Journal of Advanced Research最新文献

{"title":"Snapin mediates neuronal PANoptosis after mild traumatic brain injury via H2S-dependent S-sulfhydration of CTSD","authors":"Xueshi Chen,&nbsp;Xinqi Huang,&nbsp;Yumei An,&nbsp;Cheng Gao,&nbsp;Yuan Gao,&nbsp;Haiyan Shan,&nbsp;Luyang Tao,&nbsp;Xiping Chen,&nbsp;Mingyang Zhang","doi":"10.1016/j.jare.2026.01.039","DOIUrl":"10.1016/j.jare.2026.01.039","url":null,"abstract":"<div><h3>Introduction</h3><div>Traumatic brain injury (TBI) induces complex secondary neuronal death, yet no specific therapeutic strategies are available to ameliorate post-traumatic neurological dysfunction. PANoptosis is a coordinated cell death pathway involving apoptosis, pyroptosis, and necroptosis; however, it remains unknown whether PANoptosis contributes to mild TBI (mTBI)-induced neuronal death and what precise mechanisms govern this process.</div></div><div><h3>Objective</h3><div>This study aimed to investigate whether Snapin regulates neuronal PANoptosis following mTBI and to elucidate its functional mechanism through the hydrogen sulfide (H₂S)/ cathepsin D (CTSD) pathway.</div></div><div><h3>Methods</h3><div>We utilized a controlled cortical impact (CCI) protocol to create a model of mTBI. Neuronal Snapin was conditionally knocked down via AAV-shSnapin. PANoptosis-related proteins were evaluated using immunofluorescence staining and Western blot. Endogenous H₂S levels were measured with a sulfide ion-selective electrode. The interaction between Snapin and cystathionine β-synthase (CBS) was examined by molecular docking and co-immunoprecipitation, while S-sulfhydration of CTSD was detected using a modified biotin switch assay. Therapeutic effects were assessed through behavioral tests including the wire-grip test, open field test, beam balanced walk, novel object recognition, and Morris water maze.</div></div><div><h3>Results</h3><div>Snapin was significantly upregulated in cortical and hippocampal neurons after mTBI. Knockdown of Snapin attenuated neurodegeneration, reduced PANoptosis-related proteins, and improved neurofunctional recovery. Mechanistically, Snapin bound to CBS, disrupting H₂S metabolic homeostasis and reducing endogenous H₂S levels. The decrease in H₂S limited S-sulfhydration of pro-CTSD, promoting its maturation into active CTSD and ultimately inducing PANoptosis. Both pepstatin A and NaHS treatment conferred neuroprotection, reducing neuronal death and neuroinflammation.</div></div><div><h3>Conclusion</h3><div>Snapin promotes mTBI-induced neuronal PANoptosis by disrupting the H₂S/CTSD pathway through specific binding with CBS. Therapeutic strategies targeting Snapin, restoring H₂S homeostasis, or inhibiting CTSD activation may significantly alleviate neurological impairment and neuroinflammation post-mTBI, highlighting novel therapeutic avenues for mTBI treatment.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 911-927"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial and single-cell transcriptomics landscape of adenomyosis","authors":"Xing Yang,&nbsp;Chunjie Li,&nbsp;Junxian He,&nbsp;Bingbing Xie,&nbsp;Linyan Lv,&nbsp;Jian Xu,&nbsp;Yuan Lin,&nbsp;Chuanchuan Zhou,&nbsp;Manchao Li,&nbsp;Zhi Zeng,&nbsp;Jinfeng Tan,&nbsp;Shuqin Chen,&nbsp;Guizhong Cui,&nbsp;Guihua Liu,&nbsp;Shengbao Suo,&nbsp;Guangdun Peng,&nbsp;Xiaoyan Liang","doi":"10.1016/j.jare.2025.12.042","DOIUrl":"10.1016/j.jare.2025.12.042","url":null,"abstract":"<div><h3>Introduction</h3><div>Adenomyosis is a prevalent gynaecological disorder affecting women of reproductive age, yet the underlying etiology and cellular-molecular mechanisms driving its pathogenesis remain poorly understood. Gonadotropin-releasing hormone agonists (GnRHa) are commonly used to improve clinical pregnancy rates in affected patients; however, their effects on specific cellular niches within the diseased uterus have not been fully elucidated.</div></div><div><h3>Objective</h3><div>This study aimed to profile adenomyosis at both the single-cell and spatial transcriptomic levels to examine various cell populations and systematically evaluate the effects of GnRHa treatment.