EXCLI Journal最新文献

Mindfulness-based cognitive therapy (MBCT) demonstrates significant efficacy in improving depressive symptoms and modulating metabolic profiles. However, the specific metabolite biomarkers and metabolic pathways underlying MBCT's therapeutic effects in adolescent depression remain unclear. This study aims to identify potential metabolite biomarkers and metabolic regulation pathways associated with MBCT improvement of adolescent depression. A global untargeted metabolomics approach was employed to analyze plasma samples from 35 adolescents with depression undergoing MBCT, 35 receiving conventional treatment (CT), and 30 age- and sex-matched healthy controls. MBCT significantly alleviated anxiety and depression symptoms of adolescent patients visualized by SDS, GAD-7, and SCL-90 scores (P < 0.0001). Untargeted metabolomics analysis revealed distinct metabolic profile changes in MBCT group compared to CT group, with 203 metabolites significantly upregulated and 186 significantly downregulated in MBCT group (P < 0.05). Notably, circulating levels of metabolites such as 10,11-epoxy-3-geranylgeranylindole and paspalicine showed marked increases (P < 0.05), whereas abundances of arachidonic acid and L-glutamic acid exhibited significant decreases (P < 0.05). KEGG pathway enrichment analysis indicated that the 186 downregulated metabolites were primarily enriched in pathways such as long-term depression, synaptic vesicle cycle, GnRH signaling, and aspartate and glutamate metabolism. Pearson's correlation analysis suggested that arachidonic acid level changes was significantly correlated with clinical improvement of SDS and SCL-90 scores (adjusted P < 0.05). ROC analysis revealed that a combination of five metabolites, including 10,11-epoxy-3-geranylgeranylindole, (1S,2R)-1-C-(indol-3-yl) glycerol 3-phosphate, paspalicine, FO 2546E, and FO 2546M, exhibited strong predictive potential for MBCT efficacy (AUC = 0.9061). These findings suggested that arachidonic acid involved in the long-term depression pathway may play pivotal roles in MBCT improvement of adolescent depression. This study provides insight into the potential biomarkers and metabolic regulation mechanisms underlying MBCT's therapeutic effects and theoretical guidance for clinical practice in MBCT intervention for adolescent depression. See also the graphical abstract(Fig. 1).

Sarcopenia, a progressive loss of skeletal muscle mass and strength, leads to frailty, falls, fractures, and delayed recovery following orthopedic surgery. When combined with osteoporosis, it manifests as osteosarcopenia, exacerbating musculoskeletal fragility. Although chronic inflammation, mitochondrial dysfunction, and impaired autophagy are recognized contributors, the integrated regulation of these processes in Asian populations remains unclear. This study aimed to elucidate molecular mediators and signaling pathways connecting inflammation, autophagy, and muscle-bone degeneration using an integrated clinical-transcriptomic approach. Transcriptomic data (GSE226151) comprising vastus lateralis muscle samples from 20 sarcopenic patients and 20 age- and sex-matched healthy Asian controls were analyzed using ExDEGA, with differentially expressed genes (DEGs) defined by |log₂ fold change| ≥ 1 and FDR < 0.05. Functional enrichment via ShinyGO identified key Gene Ontology and KEGG pathways, while STRING-Cytoscape network analysis revealed four hub genes-ADAM8, BECN1, KLF4, and GBP5-with high connectivity (degree >10) enriched in cytokine-cytokine receptor interaction and PI3K-Akt pathways. Gene Set Enrichment Analysis further validated these associations. The expression of these hub genes inversely correlated with skeletal muscle index (r = -0.63 to -0.74; p < 0.01) and grip strength (r = -0.58 to -0.69; p < 0.05). Clinically, sarcopenic individuals exhibited significantly lower BMI, gait speed, and muscle mass (all p < 0.001). Integrating bioinformatics and clinical data identified these four genes as critical mediators linking inflammation, defective autophagy, and musculoskeletal decline in sarcopenia. These findings provide translational insight into the molecular mechanisms underlying osteosarcopenia and suggest potential biomarkers and therapeutic targets to improve diagnosis and treatment in aging-related musculoskeletal disorders. See also the graphical abstract(Fig. 1).

