Journal of Advanced Research最新文献

{"title":"The clinicopathologic features of fulminant myocarditis","authors":"Guanglin Cui ,&nbsp;Jiali Nie ,&nbsp;Huihui Li,&nbsp;Luyun Wang,&nbsp;Kun Miao,&nbsp;Chunxia Zhao,&nbsp;Jiangang Jiang,&nbsp;Dao Wen Wang","doi":"10.1016/j.jare.2025.06.040","DOIUrl":"10.1016/j.jare.2025.06.040","url":null,"abstract":"<div><h3>Background</h3><div>Fulminant myocarditis (FM) is the most severe form of myocarditis, characterized by rapid clinical progression and circulatory instability. However, its pathological features and their relationship to clinical presentation are not well understood.</div></div><div><h3>Objectives</h3><div>This study aims to provide an overview of the clinicopathologic features of FM.</div></div><div><h3>Methods</h3><div>A total of 80 patients with FM were enrolled between January 2021 and September 2022 in Wuhan, China. Endomyocardial biopsies and subsequent histochemical staining were performed on all patients who were followed up for 3 months. The pathological features of the myocardium were described. The relationship between myocardial inflammatory cell infiltration and clinical presentation was analyzed.</div></div><div><h3>Results</h3><div>According to hematoxylin and eosin staining, 76 out of 80 patients with FM were diagnosed with lymphocytic myocarditis, while 4 were diagnosed with eosinophilic myocarditis. Microscopically, various forms of cell degeneration were observed, especially myocardial edema and cardiomyocyte necrosis. Histochemical analysis indicated that innate immune cells (primarily macrophages and neutrophils) predominated in the acute stage of FM. Proper treatment with immunomodulatory agents, such as glucocorticoids and immunoglobulin, promoted macrophage polarization into the M2 subtype. A high density of total inflammatory cell infiltration was associated with elevated levels of inflammatory biomarkers (hs-CRP and ESR) and more severe circulatory deterioration, which necessitated more frequent use of IABP, ECMO, and pacemakers.</div></div><div><h3>Conclusions</h3><div>To date, this largest cohort of histochemical analyses of FM, based on endomyocardial biopsy samples, has revealed dominant infiltration of innate immune cells in the early stage, followed by lymphocytes. This finding suggests that the activation of innate immunity is the initial mechanism triggering the cytokine storm in FM. The results also support the beneficial effects of immunomodulatory therapy using glucocorticoids and immunoglobulins rather than immunosuppression by promoting M2 macrophage polarization. This study was registered at <span><span>https://clinicaltrials.gov/study/NCT03268642</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"81 ","pages":"Pages 945-953"},"PeriodicalIF":13.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From scaffold to effector: reframing GFAP in neurodegeneration","authors":"Yong-Heng Lu, Xiu-Ping Zhu, Song Li, Feng-Ning Zhang, Chuan-Bin Cai, Mao Tian, Yu-Hang Zhu, Ling-Hui Zeng, Jun Tan, Chang-Yin Yu, Jiang Chen","doi":"10.1016/j.jare.2026.02.051","DOIUrl":"https://doi.org/10.1016/j.jare.2026.02.051","url":null,"abstract":"<h3>Background</h3>Neurodegenerative disorders impose a growing global burden, yet disease-modifying therapies remain limited. Glial fibrillary acidic protein (GFAP) has shifted from a passive astrocytic marker to an active effector shaping neurodegenerative pathology.<h3>Aim</h3><strong>of Review:</strong> This review synthesizes mechanistic and translational evidence that defines GFAP as a proteoform-governed hub and highlights its value for biomarker-guided precision intervention.<strong>Key Scientific Concepts of Review:</strong> An extensive literature search across major databases was conducted using predefined keywords and strict inclusion criteria, covering mechanistic, pathological, and clinical studies. Evidence supports a GFAP proteoform code in which alternative splicing generates functionally distinct isoforms and PTMs encode context-dependent assembly dynamics and signaling outputs. We summarize how GFAP proteoforms integrate cytoskeletal remodeling with inflammatory transcriptional programs (notably STAT3 and NF-κB), proteostasis stress, and mitochondrial dysfunction, thereby coupling astrocyte state transitions to neuronal vulnerability and synaptic impairment. Disease trajectories are context specific: GFAP dysfunction drives primary toxicity in Alexander disease (AxD); in Alzheimer’s disease (AD), isoform-specific