AS, one of the most common forms of valvular heart disease, requiring intervention in aging populations in Europe and North America, has traditionally been viewed as a passive, degenerative condition. However, growing evidence supports a paradigm shift toward recognizing AS as an active metabolic and inflammatory disorder. This narrative review synthesizes experimental, translational, and clinical evidence published between 2015 and 2025 examining metabolic mechanisms linking valvular calcification and atrial remodeling in AS and discusses their clinical relevance in the context of transcatheter aortic valve replacement (TAVR). We discussed classical pathways involving mineral metabolism and vitamin signaling, alongside emerging roles of lipid oxidation, mitochondrial dysfunction, epigenetic regulation, and gut microbiome-derived metabolites. Further, metabolomic signatures associated with disease severity and post-TAVR outcomes were reviewed, highlighting the predominantly associative nature and current limitations of these data. Although valve replacement remains the only effective therapy for advanced AS, metabolic and multi-omics insights may improve future risk stratification and mechanistic understanding. Metabolomic profiling could be integrated at multiple points in the clinical pathway for aortic stenosis and TAVR-most promisingly for pre-procedural risk stratification. The present paper focuses on an integrative framework in which valvular calcification and atrial remodeling are viewed within a broader context of metabolic dysregulation. Future research should aim to translate molecular biomarkers into real-world diagnostics and targeted interventions.

Driven by rapid socioeconomic progress and changing lifestyles, the global burden of cardiovascular diseases (CVDs) continues to escalate, with surging morbidity and mortality rates imposing a severe threat to public health. Clinical treatments are focused on the alleviation of treatments, highlighting the need for a deeper understanding of CVDs pathogenesis and the development of targeted therapies. Recent studies have identified imbalances in intracellular Ca²⁺ homeostasis as a key pathological mechanism in the progression of CVDs. Notably, sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase 2 (SERCA2), a membrane protein encoded by the ATP2A2 gene and ranging from 97 to 115 kDa in molecular weight, plays a pivotal role in regulating intracellular Ca²⁺ levels. Extensive evidence links abnormal SERCA2 function to various CVDs, including heart failure, cardiac hypertrophy, atherosclerosis, and diabetic cardiomyopathy. This review systematically explores the regulatory mechanisms of SERCA2 expression and its functional regulation-including transcriptional regulation, post-translational modifications, and protein-protein interactions-and further investigates its pathological roles in cardiovascular diseases as well as its potential as a therapeutic target. By synthesizing current knowledge, this article aims to provide new insights for future basic research and establish a theoretical foundation for clinical applications.

The LKB1-AMPK signaling pathway is a master regulator of cellular energy homeostasis and a central hub in stress adaptation. As a conserved metabolic sensor, this pathway coordinates glucose, lipid, and protein metabolism, thereby sustaining physiological function across diverse tissues. Beyond its canonical role in energy balance, growing evidence highlights its dysregulation in multiple pathological conditions. Despite extensive mechanistic studies, the disease-specific regulation and translational potential of the LKB1-AMPK pathway remain incompletely understood. This review systematically studies the molecular basis and regulatory mechanisms of LKB1-AMPK signaling in cardiovascular diseases-including atrial fibrillation, ventricular fibrillation, myocardial infarction, cardiac hypertrophy, heart failure, and atherosclerosis-where impaired pathway activity underlies energy deficits, fibrosis, oxidative stress, and arrhythmogenesis. We further explore its involvement in metabolic disorders such as diabetes and diabetic nephropathy, in neurodegenerative diseases like Alzheimer's and Parkinson's disease, and in oncology, where LKB1 mutations drive tumorigenesis and alter therapeutic responses. Emerging strategies, including metformin, novel AMPK activators, and LKB1-based gene therapies, are highlighted as promising yet challenged by tissue specificity, off-target effects, and genetic variation. By integrating insights from cardiovascular, metabolic, neurological, and oncological research, this review underscores the pathway's potential as both a biomarker source and therapeutic target, providing a foundation for precision medicine in complex diseases.