Endometriosis is a common gynaecological condition characterised by the growth of endometrial-like tissue both within the muscular layer of the uterus and outside of it, affecting 10-15 % of women of reproductive age. This study investigated the role of the surrounding environment, specifically the potential role of follicular fluid (FF) and particularly its cytokine IL-8, in the growth and invasiveness of endometrial epithelial cells. Using the epithelial-like endometriotic cell line 12Z, we analysed cell viability and migration after exposure to three different FF pools at various dilutions. Our results demonstrated that FF increased cell viability, with the most significant effects at a 50 % (v/v) dilution after 24 h. Moreover, FF treatment reduced cell migration, while FF as a chemoattractant induced increased chemotactic cell migration, especially with pool FF1 as a chemoattractant. This FF pool contained the highest IL-8 concentration. Like FF, IL-8 showed a strong chemotactic effect, significantly reduced by inhibiting IL-8 receptors CXCR1 and CXCR2, confirming IL-8's role in chemotaxis. FF treatment induced the EMT marker N-cadherin and enhanced E-cadherin, indicating a hybrid cell EMT state. In conclusion, our study demonstrates that FF, particularly through IL-8 signalling, plays a crucial role in the pathogenesis of endometriosis by enhancing cell viability and influencing migration. These findings provide insights into how the local microenvironment contributes to disease progression. See also the graphical abstract(Fig. 1).

Head and neck squamous cell carcinoma (HNSCC) encompasses a diverse group of tumors with varying etiology, biology, and response to therapy. Among its subtypes, human papillomavirus positive HNSCC is associated with better prognosis and enhanced sensitivity to radiotherapy, chemotherapy, and immunotherapy. However, resistance still occurs and is often driven by complex molecular mechanisms that remain incompletely understood. Recent evidence highlights the pivotal role of RNA modifications-particularly N6-methyladenosine (m⁶A)-in regulating key processes such as gene expression, immune response, and treatment resistance. Dysregulation of m⁶A machinery, including methyltransferases (METTL3, METTL14), demethylases (FTO, ALKBH5), and m⁶A readers (YTHDFs, IGF2BPs), has been implicated in oncogenesis, immune evasion, and therapy failure in multiple cancers, including HNSCC. These epitranscriptomic changes intersect with hypoxia-driven signaling pathways, which reshape the tumor microenvironment, promote immunosuppression, and impair DNA repair, further contributing to resistance to conventional and targeted therapies. Moreover, in HPV-related HNSCC, viral oncoproteins modulate both RNA methylation and host immune dynamics, creating a unique biological context where m⁶A modifications may serve as mediators of HPV-specific oncogenic programs and therapeutic vulnerabilities. This review integrates current knowledge on the interplay between hypoxia, m⁶A RNA methylation, and HPV infection in HNSCC, emphasizing their combined role in shaping tumor progression and resistance. A deeper understanding of these pathways may offer new opportunities for biomarker discovery and the development of rational combination therapies. See also the graphical abstract(Fig. 1).

