Journal of Advanced Research最新文献

{"title":"CircCDYL promotes glycolysis to drive the progression of nasopharyngeal carcinoma","authors":"Yujie Yang, Yian Wang, Hongke Qu, Dan Wang, Junshang Ge, Pan Wu, Qijia Yan, Pan Chen, Bo Xiang, Ming Zhou, Can Guo, Wei Xiong, Lei Shi, Zhaoyang Zeng","doi":"10.1016/j.jare.2025.09.053","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.053","url":null,"abstract":"<h3>Introduction</h3>CircRNAs play critical roles in the onset and progression of nasopharyngeal carcinoma (NPC), although their underlying mechanisms remain incompletely understood.<h3>Objectives</h3>In this study, we investigated the mechanism of <em>circCDYL</em> in promoting the proliferation, invasion and migration of NPC <em>in vitro</em> and <em>in vivo</em>.<h3>Methods</h3>We reanalyzed RNA sequencing data (GSE137543, PRJNA391554) and validated findings with RT-qPCR and in situ hybridization experiments. Functional assays were subsequently performed both <em>in vitro</em> and <em>in vivo</em>.<h3>Results</h3>We identified <em>circCDYL</em> as being highly expressed in NPC, with its expression levels positively correlated with clinical tumor staging. Functionally, <em>circCDYL</em> promotes tumor proliferation and metastasis both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, <em>circCDYL</em> binds to the 3′-UTR of LDHA mRNA, stabilizing it and upregulating LDHA protein expression, thereby enhancing cellular glycolysis and increasing lactate production and accumulation. The elevated lactate, in turn, promotes lactylation of the actin-binding protein CFL1 at lysine 22. This modification reduces cell adhesion and stiffness, ultimately facilitating tumor cell proliferation, invasion, and migration.<h3>Conclusion</h3>These findings indicate that <em>circCDYL</em> and its downstream pathways may serve as potential diagnostic markers or therapeutic targets for NPC.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"42 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140735","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":"Therapeutic strategy for exosome-based bone regeneration to osteoporosis: Challenges and potential solutions","authors":"Anoop Puthiyoth Dayanandan, Alvin Bacero Bello, Yoshie Arai, Sang Jin Lee, Soo-Hong Lee","doi":"10.1016/j.jare.2025.09.042","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.042","url":null,"abstract":"<h3>Background</h3>Osteoporosis (OP) is a progressive bone disease marked by reduced bone mass and microarchitectural deterioration, thereby increasing fracture risk. Current therapies only partly restore bone quality and often cause side effects with long-term use. Recent studies highlight exosomes, a subtype of extracellular vesicles, as key regulators of bone remodeling with promising regenerative potential. However, their role in osteoporosis remains underexplored.<h3>Aim of review</h3>This review aims to investigate how the established role of exosomes in bone regeneration may inform novel therapeutic strategies for osteoporosis. By linking general bone repair mechanisms with osteoporotic pathology, it evaluates the translational potential and limitations of exosome-based interventions.<h3>Key scientific concepts of review</h3>Exosomes derived from mesenchymal stem cells, osteoblasts, osteoclasts, and macrophages regulate bone homeostasis by modulating osteogenesis, osteoclastogenesis, and immune responses. Their regenerative effects in non-osteoporotic settings are well documented. However, challenges such as exosome heterogeneity, rapid clearance, and poor targeting efficiency impede their direct application in osteoporosis. Recent bioengineering approaches, including osteogenic RNA or protein loading and surface modifications for bone targeting, show promise. Moreover, combining exosomes with immunomodulatory or synergistic therapies may further enhance their efficacy. Despite these advances, gaps persist in standardizing isolation techniques, ensuring batch consistency, and scaling up production for clinical use. This review consolidates current knowledge and outlines directions for adapting exosome-based bone regenerative strategies to osteoporosis treatment.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"91 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145140736","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":"Multiplexed, rapid phenotypic antibiotic susceptibility testing based on angle-resolved light scattering imaging of microfluidic droplets","authors":"Martina Graf, Arjun Sarkar, Carl-Magnus Svensson, Anne-Sophie Munser, Sven Schröder, Elke Mülle, Sundar Hengoju, Marc Thilo Figge, Miriam A. Rosenbaum","doi":"10.1016/j.jare.2025.09.047","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.047","url":null,"abstract":"<h3>Introduction</h3>There is an urgent need for rapid, high-throughput phenotypic antimicrobial susceptibility testing (AST) capable of assessing a microbial sample’s susceptibility to multiple antibiotics.