Journal of Advanced Research最新文献

{"title":"Advances in physical and chemical strategies for dentin hypersensitivity therapy","authors":"Xinru Li, Qihui Wang, Yirong Sun, Guoliang Wang, Congxiao Zhang, Jianxun Ding","doi":"10.1016/j.jare.2025.09.041","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.041","url":null,"abstract":"<h3>Background</h3>Dentin hypersensitivity (DH) is a prevalent and acute dental pain disorder marked by a brief yet sharp toothache caused by exposed dentin, often in response to thermal, chemical, and mechanical stimuli. It significantly affects a person’s quality of life, interfering with routine activities, such as eating and drinking. With an improved understanding of the mechanisms underlying DH, various physical and chemical strategies have been developed to alleviate the condition.<h3>Aim of the review</h3>This review evaluates three principal mechanistic theories underlying DH desensitization, including the Direct Innervation Hypothesis, the Odontoblast Receptor Theory, and the Hydrodynamic Theory. It provides a detailed analysis of current physical, chemical, and synergistic therapeutic methods used for desensitization. Additionally, it discusses potential future therapeutic approaches for the treatment of DH.<h3>Key scientific concepts of review</h3>This review highlights recent advancements and ongoing challenges in applying physical and chemical strategies for DH treatment. It also discusses potential future strategies and methods, offering insights into the prospects for the field.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"40 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145117011","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":"Development and clinical validation of a novel protein biomarkers-based algorithm for risk prediction and diagnosis of advanced liver fibrosis: a multi-centre study","authors":"Chloe Yu-Yan Cheung, Pei Wan, Heng Wan, Chenxin Xu, Xi Jia, Carol Ho-Yi Fong, David Tak-Wai Lui, Erfei Song, Xingying Chen, Wing-Sun Chow, Yu-Cho Woo, Kathryn Choon-Beng Tan, Wai-Kay Seto, Cunchuan Wang, Jie Shen, Karen Siu-Ling Lam, Chi-Ho Lee, Aimin Xu","doi":"10.1016/j.jare.2025.09.033","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.033","url":null,"abstract":"<h3>Introduction</h3>Type 2 diabetes (T2D) and obesity contribute significantly to the elevated risk of liver fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). However, there is a lack of reliable and cost-effective non-invasive test (NIT) for detecting liver fibrosis in T2D/obese individuals.<h3>Objectives</h3>This study aimed to develop a simple biomarker-based algorithm for detecting advanced liver fibrosis among T2D/obesity subjects with MASLD and to validate its diagnostic performance in both clinic- and community-based cohorts.<h3>Methods</h3>Diagnostic performances of circulating thrombospondin-2 (TSP2), a novel fibrosis marker, and the three individual components of Enhanced Liver Fibrosis (ELF) test were evaluated in three independent cohorts. These included a clinic-based derivation cohort (N = 846) and a community-based validation cohort (N = 803), both comprising of T2D patients with vibration-controlled transient elastography (VCTE)-diagnosed MASLD. Additionally, a clinic-based validation cohort of morbidly-obese patients with biopsy-proven MASLD (N = 223) was included. An algorithm (TaP score) based on <u>T</u>SP2 <u>a</u>nd <u>p</u>rocollagen 3 N-terminal peptide (PIIINP), a component of ELF, was constructed from the multivariate logistic regression model and compared with existing NITs, including ELF, fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS). The dual-cut-off approach was used to define the rule-in and rule-out cut-offs.<h3>Results</h3>Circulating TSP2 (AUC[95 %CI]:0.844[0.810–0.878]) and PIIINP (AUC[95 %CI]:0.843(0.807–0.875]) showed excellent diagnostic performance and were used to construct the biomarker-based algorithm. The TaP score (AUC[95 %CI]:0.900[0.874–0.925]) significantly outperformed ELF (AUC[95 %CI]:0.809[0.773–0.843]), FIB-4 (AUC[95 %CI]:0.597[0.544–0.647]) and NFS (AUC[95 %CI]:0.585[0.528–0.639]) (all DeLong P &lt; 0.001), showing high specificity (85.16 %), sensitivity (78.62 %), and negative predictive value (NPV) (95.08 %) at the optimal cut-off. This algorithm resulted in fewer patients with indeterminate results compared to ELF. Its diagnostic performance in the two external validation cohorts was comparable to that in the derivation cohort.<h3>Conclusions</h3>The TaP score demonstrated good diagnostic ability with generally better performance compared to ELF, and had the potential to be developed as a novel NIT.