</div></div><div><h3>Methods</h3><div>To characterize in depth the cellular and molecular landscape of adenomyosis, we employed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (Geo-seq) to profile 15 participants, including 11 patients with adenomyosis (three untreated and eight treated with GnRHa) and four control participants. For validation using immunofluorescence and immunohistochemistry, we included an additional two control subjects and 11 patients with adenomyosis. Furthermore, publicly available scRNA-seq datasets from samples collected during the proliferative phase of the menstrual cycle were incorporated for comparison.</div></div><div><h3>Results</h3><div>Our analysis revealed that ectopic endometrial glands in adenomyosis were enriched with ciliated epithelial cells, a feature that persisted following GnRHa treatment, suggesting a potential role of these cells in disease pathogenesis. Immune-inflammatory signatures, including elevated CD4⁺ T cells and LYVE1⁺ macrophages, were prominent in untreated adenomyosis, contributing to a pro-angiogenic microenvironment. This inflammatory and angiogenic activity was partially mitigated by GnRHa therapy. Notably, mast cells were found to be concentrated in the junctional zone, implicating this region as a potential site of disease initiation.</div></div><div><h3>Conclusion</h3><div>Our findings provide evidence for the invagination theory, highlighting the involvement of ciliated epithelial cells and immune-angiogenic crosstalk in adenomyosis pathogenesis. Moreover, this study demonstrates that GnRHa exerts therapeutic effects through the normalization of immune cell composition and restoration of epithelial-stromal interaction, offering novel mechanistic insights into its mode of action.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 775-794"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145845325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the formation mechanism of the key fresh aroma component (Z)-3-hexen-1-ol during the spreading process of lu’an Guapian green tea","authors":"Yuchuan Li,&nbsp;Hong Zhang,&nbsp;Mingle Wang,&nbsp;Fei Guo,&nbsp;Pu Wang,&nbsp;Xia Wang,&nbsp;Yuqiong Chen,&nbsp;Xiaoting Zhai,&nbsp;Xiaochun Wan,&nbsp;Dejiang Ni","doi":"10.1016/j.jare.2026.01.031","DOIUrl":"10.1016/j.jare.2026.01.031","url":null,"abstract":"<div><h3>Introduction</h3><div>The regulation of aroma quality during the postharvest processing of fresh tea leaves is a critical yet underexplored area. Green tea spreading, a key step that induces dehydration stress, significantly influences aroma formation but the underlying molecular mechanisms remain poorly understood.</div></div><div><h3>Objectives</h3><div>This study aimed to identify the optimal spreading degree for the fresh aroma quality of Lu’an Guapian (LAGP) green tea and to elucidate the key volatile compounds, biosynthetic genes, and regulatory transcription factors responsible for this process.</div></div><div><h3>Methods</h3><div>We utilized an integrated multi-omics approach, combining gas chromatography-mass spectrometry (GC–MS), gas chromatography–olfactometry-mass spectrometry (GC-O-MS), and odor activity value (OAV) analysis to profile aroma compounds. Transcriptomics was used to identify associated gene expression changes. Key findings were validated through subcellular localization, in vitro enzyme assays, transient overexpression in tea plants, promoter cloning, yeast one-hybrid (Y1H) assays, luciferase (LUC) reporter assays, electrophoretic mobility shift assays (EMSA), and exogenous ethephon treatment.</div></div><div><h3>Results</h3><div>An optimal moisture range of 68%–71% was found to maximize the fresh aroma quality. (<em>Z</em>)-3-hexen-1-ol was identified as a critical contributor, and its biosynthetic gene, <em>CsADH1</em>, was strongly upregulated. In vitro assays confirmed CsADH1′s cytoplasmic localization and its specific activity in converting (<em>Z</em>)-3-hexenal to (<em>Z</em>)-3-hexen-1-ol. Transient overexpression of <em>CsADH1</em> in tea plants significantly increased (Z)-3-hexen-1-ol production. Furthermore, we discovered that the transcription factor CsERF105 directly binds to the <em>CsADH1</em> promoter to activate its expression in response to dehydration stress and potential ethylene signal.