<h3>Objectives</h3>In this study, we have established a multiplexed rapid AST platform that employs droplet microfluidics for high-throughput single-cell based analysis, 2D angle-resolved light scattering for growth detection, and fluorescence detection via optical fibers to identify the antibiotic condition within each droplet.<h3>Methods</h3>For this, multiple antibiotic conditions are coded with fluorescence dyes and encapsulated with single cells to enable the testing of multiple antibiotics in a single experiment. We utilize convolutional neural networks (CNNs) and statistical models to assess the growth of various <em>Staphylococcus aureus</em> strains and determine the probability of susceptibility to different antibiotics.<h3>Results</h3>Our platform achieved a 95<!-- --> <!-- -->% categorical agreement with the disc diffusion reference method after just three hours of incubation, demonstrating the same level of accuracy as the established VITEK 2 system for the tested strains and antibiotics. Notably, our platform reduced the incubation time by 5–11 h compared to VITEK 2 and by 13–17 h compared to the gold standard disc diffusion method.<h3>Conclusions</h3>With the presented innovations, our technology takes a big step towards realizing true phenotypic determination of antibiotic resistance profiles for timely antimicrobial treatment decisions.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"16 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134595","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":"Analyzing and forecasting global cervical cancer burden based on WHO’s elimination strategy: insights and projections from a 1990–2021 global burden of disease (GBD) study covering 204 countries and territories","authors":"Yedong Huang, Wenyu Lin, Xiaoyun Chen, Xiangqin Zheng, Huan Yi, Lin Zhang","doi":"10.1016/j.jare.2025.09.038","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.038","url":null,"abstract":"<h3>Introduction</h3>Cervical cancer remains a major global public health challenge. In 2018, the WHO launched a strategy to eliminate cervical cancer, emphasizing the need for precise epidemiological assessments.<h3>Objectives</h3>This study utilized Global Burden of Disease (GBD) data to analyze the epidemiological indicators, geographical patterns, and temporal trends of cervical cancer, evaluating the global impact of the WHO’s strategy.<h3>Methods</h3>Data on cervical cancer from 204 countries and territories (from 1990 to 2021) were retrieved from the GBD database. The year 2018, marking the WHO’s global call for elimination, was used to divide data into two periods: 1990 to 2018 and 2019 to 2021. Trends in age-standardized incidence rates and disability-adjusted life years (DALYs) were assessed using estimated annual percentage changes (EAPCs) and joinpoint regression. The socio-demographic index (SDI) was regressed against epidemiological indicators to explore disparities. Health inequality analyses recommended by the WHO were conducted, and an autoregressive integrated moving average (ARIMA) model was applied to predict future trends.<h3>Results</h3>From 1990 to 2021, global age-standardized incidence rates and DALYs declined. During 1990 to 2018, the highest EAPC values were observed in Southern Sub-Saharan Africa (2·18), East Asia (0·69), and Eastern Europe (0·31). After 2019, a more significant improvement was noted globally. Regression analyses revealed an SDI-related gradient, with low-SDI countries lagging. Health inequality analyses showed widening disparities. ARIMA projections indicated stable incidence rates in most regions but a continued decline in DALYs.<h3>Conclusion</h3>The WHO’s strategy has contributed to a notable decline in cervical cancer burden, yet challenges persist in low-SDI regions. Strengthening global cooperation and resource allocation is essential for achieving elimination goals.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"1 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134594","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":"Circular RNA-mediated regulation of key signaling pathways in cardiovascular diseases: a review","authors":"Qianhui You, Weiwei Zhang, Chinying Koo, Chengyao Jia, Michail Spanos, Baonian Liu, Junjie Xiao, Haidong Guo","doi":"10.1016/j.jare.2025.09.048","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.048","url":null,"abstract":"Cardiovascular diseases (CVDs) are globally prevalent pathologies driven by dysregulated signaling networks. Circular RNAs (circRNAs), a class of covalently closed non-coding RNAs produced by back-splicing<!-- --> <!