Journal of Advanced Research最新文献

{"title":"Targeting mesenchymal monocyte-derived macrophages to enhance the sensitivity of glioblastoma to temozolomide by inhibiting TNF/CELSR2/p65/Kla-HDAC1/EPAS1 axis","authors":"Wei Gao, Xinmiao Long, Xiang Lin, Kun Deng, Danyang Li, Meng Huang, Xiangyu Wang, Qing Liu, Minghua Wu","doi":"10.1016/j.jare.2025.05.032","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.032","url":null,"abstract":"<h3>Introduction</h3>Temozolomide (TMZ) resistance poses a significant challenge to the treatment of aggressive and highly lethal glioblastomas (GBM). Monocyte-derived Macrophages (MDM) within the tumor microenvironment are key factors contributing to TMZ resistance in GBM. Lactate-mediated histone lysine lactylation (Kla) plays a crucial role in the regulation of tumor progression. However, the mechanism through which MDM-induced Kla expression promotes TMZ resistance in GBM remains unclear.<h3>Objectives</h3>The objective of this study s to identify a subtype of MDM with therapeutic potential target and to elucidate the mechanisms through which this subtype of MDM contributes to tumor malignant progression and TMZ resistance.<h3>Methods</h3>We integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics data to evaluate whether mesenchymal (MES) MDM is associated with poor prognosis. By establishing a subtype model of GBM cells for the first time, we validated the mechanism by which MES-MDM promotes subtype conversion of tumor cells. Using patient-derived GBM organoids and an intracranial orthotopic GBM model, we demonstrated that targeting MES-MDMs increased GBM sensitivity to TMZ treatment.<h3>Results</h3>We identified a novel MDM subtype, MES-MDM, in the hypoxic niches of the perinecrotic region characterized by high TREM1 expression, which fueled GBM progression. Hypoxia drived MES-MDM signatures by activating ATF3 transcription. MES-MDM facilitated the transition from the NPC to the MES subtype in GBM cells, in which Histone Deacetylase 1 (HDAC1) Kla, induced by the TNF-CELSR2/p65 signaling pathway, promoted this conversion, thereby promoting TMZ resistance. Targeting MES-MDM with TREM1 inhibitory peptides amplified TMZ sensitivity, offering a potential strategy for overcoming resistance to therapy in GBM. Targeting TREM1 enhanced the effectiveness of anti-PD-1 immunotherapy.<h3>Conclusion</h3>This study provides a potential therapeutic strategy for patients with MES-subtype GBM by targeting MES-MDMs in combination with TMZ or PD-1 antibody treatment.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"17 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946254","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":"An injectable nano-hydroxyapatite-incorporated hydrogel with sustained release of Notoginsenoside R1 enhances bone regeneration by promoting angiogenesis through Notch1/Akt signaling","authors":"Bizhi Tan, Xiao Liu, Shuai Chen, Yan Chen, Zhongyuan He, Zemin Ling, Fangli Huang, Rongcheng Hu, Hao Hu, Xuenong Zou, Fuzhi Ai","doi":"10.1016/j.jare.2025.05.025","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.025","url":null,"abstract":"<h3>Introduction</h3>Notoginsenoside R1 (NGR1), a bioactive compound, exhibits significant pro-angiogenic potential, making it a promising candidate for treating various diseases. Since angiogenesis and osteogenesis are synergistically coupled processes, NGR1′s capacity to stimulate blood vessel formation may critically promote bone regeneration. However, the underlying molecular mechanisms through which NGR1 promotes angiogenesis in bone repair remain to be fully elucidated.<h3>Objectives</h3>To investigate the potential mechanism by which NGR1 promotes angiogenesis and to validate the therapeutic effect of NGR1-loaded biomaterials on bone defect regeneration.<h3>Methods</h3>Human umbilical vein endothelial cells (HUVECs) were cultured in complete medium containing the screened concentration of NGR1 to investigate its pro-angiogenic phenotype and potential mechanism in <em>vitro</em>. Subsequently, an injectable nano-hydroxyapatite-incorporated GelMA hydrogel was synthesized as an active drug-delivery delivery system for NGR1. The therapeutic effect of this fabricated NGR1-loaded biomaterial on bone defect regeneration was further evaluated in a rat cranial bone defect model. The key molecules in relevant signaling pathways was analyzed by immunohistochemistry.