A detrimental role of endothelial S1PR2 in cardiac ischemia-reperfusion injury via modulating mitochondrial dysfunction, NLRP3 inflammasome activation, and pyroptosis.

Sphingosine 1-phosphate (S1P), a bioactive lipid molecule, exerts multifaceted effects on cardiovascular functions via S1P receptors, but its effects on cardiac I/R injury are not fully understood. Plasma lipidomics analysis by mass spectrometry revealed that sphingosine lipids, including sphingosine 1-phosphate (S1P), were significantly down-regulated following cardiac I/R injury in mice. The reduced S1P levels were also observed in the plasma of coronary heart disease (CHD) patients after percutaneous coronary intervention (PCI) compared with those without PCI.

The Association of Lipoprotein(a) and Neutrophil-to-Lymphocyte Ratio Combination with Atherosclerotic Cardiovascular Disease in Chinese Patients.

Objective: The association of lipoprotein(a) [Lp(a)] with atherosclerotic cardiovascular disease (ASCVD) risk can be modified by chronic systemic inflammation. The neutrophil-to-lymphocyte ratio (NLR) is a reliable and easily available marker of immune response to various infectious and non-infectious stimuli. The purpose of this study was to assess the combined effects of Lp(a) and NLR in predicting the ASCVD risk and coronary artery plaque traits.

Liver sinusoidal endothelial S1pr2 regulates experimental liver fibrosis through YAP/TGF-β signaling pathway.

The hepatic vascular niche plays an important role in the pathological process of liver fibrosis. Liver sinusoidal endothelial cells (LSECs) predominantly compose hepatic vascular niches. Endothelial cell (EC)-expressing sphingosine 1-phosphate receptor 2 (S1pr2) plays an essential role in the regulation of vascular functions.

Lymphatic endothelial sphingosine 1-phosphate receptor 1 enhances macrophage clearance via lymphatic system following myocardial infarction.

Lymphatic endothelial cell homeostasis plays important roles in normal physiological cardiac functions, and its dysfunction significantly influences pathological cardiac remodeling after myocardial infarction (MI). Our results revealed that sphingosine 1-phosphate receptor 1 (S1pr1) expression in cardiac lymphatic endothelial cells (LECs) was sharply changed after MI. It has been shown that S1pr1 tightly controlled LEC functions and homeostasis.

Endothelial S1pr2 regulates post-ischemic angiogenesis via AKT/eNOS signaling pathway.

It is important to understand the mechanism that regulates post-ischemic angiogenesis and to explore a new therapeutic target for an effective improvement of revascularization in peripheral artery disease (PAD) patients. Post-ischemic angiogenesis is a highly orchestrated process, which involves vascular endothelial cells (ECs) proliferation, migration and assembly into capillaries. We found a significant reduction of S1pr2 (sphingosine 1-phosphate receptor 2) in endothelial cells after hindlimb ischemia (HLI).

Ubc13 Promotes K63-Linked Polyubiquitination of NLRP3 to Activate Inflammasome.

NLRP3 inflammasome plays an important role in innate immune system through recognizing pathogenic microorganisms and danger-associated molecules. Deubiquitination of NLRP3 has been shown to be essential for its activation, yet the functions of Ubc13, the K63-linked specific ubiquitin-conjugating enzyme E2, in NLRP3 inflammasome activation are not known. In this study, we found that in mouse macrophages, Ubc13 knockdown or knockout dramatically impaired NLRP3 inflammasome activation.

SIRT3-mediated deacetylation of NLRC4 promotes inflammasome activation.

() infection of macrophage induces NLRC4 inflammasome-mediated production of the pro-inflammatory cytokines IL-1β. Post-translational modifications on NLRC4 are critical for its activation. Sirtuin3 (SIRT3) is the most thoroughly studied mitochondrial nicotinamide adenine dinucleotide (NAD) -dependent deacetylase.

Acquired Resistance to EGFR TKIs Mediated by TGFβ1/Integrin β3 Signaling in EGFR-Mutant Lung Cancer.

Investigation of novel molecular mechanisms is essential to develop strategies to overcome acquired resistance to EGFR tyrosine kinase inhibitors (TKI). Integrin has been demonstrated as a regulator of cancer progression. The aim of this study was to identify which specific integrins are involved and regulated in acquired resistance to EGFR TKIs in EGFR-mutant lung cancer.

Epigenetic silencing of miR-483-3p promotes acquired gefitinib resistance and EMT in EGFR-mutant NSCLC by targeting integrin β3.

All lung cancers patients with epidermal growth factor receptor (EGFR) mutation inevitably develop acquired resistance to EGFR tyrosine kinase inhibitors (TKI). In up to 30% of cases, the mechanism underlying acquired resistance remains unknown. MicroRNAs (miRNAs) is a group of small non-coding RNAs commonly dysregulated in human cancers and have been implicated in therapy resistance.

Acquisition of EGFR TKI resistance and EMT phenotype is linked with activation of IGF1R/NF-κB pathway in EGFR-mutant NSCLC.

Epithelial-mesenchymal transition (EMT) is clinically associated with acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) in non-small cell lung cancers (NSCLC). However, the mechanisms promoting EMT in EGFR TKI-resistant NSCLC have not been fully elucidated. Previous studies have suggested that IGF1R signaling is involved in both acquired EGFR TKI resistance in NSCLC and induction of EMT in some types of tumor.

Inactivation of M2 AChR/NF-κB signaling axis reverses epithelial-mesenchymal transition (EMT) and suppresses migration and invasion in non-small cell lung cancer (NSCLC).

Non-neuronal cholinergic system is involved in lung physiology and lung cancer. However, the biochemical events downstream acetylcholine (ACh) receptor activation leading to carcinogenesis and tumor progression are not fully understood. Our previous work has shown that non-neuronal ACh acts as an autoparacrine growth factor to stimulate cell proliferation and promote epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) via activation of M2 muscarinic receptor (M2R).