Bioscience Reports最新文献

Patients with ischaemic heart disease (IHD) require frequent monitoring, as the transition from stable disease to acute life-threatening events remains largely unpredictable. MicroRNAs (miRNAs), small non-coding RNAs involved in physiological and pathological processes, are released into circulation and remain stable. In this study, we aimed to determine if the serial measurement of cardiovascular-enriched circulating miRNAs could reflect changes in cardiac function in patients with IHD. Fifty-three new IHD patients participated in a five-year study with regular echocardiography, blood tests and follow-ups at 12-month intervals, with 25 followed up at five years. Serial echocardiography revealed a pattern towards worsening diastolic function over the follow-up period. RT-PCR analysis was conducted on four cardiovascular-enriched circulating miRNAs: miR-1, miR-126, miR-132 and miR-34a. Among these, only miR-1 and miR-126 showed statistically significant down-regulation starting from 24 months onwards. Linear mixed models, adjusted for body mass index and HbA1c changes, indicated significant associations between fold changes in miR-1 and miR-34a with cardiac function changes. Results from this first-ever five-year follow-up study have identified a possible link between cardiovascular-enriched miRNAs, miR-1 and -34a and cardiac function in patients with IHD, providing a foundation for prognostic tests for IHD and laying the foundation for further studies in larger populations. It is noteworthy that a significant dropout of participants may have impacted the statistical power in our study.

Myocardial stunning, characterized by transient post-ischemic contractile dysfunction despite the restoration of coronary blood flow, has been a pivotal subject of cardiovascular research. Initially perceived as a consequence of irreversible myocardial damage and fibrosis, the concept evolved in the 1970s when studies revealed that reperfusion could salvage ischemic myocardium, leading to therapies like thrombolysis, percutaneous coronary intervention, and coronary artery bypass grafting. The phenomenon of myocardial stunning was first detailed by Heyndrickx et al. and later termed by Braunwald and Kloner, challenging previous views by demonstrating that reperfusion can cause temporary yet reversible dysfunction without necrosis. Extensive research elucidated mechanisms involving reactive oxygen species (ROS), calcium overload, and impaired excitation-contraction coupling. Recent advances in proteomics and phospho-proteomics identified molecular changes linked to contractile dysfunction, extracellular matrix damage, and apoptosis. The role of epigenetics has also garnered attention for its potential to influence myocardial stunning and offer therapeutic avenues. This review comprehensively explores the historical and mechanistic landscape of myocardial stunning, recent molecular insights, and its clinical relevance. Future research directions emphasize advanced proteomic and phosphor-proteomic analyses, epigenetic mechanisms, clinical translation, non-invasive diagnostics, ROS role clarification, ischemia preconditioning impacts, and integrative systems biology. Addressing these areas will enhance our understanding and lead to improved therapeutic strategies for ischemic heart disease.

Background: Prediabetes in individuals with obesity is a high-risk state for progression to type 2 diabetes mellitus (T2DM). Circulating microRNAs (miRNAs) have emerged as promising minimally invasive biomarkers for early detection. However, their diagnostic performance and consistency across studies remain unclear.

Objectives: To evaluate circulating miRNAs as potential biomarkers for prediabetes in obese populations.

Methods: A systematic search of PubMed, MEDLINE, Scopus, and EBSCOhost was conducted (September 2012-September 2025) without language restrictions. Eligible studies included observational, clinical, and translational research assessing circulating miRNAs in plasma, serum, whole blood, or exosomes using qRT-PCR, ddPCR, microarray, or next-generation sequencing. Two reviewers independently screened studies and extracted data using a piloted form. Extracted information was synthesized qualitatively; diagnostic performance measures and reported miRNAs were tabulated.

Results: Nine circulating microRNAs (miR-27, miR-30a, miR-34a, miR-93, miR-122, miR-126, miR-146a, miR-192, and miR-193b) were consistently dysregulated in obese individuals with prediabetes across thirteen included human studies. These miRNAs were linked to key pathogenic mechanisms including chronic inflammation, insulin resistance, β-cell dysfunction, and altered adipokine signaling. Notably, inflammation-associated miRNAs (miR-27, miR-34a, miR-146a) reflected the transition from metabolically healthy to unhealthy obesity, while β-cell-related miRNAs (miR-30a, miR-126) indicated early impairment of insulin secretion. Among detection platforms, qRT-PCR remained the most sensitive and specific method for miRNA quantification, whereas microarray and next-generation sequencing provided broader profiling capability but with higher cost and complexity.

Conclusions: Circulating miRNAs demonstrate promise as diagnostic biomarkers for prediabetes in obesity. However, these findings are limited by methodological variability. Thus, large-scale and standardized studies are required to validate their clinical utility.

