the capacity to regulate lipid metabolism disorders and the onset of AF. We hypothesize that the SIRT3/AMPK signaling pathway suppresses lipid metabolism disorders, thereby mitigating salt-sensitive hypertension (SSHT)-induced susceptibility to AF.

TRIM65 promotes vascular smooth muscle cell phenotypic transformation by activating PI3K/Akt/mTOR signaling during atherogenesis.

Background And Aims: Tripartite motif (TRIM65) is an important member of the TRIM protein family, which is a newly discovered E ligase that interacts with and ubiquitinates various substrates and is involved in diverse pathological processes. However, the function of TRIM65 in atherosclerosis remains unarticulated. In this study, we investigated the role of TRIM65 in the pathogenesis of atherosclerosis, specifically in vascular smooth muscle cells (VSMCs) phenotype transformation, which plays a crucial role in formation of atherosclerotic lesions.

scATAC-Ref: a reference of scATAC-seq with known cell labels in multiple species.

Chromatin accessibility profiles at single cell resolution can reveal cell type-specific regulatory programs, help dissect highly specialized cell functions and trace cell origin and evolution. Accurate cell type assignment is critical for effectively gaining biological and pathological insights, but is difficult in scATAC-seq. Hence, by extensively reviewing the literature, we designed scATAC-Ref (https://bio.

Phosphodiesterase type 10A inhibitor attenuates lung fibrosis by targeting myofibroblast activation.

Pulmonary fibrosis (PF) is a fatal and irreversible respiratory disease accompanied by excessive fibroblast activation. Previous studies have suggested that cAMP signaling pathway and cGMP-PKG signaling pathway are continuously down-regulated in lung fibrosis, whereas PDE10A has a specifically expression in fibroblasts/myofibroblasts in lung fibrosis. In this study, we demonstrated that overexpression of PDE10A induces myofibroblast differentiation, and papaverine, as a PDE10A inhibitor used for vasodilation, inhibits myofibroblast differentiation in human fibroblasts, Meanwhile, papaverine alleviated bleomycin-induced pulmonary fibrosis and amiodarone-induced oxidative stress, papaverine downregulated VASP/β-catenin pathway to reduce the myofibroblast differentiation.

PLK1 promotes cholesterol efflux and alleviates atherosclerosis by up-regulating ABCA1 and ABCG1 expression via the AMPK/PPARγ/LXRα pathway.

Polo-like kinase 1 (PLK1) is a serine/threonine kinase involving lipid metabolism and cardiovascular disease. However, its role in atherogenesis has yet to be determined. The aim of this study was to observe the impact of PLK1 on macrophage lipid accumulation and atherosclerosis development and to explore the underlying mechanisms.

Hydrogen Sulfide Ameliorates Angiotensin II-Induced Atrial Fibrosis Progression to Atrial Fibrillation Through Inhibition of the Warburg Effect and Endoplasmic Reticulum Stress.

Atrial fibrosis is the basis for the occurrence and development of atrial fibrillation (AF) and is closely related to the Warburg effect, endoplasmic reticulum stress (ERS) and mitochondrion dysfunctions-induced cardiomyocyte apoptosis. Hydrogen sulfide (HS) is a gaseous signalling molecule with cardioprotective, anti-myocardial fibrosis and improved energy metabolism effects. Nevertheless, the specific mechanism by which HS improves the progression of atrial fibrosis to AF remains unclear.

Dynamic biomechanical effect of lower body positive pressure treadmill training for hemiplegic gait rehabilitation after stroke: A case report.

Background: Lower body positive pressure (LBPP) treadmill has potential applications for improving the gait of patients after stroke, but the related mechanism remains unclear.

Case Summary: A 62-year-old male patient suffered from ischemic stroke with hemiplegic gait. He was referred to our hospital because of a complaint of left limb weakness for 2 years.

N6-methyladenine RNA Modification (mA): An Emerging Regulator of Metabolic Diseases.

N6-methyladenine RNA modification (m6A) is an RNA methylation modification catalyzed by methyltransferase at the 6th position nitrogen atom of adenine (A), which is the most common chemical modification of eukaryotic messenger RNA (mRNA). Recently, m6A has been found to play an important role in the dynamic regulation of RNA, which is crucial for some physiological and pathophysiological processes such as adipogenesis, cell differentiation, and the immune/inflammatory response. Metabolic diseases are a series of chronic inflammatory disorders caused by metabolic dysfunction of proteins, glucose, and lipids.

Airborne Bacteria Enriched PM2.5 Enhances the Inflammation in an Allergic Adolescent Mouse Model Induced by Ovalbumin.

Air pollution events frequently occur in China during the winter. Most investigations of pollution studies have focused on the physical and chemical properties of PM2.5.

Protective Effect of Quercetin in LPS-Induced Murine Acute Lung Injury Mediated by cAMP-Epac Pathway.

