High Maternal Glycine Levels Increase the Risk of Developing Atrial Septal Defect in the Offspring.

Amino acid imbalance is linked to increased congenital heart disease risk. Here, we found women carrying rs2545801 C/C genotypes exhibited increased glycine levels and increased risk for atrial septal defects (ASDs) in their offspring. Elevated maternal glycine levels during the first trimester were correlated with a higher ASD risk in the offspring.

Proteogenomic characterization reveals that lipid droplet formation promotes esophageal squamous cell cancer progression.

Esophageal cancer is one of the most common cancers and a leading cause of cancer-related mortality in the world. Here, we have performed comprehensive characterization of genetic, transcriptomic, proteomic, and phosphoproteomic features in 293 patients with esophageal squamous cell carcinoma (ESCC). Chromosome 12q13.

Cirrhosis Promotes Cardiac Fibrosis Development by Inhibiting Notch1 in Cardiac Fibroblasts.

Cardiovascular disease risk is elevated in patients with cirrhosis. However, the underlying molecular mechanisms remain poorly understood. Herein, we found that high levels of circulating transforming growth factor (TGF)-β1 were associated with an increased risk of cardiomyopathy in cirrhosis patients.

SLC31A1 loss depletes mitochondrial copper and promotes cardiac fibrosis.

Background And Aims: Metals serve as co-factors for a host of metalloenzymes involved in mitochondrial metabolic reprogramming. Modifications in metal homeostasis are linked to epigenetic mechanisms. However, the epigenetic mechanisms through which metal affects cardiac fibrosis (CF) remain poorly understood.

Targeted mitochondrial function for cardiac fibrosis: An epigenetic perspective.

Mitochondria, commonly referred to as "energy factories"of cells, play a crucial role in the function and survival of cardiomyocytes. However, as research on cardiac fibrosis has advanced, mitochondrial dysfunction(including changes in energy metabolism, calcium ion imbalance, increased oxidative stress, and apoptosis)is now recognized as a significant pathophysiological pathway involved in cardiac remodeling and progression, which also negatively affects the function and structure of the heart. In recent years, research focusing on targeting mitochondria has gained significant attention, offering new approaches for treating cardiac fibrosis.

Branched-chain amino acids deficiency promotes diabetic cardiomyopathy by activating autophagy of cardiac fibroblasts.

More than half of the patients with type II diabetes mellitus (T2D) develop diabetic cardiomyopathy (DCM). Glycemic control alone cannot effectively prevent or alleviate DCM. Herein, we concentrated on the variations in levels of metabolites between DCM and T2D patients without cardiomyopathy phenotype.

Epigenetic regulation of mitochondrial fission and cardiac fibrosis via sFRP3 promoter methylation.

In the process of cardiac fibrosis, the balance between the Wnt/β-catenin signalling pathway and Wnt inhibitory factor genes plays an important role. Secreted frizzled-related protein 3 (sFRP3), a Wnt inhibitory factor, has been linked to epigenetic mechanisms. However, the underlying role of epigenetic regulation of sFRP3, which is crucial in fibroblast proliferation and migration, in cardiac fibrosis have not been elucidated.

Dissecting the Implications of Calumenin in Malignancy and Heterogeneity of the Microenvironment of Clear Cell Renal Cell Carcinoma Using Multi-Omics Data.

Unlabelled: Increasing evidence indicates that Calumenin (CALU), which is localized in the endoplasmic reticulum, is significantly associated with tumor progression. However, the effect of CALU on patients with clear cell renal cell carcinoma (ccRCC) is unknown. By integrating multi-omics data and molecular biology experiments, we found that CALU expression was significantly increased in tumors compared with normal tissues, and the pathological grade and prognosis of patients were correlated with CALU expression.

NOTCH1 mitochondria localization during heart development promotes mitochondrial metabolism and the endothelial-to-mesenchymal transition in mice.

Notch signaling activation drives an endothelial-to-mesenchymal transition (EndMT) critical for heart development, although evidence suggests that the reprogramming of endothelial cell metabolism can regulate endothelial function independent of canonical cell signaling. Herein, we investigated the crosstalk between Notch signaling and metabolic reprogramming in the EndMT process. Biochemically, we find that the NOTCH1 intracellular domain (NICD1) localizes to endothelial cell mitochondria, where it interacts with and activates the complex to enhance mitochondrial metabolism.

m6A epitranscriptomic modification in diabetic microvascular complications.

N6-methyladenosine (m6A) modifications are modulated by m6A methyltransferases, m6A demethylases, and m6A-binding proteins. The dynamic and reversible patterns of m6A modification control cell fate programming by regulating RNA splicing, translation, and decay. Emerging evidence demonstrates that m6A modification of coding and noncoding RNAs exerts crucial effects that influence the pathogenesis of diabetic microvascular complications that include diabetic cardiomyopathy, diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, and diabetic dermatosis.

Lactylated Apolipoprotein C-II Induces Immunotherapy Resistance by Promoting Extracellular Lipolysis.

Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism.

m6A epitranscriptomic modification of inflammation in cardiovascular disease.

Cardiovascular disease is currently the number one cause of death endangering human health. There is currently a large body of research showing that the development of cardiovascular disease and its complications is often accompanied by inflammatory processes. In recent years, epitranscriptional modifications have been shown to be involved in regulating the pathophysiological development of inflammation in cardiovascular diseases, with 6-methyladenine being one of the most common RNA transcriptional modifications.

Redox homeostasis in cardiac fibrosis: Focus on metal ion metabolism.

Cardiac fibrosis is a major public health problem worldwide, with high morbidity and mortality, affecting almost all patients with heart disease worldwide. It is characterized by fibroblast activation, abnormal proliferation, excessive deposition, and abnormal distribution of extracellular matrix (ECM) proteins. The maladaptive process of cardiac fibrosis is complex and often involves multiple mechanisms.

Ketogenic diet-produced β-hydroxybutyric acid accumulates brain GABA and increases GABA/glutamate ratio to inhibit epilepsy.

Ketogenic diet (KD) alleviates refractory epilepsy and reduces seizures in children. However, the metabolic/cell biologic mechanisms by which the KD exerts its antiepileptic efficacy remain elusive. Herein, we report that KD-produced β-hydroxybutyric acid (BHB) augments brain gamma-aminobutyric acid (GABA) and the GABA/glutamate ratio to inhibit epilepsy.

Lipid metabolism reprogramming in cardiac fibrosis.

Cardiac fibrosis is a critical pathophysiological process that occurs with diverse types of cardiac injury. Lipids are the most important bioenergy substrates for maintaining optimal heart performance and act as second messengers to transduce signals within cardiac cells. However, lipid metabolism reprogramming is a double-edged sword in the regulation of cardiomyocyte homeostasis and heart function.

Epigenetic signatures in cardiac fibrosis: Focusing on noncoding RNA regulators as the gatekeepers of cardiac fibroblast identity.

Cardiac fibroblasts play a pivotal role in cardiac fibrosis by transformation of fibroblasts into myofibroblasts, which synthesis and secrete a large number of extracellular matrix proteins. Ultimately, this will lead to cardiac wall stiffness and impaired cardiac performance. The epigenetic regulation and fate reprogramming of cardiac fibroblasts has been advanced considerably in recent decades.