</div></div><div><h3>Conclusion</h3><div>Our results demonstrate that dehydration stress and potential ethylene signal during spreading triggers CsERF105-mediated activation of <em>CsADH1</em>, which in turn enhances the biosynthesis of the key fresh aroma compound (<em>Z</em>)-3-hexen-1-ol. This study successfully links a specific spreading processing condition to a molecular regulatory module, providing crucial insights and novel targets for improving aroma quality in tea processing.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 91-104"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding intervertebral disc degeneration pathomechanics: from mechanisms to therapeutic horizons","authors":"HanLin Qiao,&nbsp;TongLei Chen,&nbsp;Jing Yu,&nbsp;Chen Li,&nbsp;Chang Gao,&nbsp;YanJun Yang,&nbsp;YiCai Zhang,&nbsp;HuiLin Yang,&nbsp;ZhanJun Yan,&nbsp;ChangDong Lin","doi":"10.1016/j.jare.2026.01.045","DOIUrl":"10.1016/j.jare.2026.01.045","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc degeneration (IVDD) is widely recognized as a key factor in various lumbar spine disorders. Biomechanical factors play a crucial role in maintaining homeostasis and influencing the degeneration process of the intervertebral disc (IVD). The nucleus pulposus (NP), located at the core of the disc, is responsible for distributing mechanical stresses from spinal movements, making it a primary site for degeneration.</div></div><div><h3>Aim of review</h3><div>This review designs to elucidate the key mechanisms of pathological mechanics in the nucleus pulposus and provide insights for biomechanically targeted therapies for disc disorders.</div></div><div><h3>Key scientific concepts of review</h3><div>This comprehensive review provides insights into physiopathology of IVD and summarizes the biomechanical models developed over the past two decades. It specializes the mechanisms of signal transduction mediated by pathomechanics in regulating nucleus pulposus cell (NPC) homeostasis, senescence, autophagy, death, and extracellular matrix remodeling. Potential therapeutic strategies grounded in biomechanics are proposed, such as the implementation of mechanical rhythms, development of pharmacological agents targeting mechanotransduction, and hydrogel encapsulation of NPCs with adjustable mechanical properties.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 381-400"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145995578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling and analyzing glucose-insulin interactions during diabetes through fractional dynamics in presence of glucagon","authors":"Parvaiz Ahmad Naik,&nbsp;Bijal M. Yeolekar,&nbsp;Kolade M. Owolabi,&nbsp;Mahesh Yeolekar","doi":"10.1016/j.jare.2026.01.020","DOIUrl":"10.1016/j.jare.2026.01.020","url":null,"abstract":"<div><h3><em>Introduction and objective:</em></h3><div>Diabetes is a chronic metabolic disorder characterized by higher blood glucose levels due to insufficient insulin production, weakened insulin action, or both. This study aims to construct and analyze a fractional-order mathematical model using the Anatanga-Baleanu derivative to investigate how glucose levels in the human body are controlled through interactions with insulin and glucagon. The objective is to thoroughly understand these interactions, which could improve current treatments and medications.</div></div><div><h3><em>Methods:</em></h3><div>A fractional-order diabetes model has been developed. Fixed points and their Ulam-Hyers stability are analyzed to ensure the mathematical reliability of the model. The qualitative dynamics are examined to capture glucose-insulin-glucagon interactions in detail. The explicit fractional Euler method is utilized to demonstrate the efficiency of the model for numerical results. Also, the existence and uniqueness of the solutions are obtained. Finally, numerical simulations validate the significance of the results, underscoring their relevance to diabetes research and treatment strategies.