Biochemistry and Biophysics Reports最新文献

{"title":"Curcumin reprograms metabolic pathways and MAPK signaling to exert antidepressant effects","authors":"Sijin Kong ,&nbsp;Lijin Wang ,&nbsp;ZiXuan Ren","doi":"10.1016/j.bbrep.2025.102399","DOIUrl":"10.1016/j.bbrep.2025.102399","url":null,"abstract":"<div><h3>Background</h3><div>Depression is a prevalent and debilitating mental disorder with limited treatment options. Curcumin, a natural compound with neuroprotective and anti-inflammatory properties, has shown potential antidepressant effects, though the underlying mechanisms remain incompletely understood.</div></div><div><h3>Methods and results</h3><div>In this study, we investigated the therapeutic effects and molecular mechanisms of curcumin in a chronic unpredictable mild stress (CUMS)-induced rat model of depression. Behavioral assessments, including the sucrose preference test, forced swim test, and open field test, demonstrated that curcumin (50 and 100 mg/kg, orally administered for 21 days) alleviated CUMS-induced anhedonia, behavioral despair, and anxiety-like behaviors, in a dose-dependent manner, with the 100 mg/kg dose exhibiting superior efficacy. Metabolomic profiling of the prefrontal cortex revealed significant metabolic disturbances in CUMS rats, particularly in starch and sucrose metabolism, which were progressively restored by curcumin. Functional enrichment analysis highlighted modulation of neuroinflammation, bioenergetic homeostasis, and signal transduction pathways as key biological processes associated with curcumin's effects. Integrated multi-omics and machine learning approaches identified the MAPK signaling pathway as a central regulatory node. qPCR validation confirmed that curcumin normalized the expression of key MAPK-related genes, including BDNF, EGFR, ERK2, JUN, RAF1, and TNF, with high-dose curcumin consistently showing the most pronounced therapeutic effects.</div></div><div><h3>Conclusion</h3><div>Our findings demonstrate that curcumin exerts potent antidepressant effects through multi-target mechanisms involving metabolic reprogramming and coordinated regulation of the MAPK signaling pathway. This study provides novel mechanistic insights into curcumin's polypharmacological actions, supporting its potential as a multi-modal therapeutic agent for depression by simultaneously modulating neurotrophic support, inflammatory responses, and intracellular signaling cascades.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102399"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations of the tumor microenvironment (TME) by exploratory gene expression analysis in recurrent glioblastoma following apatinib in combination with temozolomide","authors":"Jingjing Ge ,&nbsp;Cheng Li ,&nbsp;Fengjun Xue ,&nbsp;Chi Zhao ,&nbsp;Chenchen Kong ,&nbsp;Shaopei Qi ,&nbsp;Qianqian Duan ,&nbsp;Qin Zhang ,&nbsp;Junping Zhang","doi":"10.1016/j.bbrep.2025.102364","DOIUrl":"10.1016/j.bbrep.2025.102364","url":null,"abstract":"<div><div>Apatinib in combination with temozolomide (TMZ) has achieved reasonable clinical efficacy in the treatment of recurrent glioblastoma (rGBM), however, there are currently no clear biomarkers related to clinical efficacy or prognosis. Our retrospective study was to investigate tumor microenvironment (TME) features at the gene expression level that are associated with response and long survival benefit of rGBM treated with apatinib and TMZ. We enrolled 22 rGBMs treated with apatinib in combination with TMZ and collected their tissue samples for RNA transcriptome analysis by the Nanostring nCounter platform. The response group had 40 differentially expressed genes compared to the non-response group, with significantly up-regulated expression of genes related to endothelial cells and apoptosis. Enrichment analysis revealed that signaling pathways related to cell proliferation were down-regulated in the response group. In terms of prognosis, there were 16 differential expressed genes in the long-survival benefit group compared with the short-survival benefit group, and four tumor progression-associated genes were also down-regulated in response group expression. Hypoxia related-genes was significantly up-regulated in the long survival benefit group. Enrichment analysis showed that genes related to cell proliferation were also down-regulated in the long-survival benefit group, while the expression of signaling pathway genes related to cell activation, and immune response was significantly up-regulated. Our study suggests that the combination of apatinib and TMZ may potentially provide clinical benefits in treating rGBM by modulating genes associated with cell proliferation, promoting apoptosis, regulating hypoxia, and enhancing immune response within the tumor microenvironment.