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"10 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116596","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":"Orthosteric–allosteric dual inhibitors of PI5P4Kγ with potent antitumor activity in non-small cell lung cancer","authors":"Liang Xiong, Lei Tang (唐磊), Wenfeng Zhao, Rongtao Wang, Cheng Cheng, Daoping Wang, Yechun Xu, Lei Tang (汤磊), Yanhua Fan","doi":"10.1016/j.jare.2025.09.024","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.024","url":null,"abstract":"<h3>Introduction</h3>Phosphatidylinositol 5-phosphate 4-kinase type II gamma (PI5P4Kγ) has emerged as a promising therapeutic target in oncology due to its key role in cancer progression. However, currently available inhibitors targeting either the orthosteric or allosteric sites of PI5P4Kγ suffer from limited <em>in vitro</em> activity and in vivo validation.<h3>Objectives</h3>This study aimed to develop a highly potent and selective PI5P4Kγ inhibitor capable of simultaneously engaging both the orthosteric and allosteric sites, as well as to validate their potential in therapy for non-small cell lung cancer (NSCLC) were investigated.<h3>Methods</h3>Through the structural modification of the propionamide side chain of the pyridine ring and the N3 substituent of the quinazolinone, the structure–activity relationship (SAR) was elucidated, leading to the identification of the target compound <strong>n40</strong>. The binding mode of <strong>n40</strong> to PI5P4Kγ, was elucidated by X-ray crystallography. <em>In vitro</em> effects were assessed through KINOMEscan Technology, cell proliferation, apoptosis, and EMT analysis. In vivo efficacy was evaluated using an HCC827 xenograft mouse model. Both single-dose (up to 400 mg/kg) and repeated-dose (20–180 mg/kg/day for 28 days) toxicity studies of <strong>n40</strong> were conducted in C57BL/6 mice, with comprehensive monitoring of physiological parameters and organ toxicity indices.<h3>Results</h3>Compound <strong>n40</strong> exhibited a strong binding affinity for PI5P4Kγ (<em>K</em>_d = 6.55 nM), with 3,000-fold selectivity over other two isoforms. Additionally, it displayed sub-50 nM antiproliferative activity in NSCLC cells with higher PI5P4Kγ levels. X-ray crystallography revealed <strong>n40</strong> simultaneously binds to both orthosteric and a novel<!-- --> <!-- -->allosteric pocket. Functionally, <strong>n40</strong> induced S-phase arrest, apoptosis, and EMT reversal and PI3K/AKT signaling inhibition in a PI5P4Kγ-dependent manner. In HCC827 xenografts, <strong>n40</strong> achieved &gt; 60 % tumor growth inhibition without any observed toxicity.<h3>Conclusion</h3>This study establishes PI5P4Kγ as a druggable target in NSCLC and demonstrates that dual orthosteric–allosteric targeting is a viable strategy to achieve potent and selective PI5P4Kγ inhibitors.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"61 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116597","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":"Charge reversible-natural light responsive nanoparticles enable targeted herbicide delivery and reduction of mammalian toxicity","authors":"Junhu Xu, Wei Wang, Kunyan Guo, Guangmao Shen, Minhui Li, Gefei Hao, Kun Qian","doi":"10.1016/j.jare.2025.09.036","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.036","url":null,"abstract":"<h3>Introduction</h3>Mammalian health risks due to agrochemical exposure are becoming a global concern, increasingly. Long-term exposure to diquat (DQ) leads to multiple organ dysfunctions and increase mammal mortality. Despite existing mitigation strategies, including oxidative stress reduction and gut microbiota modulation, effective mitigation strategies for DQ poisoning remain elusive.<h3>Objectives</h3>Based on the dark gastrointestinal environment of mammals, a natural light-responsive DQ formulation was prepared, that effectively controls weeds and reduces toxicity to mammals.<h3>Methods</h3>By loading DQ onto bridged polysilsesquioxane (BPS) with charge reversal properties, a natural photo-responsive formulation of DQ@BPS was prepared. The physicochemical properties of BPS and DQ@BPS were studied with a series of characterization methods. Under natural light, the photo-controlled release properties of DQ@BPS were measured by molecular dynamics simulation. The control effect of DQ@BPS to barnyard grass was compared with that of DQ and a commercial formulation. A mouse model was used to study its toxicity. In addition, the safety of BPS in Chinese cabbage and DQ@BPS in earthworms were detected.<h3>Results</h3>We verified that DQ@BPS enable release DQ through natural light. BPS was reversed to a positive charge under natural light, and DQ was released via electrostatic repulsion, with a total release amount 7.27 times that under darkness. Compared with DQ, DQ@BPS ameliorated the liver and kidney damage while reducing body residues by over 10 times in mice, and showed effective control of barnyard grass. Furthermore, it was safe for earthworms, LC₅₀ &gt; 1000 μg/cm², and the carrier itself was safe for Chinese cabbage.<h3>Conclusion</h3>Charge-reversible-natural light-responsive nanoparticles enable to deliver herbicide with reduced mammalian toxicity. This study provides a new photo-response mechanism in agrochemical delivery systems, offering a promising approach for reducing the toxicity of agrochemicals to mammals.