</div></div><div><h3><em>Results:</em></h3><div>The findings reveal the dynamic interactions among glucose, insulin, and glucagon in diabetes, showing that higher parameter values increase peak amplitudes and prolong transients. The fractional-order glucose–insulin model, with greater flexibility than classical derivatives, captures memory effects that influence diabetes progression and highlights potential therapeutic targets for improved disease management.</div></div><div><h3><em>Conclusion:</em></h3><div>This study provides a deeper understanding of diabetes through a detailed analysis of the proposed fractional-order glucose-insulin interactive model by addressing its well-posedness, steady-state behavior, and Ulam-Hyers stability. It bridges theoretical models and experimental observations, clarifying insulin-glucagon interactions. Further, it provides a robust framework for exploring glucose regulation mechanisms and may guide researchers and clinicians in developing more effective therapeutic strategies for diabetes and related metabolic disorders.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 689-706"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145962294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tetrapeptides derived from black bean enhance osteogenesis and alleviate ovariectomy-induced bone loss via activation of BMP-2/Smad signaling","authors":"Yan Zhang,&nbsp;Chong Chen,&nbsp;Chibuike C. Udenigwe,&nbsp;Zhaojun Zheng,&nbsp;Yuanfa Liu","doi":"10.1016/j.jare.2026.01.012","DOIUrl":"10.1016/j.jare.2026.01.012","url":null,"abstract":"<div><h3>Introduction</h3><div>Osteoporosis, a “silent killer” among the elderly, is marked by progressive bone loss and microstructural deterioration. Oligopeptides derived from black bean, particularly tetrapeptides, have shown notable osteogenic potential, yet their therapeutic roles in regulating bone metabolism and preventing osteoporosis remain unclear.</div></div><div><h3>Objectives</h3><div>This study explored the osteoanabolic effects of black bean-derived tetrapeptides and elucidated their underlying mechanisms.</div></div><div><h3>Methods</h3><div><em>In vitro</em> assays were conducted using MC3T3-E1 pre-osteoblasts derived from mouse calvaria to assess osteogenic differentiation upon tetrapeptide treatment. Six black bean tetrapeptides were evaluated, including KIGT, KGVG, KTGV, SIKL, KLGT, and SLKL. <em>In vivo</em> efficacy was evaluated in an ovariectomized mouse model of osteoporosis via intragastric administration. Based on molecular docking, the mechanisms were explored using Western blotting and immunofluorescence and validated through pathway inhibitor and siRNA knockdown experiments.</div></div><div><h3>Results</h3><div>All six tetrapeptides significantly stimulated the osteogenic differentiation of MC3T3-E1 pre-osteoblasts, particularly during early osteogenesis. Notably, the peptides all exhibited osteogenic effects at low doses (0.1 μM), although their optimal concentrations varied. Mechanistic studies revealed a shared anabolic pathway among the tetrapeptides, in which lysine residues may play a pivotal role in mediating their similar interactions with bone morphogenetic protein-2 (BMP-2), thereby activating the BMP-2/Smad signaling. Furthermore, this potent osteoanabolic efficacy was confirmed in osteoporotic mice, where a 10-week treatment with black bean oligopeptides (&lt;1 kD), KIGT, and KGVG (100 mg/kg) markedly attenuated bone loss.</div></div><div><h3>Conclusion</h3><div>Lysine-containing tetrapeptides derived from black bean exert direct osteoanabolic activity by targeting BMP-2/Smad signaling in osteoblasts. These findings support their potential as novel anabolic candidates against osteoporosis, paving the way for the development of oligopeptide-based therapies targeting bone health.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 17-30"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145947135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNFSF10 drives hyperactive immune responses via NLRP3 inflammasome and endoplasmic reticulum stress in autoimmune and inflammatory diseases","authors":"Huilin Zhang,&nbsp;Yaoyao Chen,&nbsp;Yingmei Li,&nbsp;Chang Chen,&nbsp;Bingjie Wang,&nbsp;Fanxiang Yin,&nbsp;Yunling Zhu,&nbsp;Jiani Li,&nbsp;Jin Li,&nbsp;Ping Tang,&nbsp;Juanxia Zhou,&nbsp;Shaohua Yan,&nbsp;Bo Qin,&nbsp;Qingxuan Xin,&nbsp;Shuya Wang,&nbsp;Qiankun Yang,&nbsp;Baohong Yue,&nbsp;Yong Jiang,&nbsp;Rongqun Guo","doi":"10.1016/j.jare.2026.01.029","DOIUrl":"10.1016/j.jare.2026.01.029","url":null,"abstract":"<div><h3>Introduction</h3><div>Autoimmune and inflammatory diseases are characterized by multifaceted pathogenesis, demanding effective therapeutic strategies.