Despite the well-known role of hypoxia-driven inflammatory mediators in the pathogenesis of hypoxic pulmonary hypertension, their involvement in high-altitude (HA) illnesses, particularly high-altitude pulmonary edema (HAPE), remains unclear. The present study uses an integrated clinical, transcriptomic, proteomic, and long noncoding RNA (lncRNA) profiling of 83 individuals, including HAPE patients segregated into mild, moderate, and severe categories, HAPE-free sojourners, and long-term HA residents, to highlight the molecular and immunological changes associated with HAPE and its severity. Clinical assessments revealed significantly reduced peripheral oxygen saturation and elevated respiratory parameters in HAPE patients. Differential gene expression and functional enrichment analyses identified 515 significantly differentially expressed genes, with marked enrichment of inflammatory and hypoxia-associated pathways. Protein-protein interaction network analysis revealed eighteen hub genes, including toll-like receptor (TLR) 2 and Forkhead box O3 (FOXO3), with strong diagnostic potential. Immune cell deconvolution analysis and hematological profiling indicated a prominent increase in neutrophil proportion. Interestingly, oncostatin M (OSM), a hypoxia-regulated predominant cytokine produced by neutrophils, was revealed in the cytokine and transcriptomic profiling, highlighting its role in inflammation and extracellular matrix degradation. Co-expression network analysis notably revealed significant alterations that formed a gene module exhibiting a strong correlation with immune response, leukocyte adhesion, and ncRNA processing pathways. Interestingly, these co-expressed partners, LINC01093 and immune-regulatory genes like interleukin-18 receptor 1 and TLR5, appear to regulate the NF-κB signaling pathway, one of the positively enriched pathways in our analysis. Overall, this multiomics approach highlighted a strong inflammatory signature and lncRNA-mRNA interactions associated with HAPE.

Bone Morphogenetic Protein-9 (BMP-9), a circulating cytokine belonging to the TGF-β superfamily, is increasingly recognized as a critical regulator of tissue homeostasis with diverse roles in both health and disease. This review recapitulates current knowledge regarding BMP-9, shifting focus beyond its traditional association with bone formation to highlight its significant influence on physiology and pathology in the liver but also in other tissues and organs. We discuss how BMP-9 exerts intricate control over various cell types, affecting key processes such as angiogenesis, macrophage polarization, and regeneration. Intriguingly, while in the liver, BMP-9 contributes to the maintenance of sinusoidal endothelial cell quiescence and Kupffer cell identity, dysregulation of its signaling can as well promote fibrosis. The complexity of BMP-9 function is further compounded by its cross-talks with other signaling molecules like TGF-β, as well as non-Smad pathways. In this review, we summarize current knowledge about the functions of BMP-9 in humans and discuss its therapeutic potential.

The cytokine tumor necrosis factor (TNF), a major regulator of inflammatory responses, exists in both a membrane-bound form and a soluble form. We used the nonselective TNF inhibitor etanercept and the selective inhibitor XPro1595 and compared supraspinatus muscle cytokine levels, histology, and proteomic signatures in mice after supraspinatus tendon tear. The aim was to investigate the effect of anti-TNF treatment on the early inflammatory response in the muscle after tendon tear. In addition, the effect on body composition and bone mineral content was compared in naive mice after 2 months of treatment with either etanercept or XPro1595 using dual-energy X-ray absorptiometry (DEXA) and micro-CT. Inhibition of TNF did not significantly affect DEXA indexes of body composition nor bone microarchitecture, apart from increased structure model index and decreased bone surface density at 14 days, and bone surface to volume ratio at 2 months. Supraspinatus tendon tear caused extensive inflammatory changes in the supraspinatus muscle and initiated a regenerative response. However, TNF inhibition did not significantly affect these processes recorded as density in the lesioned supraspinatus muscle of macrophages and myogenin-positive nuclei. Although both inhibitors had an effect on mitochondrial proteins, particularly etanercept tended to modulate mitochondrial function, and eternacept also influenced NF-κB signaling. Modulation of the mitochondrial proteome and the influence on NF-κB signaling seen after etanercept treatment could correspond with its known effect on apoptosis.

Human ecdysoneless (ECD), the human ortholog of Ecd protein of Drosophila melanogaster, is a highly conserved protein. This protein comprises a well-folded N-terminal domain and a disordered C-terminal domain; these domains interact with multiple proteins and are involved in diverse biological processes, including cell cycle regulation, transactivation, pre-mRNA splicing, and glucose metabolism. ECD is highly expressed in various cancers, and its elevated expression is associated with poor prognosis in several types of human cancers. Therefore, it can serve as a potential biomarker and therapeutic target for treating tumors. This review focuses on the currently available knowledge of the physiological and pathological functions of ECD; moreover, the directions of prospective research in the relevant field have been discussed.