-- -->mechanism, in which a downstream 5′ splice site joins an upstream 3′ splice site, have emerged as critical regulators of CVD pathogenesis. This review examines their lifecycle, including biogenesis, nuclear export mechanisms, subcellular localization, and degradation, along with their functional roles in microRNA sequestration, protein interactions, transcriptional regulation, and polypeptide translation. Recent advances in circRNA engineering are also discussed, including <em>in vitro</em> synthesis strategies, delivery platforms, vaccine development, gene editing, and aptamers (synthetic high-affinity nucleic acid ligands).<!-- --> <!-- -->Furthermore, we explore the latest findings that focus on how circRNAs modulate these core CVD-related pathways. The unique expression patterns and engineering potential of circRNAs render them valuable candidates for biomarker and therapy development. This review connects the fundamental biology of circRNAs to recent technological advances, offering a roadmap for leveraging the functional interaction between circRNAs and signaling pathways in CVD precision medicine.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"28 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134593","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":"Periventricular gradient of normal-appearing white matter in normal aging and multiple neurological diseases","authors":"Zhizheng Zhuo, Xiaolu Xu, Decai Tian, Runzhi Li, Yutong Bai, Yulu Shi, Siyao Xu, Shan Lv, Guanmei Cao, Geli Hu, Jun Xu, Jianguo Zhang, Fu-Dong Shi, Declan Chard, Frederik Barkhof, Sven Haller, Xinghu Zhang, Yunyun Duan, Yaou Liu","doi":"10.1016/j.jare.2025.08.059","DOIUrl":"https://doi.org/10.1016/j.jare.2025.08.059","url":null,"abstract":"<h3>Introduction</h3>A potential inflammation-associated periventricular gradient of normal-appearing white matter (NAWM) abnormalities has been identified in multiple sclerosis, but its presence in normal aging and other neurological diseases remains unclear.<h3>Objectives</h3>We aimed to determine whether a periventricular gradient of NAWM abnormalities occurs in normal aging and other neurological diseases.<h3>Methods</h3>A total of 290 Alzheimer’s disease, 262 Parkinson’s disease, 154 cerebral small vessel disease, 212 multiple sclerosis, as well as 344 younger healthy controls (HCs), 344 middle-aged HCs, and 398 older HCs with available MR diffusion images were included in this study. The periventricular gradient (the slope of regression model) in NAWM of normalized neurite density (NDI) and orientation dispersion indices (ODI), derived from diffusion MRI, was calculated using linear mixed models. Its associations with other MRI measures, clinical variables, and brain-wide gene expression were analyzed. Additional sensitivity and replication analyses were conducted.<h3>Results</h3>The periventricular gradients of both normalized NDI and ODI were observed in older HCs and all neurological disease groups. Such periventricular gradients play mediating roles between choroid plexus volume (a marker of neuroinflammation) and NAWM NDI or ODI, white matter hyperintensity volume, white and gray matter volumes, especially in neurological diseases. They exhibited both direct and indirect associations with cognitive and physical performance in normal aging and multiple neurological diseases. We observed correlations between periventricular gradients and underlying inflammatory, endothelial and synaptic gene expression. Sensitivity and replication analyses confirmed the main findings.<h3>Conclusion</h3>Clinically relevant periventricular gradients in tissue diffusion characteristics occur in normal aging and multiple neurological diseases, and share some underlying pathological mechanisms.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"8 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134596","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":"Global, regional, and national burden of cardiovascular diseases among postmenopausal women, 1990–2040: a systematic analysis for the global burden of disease study 2021","authors":"Shuangfei Xu, Shang Jia, Shaoqiang Yang, Delong Li, Ejuan Zhang, Fang Lei, Meng-Liu Zeng, Lijin Lin","doi":"10.1016/j.jare.2025.09.039","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.039","url":null,"abstract":"<h3>Background</h3>Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. In postmenopausal women, physiological changes and hormonal transitions accelerate cardiovascular risk, yet global, sex-specific evidence for this group remains limited. Understanding their burden is essential to address biological vulnerabilities and structural inequities.<h3>Aim of review</h3>This review provides the first comprehensive global, regional, and national assessment of CVD burden among women aged ≥ 55 years from 1990 to 2021 and projects trends to 2040. It synthesizes epidemiological patterns, socio-demographic disparities, and major modifiable risk factors, with the goal of informing gender-sensitive and equity-oriented cardiovascular prevention and policy strategies.