mechanisms intersect with amyloidogenic machinery and track early preclinical astrocyte activation; and in frontotemporal dementia (FTD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS), GFAP reflects inflammatory–metabolic coupling during progression. Translationally, ultrasensitive plasma assays reveal GFAP elevation years to decades before symptom onset, complementing NfL and amyloid/tau within AT(N)-oriented diagnostic frameworks. Therapeutically, we evaluate precision strategies beyond global suppression, including ASO-based modulation, targeting STAT3/NF-κB-driven reactive programs, and restoring proteostasis via chaperone/autophagy pathways. Future progress hinges on isoform-/PTM-specific probes, conformational sensors, and spatial proteomic atlases validated in prospective longitudinal cohorts. In conclusion, GFAP represents both a mechanistic driver and a scalable biomarker, offering a translationally actionable axis to advance precision medicine in neurodegeneration.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"25 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147329727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of immune features and discovery of potential biomarkers for ankylosing spondylitis using deep plasma proteomics","authors":"Xiaohan Xu ,&nbsp;Wanlin Liu ,&nbsp;Bo Pang ,&nbsp;Yu Wang ,&nbsp;Hongying Zhen ,&nbsp;Quan Jiang ,&nbsp;Yuening Chen ,&nbsp;Kun Yang ,&nbsp;Jinjie Shi ,&nbsp;Jie Ma ,&nbsp;Hongxiao Liu","doi":"10.1016/j.jare.2025.05.052","DOIUrl":"10.1016/j.jare.2025.05.052","url":null,"abstract":"<div><h3>Introduction</h3><div>Ankylosing spondylitis (AS) is a systemic inflammatory disorder that predominantly involves the axial skeleton, often leading to irreversible structural damage and disability. Although several therapeutic measurements are available, limitations in efficacy and long-term outcomes remain significant. Therefore, identifying novel biomarkers and therapeutic targets is of critical importance for optimizing clinical management and prognostic evaluation in AS patients.</div></div><div><h3>Objectives</h3><div>This study aims to elucidate the immune features and discover potential biomarkers for AS by the integration of deep plasma proteomics and deep learning strategies.</div></div><div><h3>Methods</h3><div>The deep quantitative proteomics was applied to analyze the plasma samples from 104 participants of AS patients with active and stable stages, along with healthy controls. The immune and functional features of AS patients in different stages were assessed. By integrating random forest (RF) with orthogonal partial least squares discriminant analysis (OPLS-DA), a machine learning model-based score matrix was constructed to identify biomarkers. ELISA experiments were performed on an independent cohort of 79 participants to confirm the potential biomarkers for AS.</div></div><div><h3>Results</h3><div>Patients with AS exhibit significant dysregulation in the distributions and characteristics of immune cells. Several key proteins involved in integrin signaling pathway were significantly differentially expressed in patients with AS, highlighting the pathway’s role in the pathogenesis of AS. Four proteins including SAA1, FERMT3, ILK, and TLN1, were identified as potential biomarkers for AS and further verified by ELISA experiments.</div></div><div><h3>Conclusions</h3><div>By integrating the machine learning-based method with deep proteomics analysis, we explored the pathological mechanism and identified biomarkers for AS. Our study provides insights into the distinct protein expression patterns and pathogenesis of AS and may contribute to diagnosis, long-term monitoring, and therapy for this disease.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"81 ","pages":"Pages 223-234"},"PeriodicalIF":13.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comprehensive examination of the impact of environmental pollution on lung cancer: A review","authors":"Hongyan Zhang ,&nbsp;Hongyi Wei ,&nbsp;Sijia Han ,&nbsp;Lufeng Zheng ,&nbsp;Xiaodong Chen ,&nbsp;Ziwei Li ,&nbsp;Lanbo Wang","doi":"10.1016/j.jare.2025.06.006","DOIUrl":"10.1016/j.jare.2025.06.006","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer is a leading cause of death worldwide, with environmental factors playing critical roles in its development and progression. Respirable and food-borne contaminants are major contributors to lung cancer onset, influencing various physiological pathways that lead to lung injury and tumor formation.