Polyoxometalates Ameliorate Metabolic Dysfunction-Associated Steatotic Liver Disease by Activating the AMPK Signaling Pathway.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver disorder, has garnered increasing attention globally owing to its associated health complications. However, the lack of available therapeutic medications and inadequate management of complications in metabolic dysfunction-associated steatohepatitis (MASH) present significant challenges. There are little studies evaluating the effectiveness of POM in treating MASLD.

Daucosterol alleviates heart failure with preserved ejection fraction through activating PPAR pathway.

Heart failure with preserved ejection fraction (HFpEF) has been increasing in the population in recent years and is mainly characterized by preserved left ventricle ejection fraction (LVEF), diastolic dysfunction and systemic inflammation. Daucosterol (DAU), a glycoside of -sitosterol, has good anti-inflammatory and antioxidative properties; however, its effects and mechanisms in HFpEF have not been investigated. To detect whether DAU could alleviate HFpEF, C57BL/6J male mice were fed with N-nitro-l-arginine methyl ester (L-NAME) in drinking water and high fat diet (HFD) and treated with DAU by gavage (i.

Blocking the PD-1 signal transduction by occupying the phosphorylated ITSM recognition site of SHP-2.

Targeting the PD-1/PD-L1 axis with small-molecular inhibitors is a promising approach for immunotherapy. Here, we identify a natural pentacyclic triterpenoid, Pygenic Acid A (PA), as a PD-1 signaling inhibitor. PA exerts anti-tumor activity in hPD-1 knock-in C57BL/6 mice and enhances effector functions of T cells to promote immune responses by disrupting the PD-1 signaling transduction.

CRISPR screening identifies PRMT1 as a key pro-ferroptotic gene via a two-layer regulatory mechanism.

Ferroptosis is a form of nonapoptotic cell death characterized by iron-dependent peroxidation of polyunsaturated phospholipids. However, much remains unknown about the regulators of ferroptosis. Here, using CRISPR-Cas9-mediated genetic screening, we identify protein arginine methyltransferase 1 (PRMT1) as a crucial promoter of ferroptosis.

Geniposide alleviates heart failure with preserved ejection fraction in mice by regulating cardiac oxidative stress via MMP2/SIRT1/GSK3β pathway.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome with cardiac dysfunction, fluid retention and reduced exercise tolerance as the main manifestations. Current treatment of HFpEF is using combined medications of related comorbidities, there is an urgent need for a modest drug to treat HFpEF. Geniposide (GE), an iridoid glycoside extracted from Gardenia Jasminoides, has shown significant efficacy in the treatment of cardiovascular, digestive and central nervous system disorders.

New advances in drug development for metabolic dysfunction-associated diseases and alcohol-associated liver disease.

Metabolic disorders are currently threatening public health worldwide. Discovering new targets and developing promising drugs will reduce the global metabolic-related disease burden. Metabolic disorders primarily consist of lipid and glucose metabolic disorders.

Inhibition of vascular calcification by Compound Danshen Dripping Pill through multiple mechanisms.

Background: Vascular calcification refers to the abnormal accumulation of calcium in the walls of blood vessels and is a risk factor often overlooked in cardiovascular disease. However, there is currently no specific drug for treating vascular calcification. Compound Danshen Dripping Pill (CDDP) is widely used to treat cardiovascular diseases, but its effect on vascular calcification has not been reported.

Liver ChREBP deficiency inhibits fructose-induced insulin resistance in pregnant mice and female offspring.

High fructose intake during pregnancy increases insulin resistance (IR) and gestational diabetes mellitus (GDM) risk. IR during pregnancy primarily results from elevated hormone levels. We aim to determine the role of liver carbohydrate response element binding protein (ChREBP) in insulin sensitivity and lipid metabolism in pregnant mice and their offspring.

Hippo-signaling-controlled MHC class I antigen processing and presentation pathway potentiates antitumor immunity.

The major histocompatibility complex class I (MHC class I)-mediated tumor antigen processing and presentation (APP) pathway is essential for the recruitment and activation of cytotoxic CD8 T lymphocytes (CD8 CTLs). However, this pathway is frequently dysregulated in many cancers, thus leading to a failure of immunotherapy. Here, we report that activation of the tumor-intrinsic Hippo pathway positively correlates with the expression of MHC class I APP genes and the abundance of CD8 CTLs in mouse tumors and patients.

Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/β-catenin signalling pathway.

Introduction: Vascular calcification, a devastating vascular complication accompanying atherosclerotic cardiovascular disease and chronic kidney disease, increases the incidence of adverse cardiovascular events and compromises the efficacy of vascular interventions. However, effective therapeutic drugs and treatments to delay or prevent vascular calcification are lacking.