<h3>Key scientific concepts of review</h3>Data were obtained from the Global Burden of Disease (GBD) Study 2021, encompassing 204 countries and territories. Incidence, prevalence, mortality, and disability-adjusted life years (DALYs) were analyzed using age-standardized rates (ASRs). Temporal trends were quantified with estimated annual percentage changes (EAPCs), and decomposition analysis identified demographic (population growth, aging) and epidemiological contributions. Inequalities were evaluated using slope and concentration indices across socio-demographic index (SDI) levels. Bayesian age–period–cohort models were applied to forecast CVD burden through 2040. Key findings indicate that although ASIR and ASMR declined globally, absolute CVD cases and deaths nearly doubled due to demographic expansion. Disparities widened: high-SDI regions achieved the steepest reductions, while low-SDI regions showed slower progress or worsening trends. Ischemic heart disease and stroke remained the dominant contributors, endocarditis was the fastest-rising subtype, and high systolic blood pressure consistently emerged as the leading modifiable risk factor. Collectively, these findings highlight a growing and uneven burden of CVD in postmenopausal women. Strengthened hypertension control, integrated prevention strategies, and investment in primary healthcare—particularly in low-SDI settings—are urgently needed. This review provides a woman-centered evidence base to support equitable cardiovascular health policy and resource allocation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"28 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134511","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":"Roles of Msx2 in exogen control: modulating the stem cell niche during the transition from hair shedding to regeneration","authors":"Qi Chen, Wen-Chien Jea, Ting-Xin Jiang, Ping Wu, Chi Zhang, Ji Li, Mingxing Lei, Cheng-Ming Chuong, Ya-Chen Liang","doi":"10.1016/j.jare.2025.09.040","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.040","url":null,"abstract":"<h3>Introduction</h3>The exogen phase of the hair follicle cycle, during which club hairs are shed and new hairs emerge, represents a critical transitional step involving distinct structural remodeling and adhesive changes. Despite its fundamental importance, the molecular mechanisms orchestrating exogen remain largely unknown.<h3>Objective</h3>To investigate the role of Msx2 in regulating hair anchoring, hair follicle stem cell (HFSC) lineage commitment, and extracellular matrix (ECM) remodeling during exogen.<h3>Methods</h3>We employed <em>Msx2</em>-knockout (KO) mice, bulk RNA sequencing, and late exogen transcriptome comparisons to identify differentially expressed genes (DEGs) and disrupted pathways. Additionally, protein interaction assays were conducted for functional studies.<h3>Results</h3><em>Msx2</em> deficiency mice still form new bulges containing HFSCs for subsequent hair cycles, but this resulted in the failed anchoring of older bulges and club hairs, leading to aberrant hair retention and accelerated hair shedding. Transcriptomic analysis revealed widespread transcriptional reprogramming, particularly in ECM-related genes, with significant overlap between <em>Msx2</em>-KO HFSCs and late exogen DEGs. <em>Msx2</em>-KO mice exhibited downregulated adhesion molecules, disrupted HFSC niche integrity, increased keratinization, and aberrant differentiation in HFSC and hair germ cells. Mechanistically, MSX2 directly interacts with SMAD proteins to regulate TGF-β signaling, thereby modulating ECM gene expression and suppressing HFSC trans-epidermal differentiation.<h3>Conclusions</h3>Our findings establish <em>Msx2</em> as a master regulator of exogen control, orchestrating hair shedding, HFSC niche stability, and ECM remodeling. This study provides new insights into hair follicle cycling dynamics and identifies Msx2 as a potential therapeutic target for promoting hair regeneration and mitigating alopecia phenotypes.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"37 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127700","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":"Disphosphate based hydrogel microspheres for targeted transarterial radioembolization and chemoembolization therapies","authors":"Xuexiao Li, Binyan Zhong, Nan Jiang, Jintao Huang, Di Hu, Ruoran Zhou, Jianfeng Zeng, Wenmiao Shu, Guangxin Duan, Shuwang Wu, Ling Wen","doi":"10.1016/j.jare.2025.09.044","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.044","url":null,"abstract":"<h3>Introduction</h3>Transarterial radioembolization (TARE) is a highly effective treatment for unresectable hepatocellular carcinoma (HCC). However, current clinically available radioactive ⁹⁰Y resin microspheres face significant challenges such as isotope leakage and low specific activity, compromising the safety and therapeutic efficacy.