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"23 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103632","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":"Integrative epitranscriptomic and transcriptomic characterization in human colorectal cancer","authors":"Ting Gong, Sudhir Kumar Rai, Yong Zhu, Yutong Wang, Yu Chen, Li Ma, Xiaomou Wei, Zhougui Ling, Asmita Pandey, Yujia Qin, Matthew Huo, Mayumi Jijiwa, Masaki Nasu, Zao Zhang, Shaoqiu Chen, Zitong Gao, Xiamin Hu, Ken Nakastu, Hua Yang, Yuanyuan Fu, Youping Deng","doi":"10.1016/j.jare.2025.09.037","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.037","url":null,"abstract":"<h3>Introduction</h3>Despite significant progress in understanding the molecular basis of colorectal cancer (CRC), the precise mechanisms driving its development and progression remain poorly defined. This gap limits the identification of novel therapeutic targets and the development of effective early detection methods. N6-methyladenosine (m6A) has merged as a key role in CRC pathogenesis. But research on mRNA methylation in CRC remains sparse.<h3>Objectives</h3>We aimed to address the roles of m6A modifications in CRC and to understand how mRNA methylation contributes to CRC development and progression.<h3>Methods</h3>We obtained a comprehensive mapping of altered m6 peaks within mRNAs using Methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) from 34 CRC samples and 34 adjacent normal tissue samples and dissect molecular mechanisms of identified key CRC gene(s). By integrating these data, we identified differentially expressed mRNAs with altered m6A levels. Further analysis identified 119 overlapping peaks with both significantly altered RNA methylation and expression levels. Finally, we analyzed the relationship between m6A-regulated gene expression and Immune infiltrates using CRC patient-derived PBMC samples. Additionally, we established a subcutaneous xenograft tumor model to explore the role of SIM2 in CRC progression.<h3>Results</h3>Our comprehensive analysis of 68 fresh-frozen CRC samples identified 119 overlapping m6A peaks across 77 genes, classified based on m6A and mRNA expression changes. Survival analyses revealed a signature of m6A-modified genes with prognostic potential. These methylated genes were significant associated with immune cell profiles in the tumor microenvironment and immune checkpoints regulation, highlighting m6A as a promising immunotherapeutic target for CRC. SIM2 emerged as a key candidate, exhibiting elevated m6A and RNA expression levels in tumors and Macrophage M2 cells. NTMT1 (a writer) and YTHDF1 (a reader) were identified as pivotal regulators of m6A modifications in the 5′-UTR of SIM2 mRNA, emphasizing their role in CRC progression. Silencing methylated SIM2 significantly suppressed tumor growth, suggesting its potential as a therapeutic target.<h3>Conclusion</h3>Our integrative analyses provide a valuable resource for unraveling the molecular landscape of CRC. These finding offer new insight for advancing diagnostic precision and refining prognostic and therapeutic strategies for CRC.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"78 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103631","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":"Tryptophan metabolism in psoriasis and its complications: Future opportunities","authors":"Xiyuan He, Yueting Mo, Peixin Shi, Yini Xu, Mingmei Zhou, Ting Zhang","doi":"10.1016/j.jare.2025.09.034","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.034","url":null,"abstract":"Tryptophan (Trp) metabolism encompasses primary three pathways: the kynurenine pathway, the serotonin pathway, and the indole pathway. These pathways are intricately involved in the physiological and pathological processes underlying psoriasis, exerting broad regulatory effects on immune function, inflammation responses, keratinocytes proliferation, angiogenesis, and intestinal homeostasis. Key enzymes and metabolites within the Trp metabolic pathway have been implicated in the development and progression of psoriasis. Disruptions in Trp metabolism have been observed in psoriasis and its associated complications, with alterations in certain metabolite levels noted following improvements in disease symptoms. Emerging evidence indicates that targeted therapies modulating Trp metabolism have demonstrated efficacy in clinical applications, offering valuable insights for medication selection in psoriasis treatment. This review aims to summarize the most recent research findings regarding the role of Trp metabolism in psoriasis and its comorbidities, as well as the therapeutic potential of targeting Trp metabolic pathways.