<h3>Results</h3>In <em>vitro</em> experiments demonstrated that NGR1 exhibits good biocompatibility and angiogenic capacity, as it promoted cell proliferation, enhanced cell migration, upregulated the angiogenic-related gene expression, and increased the protein expression of VEGF and VEGFR-2. Furthermore, the implantation of the injectable nano-hydroxyapatite-incorporated GelMA hydrogel loaded with NGR1 significantly enhanced bone defect regeneration in a rat cranial bone defect model compared to hydrogel-only group. Additionally, NGR1 supplementation markedly upregulated CD31 expression during bone formation, suggesting its role in coupling of angiogenesis and osteogenesis. Mechanistically, both in <em>vivo</em> and in <em>vitro</em> experiments indicated that NGR1 likely promote angiogenesis <em>via</em> activating Notch1/Akt singling pathway during bone regeneration.<h3>Conclusions</h3>These findings indicate that NGR1 promotes angiogenesis through Notch1/Akt signaling activation during bone regeneration, which might offer potential therapeutic targets for bone-related diseases. Moreover, the application of NGR1-loaded biomaterials could represent a promising strategy to enhance bone regeneration.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"122 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946255","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":"NSP6 regulates calcium overload-induced autophagic cell death and is regulated by KLHL22-mediated ubiquitination","authors":"Xingyu Tao, Yanan Wang, Jiangbo Jin, Huilin Yan, Hui Yang, Xiaorui Wan, Ping Li, Yanghua Xiao, Qi Yu, Lingjiao Liu, Yang Liu, Tianyu Han, Wei Zhang","doi":"10.1016/j.jare.2025.05.031","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.031","url":null,"abstract":"<h3>Introduction</h3>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a substantial global threat. SARS-CoV-2 nonstructural proteins (NSPs) are essential for impeding the host replication mechanism while also assisting in the production and organization of new viral components. However, NSPs are not incorporated into viral particles, and their subsequent fate within host cells remains poorly understood. Additionally, their role in viral pathogenesis requires further investigation.<h3>Objectives</h3>This study aimed to discover the ultimate fate of NSP6 in host cells and to elucidate its role in viral pathogenesis.<h3>Methods</h3>We investigated the effects of NSP6 on cell death and explored the underlying mechanism; moreover, we examined the degradation mechanism of NSP6 in human cells, along with analysing its correlation with coronavirus disease 2019 (COVID-19) severity in patient peripheral blood mononuclear cells (PBMCs).<h3>Results</h3>NSP6 was demonstrated to induce cell death. Specifically, NSP6 interacted with EI24 autophagy-associated transmembrane protein (EI24) to increase intracellular Ca²⁺ levels, thereby enhancing the interactions between unc-51-like autophagy activating kinase 1 (ULK1) and RB1 inducible coiled-coil 1 (RB1CC1/FIP200), as well as beclin 1 (BECN1) and phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3). This cascade ultimately triggers autophagy, thus resulting in cell death. Additionally, we discovered that the homeostasis of the NSP6 protein was regulated by K48-linked ubiquitination. We identified kelch-like protein 22 (KLHL22) as the E3 ligase that was responsible for ubiquitinating and degrading NSP6, restoring intracellular calcium homeostasis and reversing NSP6-induced autophagic cell death. Moreover, NSP6 expression levels were observed to be positively associated with the severity of SARS-CoV-2-induced disease.<h3>Conclusion</h3>This study reveals that KLHL22-mediated ubiquitination controls NSP6 stability and that NSP6 induces autophagic cell death via calcium overload, highlighting its cytotoxic role and suggesting therapeutic strategies that target calcium signaling or promote NSP6 degradation as potential interventions against COVID-19.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"7 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940161","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":"Revealing the multiple faces of LRG1: gene expression, structure, function, and therapeutic potential","authors":"Ding Wang, Di Di, Bo Jiang, Yunlong Wang, Zhenqi Jiang, Yuchen Jing, Huizhe Wu, Shijie Xin","doi":"10.1016/j.jare.2025.05.024","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.024","url":null,"abstract":"<h3>Background</h3>As the structural characterization of the Leucine-rich alpha-2-glycoprotein 1 (LRG1) protein progresses, its functional diversity has been increasingly unveiled, highlighting its clinical relevance in elucidating disease pathogenesis and identifying potential therapeutic targets.<h3>Aim of review</h3>Grounded in structural biology principles, this review systematically examines the regulatory mechanisms, pathological functions, and intervention strategies associated with LRG1, providing a theoretical foundation for translating these insights into clinical drug therapies.