<h3>Objectives</h3>To address these challenges, we propose a novel diphosphonate based hydrogel microspheres (DPMs) for safer and more effective TARE therapies. The diphosphonate have a strong chelating capability with various metal ions which provide a universal strategy for tightly labelling the hydrogel microsphere with different therapeutic metal nuclides.<h3>Methods</h3>In this study, DPMs were fabricated via microfluidic technology, followed by ¹⁷⁷Lu radiolabeling and doxorubicin (DOX) loading. Physicochemical characterization, radiostability assays, and dual-modality therapeutic efficacy were systematically evaluated in vitro and in orthotopic HCC rabbit models, with biosafety validated through histopathology and serum biochemistry.<h3>Results</h3>DPMs achieved a labeling efficiency of 98.3 % within 15 min. Meanwhile, the radiolabeling rate maintained 99 % over 7 days in a 10 % fetal bovine serum solution, demonstrating exceptional radiostabilty. The high in vitro radiostability is also consistent with in vivo experiments. Additionally, the porous structure of DPMs enables high loading and controlled release of chemotherapeutic drugs, making the hydrogel microspheres also the ideal carriers for transcatheter arterial chemoembolization (TACE). By combining TARE and TACE, we have developed a novel ¹⁷⁷Lu-DPMs@DOX platform, exhibiting remarkable therapeutic performance against HCC without any observed side effect.<h3>Conclusion</h3>This study introduces a groundbreaking approach using highly effective diphosphonate based microspheres to deliver precise, safe, and powerful treatment for unresectable HCC and other challenging tumors","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"7 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117010","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":"Bisphenol S drives breast cancer metastasis by inhibiting dopamine receptor D2 to activate the Akt/GSK3β oncogenic axis","authors":"Sicheng Liu, Ping Deng, Chengmeng Liu, Huihui Hong, Qixue Zheng, Jinxian Lin, Jiayi Li, Zhulin Du, Lingling Yang, Kun Luo, Haiyan Yu, Zhengwei Liang, Zhengping Yu, Huifeng Pi, Zhou Zhou","doi":"10.1016/j.jare.2025.09.045","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.045","url":null,"abstract":"<h3>Introduction</h3>Bisphenol S (BPS), a substitute for bisphenol A (BPA), serves as an endocrine disruptor implicated in breast cancer (BC) progression, but its mechanisms remain unclear.<h3>Objectives</h3>This study aimed to elucidate the underlying mechanisms of BPS effects on BC metastasis through <em>in vivo</em> and <em>in vitro</em> experiments.<h3>Methods</h3>Transgenic MMTV-Erbb2 mice that spontaneously developed breast tumors were orally administered BPS (50 μg/L) for 19 weeks, and BC cells were exposed to BPS (0, 0.01, 0.1, or 1 μM) for 72 h to examine the effects of BPS exposure on the migration and invasion of BC cells. Furthermore, we employed transcriptomics, KEGG enrichment analysis and Comparative Toxicogenomics Database (CTD) predictions to explore the potential mechanisms underlying BPS −induced BC metastasis. In addition, we used tissue microarray (TMA) and public databases to reveal DRD2′s critical role in BC progression.<h3>Results</h3>Our results indicated that low-dose BPS (50 μg/L, approximately 6.14 μg/kg/day) facilitated BC metastasis both <em>in vitro</em> and <em>in vivo</em>. Transcriptomic analysis identified DRD2 as a critical regulator of migration and invasion in BPS-exposed MCF-7 cells. Furthermore, KEGG enrichment analysis coupled with the CTD demonstrated that BPS enhanced the migration and invasion of BC cells via the Akt/GSK3β signaling pathway activation. Importantly, DRD2 overexpression apparently blocked the Akt/GSK3β pathway, effectively reversing BPS-induced metastasis of BC both <em>in vitro</em> and <em>in vivo</em>. Intriguingly, TMA and public database analyses revealed a marked decrease of DRD2 levels in BC tissues, which were inversely correlated with p-Akt levels in BC tissues and positively associated with the poor clinical characteristics of BC patients.<h3>Conclusion</h3>BPS exposure reduces DRD2 levels, activating Akt/GSK3β signaling to drive BC metastasis. These findings highlight the risk of BPS as a BPA alternative and unravel mechanistic insights into the role of environmental endocrine disruptors in cancer progression.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"89 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117008","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}