Targeting pancreatic cancer glutamine dependency confers vulnerability to GPX4-dependent ferroptosis.

Pancreatic ductal adenocarcinoma (PDAC) relies heavily on glutamine (Gln) utilization to meet its metabolic and biosynthetic needs. How epigenetic regulators contribute to the metabolic flexibility and PDAC's response and adaptation to Gln scarcity in the tumor milieu remains largely unknown. Here, we elucidate that prolonged Gln restriction or treatment with the Gln antagonist, 6-diazo-5-oxo-L-norleucine (DON), leads to growth inhibition and ferroptosis program activation in PDAC.

Tumor cell-intrinsic epigenetic dysregulation shapes cancer-associated fibroblasts heterogeneity to metabolically support pancreatic cancer.

The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of cancer-associated fibroblasts (CAFs) as part of the host response to tumor cells. The origins and functions of transcriptionally diverse CAF populations in PDAC remain poorly understood. Tumor cell-intrinsic genetic mutations and epigenetic dysregulation may reshape the TME; however, their impacts on CAF heterogeneity remain elusive.

Clostridium butyricum and its metabolite butyrate promote ferroptosis susceptibility in pancreatic ductal adenocarcinoma.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited therapeutic options. The diversity and composition of the intratumoral microbiota are associated with PDAC outcomes, and modulating the tumor microbiota has the potential to influence tumor growth and the host immune response. Here, we explore whether intervention with butyrate-producing probiotics can limit PDAC progression.

The diverse pancreatic tumor cell-intrinsic response to IFNγ is determined by epigenetic heterogeneity.

IFNγ signaling is mainly mediated through the activation of the canonical JAK-STAT signaling pathway, transcription factors, and epigenetic modifications. The activation of IFNγ signaling pathway may provide a novel option for tumor immunotherapy, but the outcomes remain controversial. In fact, recent studies suggest that the resistance to IFNγ-dependent immunotherapies is commonly derived from the tumor cell-intrinsic heterogeneity, the molecular mechanism of which remains elusive.

Elevated circulating levels of gasdermin D are related to acute myocardial infarction and pyrogptosis.

Background: Acute myocardial infarction (AMI) is one of the leading contributors to morbidity and mortality worldwide, with a prevalence of nearly three million people, and more than one million deaths reported in the United States every year. Gasdermin D (GSDMD) is involved in the development of atherosclerosis as a key protein of proptosis. This study was designed to determine the potential relationship of GSDMD with AMI in Chinese patients.

Tumor Cell-Intrinsic SETD2 Deficiency Reprograms Neutrophils to Foster Immune Escape in Pancreatic Tumorigenesis.

Genetic and epigenetic alterations play central roles in shaping the immunosuppressive tumor microenvironment (TME) to evade immune surveillance. The previous study shows that SETD2-H3K36me3 loss promotes KRAS-induced pancreatic tumorigenesis. However, little is known about its role in remodeling the TME and immune evasion.

1,25(OH)D Strengthens the Vasculogenesis of Multipotent Mesenchymal Stromal Cells from Rat Bone Marrow by Regulating the PI3K/AKT Pathway.

Background: Multipotent mesenchymal stromal cells (MSCs) have recently been reported to promote vasculogenesis by differentiating into endothelial cells and releasing numerous cytokines and paracrine factors. However, due to low cell activity, their potential for clinical application is not very satisfactory. This study aimed to explore the effects and mechanisms of 1,25-dihydroxyvitamin D (1,25(OH)D) on the vasculogenesis of MSCs.

Nicotinic Agonist Inhibits Cardiomyocyte Apoptosis in CVB3-Induced Myocarditis via 34-nAChR/PI3K/Akt-Dependent Survivin Upregulation.

Background: Cardiomyocyte apoptosis is critical for the development of coxsackievirus B3- (CVB3-) induced myocarditis, which is a common cardiac disease that may result in heart failure or even sudden death. Previous studies have associated CVB3-induced apoptosis with the downregulation of antiapoptotic proteins. Here, attempts were made to examine whether nicotinic acetylcholine receptors (nAChRs), especially 34-nAChRs, were a novel therapeutic antiapoptotic target via the activation of survivin, a strong antiapoptotic protein, in viral myocarditis (VMC).