This study investigates the effect of pasteurized Bacteroides thetaiotaomicron (PB.t) and its extracellular vesicles (B.t-EVs) on metabolic parameters, diabetes- and inflammation-related gene expression, and microbiota composition in type 2 diabetes mellitus (T2DM). A total of forty-eight male Wistar rats were randomly divided into normal controls (NC, n=24) and T2DM-induced rats (n=24), and each group was further subdivided to receive phosphate-buffered saline (PBS), PB.t, or B.t-EVs by gavage daily for five consecutive weeks. The effects on obesity indices, glycemic markers, lipid profile, expression of diabetes- and inflammation-related genes in the liver and colon, and targeted changes in gut microbiota were assessed. Treatment with B.t-EVs and PB.t was associated with reductions in obesity indices (body weight, body mass index, and Lee index) and fasting blood glucose compared to the T2DM-PBS group; however, this reduction was significant only in T2DM-B.t-EVs rats (P≤0.0142). Both interventions yielded significant improvements in metabolic parameters, as demonstrated by decreased serum insulin, triglyceride, and total cholesterol levels, reduced homeostatic model assessment for insulin resistance (HOMA-IR), and improved glucose tolerance (all P≤0.0382). Both treatments reduced with downregulation of endocannabinoid system receptor 1 (CB1) expression and increased CB2 and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) gene expression in the liver (all P≤0.0018). In the colon, PB.t and B.t-EVs significantly downregulated interleukin (IL)-1β, IL-6, and CB1 genes. They also upregulated IL-4, IL-10, and CB2 genes (all P≤0.0004). Targeted microbiota analysis showed increased abundances of Bacteroidetes, Faecalibacterium prausnitzii, and B.t, accompanied by a reduced level of Firmicutes, Actinobacteria and Firmicutes/Bacteroidetes (F/B) ratio (P≤0.0492). Additionally, treatment with B.t-EVs increased the abundance of Clostridium cluster IV (P=0.0085). Histological findings indicated reduced pancreatic damage in the treated groups. Altogether, these results suggest that PB.t and B.t-EVs, as paraprobiotic and postbiotic candidates, may improve metabolic health, reduce inflammation, and modulate gut microbiota composition in T2DM. See also the graphical abstract(Fig. 1).

Transportation noise from road, rail, and aircraft traffic is now recognized as a major cardiovascular risk factor. In Europe, more than 113 million people are chronically exposed to levels above 55 dB(A), resulting in an estimated 1.3 million healthy life-years lost annually from traffic-related noise. Large epidemiological studies consistently demonstrate associations with ischemic heart disease, heart failure, stroke, and type 2 diabetes, with additional links to hypertension, atrial fibrillation, and obesity. Translational and experimental research has clarified the biological plausibility of these findings. The central "noise reaction model" involves activation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis, with subsequent release of catecholamines and cortisol. These stress responses provoke endothelial dysfunction, vascular inflammation, and oxidative stress, largely through NADPH oxidase 2 activation and nitric oxide synthase uncoupling. At the molecular level, noise alters gene expression networks, disrupts circadian clock regulation, downregulates FOXO3, and induces pro-inflammatory epigenetic modifications. Neuroimaging studies reveal chronic noise activates the amygdala, linking stress perception to vascular inflammation and major adverse cardiovascular events. Adverse effects are most pronounced at night, when noise fragments restorative sleep and amplifies neurohormonal imbalance. Importantly, these pathways overlap with mechanisms of traditional cardiovascular risk factors - diabetes, hypertension, smoking, and hyperlipidemia - suggesting that noise accelerates vascular aging through convergent mechanisms. Combined exposure to noise and air pollution further exerts additive or synergistic effects, underscoring the value of the exposome concept in identifying vulnerable populations. Transportation noise should therefore be considered an established cardiovascular risk factor, requiring equal priority in prevention guidelines and public health policy. See also the graphical abstract(Fig. 1).

Chronic wounds are characterized by prolonged healing durations and disrupted progression through the normal phases of wound healing, hemostasis, inflammation, proliferation, re-epithelialization and remodeling. These wounds are often complicated by persistent infections and underlying conditions like diabetic mellitus, which hinders effective tissue regeneration. Traditional dressings provide limited therapeutic benefits; therefore, recent advancements in wound care have introduced peptide-based therapies that have gained considerable attention for their multifunctional roles in modulating wound repair. Peptides possess intrinsic antimicrobial, anti-inflammatory, angiogenic, and pro-regenerative properties, enabling them to regulate diverse cellular and molecular events across all stages of healing. This review highlights the mechanistic roles of therapeutic peptides in regulating and orchestrating wound healing applications. We further classify bioactive peptides derived from microbial, animal, and plant sources with documented roles in wound healing, and also address synthetic peptides engineered for wound healing. We discussed the peptide-based hydrogels, recent advancements in peptide-based hydrogels in wound healing, and also those hydrogels that are currently under investigation in clinical trials. The primary objective of this review is to provide the readers a detailed overview of the advancements in wound healing studies especially peptide incorporated hydrogels. See also the graphical abstract(Fig. 1).