Objectives: This study was designed to test the therapeutic effects and mechanism of Moscatilin (also known as dendrophenol) from Dendrobium huoshanense (an eminent traditional Chinese medicine) in suppressing vascular calcification in vitro, ex vivo and in vivo.

CD36 inhibition reduces non-small-cell lung cancer development through AKT-mTOR pathway.

Lung cancer is the most common cause of cancer-related deaths worldwide and is caused by multiple factors, including high-fat diet (HFD). CD36, a fatty acid receptor, is closely associated with metabolism-related diseases, including cardiovascular disease and cancer. However, the role of CD36 in HFD-accelerated non-small-cell lung cancer (NSCLC) is unclear.

Triglyceride-glucose index is a predictor of the risk of prostate cancer: a retrospective study based on a transprostatic aspiration biopsy population.

Background: Current research suggests that prostate cancer (PCa), one of the most common cancers in men, may be linked to insulin resistance (IR).Triglyceride-glucose index (TyG index) was made for a marker of insulin resistance. We investigated the relationship between the TyG index and the risk of PCa.

Berberine protects mice against type 2 diabetes by promoting PPARγ-FGF21-GLUT2-regulated insulin sensitivity and glucose/lipid homeostasis.

Type 2 diabetes (T2D) is a chronic, burdensome disease that is characterized by disordered insulin sensitivity and disturbed glucose/lipid homeostasis. Berberine (BBR) has multiple therapeutic actions on T2D, including regulation of glucose and lipid metabolism, improvement of insulin sensitivity and energy expenditure. Recently, the function of BBR on fibroblast growth factor 21 (FGF21) has been identified.

Association of triglyceride-glucose index with the risk of prostate cancer: a retrospective study.

Background: Prostate cancer is the most common malignancy in men, and its incidence is increasing year by year. Some studies have shown that risk factors for prostate cancer are related to insulin resistance. The triglyceride-glucose (TyG) index is a marker of insulin resistance.

The pterostilbene-dihydropyrazole derivative Ptd-1 ameliorates vascular calcification by regulating inflammation.

Vascular calcification is an independent risk factor for cardiovascular disease. However, there is still a lack of adequate treatment. This study aimed to examine the potential of (E)-1-(5-(2-(4-fluorobenzyloxy)Styryl)-4,6-dimethoxyphenyl)-3-methyl-4,5-dihydro-1H-pyrazole-1-yl) ethyl ketone (Ptd-1) to alleviate vascular calcification.

Hydroxypropyl-β-cyclodextrin inhibits the development of triple negative breast cancer by enhancing antitumor immunity.

Triple negative breast cancer (TNBC) is regarded as one of the most aggressive forms of breast cancer. Hydroxypropyl-β-cyclodextrin (HP-β-CD) has been used as a therapeutic agent for Niemann-Pick disease Type C (NPC). However, the exact actions and mechanisms of HP-β-CD on TNBC are not fully understood.

Protein Z and Protein Z-dependent protease inhibitor in patients with acute ischemic stroke: A prospective mechanistic study.

Objectives: Protein Z (PZ) /Protein Z-dependent protease inhibitor (ZPI) (PZ/ZPI) system is a new anticoagulant system discovered in recent years, which plays an important role in many diseases. We aimed to compare the plasma PZ/ZPI levels of acute ischemic stroke (AIS) patients and non-stroke control participants and the role of PZ/ZPI in the development of stroke was preliminarily analyzed.

Materials And Methods: Enzyme linked immunosorbent assay (ELISA) was used to detect and compare plasma PZ levels of 86 patients with acute AIS and 85 non-stroke control patients.

Glabridin Ameliorates Alcohol-Caused Liver Damage by Reducing Oxidative Stress and Inflammation via p38 MAPK/Nrf2/NF-κB Pathway.

Licorice is a traditional and versatile herbal medicine and food. Glabridin (Gla) is a kind of isoflavone extracted from the licorice root, which has anti-obesity, anti-atherosclerotic, and antioxidative effects. Alcoholic liver disease (ALD) is a widespread liver disease induced by chronic alcohol consumption.

Identification of circulating T-cell immunoglobulin and mucin domain 4 as a potential biomarker for coronary heart disease.

Efferocytosis, the process of engulfing and removing apoptotic cells, is attenuated in vulnerable plaques of advanced atherosclerosis. T-cell immunoglobulin and mucin domain 4 (TIMD4) is a recognition receptor protein for efferocytosis that has been implicated in atherosclerosis mouse models. However, the role of serum-soluble TIMD4 (sTIMD4) in coronary heart disease (CHD) remains unknown.