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"55 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088918","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":"Epac1 deletion attenuates Müller glial pathological activation and mitigates retinal neurodegeneration in ischemia-induced retinopathy","authors":"Shuizhen Shi, Fan Xia, Zhongqiao Lu, Erick Palacios, Fang Mei, Massoud Motamedi, Xiaodong Cheng, Hua Liu, Wenbo Zhang","doi":"10.1016/j.jare.2025.09.031","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.031","url":null,"abstract":"<h3>Introduction</h3>Ischemia-induced retinopathies, such as retinopathy of prematurity and proliferative diabetic retinopathy, are major causes of vision loss. Both pathological neovascularization and neuronal damage contribute to vision impairment in these conditions, yet current therapies primarily target neovascularization and may further compromise neuronal health.<h3>Objectives</h3>Cyclic AMP (cAMP) is a widely recognized second messenger regulating diverse physiological and pathological processes. Exchange protein directly activated by cAMP (Epac) is a recently identified effector of cAMP signaling. This study aimed to investigate the role of Epac1 in ischemia-induced retinopathy and elucidate its underlying mechanisms using a mouse model of oxygen-induced retinopathy (OIR).<h3>Methods</h3>A mouse OIR model was established by exposing pups to 70% oxygen from postnatal day 7 (P7) to P12. Retinal structure and neuronal survival were assessed by H&amp;E staining, TUNEL assay and immunostaining. Single-cell RNA sequencing (scRNA-seq), immunostaining, qPCR, Western blot, and proximity ligation assay were used to investigate cellular and molecular mechanisms by which Epac1 contributes to retinal pathology in OIR.<h3>Results</h3>Genetic deletion of Epac1 significantly protected against retinal neuronal loss and attenuated Müller glial activation in addition to reducing pathological neovascularization and promoting vascular repair. scRNA-seq revealed substantial transcriptomic alterations in Müller cells during OIR, including the emergence of reactive subclusters with distinct pathological roles, which were mitigated by Epac1 deletion. At the molecular level, Epac1 deletion restored ischemia-reduced VEGFR2 level in Müller cells during OIR, while Epac activation promoted VEGFR2 internalization and impaired VEGF signaling and its neuroprotective effects in primary Müller cells.<h3>Conclusion</h3>These findings reveal a novel role for Epac1 in promoting retinal neurodegeneration in a mouse model of OIR through modulation of VEGF signaling in Müller cells. Targeting Epac1 may thus provide therapeutic benefit by preserving neuronal integrity in addition to its effects on vascular pathology.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"38 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083819","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 complex link of the folate-homocysteine axis to myocardial hypertrophy and heart failure: from mechanistic exploration to clinical vision","authors":"Yi Wang, , Meiqing Liu, Linxi Chen","doi":"10.1016/j.jare.2025.09.026","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.026","url":null,"abstract":"<h3>Background</h3>Globally, the pathogenesis and progression of many human diseases are intimately associated with folate metabolism disorder. Emerging evidence from recent investigations has underscored the pivotal role of folate metabolism in cardiovascular homeostasis, particularly in the context of myocardial hypertrophy and heart failure (HF). Despite a wealth of pre-existing research, the underlying pathophysiological mechanisms remain not fully elucidated.<h3>Aim of review</h3>To deeply explore the complex interrelationships among folate metabolism, myocardial hypertrophy, and heart failure, this review systematically elucidates the impact of the folate-homocysteine (Hcy) axis on myocardial hypertrophy and HF progression, integrating both experimental evidence and clinical observations. This review also investigates how genetic variations, and environmental factors modulate folate metabolism, and their mechanistic links to the development of myocardial hypertrophy and heart failure. Additionally, the review explores epigenetic modifications and their intricate crosstalk with the folate-homocysteine-heart disease axis, providing a comprehensive framework of the underlying pathophysiology. Finally, it proposes potential therapeutic strategies targeting the folate-homocysteine axis for myocardial hypertrophy and HF.<h3>Key scientific concepts of review</h3>Folate deficiency can lead to homocysteine accumulation, resulting in hyperhomocysteinemia (HHcy), which contributes to the development of myocardial hypertrophy and HF. Correcting the imbalance of the folate-homocysteine axis may interrupt this pathological cascade, positioning the folate-homocysteine axis as a potential target for the treatment of myocardial hypertrophy and HF.