</div></div><div><h3>Aim of Review</h3><div>This review aims to examine the effects of common environmental pollutants on lung cancer development, highlighting the role of specific contaminants, such as PM2.5 (particulate matter with aerodynamic diameter less than 2.5  µm) and nitrogen oxides, and warning people to pay more attention to environmental pollutants.</div></div><div><h3>Key Scientific Concepts of Review</h3><div>Environmental pollutants play a significant role in increasing the susceptibility to lung cancer by triggering various biological mechanisms that lead to lung injury and tumorigenesis. Excessive PM2.5 exposure contributes to the overall burden of lung cancer via Wnt/β-catenin, Reactive oxygen species-DNA methyltransferases (ROS-DNMT), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt), Janus kinase/signal transducers and activators of transcription (JAK/STAT) signalling pathways. The primary mechanisms by which NO contributes to the occurrence and development of pulmonary neoplasm revolve around the production and regulation of ROS. Occupational exposure and ecosystem pollution to hazardous substances, including microplastics, pesticides, asbestos, cadmium, and nickel, are the well-established risk factors for the development of lung cancer via DNA damage, oxidative stress, and inflammation pathways. This review emphasizes the importance of effective prevention strategies for lung cancer by reducing environmental pollution levels.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"81 ","pages":"Pages 273-286"},"PeriodicalIF":13.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytoskeletal-related genes function as checkpoints for the maintenance of VSMC contractile phenotype and prevent pathological remodeling in arterial diseases","authors":"Yunchang Liu ,&nbsp;Liping Zeng ,&nbsp;Qi Cai ,&nbsp;Yunfei Zeng ,&nbsp;Shuo Zheng ,&nbsp;Xue Gong ,&nbsp;Lu Zhou ,&nbsp;Miao Tian ,&nbsp;Lianglong Chen ,&nbsp;Gengze Wu ,&nbsp;Chunyu Zeng","doi":"10.1016/j.jare.2025.05.065","DOIUrl":"10.1016/j.jare.2025.05.065","url":null,"abstract":"<div><h3>Introduction</h3><div>Arterial pathological remodeling, central to arterial diseases including atherosclerosis and aortic aneurysms, is characterized by vascular smooth muscle cell (VSMC) phenotypic switching with concomitant loss of contractile markers. Uncovering the molecular changes initiating phenotypic transition may advance the understanding of vascular pathogenesis and provide new therapeutic strategies.</div></div><div><h3>Objectives</h3><div>To construct a cross-species integrative model of VSMC transition in arterial diseases including atherosclerosis and aortic aneurysm, identify key genes regulating phenotypic switching in the trajectory from contractile to other phenotypes, and further validate their function in arterial remodeling models.</div></div><div><h3>Methods</h3><div>Public single-cell RNA-seq datasets were analyzed to map VSMC transcriptional dynamics and identify regulated gene expression patterns during transition. The changes were further checked using experimental animal aneurysm samples and PDGF-BB treated VSMCs. Functional validation included <em>in vitro</em> siRNA-mediated knockdown using primary VSMCs and <em>in vivo</em> gene-manipulated (AAv-shRNA/Adv-overexpression) wire-injury models.</div></div><div><h3>Results</h3><div>Dysregulation of cytoskeletal-related genes (<em>Fblim1</em>, <em>Tns1</em>, and <em>Synpo2</em>) may cause disarrangement of actin cytoskeleton, and were identified as checkpoint process before VSMCs transition initiation. Knockdown of target genes suppressed contractile markers, enhanced proliferation, migration, and disrupted cytoskeleton architecture in VSMCs. In animal models, gene down-regulation exacerbated pathological remodeling while over-expression partially reverted these effects.</div></div><div><h3>Conclusion</h3><div>The findings highlight the critical role of cytoskeleton-related genes in arterial diseases that function as a critical checkpoint in preventing VSMC pathological phenotypic switching.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"81 ","pages":"Pages 689-707"},"PeriodicalIF":13.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burden of bacterial antimicrobial resistance in China: a systematic analysis from 1990 to 2021 and projections to 2050","authors":"Jian Xu ,&nbsp;Jingyu Liu ,&nbsp;Xiaowei Li,&nbsp;Liang Zhao,&nbsp;Jianzhong Shen,&nbsp;Xi Xia","doi":"10.1016/j.jare.2025.06.021","DOIUrl":"10.1016/j.jare.2025.06.021","url":null,"abstract":"<div><h3>Introduction</h3><div>Antimicrobial resistance (AMR) has emerged as a critical health challenge; however, there is a paucity of in-depth reports outlining its burden and trends in China.