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102364"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145691634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TMEM207-mediated the impairment of skin regeneration through YAP sequestration in an allergic contact dermatitis model","authors":"Shusuke Nomura,&nbsp;Yusuke Kito,&nbsp;Chiemi Saigo,&nbsp;Tamotsu Takeuchi","doi":"10.1016/j.bbrep.2025.102409","DOIUrl":"10.1016/j.bbrep.2025.102409","url":null,"abstract":"<div><h3>Aim</h3><div>The Yes-associated protein (YAP) family of transcriptional coactivators has emerged as a potent promoter of cell proliferation in many types of stem/progenitor cells and cancers. Skin is a squamous epithelium that is continuously regenerated by stem/progenitor cells in the basal layer and is capable of wound healing, and YAP also plays an important role in maintaining skin homeostasis and cellular proliferation. Therefore, we focused on YAP and investigated the importance of YAP regulation in allergic contact dermatitis from the perspective of wound healing and regeneration.</div></div><div><h3>Methods</h3><div>We investigated the expression and pathological characteristics of Transmembrane protein 207 (TMEM207), focusing on YAP-mediated regulation in atopic models, as abnormal TMEM207 expression may cause various functional abnormalities or regulate the function of YAP.</div></div><div><h3>Results</h3><div>TMEM207 was detected not only in the stomach and large intestine but also in the bulge region of the sebaceous glands and hair roots in mice expressing TMEM207. In addition, ATP binding cassette subfamily B member 1 (ABCB1) expression decreased in the sebaceous glands, and MIB E3 Ubiquitin Protein Ligase 1 (MIB-1) expression diminished in the epidermis. Furthermore, although we were unable to confirm the binding of TMEM207 to NEDD4, we confirmed the binding of TMEM207 to the Yes1-associated transcription factor (YAP) by immunoprecipitation, and a decrease in the nuclear localization of YAP was observed by immunohistochemical staining.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that abnormal expression of TMEM207 is involved in the decline of skin regeneration capacity through YAP, leading to the aggravation of Allergic contact dermatitis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102409"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145747950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological validation of a cryo-TEM-based detection method for empty capsid ratio in recombinant adeno-associated virus","authors":"Lingyi Xu ,&nbsp;Jinhuan Chen ,&nbsp;Wei Zhu ,&nbsp;Yaokun Zhao ,&nbsp;Fangfang Zheng ,&nbsp;Rong Du ,&nbsp;Yuwei Jiang ,&nbsp;Yidan Yang ,&nbsp;Yuanyuan Chen ,&nbsp;Yuanshu Dong ,&nbsp;Zhengxi Zhang ,&nbsp;Yong Tong","doi":"10.1016/j.bbrep.2025.102397","DOIUrl":"10.1016/j.bbrep.2025.102397","url":null,"abstract":"<div><div>Recombinant adeno-associated virus (rAAV) is one of the most promising vectors for gene therapy. It consists of a protein capsid that encapsulates the genetic material. However, during the production process, except for the full particles containing the genome, a variety of types of particles are also produced concomitantly, such as empty particles (no DNA encapsulated in the capsid), viral fragments, damaged viruses, and viral aggregates. Empty particles have been reported to induce unnecessary immune response and reduce transduction efficiency. Therefore, a quantitative method that objectively assesses the content of rAAV particles containing the genome is crucial for quality measurement. In this study, we developed a technique to detect the proportion of empty capsids in rAAV samples by using cryogenic transmission electron microscopy (cryo-TEM). This method not only accurately quantifies the percentage of empty capsids, but also allows for the characterization and analysis of other different particle types within the sample. Our comprehensive evaluation of specificity, precision, accuracy, linearity, and limit of quantitation (LOQ) demonstrates the advantages of cryo-TEM technology for the quantitative analysis of rAAV empty capsid ratio. Moreover, this research offers a thorough, multidimensional approach to enhance the understanding and implementation of quality control for rAAV.