</div></div><div><h3>Objectives</h3><div>TNFSF10 is typically regarded as a pro-apoptotic ligand, yet its functions under physiological and pathological conditions remain elusive.</div></div><div><h3>Methods</h3><div>scRNA-seq analysis of immune cells from patients with aplastic anemia (AA) was performed to identify the crucial DEGs,with TNFSF10 being highlighted as a key regulator. Tnfsf10-deficient mice were used to establish an AA mouse model, and other mouse models, such as ER stress, aGVHD, radiation-induced aging, and IBD, which facilitated the exploration of the biological function of TNFSF10.</div></div><div><h3>Results</h3><div>Here, we show that TNFSF10 contributes to the imbalance of immune homeostasis and immunogenic cell death (ICD) under pathological circumstances. The ICD-provoking effect and proinflammatory property of TNFSF10 is associated with the activation of the NF-κB pathway and NLRP3 inflammasome. Additionally, TNFSF10 is a crucial amplifier of endoplasmic reticulum stress by enhancing the expression of PPP1R15A, thereby contributing to NLRP3 inflammasome activation. Moreover, TNFSF10-associated ER stress is a driver of surface Calreticulin (CALR) exposure, which transmits an “eat me” signal to hyperactivated immune cells and accelerates the clearance of hematopoietic cells. We also found that AA-specific exosomes may contribute to ER stress and the expression of TNFSF10.</div></div><div><h3>Conclusion</h3><div>Collectively, our study reveals the key role of TNFSF10 in autoimmune and inflammatory diseases, integrating the NF-κB, NLRP3 inflammasome, and ER stress pathways, and further accelerating the disease process.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 297-317"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145972619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of pericytes in homeostasis and cardiovascular disease: A comprehensive review","authors":"Hongbin Zang,&nbsp;Xuemei Li,&nbsp;Xiaoxi Yang,&nbsp;Xiaoman Li,&nbsp;Xinyue Chen,&nbsp;Ce Wang,&nbsp;Sicong Guo","doi":"10.1016/j.jare.2026.02.037","DOIUrl":"10.1016/j.jare.2026.02.037","url":null,"abstract":"<div><h3>Background</h3><div>Pericytes, as critical mural cells of the vascular wall, play multifaceted and context-dependent roles in maintaining vascular integrity, regulating microcirculatory homeostasis, and mediating interactions between the vasculature and surrounding tissues. Beyond their canonical functions in vascular stabilization and angiogenesis, recent preclinical and clinical studies have increasingly implicated pericyte dysfunction in the pathogenesis of various cardiovascular diseases (CVDs), including atherosclerosis, myocardial ischemia–reperfusion (I/R) injury, pulmonary arterial hypertension (PAH), and ischemic stroke.</div></div><div><h3>Aim of review</h3><div>This review aims to comprehensively collate and analyze recent progress in understanding pericyte biology in major CVDs. Specifically, it determines the core roles of pericytes in atherosclerosis based on mediating plaque neovascularization, promoting plaque instability via detachment or pro-inflammatory activation, myocardial I/R injury based on regulating microvascular permeability, participating in post-infarction fibrosis and vascular repair), PAH based on abnormal proliferation and differentiation leading to pulmonary vascular remodeling, and ischemic stroke based on maintaining blood–brain barrier integrity, modulating neurovascular unit repair.