Diabetes mellitus (DM) is a progressive metabolic disease characterized by chronic hyperglycemia and caused by different degree of pancreatic islet dysfunction and/or insulin resistance (IR). Long course DM can lead to a variety of macrovascular and microvascular complications which involve artery vessels, heart, kidney, retina, nervous system, etc. In recent years, DM has attracted more and more attention due to its high morbidity and mortality. In addition to achieve effective glycemic control, prevention of complications has also been considered a priority for type 2 diabetes mellitus (T2DM) management. Herein, we provide a comprehensive overview on the pharmacotherapeutics for T2DM and perspectives on the future directions of basic and translational research on anti-diabetic therapy and pharmatheutical development of new drugs.

  Background  Apelin, an endogenous ligand of G-protein coupled receptor (GPCR), is a secreted peptide involved in the development of various tumors. However, the relationship between apelin and nonsmall cell lung cancer (NSCLC) is not quite clear. This study was designed to investigate the effect and mechanism of apelin on cell proliferation, migration and invasion of NSCLC cells.  Methods  Twelve NSCLC specimens were collected for hematoxylin-eosin (HE) staining and immunohistochemistry analyses. Cell proliferation was examined by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and cell migration and invasion were assessed using wound-healing and transwell assays. The subcellular location of yes associated protein 1 (YAP1) in A549 cells was determined by immunofluorescence. The mRNA and protein levels in NSCLC tissues and cell lines were measured by qRT-PCR and western blot, respectively.  Results  Apelin was upregulated in tumor tissues compared with the adjacent tissues. Apelin promoted proliferation, migration, and invasion of A549 and H460 cells, which was reversed by competitive apelin receptor (APJ) antagonist ML221. Additionally, apelin upregulated YAP1 expression, whereas silence of YAP1 by small interfering RNA (siRNA) attenuated apelin-induced cell proliferation, migration and invasion and suppressed epithelial-mesenchymal transition progression.  Conclusion  Apelin promotes NSCLC cells proliferation, migration, and invasion by modulating YAP1 and might be a potential therapeutic target for NSCLC treatment.

Hypertension is the most common cardiovascular condition in clinical practice and a major risk factor for stroke and cardiovascular events. There are more than 270 million hypertension patients in China, and the prevalence of hypertension in the high-latitude cold areas is significantly higher than in the low-latitude warm areas. The unique epidemiological characteristics and risk factors of hypertension in the cold regions of China urge for establishment of the prevention and control system for targeted and more effective management of the condition.

  Background  Myocardial infarction (MI) is associated with higher morbidity and mortality in the world, especially in cold weather. YBX1 is an RNA-binding protein that is required for pathological growth of cardiomyocyte by regulating cell growth and protein synthesis. But YBX1, as an individual RNA-binding protein, regulates cardiomyocytes through signaling cascades during myocardial infarction remain largely unexplored.  Methods  In vivo, the mouse MI model was induced by ligating the left anterior descending coronary artery (LAD), and randomly divided into sham operation group, MI group, MI+ YBX1 knockdown/overexpression group and MI+ negative control (NC) group. The protective effect of YBX1 was verified by echocardiography and triphenyltetrazolium chloride staining. In vitro, mitochondrial-dependent apoptosis was investigated by using CCK8, TUNEL staining, reactive oxygen species (ROS) staining and JC-1 staining in hypoxic neonatal mouse cardiomyocytes (NMCMs).  Results  YBX1 expression of cardiomyocytes was downregulated in a mouse model and a cellular model on the ischemic condition. Compared to mice induced by MI, YBX1 overexpression mediated by adeno-associated virus serotype 9 (AAV9) vector reduced the infarcted size and improved cardiac function. Knockdown of endogenous YBX1 by shRNA partially aggravated ischemia-induced cardiac dysfunction. In hypoxic cardiomyocytes, YBX1 overexpression decreased lactic dehydrogenase (LDH) release, increased cell viability, and inhibited apoptosis by affecting the expression of apoptosis related proteins, while knockdown of endogenous YBX1 by siRNA had the opposite effect. Overexpression of YBX1 restored mitochondrial dysfunction in hypoxic NMCMs by increasing mitochondrial membrane potential and ATP content and decreasing ROS. In hypoxic NMCMs, YBX1 overexpression increased the expression of phosphorylated phosphatidylinositol 3 kinase (PI3K)/AKT, and the antiapoptosis effect of YBX1 was eliminated t by LY294002, PI3K/AKT inhibitor.  Conclusion  YBX1 protected the heart from ischemic damage by inhibiting the mitochondrial-dependent apoptosis through PI3K/AKT pathway. It is anticipated that YBX1 may serve as a novel therapeutic target for MI.

  Background and Objective  Cardiac fibrosis is a pathological reparative process that follows myocardial infarctionand is associated with compromised cardiac systolic and reduced cardiac compliance. The Wnt signaling pathway is closely implicated in organ fibrosis, and Notum, a highly conserved secreted inhibitor, modulates Wnt signaling. The objective of this study was to explore the role and mechanism of Notum in cardiac fibrosis.  Methods  A mouse model of cardiac remodeling was established through left coronary artery ligation surgery, with the addition of Notum injection following myocardial infarction surgery. The protective effect of Notum on myocardial infarction was assessed by evaluating cardiac function, including survival rate, echocardiographic assessment, and cardiac contraction analyses. Inflammatory cell necrosis and infiltration were confirmed through H & E and Masson staining. The expression of fibrosis-related genes and β-catenin pathway markers was detected using Western blot quantificational RT-PCR (qRT-PCR). Additionally, EdU, wound healing, and immunofluorescence staining analyses were performed to detect the effect of Notum's in transforming growth factor beta-1 (TGF-β1) induced myofibroblast transformation.  Results  The administration of Notum treatment resulted in enhanced survival rates, improved cardiac function, and decreased necrosis and infiltration of inflammatory cells in mice subjected to left coronary artery ligation. Furthermore, Notum effectively impeded the senescence of cardiac fibroblasts and hindered their pathological transformation into cardiac fibroblasts. Additionally, it significantly reduced collagen production and attenuated the activation of the Wnt/β-catenin pathway. Our preliminary investigations successfully demonstrated the therapeutic potential of Notum in both fibroblasts in vitro and in a mouse model of myocardial infarction-induced cardiac fibrosis in vivo.  Conclusion  Notum inhibition of the Wnt/β-catenin signaling pathway and cardiac fibroblast senescence ultimately hampers the onset of cardiac fibrosis. Our findings suggest that Notum could represent a new therapeutic strategy for the treatment of cardiac fibrosis.