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102397"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145747999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioanalytical methods for quantification of Bevacizumab in human serum: ELISA versus MSD","authors":"Vikas Chandnani ,&nbsp;Sanjay Tiwari ,&nbsp;Manoj Bob ,&nbsp;S.G. Vasantharaju ,&nbsp;Gundawar Ravi ,&nbsp;A. Supraja ,&nbsp;Amol Pawar ,&nbsp;Suhas Khandave ,&nbsp;Sandeep Jagtap ,&nbsp;Muddukrishna Badamane Sathyanarayana","doi":"10.1016/j.bbrep.2026.102465","DOIUrl":"10.1016/j.bbrep.2026.102465","url":null,"abstract":"<div><div>Bevacizumab (BVZ) is an anti-vascular Endothelial Growth Factor-A monoclonal antibody (mAb) widely used in oncology and ophthalmology indications globally. Accurate quantification of mAbs in biological fluids is an essential prerequisite for determining pharmacokinetic (PK) parameters to assess the relationship between drug exposure and response. We developed and evaluated PK assays for BVZ in human serum using enzyme-linked immunosorbent assays (ELISA) and Meso Scale Discovery (MSD) immunoassay platforms to assess sensitivity and performance. The ELISA method, employing a Streptavidin-Biotin detection system with anti-idiotypic antibodies, demonstrated five times greater sensitivity than the conventional horseradish peroxidase-based ELISA format. The validated PK bridging ELISA achieved a quantification range of 10–220 ng/mL, extendable to 5000 ng/mL via dilution. In contrast, the MSD assay utilized electrochemiluminescence detection with Sulfo Tag labeling, offering a 20-fold higher sensitivity and detecting BVZ at concentrations as low as 500 pg/mL. This parallel evaluation concluded that ELISA is suitable for routine PK analysis due to its robustness and cost-efficiency. At the same time, MSD is advantageous for detecting BVZ at low concentrations in early-phase clinical trials and ophthalmic applications where serum levels are minimal.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102465"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review and meta-analysis of the relationship between neuroinflammation and blood-brain barrier based on in vitro models","authors":"Junwei Zhao,&nbsp;Anyongqi Wang,&nbsp;Xiang Li","doi":"10.1016/j.bbrep.2026.102479","DOIUrl":"10.1016/j.bbrep.2026.102479","url":null,"abstract":"<div><div>The blood-brain barrier (BBB) plays a crucial role in maintaining homeostasis within the central nervous system (CNS). Neuroinflammation disrupts the integrity of the BBB. However, there is a lack of comprehensive synthesis of <em>in vitro</em> evidence on this topic. This study aims to systematically review <em>in vitro</em> research examining the effects of neuroinflammatory stimuli on the structure and function of the BBB. PubMed, EMBASE, and Web of Science were searched for studies published between November 2014 and November 2024. Included studies employed <em>in vitro</em> BBB models to assess effects of defined neuroinflammatory on structural and functional. Pooled standardized mean differences (SMD) with 95 % confidence intervals (CI) were calculated using random effects models. Meta-analysis was performed using R. Overall, 55 studies were included. Neuroinflammation was found to significantly decrease transendothelial electrical resistance (TEER) (−2.15, 95 % CI [-2.73, −1.56]) while increasing permeability (2.75, 95 % CI [1.71, 3.79]). Subgroup analyses showed that co-culture models exhibited more severe disruptions compared to mono-cultures measured by a significant decrease in TEER (<em>p</em> &lt; 0.05). Human-derived cells displayed heightened decreases in TEER and increased permeability compared to non-human derived cells (<em>p</em> &lt; 0.05). Co-cultures of endothelial cells and pericytes exhibited pronounced effects of decreased TEER compared to endothelial cells alone (<em>p</em> &lt; 0.05). Stimulation periods exceeding 24 h led to significant changes. Lipopolysaccharide (LPS) caused significant disruptions. Experiments conducted with transwell systems were more sensitive to changes in TEER compared to non-transwell systems (<em>p</em> &lt; 0.05). <em>In vitro</em> evidence confirms neuroinflammation disrupts BBB integrity through reduced TEER, increased permeability. Human-derived cells, particularly hiPSC-derived models, endothelial-pericytes co-cultures, and exposure to LPS exceeding 24 h most effectively replicate pathophysiological disruption, potentially offering optimal platforms for exploring neurological disease-related mechanisms and therapeutic strategy in the future.