Quercetin (Que) as an abundant flavonol element possesses potent antioxidative properties and has protective effect in lipopolysaccharide (LPS)-induced acute lung injury (ALI), but the specific mechanism is still unclear, so we investigated the effect of Que from in vivo and in vitro studies and the related mechanism of cAMP-PKA/Epac pathway. The results in mice suggested that Que can inhibit the release of inflammatory cytokine, block neutrophil recruitment, and decrease the albumin leakage in dose-dependent manners. At the same time, Que can increase the cAMP content of lung tissue, and Epac content, except PKA.

Effects of inactivated Bordetella pertussis on phosphodiesterase in the lung of ovalbumin sensitized and challenged rats.

This paper indicated that inactivated Bordetella pertussis (iBp) can enhance the lung airway hyperreactivity of the rats sensitized and challenged with OVA. The mechanisms were involved in the upregulation of cAMP-PDE activity and PDE4A, PDE4D, and PDE3 gene expression in the lungs. But only PDE4 activity was different between the OVA and OVA+iBp groups, and PDE4D expression was significantly increased in iBp rats alone.

[Progress in PDE4 targeted therapy for inflammatory diseases].

cAMP-specific phosphodiesterase type 4 (PDE4) is one of the hot targets for treatment of inflammatory diseases. PDE4 inhibitors can suppress inflammation by increasing the concentration of cAMP in inflammatory cells. The efficacy and safety evaluations of several PDE4 inhibitors are currently carried on in clinical trials, for example GSK256066 in asthma, roflumilast and GSK256066 in chronic obstructive pulmonary disease, tetomilast in inflammatory bowel disease, and apremilast in dermatitis and arthritis etc.

Effects of local anesthetics on contractions of pregnant and non-pregnant rat myometrium in vitro.

In order to determine whether local anesthetics directly affect the propagation and strength of myometrial contractions, we compared the effects of bupivacaine, ropivacaine, lidocaine and tetracaine on the contractions of myometrium isolated from pregnant and non-pregnant rats. Full-thickness myometrial strips were obtained from 18- to 21-day pregnant and non-pregnant Sprague-Dawley rats and incubated in an organ bath. When spontaneous contractions became regular, strips were exposed to cumulative concentrations of the four local anesthetics ranging from 0.

MiR-122 increases sensitivity of drug-resistant BEL-7402/5-FU cells to 5-fluorouracil via down-regulation of bcl-2 family proteins.

To investigate the changes in drug sensitivity of miR-122 transfected BEL-7402/5-FU cells. MiR-122 and negative miRNA expression vectors were constructed and stably transfected into BEL-7402/5-FU cells. Real-time RT-PCR was used to detect the level of miR-122, Bcl-XL, Bcl-2 and P53 mRNA.

Monoammonium glycyrrhizinate inhibited the inflammation of LPS-induced acute lung injury in mice.

Monoammonium glycyrrhizinate (MAG) was the aglycone of glycyrrhizin derived from licorice. In this study, the anti-inflammatory effects of MAG on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the possible mechanisms involved in this protection were investigated. Pretreatment with MAG prior to the administration of intratracheal LPS significantly induced a decrease in lung wet weight/dry weight ratio, in total leukocyte number and neutrophil percent in the BALF, and in myeloperoxidase (MPO) activity of lung in dose-dependent manners.

Action of a Novel PDE4 inhibitor ZL-n-91 on lipopolysaccharide-induced acute lung injury.

In the present study, we investigated the effect of classic PDE4 inhibitor rolipram and novel PDE4 inhibitor ZL-n-91 on LPS-induced acute lung injury (ALI) in mice and its mechanism. ALI was induced in ICR mice by instilling intratracheally with LPS, and mice were divided into seven groups: control (Saline), LPS group, ZL-n-91 (3 microg, 10 microg, and 30 microg kg(-1), ip), Rolipram (1.0 mg kg(-1), ip) and dexamethasone (0.

Zl-n-91, a selective phosphodiesterase 4 inhibitor, suppresses inflammatory response in a COPD-like rat model.

Chronic obstructive pulmonary disease (COPD) is defined as a disease state characterized by poorly reversible airflow limitation induced by cigarette smoking and/or other noxious particle and gases. Phosphodiesterase (PDE) 4 inhibitors are known to elevated cAMP concentrations in inflammatory cells, leading to inhibition of inflammatory response, relaxation of smooth muscle in the airway, and modulation of sensory nerves in the lung as well. To investigate whether Zl-n-91, a new selective PDE4 inhibitor, could decrease inflammation and improve lung function in a COPD-like rat model, male Sprague-Dawley rats are used to challenge with lipopolysaccharide (LPS) and cigarette smoking (CS) exposure to induce COPD-like animal model.

Propofol pretreatment attenuates aquaporin-4 over-expression and alleviates cerebral edema after transient focal brain ischemia reperfusion in rats.

Background: Cerebral edema is a major threat for stroke victims. Most studies have focused on the neuroprotective activities of propofol, addressing infarct volume rather than cerebral edema. Aquaporin-4 (AQP4) plays an important role in maintaining brain water homeostasis under various neurological insults.