Mitochondria-associated endoplasmic reticulum membrane (MAM): a dark horse for diabetic cardiomyopathy treatment.

Diabetic cardiomyopathy (DCM), an important complication of diabetes mellitus (DM), is one of the most serious chronic heart diseases and has become a major cause of heart failure worldwide. At present, the pathogenesis of DCM is unclear, and there is still a lack of effective therapeutics. Previous studies have shown that the homeostasis of mitochondria and the endoplasmic reticulum (ER) play a core role in maintaining cardiovascular function, and structural and functional abnormalities in these organelles seriously impact the occurrence and development of various cardiovascular diseases, including DCM.

Emerging role of antidiabetic drugs in cardiorenal protection.

The global prevalence of diabetes mellitus (DM) has led to widespread multi-system damage, especially in cardiovascular and renal functions, heightening morbidity and mortality. Emerging antidiabetic drugs sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4i) have demonstrated efficacy in preserving cardiac and renal function, both in type 2 diabetic and non-diabetic individuals. To understand the exact impact of these drugs on cardiorenal protection and underlying mechanisms, we conducted a comprehensive review of recent large-scale clinical trials and basic research focusing on SGLT2i, GLP-1RAs, and DPP-4i.

VDR Activation Attenuates Renal Tubular Epithelial Cell Ferroptosis by Regulating Nrf2/HO-1 Signaling Pathway in Diabetic Nephropathy.

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. Ferroptosis, a new form of cell death, plays a crucial role in the pathogenesis of DN. Renal tubular injury triggered by ferroptosis might be essential in this process.

Broadening horizons: the multifaceted functions of ferroptosis in kidney diseases.

Ferroptosis is an iron-dependent programmed cell death pattern that is characterized by iron overload, reactive oxygen species (ROS) accumulation and lipid peroxidation. Growing viewpoints support that the imbalance of iron homeostasis and the disturbance of lipid metabolism contribute to tissue or organ injury in various kidney diseases by triggering ferroptosis. At present, the key regulators and complicated network mechanisms associated with ferroptosis have been deeply studied; however, its role in the initiation and progression of kidney diseases has not been fully revealed.

Diabetic cardiomyopathy: Early diagnostic biomarkers, pathogenetic mechanisms, and therapeutic interventions.

Diabetic cardiomyopathy (DCM) mainly refers to myocardial metabolic dysfunction caused by high glucose, and hyperglycemia is an independent risk factor for cardiac function in the absence of coronary atherosclerosis and hypertension. DCM, which is a severe complication of diabetes, has become the leading cause of heart failure in diabetic patients. The initial symptoms are inconspicuous, and patients gradually exhibit left ventricular dysfunction and eventually develop total heart failure, which brings a great challenge to the early diagnosis of DCM.

Research advance of natural products in tumor immunotherapy.

Cancer immunotherapy has emerged as a novel anti-tumor treatment. Despite significant breakthroughs, cancer immunotherapy remains focused on several types of tumors that are sensitive to the immune system. Therefore, effective strategies to expand its indications and improve its efficacy become key factors for the further development of cancer immunotherapy.

The promising immune checkpoint LAG-3 in cancer immunotherapy: from basic research to clinical application.

LAG-3, a type of immune checkpoint receptor protein belonging to the immunoglobulin superfamily, is confirmed to be expressed on activated immune cells, mainly including activated T cells. LAG-3 can negatively regulate the function of T cells, exerting important effects on maintaining the homeostasis of the immune system under normal physiological conditions and promoting tumor cells immune escape in the tumor microenvironment. Given its important biological roles, LAG-3 has been regarded as a promising target for cancer immunotherapy.

Discovery of Potent and Selective 2-(Benzylthio)pyrimidine-based DCN1-UBC12 Inhibitors for Anticardiac Fibrotic Effects.

DCN1, a co-E3 ligase, interacts with UBC12 and activates cullin-RING ligases (CRLs) by catalyzing cullin neddylation. Although DCN1 has been recognized as an important therapeutic target for human diseases, its role in the cardiovascular area remains unknown. Here, we first found that DCN1 was upregulated in isolated cardiac fibroblasts (CFs) treated by angiotensin (Ang) II and in mouse hearts after pressure overload.

Myofibroblast Deficiency of LSD1 Alleviates TAC-Induced Heart Failure.

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Discovery of [1,2,4]triazolo[1,5-a]pyrimidines derivatives as potential anticancer agents.

In this work, we reported the discovery of compound 6i with potent antiproliferative activity against MGC-803. Among these compounds, the most potent compound 6i could effectively inhibit MGC-803 (IC = 0.96 μM), being around 38-fold selectivity over GES-1.

Design, synthesis and biological evaluation of novel thiosemicarbazone-indole derivatives targeting prostate cancer cells.

To discover novel anticancer agents with potent and low toxicity, we designed and synthesized a range of new thiosemicarbazone-indole analogues based on lead compound 4 we reported previously. Most compounds displayed moderate to high anticancer activities against five tested tumor cells (PC3, EC109, DU-145, MGC803, MCF-7). Specifically, the represented compound 16f possessed strong antiproliferative potency and high selectivity toward PC3 cells with the IC value of 0.

Drug repurposing: Discovery of troxipide analogs as potent antitumor agents.

Drug repurposing plays a vital role in the discovery of undescribed bioactivities in clinical drugs. Based on drug repurposing strategy, we for the first time reported a novel series of troxipide analogs and then evaluated their antiproliferative activity against MCF-7, PC3, MGC-803, and PC9 cancer cell lines and WPMY-1, most of which showed obvious selectivity toward PC-3 over the other three cancer cell lines and WPMY-1. Compound 5q, especially, could effectively inhibit PC3 with an IC value of 0.

Targeting the Bcl-2 family and P-glycoprotein reverses paclitaxel resistance in human esophageal carcinoma cell line.

Paclitaxel (PTX) is one of the most effective drugs used in the treatment of esophageal cancer, however, paclitaxel resistance represents a key limitation during the treatment process. In this study, we investigated the changes of Bcl-2 family members in the moderate paclitaxel-resistance of esophageal carcinoma EC109/PTX cells both in vitro and in vivo. Moreover, we evaluated the reversal effect using siRNAs and the recombinant inhibitor TW37 targeting Bcl-2, Bcl-XL and Mcl-1.

Bone morphogenetic protein 4 is overexpressed in and promotes migration and invasion of drug-resistant cancer cells.

Drug resistance and metastasis significantly hinder chemotherapy and worsen prognoses in cancer. Bone morphogenetic protein 4 (BMP4) belongs to the TGF-β superfamily, has broad biological activities in cell proliferation and cartilage differentiation and is also able to induce migration and invasion. Herein, we investigated the role of BMP4 in the regulation of metastasis in paclitaxel-resistant human esophageal carcinoma EC109 cells (EC109/Taxol) and docetaxel-resistant human gastric cancer MGC803 cells (MGC/Doc).

Chimeric VLPs with GII.3 P2 domain in a backbone of GII.4 VP1 confers novel HBGA binding ability.

Noroviruses (NoVs) are a leading cause of non-bacterial acute gastroenteritis worldwide. The prevalence of Genogroup II, genotype 3 (GII.3) NoVs is secondary to the epidemic GII.

Characterization of virus-like particles derived from a GII.3 norovirus strain distantly related with current dominating strains.

Genogroup II, genotype 3 noroviruses (GII.3 NoVs) are secondary to GII.4 NoVs in causing acute non-bacterial gastroenteritis worldwide.