<h3>Key scientific concepts of review</h3>LRG1, distinguished by its leucine-rich repeat motifs, plays a pivotal role in various physiological and pathological processes. This review presents a comprehensive analysis of LRG1′s multifaceted characteristics and its implications in disease. Initially, the regulatory mechanisms modulating <em>LRG1</em> gene expression are detailed, encompassing both transcriptional and post-transcriptional controls. The structural attributes and distributions of LRG1 are subsequently outlined, with an emphasis on the functional relevance of its leucine-rich repeat motifs. Furthermore, the review elaborates on the molecular interactions through which LRG1 engages with distinct receptors, triggering downstream signaling pathways involved in pathological processes. Finally, current therapeutic approaches targeting LRG1 and its receptors are summarized, alongside prospective research avenues for innovative therapeutic development.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"35 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940318","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":"Induction of cellular senescence by androgen receptor agonist or antagonist is mediated via two novel common DYRK1A-DREAM and cyclin G2 signaling pathways in castration-resistant prostate cancer","authors":"Golnaz Atri Roozbahani, Mehdi Heidari Horestani, Katrin Schindler, Julia Kallenbach, Aria Baniahmad","doi":"10.1016/j.jare.2025.05.019","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.019","url":null,"abstract":"<h3>Background</h3>Castration-resistant prostate cancer (CRPC) is a deadly disease that in addition to being resistant to androgen deprivation often exhibits also resistant to androgen receptor (AR)-antagonists. Supraphysiological androgen levels (SAL) are used in the bipolar androgen therapy in clinical phase trials to inhibit CRPC.<h3>Methods</h3>Co-immunoprecipitation, immunofluorescence, growth and cell senescence assays, mouse xenografted CRPC, AR target gene analyses of organs, analyses of RNA-seq, ChIP-seq and patient-derived xenografts, qRT-PCR, 3D tumor spheroids, knockdown experiments.<h3>Results</h3>Both AR-antagonists and –agonist at SAL induce cellular senescence despite acting oppositely on AR transcriptional activity. Here, we identified two common growth inhibitory pathways induced by SAL and AR-antagonists. Using the novel AR-antagonist compound 28 (C28), that inhibits also those AR mutants mediating therapy resistance, represses growth including CRPC tumor spheroids and mouse xenografted tumors. Mechanistically, C28 reduces phosphorylation of AR at serine 81 and HSP27 required for AR transcriptional activity and enhances AR-p130 interaction. Notably, increased p130 levels were also detected by SAL treatment leading to activation of DREAM complex signaling and induction of cellular senescence indicating that both AR-agonist and –antagonist use the same pathway for growth repression. Inhibition of DYRK1A, a key kinase to activate DREAM complex, blocks C28- and SAL-induced cellular senescence. Both C28 and SAL also induces the atypical cyclin G2 (<em>CCNG2</em>), which also mediates cellular senescence. Induction of <em>CCNG2</em> is confirmed in CRPC tumor spheroids and xenograft tumors of treated mice. The second-generation AR-antagonist Darolutamide (Dar) also activates DREAM complex and <em>CCNG2</em>.<h3>Conclusion</h3>Taken together, these findings suggests the identification of two common pathways induced by AR-antagonists and SAL, used in bipolar androgen therapy, to mediate growth inhibition and induction of cellular senescence in CRPC.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"130 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933352","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":"Osteoimmunity-Regulating biospun 3D silk scaffold for bone regeneration in critical-size defects","authors":"Qian Zhang, Zulan Liu, YuanYuan He, Tianci Huang, Xiao Yang, Lian Duan, Dingpei Long, Fangyin Dai, Lan Cheng, Subhas C. Kundu","doi":"10.1016/j.jare.2025.04.032","DOIUrl":"https://doi.org/10.1016/j.jare.2025.04.032","url":null,"abstract":"<h3>Introduction</h3>Silk-based biomaterials have received a great deal of attention in tissue engineering research for bone repair. Current silk-based materials are typically derived from silk protein solutions, but the limited solubility and solution stability of silk protein solution, coupled with problems such as high preparation cost and low productivity, which severely restrict the application of silk-based materials.<h3>Objective</h3>To address the challenges associated with the complex extraction process and inferior mechanical properties of silk protein or silk fiber-based materials in bone scaffold preparation, flat cocoon silk-based materials were developed to assess their potential for repairing large bone defects.