Protein-protein interactions (PPIs) are fundamental regulators of cellular function and disease. Systematic mapping of the interactome is essential for identifying therapeutic targets and advancing drug design, a pursuit that has driven significant innovation to capture the spatiotemporal regulation of PPIs in vivo. This review summarizes this methodological revolution. We outline foundational, first-generation techniques-yeast two-hybrid and co-immunoprecipitation-which established frameworks for binary interaction mapping and static network generation, especially when integrated with mass spectrometry. The discussion then pivots to second-generation methods, including proximity-dependent labeling and advanced imaging, which enable the capture of PPIs within their native, dynamic cellular contexts. We provide a comparative analysis of these techniques, detailing their principles, strengths, and limitations. The review concludes with a practical framework for method selection and a perspective on emerging frontiers-such as spatial proteomics and single-cell interactomics-that are poised to further decode the evolving interactome. This concise overview serves as a strategic guide for specialists adopting new techniques and a broader audience integrating network-level data into their research.

Obesity is a chronic metabolic disorder characterized by excessive accumulation of body fat and is a major risk factor for various diseases, including type 2 diabetes, hypertension, and cardiovascular diseases. This study investigated the anti-obesity effects of cannabigerol-dominant C. sativa inflorescence extracts (CEs) obtained using various ethanol concentrations. The extracts were analyzed by UPLC to determine their major components. Additionally, anti-obesity mechanisms of the extracts were further determined through RT-qPCR and Western blot analysis to evaluate gene and protein expression levels. A total of seven cannabinoids, including cannabigerol as a major constituent, were identified within CE. Differentiation of 3T3-L1 cells was dose-dependently inhibited by CE at all ethanol concentrations. Furthermore, the gene and protein expression levels of key adipogenic and lipogenic markers, such as PPARγ, C/EBPα, SREBP-1c, and FAS, were significantly downregulated by CE treatment. In contrast, the expression of factors involved in lipolysis and white adipose tissue browning, such as HSL, ATGL, UCP1, and PGC-1α, was markedly increased by CE treatment. These effects were enhanced in an ethanol concentration-dependent manner. In conclusion, these results demonstrate that cannabigerol-dominant C. sativa effectively mitigates obesity by suppressing adipogenesis and lipogenesis while concurrently stimulating lipolysis and white adipose tissue browning.

Post-transcriptional regulation of gene expression is influenced by RNA-binding proteins (RBPs) and small non-coding RNAs that bind to conserved mRNA sequences to modulate mRNA processing. These regulatory molecules affect the structural conformation of mRNAs, creating formations like G-quadruplexes (G4s), which alter translation initiation and regulatory-factor site accessibility. Recent studies have highlighted Nuclear factor erythroid 2-related factor 2 (NRF2) as a key regulator of cellular redox homeostasis and cellular response to oxidative stress. An intriguing feature of NRF2 is the structural formation of its 5' untranslated region (UTR), which may promote or inhibit translation initiation depending on the cellular context. In this study with minigenes, we provide in vitro evidence of RNA G4s in the NRF2 mRNA's 5' UTR under basal (no stress) conditions. Achieved via electrophoretic mobility shift assay and fluorescence spectra in the presence of Pyridostatin. Understanding how structural motifs within NRF2 5' UTRs influence mRNA function provides insights into a common molecular mechanism underlying diseases where NRF2 is dysregulated, like cancers, cardiovascular disease, and neurodegeneration, and highlights potential therapeutic avenues through regulation of NRF2.

Aging is a multifactorial biological process marked by the progressive decline in cellular and physiological functions, increasing susceptibility to chronic diseases and mortality. Recent research has identified the gut microbiome as a key modulator of aging, influencing immune regulation, metabolic homeostasis, and neuroendocrine signaling. A diverse and balanced gut microbiota promotes healthspan by supporting gut barrier integrity, nutrient metabolism, and anti-inflammatory responses, whereas dysbiosis contributes to the onset and progression of age-related diseases, including neurodegeneration, cardiovascular conditions, cancer, and metabolic disorders. Currently, anti-aging interventions targeting key aging pathways, such as insulin/IGF-1 signaling, mTOR, AMPK, and sirtuins, are a major focus in the field of geroscience. Compounds such as metformin, rapamycin, anti-inflammatories, GLP-1 agonists, senolytics, spermidine, SGLT2 inhibitors, and sirtuin activators have shown lifespan extension in animal models. In humans, some of these interventions are associated with improvements in healthspan-related outcomes, including metabolic, cardiovascular, musculoskeletal, respiratory, cognitive and ocular functions. Notably, the gut microbiome may serve as both a mediator and modulator of these interventions, influencing drug metabolism, efficacy, and host responses. This review synthesizes current evidence on the gut microbiome's role in aging, examining its role as both mediator and modulator of longevity interventions and how microbiome-associated mechanisms intersect with emerging anti-aging therapeutics.