</div></div><div><h3>Objectives</h3><div>This study aimed to systematically assess the burden of bacterial AMR in China from 1990 to 2021 and project future trends up to 2050, providing critical insights for AMR control and policy-making.</div></div><div><h3>Methods</h3><div>We analyzed data from the Global Burden of Disease Study 2021, encompassing 12 infectious syndromes, 64 pathogens (including 22 with AMR), and 84 pathogen-drug combinations. The burden was quantified by deaths and disability-adjusted life years under two counterfactual scenarios: those associated with AMR and those attributable to AMR. Trends were assessed using joinpoint regression analysis, and future projections up to 2050 were modeled using an autoregressive integrated moving average approach.</div></div><div><h3>Results</h3><div>In 2021, AMR was attributable to approximately 160,268 (95% uncertainty intervals [UI]: 132,375–188,160) deaths in China, with up to 711,852 (95% UI: 586,447–837,256) fatalities associated with AMR. The most lethal infectious syndrome was bloodstream infections, with key pathogen-drug combinations including methicillin-resistant <em>Staphylococcus aureus</em> (MRSA), carbapenem-resistant <em>Streptococcus pneumoniae</em>, and carbapenem-resistant <em>Acinetobacter baumannii</em>. Between 1990 and 2021, there was a substantial decrease in the burden among children under the age of five, primarily due to a decline in fatalities caused by carbapenem-resistant <em>S. pneumoniae</em>. In contrast, the burden increased among individuals aged 45 and older, with MRSA identified as the principal contributor. Projections indicate that by 2050, AMR could be associated with 769,432 deaths in China, of which 180,123 directly attributable to AMR.</div></div><div><h3>Conclusion</h3><div>Our findings provide a comprehensive evaluation of AMR burden in China, highlighting the urgent need for targeted interventions to prevent and control resistant infections, particularly among older adults.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"81 ","pages":"Pages 809-822"},"PeriodicalIF":13.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144269137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S-sulfhydration: Novel insights into the antioxidant and antiinflammation in age-related diseases","authors":"Fei Liu ,&nbsp;Lan Li ,&nbsp;Longhui Yuan ,&nbsp;Jingchao Yang ,&nbsp;Xi Tang ,&nbsp;Jingping Liu ,&nbsp;Shuyun Liu ,&nbsp;Younan Chen ,&nbsp;Yanrong Lu ,&nbsp;Jingqiu Cheng ,&nbsp;Yujia Yuan","doi":"10.1016/j.jare.2025.06.038","DOIUrl":"10.1016/j.jare.2025.06.038","url":null,"abstract":"<div><h3>Background</h3><div>Hydrogen sulfide (H₂S) and hydrogen polysulfide-induced S-sulfhydration are critical posttranslational modifications that specifically target cysteine residues within proteins. Degenerative diseases are often characterized by oxidative stress and inflammaging, ultimately leading to progressive organ dysfunction. Emerging evidence underscores the essential role of S-sulfhydration in modulating mitochondrial synthesis, energy metabolism, and cellular homeostasis during aging. However, the intricate pathways and molecular regulators that connect S-sulfhydration to degenerative pathologies remain insufficiently elucidated.</div></div><div><h3>Aim of review</h3><div>This review aims to delineate the biological significance of S-sulfhydration in the context of age-associated degenerative disorders especially in redox balance and inflammatory response, including neurodegenerative diseases, osteoarthrosis, osteoporosis, and age-related renal pathologies. In addition, the redox-adaptive S-sulfhydration and clinical applications based on S-sulfhydration-related delivery strategies are proposed, which may reveal novel therapeutic interventions in combating aging.</div></div><div><h3>Key scientific concepts of review</h3><div>This review provides a detailed synthesis of the cellular and molecular mechanisms by which S-sulfhydrated target proteins mitigate senescence phenotypes through antioxidative and anti-inflammatory pathways. Nonetheless, the dual role of S-sulfhydration highly depends on threshold-dependent signaling correlated with H₂S synthetase. Moreover, the dynamic compensatory mechanism of S-sulfhydration plays a critical role in the interaction between oxidative stress and inflammatory stress during the aging process, which identifies S-sulfhydration-mediated redox homeostasis as a promising avenue for therapeutic interventions aimed at mitigating the progression of degenerative diseases.