</div></div><div><h3>Key scientific concepts of review</h3><div>By integrating evidence from preclinical models such as lineage-tracing mice, disease-specific animal models and clinical samples, this review elucidates the common and disease-specific mechanisms linking pericyte dysfunction to CVD pathogenesis, and highlights the therapeutic promise of targeting pericyte biology. Key scientific concepts explored include the interplay between pericyte phenotypic plasticity and microenvironmental cues, the role of pericyte-endothelial cell crosstalk in vascular homeostasis and dysfunction, and the clinical relevance of pericyte subpopulation heterogeneity. Ultimately, this work provides novel mechanistic insights into CVD progression and offers a framework for advancing pericyte-directed therapeutic development, bridging the gap between basic research and clinical application to improve outcomes for patients with cardiovascular disorders.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 659-675"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146210060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of protein signature of fine particulate matter with MASLD: the underlying pathways and Mendelian randomization analysis","authors":"Shanshan Ran,Dashan Zheng,Zijun Yang,Yao Huang,Shengtao Wei,Peng Hu,Jingyi Zhang,Fei Tian,Hualiang Lin","doi":"10.1016/j.jare.2026.10.021","DOIUrl":"https://doi.org/10.1016/j.jare.2026.10.021","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"83 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149150571","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":"Activated hepatic stellate cell-derived exosomal miR-23a-3p promotes hepatocellular carcinogenesis by regulating DUSP5/ERK signaling","authors":"Xiaona Lu,&nbsp;Jia Shi,&nbsp;Wenlan Zheng,&nbsp;Shihan Yu,&nbsp;Xuemei Zhang,&nbsp;Hai Feng,&nbsp;Yueqiu Gao,&nbsp;Zhuo Yu","doi":"10.1016/j.jare.2026.01.038","DOIUrl":"10.1016/j.jare.2026.01.038","url":null,"abstract":"<div><h3>Introduction</h3><div>Activation of hepatic stellate cells (HSCs) is a core driver of liver fibrosis and may contribute to the evolution to hepatocellular carcinoma (HCC). Exosomes mediate intercellular signaling by transporting bioactive molecules, yet the role of activated HSC-derived exosomes in hepatocarcinogenesis remains unexplored.</div></div><div><h3>Objectives</h3><div>This study aims to investigate whether and how activated HSCs induce hepatocarcinogenesis through the mediation of exosomes.</div></div><div><h3>Methods</h3><div>Exosomes from activated HSCs were isolated and applied to hepatocytes to assess malignant transformation via immunoblotting, soft-agar colony formation, and xenograft assays. Oncogenic miRNAs were screened by sequencing and validated by qPCR. Target genes and signaling pathways were identified through transcriptomics, bioinformatics, and dual-luciferase assays. Functional roles of miRNAs and downstream pathways were confirmed via gain/loss-of-function experiments. Clinical correlations and diagnostic potential of exosomal miRNAs were evaluated using patient samples.</div></div><div><h3>Results</h3><div>Exosomes from activated HSCs induced hepatocyte malignant transformation <em>in vitro</em> and tumorigenesis in vivo. MiR-23a-3p was markedly enriched in activated HSC-derived exosomes and exerted oncogenic effect upon delivery to recipient hepatocytes. Mechanistically, exosomal miR-23a-3p directly targeted DUSP5 in hepatocytes, thereby suppressing its expression and subsequently activating pro-oncogenic ERK signaling. Notably, the miR-23a-3p/DUSP5/ERK signaling axis exhibited progressive activation that paralleled histopathological transitions from fibrosis to HCC in both murine models and clinical specimens. Clinically, elevated plasma exosomal miR-23a-3p levels demonstrated significant diagnostic merit for detecting precancerous lesions and predicting HCC onset in patient cohorts.</div></div><div><h3>Conclusion</h3><div>Our results indicate that activated HSCs secrete exosomes enriched with miR-23a-3p, which directly target to inhibit DUSP5, and subsequently activate ERK signaling in hepatocytes, leading to the initiation of cellular malignant transformation and tumorigenesis.</div></div>","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"88 ","pages":"Pages 319-334"},"PeriodicalIF":17.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145993473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}