Mitochondria, the cell's powerhouses, generate ATP to sustain essential biological functions. Dysfunctional mitochondria can lead to cell death and subsequent tissue damage. Mitochondrial impairment is a key driver of cellular dysfunction in cardiomyocytes, endothelial cells, and macrophages, contributing to cardiovascular diseases such as atherosclerosis, myocardial ischemia-reperfusion injury, and cardiac hypertrophy. The signal transducer and activator of transcription (STAT) family regulates immune responses, apoptosis, and cell proliferation. Despite evidence suggesting that STATs influence mitochondrial pathways in various cardiovascular conditions, their roles are often contradictory and context-dependent. This review examines the structural and functional dynamics of STATs, their upstream and downstream signaling networks, and therapeutic strategies targeting STAT3 (the most extensively studied isoform), with a particular focus on natural compounds and pharmacological inhibitors. By synthesizing current findings, this review offers valuable insights into STATs as potential therapeutic targets for mitochondrial dysfunction in cardiovascular diseases, while also highlighting directions for future research.

Lactylation serves as a vital link between cellular metabolism and epigenetic regulation and plays a pivotal role in muscle biology. Muscle tissue is the primary site of lactate production; its unique metabolic environment confers dynamism, specificity and functional diversity for lactylation. Under physiological conditions, lactylation regulates myocyte energy metabolism, proliferation, differentiation, and exercise adaptation through a dynamic "writer-eraser-reader" mechanism. In pathological states, lactate imbalance directly contributes to the progression of various muscular disorders. For instance, diminished histone lactylation during muscle aging suppresses the expression of genes critical for DNA repair and protein homeostasis. Aberrant lactylation is involved in the development of insulin resistance and diabetic cardiomyopathy. Furthermore, lactylation exerts dual effects in cardiovascular diseases; it provides protection by enhancing the transcription of repair genes and simultaneously aggravates injury by promoting processes such as fibrosis and ferroptosis. Collectively, these findings underscore the importance of lactylation in muscular pathologies and provide a theoretical foundation for the development of therapies that target this modification process. As the regulatory mechanisms of lactylation have become clearer, precise interventions targeting specific modification sites are expected to open new therapeutic avenues for muscular diseases.

Asian language speakers with limited English proficiency (LEP) face significant barriers to accessing adequate mental health care. Despite worsening mental health outcomes for this population, there is limited research examining the availability of Asian language mental health treatment in the US.

To quantify trends and analyze disparities in the geographic availability of Asian language mental health treatment from 2015 to 2024.

This cross-sectional study of US mental health facilities from April 30, 2015, to December 9, 2024, used longitudinal data from the nationally representative Mental Health and Addiction Treatment Tracking Repository linked with county-level demographic data from the 2023 American Community Survey. Facilities were included if they completed the National Mental Health Services Survey or the National Substance Use and Mental Health Services Survey.

Primary outcomes included the annual proportion of mental health facilities offering Asian language services and the proportion of counties with at least 1 such facility. For 2024, facility-level characteristics associated with Asian language services were assessed and geographic mismatches between service availability and the proportion of Asian language-speaking individuals with LEP were mapped.

The study included 3847 mental health facilities. Of these, 214 facilities (5.6%) offered services in at least 1 Asian language in 2024 (including Arabic, Chinese, Farsi, Hindi, Hmong, Japanese, Korean, Tagolog, and Vietnamese). The proportion peaked at 265 facilities (6.9%) in 2021, then declined from 2022 to 2024. The number of counties with at least 1 facility with Asian language services was 98 (6.3%) in 2024. Facilities offering Asian language services were concentrated in metropolitan areas (208 [97.2%]), particularly in California (57 [26.6%]) and the Northeast (52 [24.3%]). Rural areas lacked such services (3 of 485 rural facilities [0.6%] in 2024), even in counties with substantial populations of Asian language-speaking individuals with LEP (0 of 5 facilities).

This cross-sectional study found a persistent geographic mismatch between the mental health needs of Asian language-speaking individuals with LEP and the availability of appropriate linguistic services. The gap was pronounced in rural areas. The findings suggest that policies aimed at expanding the behavioral health workforce and increasing access to culturally and linguistically competent services to reduce ongoing disparities in mental health outcomes and access to care are urgently needed.