The global nutritional transition has led to the increased frequency and severity of chronic degenerative diseases worldwide, primarily driven by chronic inflammatory stress. At mealtimes, various pharmaceutical products aim to prevent such inflammatory stress, but they usually cause various systemic side effects. Therefore, the supplementation of natural and safe ingredients is a promising strategy to reduce the risk and severity of inflammatory stress-related diseases. Palmitoylethanolamide (PEA), an endocannabinoid-like mediator, has been extensively studied for its diverse actions, including anti-inflammatory, antimicrobial, immunostimulatory, neuroprotective, and pain-reducing effects, with high tolerability and safety in both animals and humans. Because of its multiple molecular targets and mechanisms of action, PEA has demonstrated therapeutic benefits in various diseases, including neurological, psychiatric, ophthalmic, metabolic, oncological, renal, hepatic, immunological, rheumatological, and gastrointestinal conditions. The current review highlights the roles and functions of PEA in various physiological and pathological conditions, further supporting its use as an important dietary agent.

The skeletal muscle is the largest organ present in the body and is responsible for mechanical activities like maintaining posture, movement, respiratory function, and support for the health and functioning of other systems of the body. Skeletal muscle atrophy is a condition characterized by a reduction in muscle size, strength, and activity, which leads to an increased dependency on others for movement, an increased risk of falls, and a reduced quality of life. Various conditions like osteoarthritis, osteoporosis, and fractures are directly associated with increased muscle atrophy. Additionally, numerous risk factors, like aging, malnutrition, physical inactivity, and certain disease conditions, through distinct pathways, negatively affect skeletal muscle health and lead to muscle atrophy. Among various determinants of overall muscle health, the rate of muscle protein synthesis and degradation is an important parameter that eventually alters the fate of overall muscle health. In conditions of excessive skeletal muscle atrophy, including sarcopenia, the rate of muscle protein degradation usually exceeds the rate of protein synthesis. The availability of amino acids in the systemic circulation is a crucial step in muscle protein synthesis. The current review aims to consolidate the existing evidence on amino acids, highlight their mechanisms of action, and assess their roles and effectiveness in enhancing skeletal muscle health.

Intermediate filaments (IFs) in human cells are the products of six distinct gene families, all sharing homology in a core rod domain. These IFs assemble into non-polar polymers, providing cytoplasmic and nuclear mechanical support. Recent research has revealed the active and dynamic properties of IFs and their binding partners. This regulation extends beyond cell mechanics to include migration, mechanotransduction, and tumor growth. Therefore, this comprehensive review aims to catalog all human IF genes and IF-associated proteins (IFAPs), detailing their names, sizes, functions, associated human diseases, relevant literature, and links to resources like UniProt and the Protein Atlas database. These links provide access to additional information such as protein structure, subcellular localization, disease-causing mutations, and pathology. Using this catalog, we will provide an overview of the current understanding of the biological functions of IFs and IFAPs. This overview is crucial for identifying gaps in their characterization and understanding IF-mediated mechanotransduction. Additionally, we will consider potential future research directions.

Chronic hypoxia is a key factor in the pathogenesis of cardiovascular diseases, including ischemia, heart failure, and hypertension. Under hypoxia, oxygen deficiency disrupts oxidative phosphorylation in mitochondria, impairing ATP production and generating reactive oxygen species (ROS). These reactive species induce mitochondrial dysfunction, leading to oxidative stress, calcium imbalance, and activation of apoptosis pathways. The mitochondrial ATP-sensitive potassium channel (mitoK_ATP) and mitochondrial permeability transition pore (mPTP) channels are particularly affected, contributing to membrane potential loss, cytochrome c release, and cell death. This review delves into the molecular mechanisms underlying hypoxia-induced cardiovascular diseases, with a focus on mitochondrial impairment, ion channel dysfunction, and ROS overproduction. Additionally, we examine hypoxia-inducible factor 1-alpha (HIF-1α) as a biomarker of cellular adaptation and discuss therapeutic strategies targeting mitochondrial function and oxidative stress. Antioxidants and compounds modulating key ion channels, such as mitoK_ATP and mPTP, are highlighted as promising interventions for mitigating hypoxia-induced damage. Furthermore, we emphasize the potential of integrating in vitro, in vivo, and in silico studies to develop novel therapies aimed at preserving mitochondrial integrity and preventing cardiovascular diseases.