<h3>Methods</h3>We converted the upper cluster mesh’s three-dimensional structure into a two-dimensional flattened plate and controlled the thickness and area of the flattened silkworm cocoons by adjusting the number of mature silkworms and spitting time to match the needs of different sites and bone defect areas. After being hot-pressed, the flattened silkworm cocoons were mixed with PLA to form an excellent tissue engineering scaffold material with a highly porous structure.<h3>Results</h3>The 3D FSC/PLA scaffold demonstrated superior mineralization, mechanical resilience, and biocompatibility. Notably, it promoted anti-inflammatory gene expression, suppressed inflammatory responses through M2 macrophage polarization, and enhanced bone formation and angiogenesis by modulating key pathways, including PI3K-AKT, Wnt, MAPK, and Notch.<h3>Conclusions</h3>By using silkworm larvae to directly create a scaffold, a three-dimensional matrix with properties similar to extracellular matrix and a gradient structure that closely resembles cortical bone was created. This process effectively modulates the immune balance for fibroin dissolution and regeneration. The targeted infiltration of PLA within the 3D silk matrix enabled precise control over porosity and degradation, fostering optimal cellular adhesion and proliferation. As an osteoimmunity-regulating scaffold, it holds significant promise for enhancing bone regeneration and offers a robust foundation for repairing large-scale bone defects.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"213 4 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940160","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":"New insight into the role of SOCS family in immune regulation and autoimmune pathogenesis","authors":"Shiyi Liu, Mingwei Wang, Liangjie Xu, Daihua Deng, Liwei Lu, Jie Tian, Dongmei Zhou, Ke Rui","doi":"10.1016/j.jare.2025.05.020","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.020","url":null,"abstract":"<h3>Background</h3>Suppressor of cytokine signaling (SOCS) proteins regulate signal transduction by interacting with cytokine receptors and signaling proteins and targeting associated proteins for degradation. Recent studies have demonstrated that the SOCS proteins serve as crucial inhibitors in cytokine signaling networks and play a pivotal role in both innate and adaptive immune responses.<h3>Aim of Review</h3>In this review, we aim to discuss recent advancements in understanding the complex functions of SOCS proteins in various immune cells, as well as the effects of SOCS proteins in human health and diseases. Increasing evidence indicates that SOCS proteins are frequently dysregulated in developing autoimmune diseases, suggesting that therapeutic targeting of SOCS proteins could provide clinical benefit.<h3>Key Scientific Concepts of Review</h3>This review provides a comprehensive understanding of SOCS proteins in immune regulation and autoimmune pathogenesis, it also highlights the role of SOCS-related mimetic peptides in immunotherapy.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"9 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930999","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":"Antimycin A inhibits alpha-herpesvirus replication by disrupting the formation of pyrimidinosomes","authors":"Yong-Qi Guo, Meng-Hang Wang, Ning Tang, Yu-Bo Zhao, Li-Jing Wo, De-Xin Liang, Rui Huang, Yan-Dong Tang, Ying-Jie Sun, Xin Yin","doi":"10.1016/j.jare.2025.05.016","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.016","url":null,"abstract":"<h3>Introduction</h3>Alpha-herpesvirus poses significant health risks to humans and challenges to animal husbandry. Currently, the clinically approved antiviral drug Acyclovir exhibits limitations, including drug resistance and adverse effects. The development of broad-spectrum antiviral agents against alpha-herpesvirus is urgently needed.<h3>Objective</h3>This study aimed to discover a novel antiviral drug with the capacity to broadly inhibit various alpha-herpesviruses.<h3>Methods</h3>In this study, we conducted a high-content screening of 1,500 chemical compounds to identify potential antiviral candidates. The antiviral mechanisms were explored using phenotypic experiments, untargeted metabolomics, and molecular docking.<h3>Results</h3>We discovered that Antimycin A effectively inhibits the replication of various alpha-herpesviruses, including herpes simplex virus 1 (HSV-1), bovine herpesvirus 1 (BHV-1), and pseudorabies virus (PRV). Our study revealed that Antimycin A inhibits viral replication by disrupting the formation of pyrimidinosomes that are essential for efficient viral infection. Finally, Antimycin A effectively inhibited viral infection, prevented tissue damage, and enhanced survival in PRV-infected BALB/c mice, confirming its <em>in vivo</em> efficacy.