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"102 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088920","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":"Cancer stem cell plasticity in shaping drug resistance landscapes in prostate cancer","authors":"Xiaoyu Zhang, Xiaoqing Zhang, Qing Bao, Rong Li, Xinpei Deng, Jingna Cao, Huan Wang, Dong Chen, Yutian Zou, Hailin Tang","doi":"10.1016/j.jare.2025.09.028","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.028","url":null,"abstract":"<h3>Background</h3>Prostate-related diseases exhibit an extremely high incidence among aging males, including Benign Prostatic Hyperplasia (BPH) and prostate Cancer (PCa). Prostate stem cells are critical for prostate development, adult tissue homeostasis, and injury repair, and are also considered potential cells of origin for tumorigenesis. Recent studies have demonstrated that various prostate stem cell populations serve as key drivers in both the initiation and progression of prostatic diseases, while also contributing to therapy resistance. Consequently, prostate stem cells have emerged as promising therapeutic targets for both fundamental research and clinical translational studies.<h3>Aim of review</h3>This review provides a comprehensive summary of the identity and characteristics of various prostate epithelial stem cells, elaborating on the cell fate and function of different prostate stem cells under both physiological and pathological conditions. Additionally, the review offers theoretical evidence linking the lineage plasticity of prostate stem cells to the drug resistance observed in prostate diseases, and critically discusses both the limitations and therapeutic potential of emerging stem cell-targeting strategies.<h3>Key scientific concepts of review</h3>This review integrates contemporary knowledge regarding the identity and cellular plasticity of prostate stem cell subpopulations across physiological and pathological contexts, encompassing prostate development, tissue homeostasis, inflammatory responses, and oncogenesis. These stem cells demonstrate critical adaptability to microenvironmental challenges, underpinning essential functions in epithelial regeneration, neoplastic initiation, and tumor evolution. Significantly, their capacity to dynamically reprogram cellular fate trajectories has been shown to fundamentally underpin mechanisms of therapeutic evasion, fostering the emergence of treatment resistance. Collectively, these insights position the molecular targeting of prostate stem cells as a novel therapeutic paradigm for managing advanced prostate malignancies.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"89 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088919","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":"Vascular mechanical forces and vascular diseases","authors":"Shiwen Liu, Jun Cai, Zhenzhen Chen","doi":"10.1016/j.jare.2025.09.013","DOIUrl":"https://doi.org/10.1016/j.jare.2025.09.013","url":null,"abstract":"<h3>Background</h3>Blood vessels are continuously exposed to mechanical forces, mainly including shear stress, cyclic stretch, and hydrostatic pressure. These forces regulate the functions of endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) through complex mechanosensing and signal transduction pathways, which are essential for maintaining vascular homeostasis. However, under pathological conditions, they can contribute to the development of vascular diseases, such as atherosclerosis, hypertension, and aortic aneurysm.<h3>Aim of review</h3>This review aims to synthesize the mechanosensors and downstream signaling pathways of vascular mechanical forces in ECs and VSMCs, emphasizing their effects on cell behaviors and their involvement in the onset and progression of atherosclerosis, hypertension and aortic aneurysms.<h3>Key scientific concepts of review</h3>Multiple molecules and structures – including ion channels, G-protein coupled receptors, cellular junction molecules, and other membrane structures – act as mechanosensors of vascular mechanical forces and trigger multiple downstream signal transduction pathways. The pathological alterations in shear stress, cyclic stretch, and hydrostatic pressure regulate the functions and behaviors of ECs and VSMCs, including cellular proliferation, migration, apoptosis, oxidative stress, endothelial permeability, etc. These responses induce vascular inflammation, dysfunction and remodeling, which eventually contributes to the onset and progression of atherosclerosis, hypertension, and aortic aneurysms. This review also highlights the underestimated role of hydrostatic pressure in atherosclerosis and hypertension, as well as other research gaps and future directions for vascular mechanical forces research. Understanding and therapeutically modulating these biomechanical pathways may ultimately facilitate more effective prevention and treatment of vascular diseases","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"79 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145083821","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}