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102479"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146163947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced anticancer activity of nanoemulsified cardamom extract via modulation of apoptosis- and lncRNA-associated pathways in colorectal cancer cells","authors":"Tahoora Soltani ,&nbsp;Mohammad Karimian ,&nbsp;Hamidreza Vaziri ,&nbsp;Merat Karimi ,&nbsp;Majid Nejati","doi":"10.1016/j.bbrep.2026.102455","DOIUrl":"10.1016/j.bbrep.2026.102455","url":null,"abstract":"<div><div>Colorectal cancer is a common, deadly disease, highlighting the need for safe and effective treatments. This study compared the anticancer effects of crude and nanoemulsified <em>Elettaria cardamomum</em> (cardamom) extract on HCT-116 colorectal cancer cells. Both the crude extract and nanoemulsion were prepared, and the nanoemulsion was characterized using transmission electron microscopy and dynamic light scattering. In an <em>in vitro</em> study, cell viability was measured by MTT assay, apoptosis by Annexin V/PI staining, and migration by scratch assay. The expression of genes related to apoptosis, migration, and angiogenesis, as well as lncRNAs MALAT1, NEAT1, and GAS5, was analyzed using real-time PCR. Physicochemical analysis showed spherical nanoemulsion particles with two size populations in a multimodal distribution. The IC₅₀ was found to be 279 μg/mL for crude extract and 54.36 μg/mL for the nanoemulsion. Our molecular findings showed that the cardamom nanoemulsion exerted significantly stronger anticancer effects than the crude extract, including a greater decrease in cell viability, increased apoptosis, and more effective migration inhibition. Gene expression analysis showed that the nanoemulsion upregulated BAX and GAS5 while downregulating BCL2, MMP2, MMP9, HIF1A, VEGFA, MALAT1, and NEAT1. These expression changes were particularly pronounced at early time points compared to the crude extract. Bioinformatic analyses identified correlations between these lncRNAs and crucial genes involved in cell survival, migration, and angiogenesis, emphasizing possible lncRNA-miRNA-mRNA regulatory axes. The cardamom nanoemulsion demonstrates enhanced anticancer activity relative to the crude extract and could represent a novel therapeutic approach for colorectal cancer by modulating lncRNAs and related molecular pathways.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102455"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146140800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenic functions of polypyrimidine tract-binding protein 1 in breast cancer metabolism and progression","authors":"Manabu Futamura ,&nbsp;Yoshihisa Tokumaru ,&nbsp;Akira Nakakami ,&nbsp;Yoshimi Niwa ,&nbsp;Junichi Mase ,&nbsp;Emiri Sugiyama ,&nbsp;Mai Okawa ,&nbsp;Kana Matsuda ,&nbsp;Ryutaro Mori ,&nbsp;Yukihiro Akao ,&nbsp;Nobuhisa Matsuhashi","doi":"10.1016/j.bbrep.2026.102458","DOIUrl":"10.1016/j.bbrep.2026.102458","url":null,"abstract":"<div><div>Polypyrimidine tract-binding protein 1 (PTBP1) is an RNA-binding protein that regulates alternative splicing and primarily acts as a splicing repressor. Previous studies have shown that PTBP1 is closely linked to cancer metabolism through regulation by miR-133b and miR-124, which inhibit PTBP1 expression and modulate the splicing of the pyruvate kinase muscle (PKM) gene. Increased PTBP1 expression promotes PKM2 production and enhances glycolysis-dependent metabolism, a hallmark of cancer known as the Warburg effect. Clinical and experimental analyses were conducted to investigate the role of PTBP1 in breast cancer (BC). <em>In silico</em> investigations using The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets revealed a significant association between PTBP1 overexpression and poor prognosis. <em>In vitro</em>, PTBP1 knockdown in BC cell