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"81 ","pages":"Pages 915-933"},"PeriodicalIF":13.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144305257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crotonylation driving Streptococcus pneumoniae adaption and virulence","authors":"Nan Li ,&nbsp;Jianpeng Zhuang ,&nbsp;Jiayi Wu,&nbsp;Zhuoti Xue,&nbsp;Jiayi Xu,&nbsp;Zuye Fang,&nbsp;Yundan Zheng,&nbsp;Yun Liu,&nbsp;Yunpeng Yang,&nbsp;Xinyu Ye,&nbsp;Qing-Yu He,&nbsp;Xuesong Sun","doi":"10.1016/j.jare.2025.06.045","DOIUrl":"10.1016/j.jare.2025.06.045","url":null,"abstract":"<div><h3>Introduction</h3><div>To cope with the host’s stressful environment and immune clearance, some drug-resistant bacteria have reduced their virulence. Protein post-translational modifications (PTMs) are known to regulate numerous critical biological processes; however, their specific role in modulating bacterial virulence remains poorly understood.</div></div><div><h3>Objective</h3><div>This study seeks to elucidate the mechanistic role of lysine crotonylation (Kcr) in modulating <em>Streptococcus pneumoniae</em> virulence and adaptive survival.</div></div><div><h3>Methods</h3><div>This study employed quantitative differential proteomics combined with animal models to delineate the critical role of Kcr in the adaptive survival of clinically multidrug-resistant bacterial strains. A crotonyltransferase was identified via knockout/overexpression screening, and its regulatory role was characterized using multi-omics characterization methods, including biochemical and molecular biology assays. Antibody-based enrichment coupled with proteomic techniques was utilized to map the enzyme-substrate network of the crotonyltransferase while comprehensive biochemical analyses-including isothermal titration calorimetry (ITC), hemolysis assays, immunoblotting, circular dichroism (CD) spectroscopy and molecular docking, deciphered its mechanism in modulating the virulence effector pneumolysin (PLY).</div></div><div><h3>Results</h3><div>Our results reveal that mice infected with clinically multidrug-resistant <em>S.pn</em> strains exhibit enhanced invasiveness but attenuated virulence. Quantitative proteomics reveal that Kcr serves as a critical regulator of bacterial virulence and host adaptation. SPD_0839 functions as a crotonyltransferase in <em>S.pn</em>, with Phe93 as its critical catalytic residue. SPD_0839 upregulates 205 Kcr sites on 153 substrates, enhancing the Kcr levels of key enzymes involved in energy metabolism, thereby regulating ATP production. Notably, SPD_0839 modulates the function of the key virulence factor PLY by catalyzing Kcr at Lys171 and Lys442, increases its pore-forming activity and ultimately enhances bacterial hemolysis activity and virulence.</div></div><div><h3>Conclusion</h3><div>Our findings shed light on the molecular mechanisms underlying PLY hemolytic activity regulated by Kcr, revealing its importance in bacterial survival and virulence. Overall, this research provides valuable insights into the important biological roles of Kcr in <em>S.pn</em> and offers potential theoretical foundations for developing new antibacterial drugs.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"81 ","pages":"Pages 453-468"},"PeriodicalIF":13.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exogenous melatonin alleviates abnormal glucose metabolism in the breast muscle under long-term light exposure through the parasympathetic pathway","authors":"Miao Yu ,&nbsp;Mengjie Xu ,&nbsp;Guangju Wang ,&nbsp;Jinghai Feng ,&nbsp;Minhong Zhang","doi":"10.1016/j.jare.2025.05.046","DOIUrl":"10.1016/j.jare.2025.05.046","url":null,"abstract":"<div><h3>Introduction</h3><div>Human beings and animals have been exposed to long-term artificial lighting environments to induce glucose metabolism disorder. Melatonin (MT) is involved in the regulation of glucolipid metabolism, and can prevent skeletal muscle wasting as well as sarcopenia-associated diseases. However, the effect of exogenous MT on skeletal muscle glucose metabolism and the involvement of the parasympathetic pathway have not been clarified. Objectives: To investigate the role of parasympathetic regulatory