<h3>Conclusion</h3>Antimycin A emerges as a promising lead candidate for the development of antiviral therapies against alpha-herpesvirus infections.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"76 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931232","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":"The functions of gut microbiota-mediated bile acid metabolism in intestinal immunity","authors":"Yanmin He, Weike Shaoyong, Yanli Chen, Menglin Li, Yujie Gan, Lu Sun, Yalin Liu, Yizhen Wang, Mingliang Jin","doi":"10.1016/j.jare.2025.05.015","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.015","url":null,"abstract":"<h3>Background</h3>Bile acids, derived from cholesterol in the liver, consist a steroidal core. Primary bile acids and secondary bile acids metabolized by the gut microbiota make up the bile acid pool, which modulate nuclear hormone receptors to regulate immunity. Disruptions in the crosstalk between bile acids and the gut flora are intimately associated with the development and course of gastrointestinal inflammation.<h3>Aim of review</h3>This review provides an extensive summary of bile acid production, transport and metabolism. It also delves into the impact of bile acid metabolism on the body and explores the involvement of bile acid-microbiota interactions in various disease states. Furthermore, the potential of targeting bile acid signaling as a means to prevent and treat inflammatory bowel disease is proposed.<h3>Key scientific concepts of review</h3>In this review, we primarily address the functions of bile acid-microbiota crosstalk in diseases. Firstly, we summarize bile acid signalling and the factors influencing bile acid metabolism, with highlighting the immune function of microbially conjugated bile acids and the unique roles of different receptors. Subsequently, we emphasize the vital role of bile acids in maintaining a healthy gut microbiota and regulating the intestinal barrier function, energy metabolism and immunity. Finally we explore differences of bile acid metabolism in different disease states, offering new perspectives on restoring the host’s health and the gastrointestinal ecosystem by targeting the gut microbiota-bile acid-bile acid receptor axis.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"50 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931177","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":"SARS-CoV-2 damages cardiomyocyte mitochondria and implicates long COVID-associated cardiovascular manifestations","authors":"Wenliang Che, Shuai Guo, Yanqun Wang, Xiaohua Wan, Bingyu Tan, Hailing Li, Jiasuer Alifu, Mengyun Zhu, Zesong Chen, Peiyao Li, Lei Zhang, Zhaoyong Zhang, Yiliang Wang, Xiaohan Huang, Xinsheng Wang, Jian Zhu, Xijiang Pan, Fa Zhang, Peiyi Wang, Sen-Fang Sui, Zheng Liu","doi":"10.1016/j.jare.2025.05.013","DOIUrl":"https://doi.org/10.1016/j.jare.2025.05.013","url":null,"abstract":"<h3>Introduction</h3>With the COVID-19 pandemic becoming endemic, vigilance for Long COVID-related cardiovascular issues remains essential, though their specific pathophysiology is largely unexplored.<h3>Objectives</h3>Our study investigates the persistent cardiovascular symptoms observed in individuals long after contracting SARS-CoV-2, a condition commonly referred to as “Long COVID”, which has significantly affected millions globally.<h3>Methods</h3>We meticulously describe the cardiovascular outcomes in five patients, encompassing a range of severe conditions such as sudden cardiac death during exercise, coronary atherosclerotic heart disease, acute inferior myocardial infarction, and acute myocarditis.<h3>Results</h3>All five patients were diagnosed with myocarditis, confirmed through endomyocardial biopsy and histochemical staining, which identified inflammatory cell infiltration in their heart tissue. Crucially, electron microscopy revealed widespread mitochondrial vacuolations and the presence of myofilament degradation within the cardiomyocytes of these patients. These findings were mirrored in SARS-CoV-2-infected mice, suggesting a potential underlying cellular mechanism for the cardiac effects associated with Long COVID.<h3>Conclusion</h3>Our findings demonstrate a profound impact of SARS-CoV-2 on mitochondrial integrity, shedding light on the cardiovascular implications of Long COVID.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"22 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932653","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}