lines (MCF7, SK-BR-3, and MDA-MB-231) increased PKM1 expression and the PKM1/PKM2 ratio, leading to reduced cell proliferation. ATP production increased in MCF7 and SK-BR-3 cells, but not in MDA-MB-231. Although NADH levels were elevated in MCF7 and MDA-MB-231 cells, lactate accumulation was most prominent in MDA-MB-231 cells. qRT-PCR analysis of surgical BC specimens confirmed significantly higher PTBP1 expression in tumour tissues than in adjacent normal breast tissues, with expression positively correlating with tumour grade. These findings collectively demonstrate that PTBP1 is overexpressed in BC and drives cancer-specific metabolic reprogramming associated with the Warburg effect. Therefore, PTBP1 may act as an oncogenic regulator of breast cancer metabolism and serve as a potential therapeutic target.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102458"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Capsaicin responses in Drosophila: Exploring the possibility of establishing a new Non-TRPV1 model","authors":"Gerardo Flores-Iga,&nbsp;Mohankumar Amirthalingam,&nbsp;Carlos Lopez-Ortiz,&nbsp;Padma Nimmakayala,&nbsp;Umesh K. Reddy","doi":"10.1016/j.bbrep.2026.102515","DOIUrl":"10.1016/j.bbrep.2026.102515","url":null,"abstract":"<div><div>Capsaicin, the primary pungent compound in chili peppers, activates the heat-sensitive ion channel transient receptor potential vanilloid 1 (TRPV1) in mammals, eliciting the characteristic burning sensation. On the other hand, <em>Drosophila melanogaster</em> is a powerful invertebrate genetic model for linking gene function to behavior and physiology that lacks an ortholog of TRPV1, providing a unique opportunity to uncover how capsaicin affects organisms that do not possess this canonical receptor. Although Drosophila exhibits measurable responses to capsaicin, it remains unclear whether these effects reflect direct sensory detection or indirect metabolic and stress-related processes, as mechanistic evidence remains inconclusive. Here, we synthesize capsaicin-related studies in Drosophila, with a particular emphasis on reconciling opposing findings. We propose emerging conceptual frameworks based on convergent evidence implicating chemosensory pathways, metabolic processes, and physiological responses, and highlight key directions for future research aimed at clarifying the multifaceted interaction of capsaicin in TRPV1-lacking systems.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102515"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EWSR1 as a regulatory target in hepatic stellate cell apoptosis and liver fibrosis therapy","authors":"Zhang Shiwan ,&nbsp;Luo Guangcheng ,&nbsp;Maisarah Abdul Mutalib","doi":"10.1016/j.bbrep.2026.102526","DOIUrl":"10.1016/j.bbrep.2026.102526","url":null,"abstract":"<div><div>Liver fibrosis is a progressive condition driven by hepatic stellate cell (HSC) activation and resistance to apoptosis, culminating in excessive extracellular matrix (ECM) accumulation and organ dysfunction. Current antifibrotic therapies remain limited, as most target broad pathways such as TGF-β signaling or oxidative stress without addressing upstream regulators. Emerging evidence identifies the RNA-binding protein Ewing Sarcoma Breakpoint Region 1 (EWSR1) as a pivotal modulator of HSC fate. Through transcriptional regulation, non-coding RNA networks, and stress-granule dynamics, EWSR1 integrates TGF-β signaling, oxidative stress responses, and apoptosis resistance. Inhibition of EWSR1 has been reported in experimental models to suppress fibrosis-related gene expression and restore apoptotic sensitivity in activated HSCs, highlighting its therapeutic potential. This review critically synthesizes recent insights into EWSR1 biology, its crosstalk with profibrotic pathways, and its regulatory influence on HSC activation. We further compare EWSR1 with conventional antifibrotic approaches, outline research gaps, and propose directions for translational development. By positioning EWSR1 as a novel molecular node in fibrogenesis, this article underscores its promise as a next-generation therapeutic target for halting or reversing liver fibrosis.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"45 ","pages":"Article 102526"},"PeriodicalIF":2.2,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147375951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}