pathway in the mediating the effects of exogenous MT on skeletal muscle glucose metabolism following long-term light exposure. Methods: This study established rapid growth period broiler models, while characterized muscle histological analysis, glucose metabolism indexes and related genes expression through parasympathetic activation, exogenous MT administration and exogenous MT with parasympathetic inhibition experiments. Results: Long-term light exposure inhibited muscle glycogen synthesis, promoted muscle glycogen decomposition, increased anaerobic glycolysis, decreased aerobic respiration and induced the injury in breast muscle. Parasympathetic activation and exogenous MT caused a marked improvement in muscle glycogen accumulation, aerobic glycolysis and the injury in breast muscle. The exogenous MT beneficial functions were alleviated by parasympathetic inhibition. Furthermore, parasympathetic activation and exogenous MT administration protected cecal microbiota homeostasis, by improving stability of the gut microbiota community and increasing the relative abundance of <em>Lactobacillus</em>. <em>Lactobacillus</em> abundance was positively associated with muscle glycogen accumulation. Conclusion: Taken together, this study highlighted the role of the novel parasympathetic regulatory pathway in the effects of exogenous MT in maintaining glucose metabolism homeostasis and restoring the damage in skeletal muscle with long-term light exposure. The results indicate that gut microbiota are involved in the MT-parasympathetic regulatory network. This study filles the gap in autonomic nervous-endocrine regulation under long light exposure, and provides a new insight to alleviate long light exposure-induced glucose metabolism disorders to improve the growth and health of humans and animals.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"81 ","pages":"Pages 175-193"},"PeriodicalIF":13.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144165486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptation of plateau frog peptide: From antimicrobial to angiogenic and proliferative functions","authors":"Kaixun Cao ,&nbsp;Liting Zhang ,&nbsp;Min Yang ,&nbsp;Jinai Gao ,&nbsp;Congshuang Deng ,&nbsp;Xiaoshan Huang ,&nbsp;Qian Chen ,&nbsp;Qiumin Lu ,&nbsp;Yizhe Cheng ,&nbsp;Shaoyang Gao ,&nbsp;Hui Cao ,&nbsp;Ren Lai","doi":"10.1016/j.jare.2025.06.013","DOIUrl":"10.1016/j.jare.2025.06.013","url":null,"abstract":"<div><h3>Introduction</h3><div>Amphibian skin peptides, particularly defensins, play important roles in environmental adaptation, but often exhibit functional redundancy. SC17-2, a novel peptide from the high altitude frog Nanorana parkeri, exhibits unique angiogenesis and cell migration promoting activities, allowing adaptation to the extreme environment of the Tibetan Plateau with high UV radiation and low microbial diversity.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate the adaptive role of SC17-2 in high-UV environments, its functional differences from typical defensins, and its potential biomedical applications in wound healing and angiogenesis.</div></div><div><h3>Methods</h3><div>Bioinformatics analyses, including sequence alignment and ancestral reconstruction, identified positively selected amino acid sites in SC17-2. Molecular docking examined its interaction with the epidermal growth factor receptor (EGFR). <em>In vitro</em> and <em>in vivo</em> experiments, using mouse and zebrafish models, assessed its wound healing and angiogenic properties.</div></div><div><h3>Results</h3><div>SC17-2 exhibited no antimicrobial activity, but it demonstrated antioxidant activity and potent wound healing and angiogenic properties. Molecular docking indicated that SC17-2 interacts with EGFR, potentially activating downstream signalling pathways. <em>In vivo</em> experiments showed that SC17-2 significantly accelerated wound healing by promoting collagen regeneration and angiogenesis, in some aspects outperforming VEGF.</div></div><div><h3>Conclusion</h3><div>SC17-2 represents a unique functional divergence in amphibian peptides, driven by ecological adaptation rather than microbial pressure. Its ability to promote angiogenesis and cell migration highlights its potential as a novel therapeutic agent for regenerative medicine, shaped by the extreme conditions of the Tibetan Plateau.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"81 ","pages":"Pages 287-300"},"PeriodicalIF":13.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}