Early screening is crucial for the prevention of intestinal-type gastric cancer. The current study aimed to ascertain the molecular evolution of intestinal-type gastric cancer based on the Correa cascade for precise gastric cancer screening. We collected sequential lesions of the Correa cascade in the formalin-fixed and paraffin-embedded endoscopic submucosal dissection (ESD)-resected specimens from 14 Chinese patients by microdissection, and subsequently determined the profiles of somatic aberrations during gastric carcinogenesis using whole-exome sequencing, identifying multiple variants at different Correa stages. The results showed that TP53, PCLO, and PRKDC were the most frequently mutated genes in early gastric cancer (EGC). We found a high frequency of TP53 alterations in low-grade intraepithelial neoplasia (LGIN), which further increased in high-grade intraepithelial neoplasia (HGIN) and EGC. Intestinal metaplasia (IM) showed no significant correlation with EGC in terms of mutational spectra, whereas both LGIN and HGIN showed higher genomic similarities to EGC, compared with IM. Based on Jaccard similarity coefficients, we constructed three evolutionary models, with most patients showing linear progression from LGIN to HGIN, ultimately resulting in EGC. The extracellular matrix-receptor interaction pathway was revealed to be involved in the linear evolution. Additionally, the retrospective validation study of 39 patients diagnosed with LGIN indicated that PRKDC mutations, in addition to TP53 mutations, may drive LGIN progression to HGIN or EGC. In conclusion, the current study unveils the genomic evolution across the Correa cascade of intestinal-type gastric cancer, elucidates the underlying molecular mechanisms of gastric carcinogenesis, and provides evidence for potential personalized gastric cancer surveillance.

Colorectal cancer (CRC) ranks among the top five most common malignant tumors worldwide and has a high mortality rate. Angiogenesis plays an important role in CRC progression; however, anti-angiogenesis therapy still has many limitations. Long non-coding RNAs (lncRNAs) participate in tumor progression by regulating the expression of vascular endothelial growth factor in metastatic CRC. Thus, targeting specific lncRNAs may provide some new hope for anti-angiogenic strategies. Through analyzing data from both clinical samples and The Cancer Genome Atlas database, we found that the lncRNA LINC01503 was specifically upregulated in CRC tissues and was associated with tumor progression and poor overall survival. We also demonstrated that LINC01503 enhanced the capacity for tube formation and migration of vascular endothelial cells, thus promoting CRC tumorigenesis by upregulating vascular endothelial growth factor A (VEGFA) expression in CRC cells. Mechanistically, LINC01503 promoted the expression of VEGFA by simultaneously regulating both mRNA and protein stability of VEGFA by binding to miR-342-3p and the chaperone HSP60, respectively. The upregulation of LINC01503 in CRC cells was attributed to the CREB-binding protein CBP/p300-mediated H3K27 acetylation of the LINC01503 promoter region. Taken together, our findings clarify the mechanism by which LINC01503 may promote CRC angiogenesis, implying that LINC01503 may serve as a potential prognostic biomarker and therapeutic target for CRC.

Adiponectin receptor 1 (Adipor1) deficiency has been shown to inhibit Th17 cell differentiation and reduce joint inflammation and bone erosion in antigen-induced arthritis mice. Additional emerging evidence indicates that Th17 cells may differentiate into pathogenic (pTh17) and non-pathogenic (npTh17) cells, with the pTh17 cells playing a crucial role in numerous autoimmune and inflammatory conditions. In the current study, we found that Adipor1 deficiency inhibited pTh17 differentiation in vitro and induced mitochondrial dysfunction in pTh17 cells. RNA sequencing demonstrated a significant increase in the expression levels of Fundc1, a gene related to mitochondrial function, in Adipor1-deficient CD4⁺ T cells. Fundc1 knockdown in Adipor1-deficient CD4⁺ T cells partially reversed the effects of Adipor1 deficiency on mitochondrial function and pTh17 differentiation. In conclusion, the current study demonstrated a novel role of Adipor1 in regulating mitochondrial function via Fundc1 to promote pTh17 cell differentiation, providing some insight into potential therapeutic targets for autoimmune and inflammatory diseases.