Biology Direct最新文献

{"title":"Mitochondrial RNA polymerase is a critical mediator of LPS-induced inflammatory responses and septic shock.","authors":"Jie Qiong Ping, Tao Guo, Shi Wei Zhang, Cheng Kong, Xiang Yu Gao, Hong Peng Li","doi":"10.1186/s13062-026-00917-x","DOIUrl":"https://doi.org/10.1186/s13062-026-00917-x","url":null,"abstract":"<p><p>Sepsis, particularly septic shock, is a life-threatening condition driven by a dysregulated inflammatory response. Mitochondria are vital for orchestrating the LPS (lipopolysaccharide)-induced innate immune response. At the core of mitochondrial functionality lies mitochondrial RNA Polymerase (POLRMT). This study delineates POLRMT's functional role and underlying mechanisms in LPS-induced pro-inflammatory responses across various macrophage models and in vivo. Through multiple genetic strategies, including stable shRNA-mediated knockdown and CRISPR/Cas9-mediated ablation, we demonstrated that POLRMT deficiency in THP-1 human macrophages, peripheral blood mononuclear cells (PBMCs), and murine bone marrow-derived macrophages (BMDMs) consistently attenuated LPS-induced transcriptional upregulation and secretion of key pro-inflammatory cytokines (IL-1β, TNF-α, IL-6). Conversely, POLRMT overexpression in THP-1 cells augmented these inflammatory responses. LPS-induced enhancements in mitochondrial Complex I activity and ATP content, alongside NFκB activation, were dependent on POLRMT expression. Genetic perturbation of POLRMT directly correlated with altered mitochondrial function and NFκB activity. Pharmacological inhibition of POLRMT with a specific inhibitor IMT1 also suppressed LPS-induced cytokine production, mitochondrial activation, and NFκB activity in vitro. The in vivo studies revealed that knockdown of POLRMT in CD68-expressing cells protected mice from LPS-induced septic shock, reducing mortality and systemic cytokine levels. Oral administration of IMT1 similarly conferred protection against septic shock, correlating with diminished circulating pro-inflammatory cytokines and reduced NFκB activity in murine PBMCs. Collectively, these findings establish POLRMT as a mediator of LPS-induced inflammatory responses in macrophages/monocytes.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149243226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiomics, multi-species profiling, and animal validation identify mitoxyperilysis as a conserved therapeutic target in metabolic dysfunction-associated steatohepatitis.","authors":"Hanjie Liu, Cong Qi, Ruixia Lu, Chuan An, Yangzhiyuan Wang, Shumiao Li, Rui Zhu, Xingzhong Feng, Huijuan Gao","doi":"10.1186/s13062-026-00902-4","DOIUrl":"10.1186/s13062-026-00902-4","url":null,"abstract":"<p><strong>Background & aims: </strong>Metabolic dysfunction-associated steatohepatitis (MASH) is driven by complex intercellular communication and regulated cell death pathways. Mitoxyperilysis, a recently characterized form of regulated lytic cell death, remains poorly defined in MASH. Here, we integrated multiomics, cross-species transcriptomics, machine learning, and in vivo models to dissect mitoxyperilysis activation and its therapeutic relevance in MASH.</p><p><strong>Methods: </strong>Single‑cell and spatial transcriptomic datasets from mouse and human MASH livers were analyzed. Cell-cell communication was inferred using CellChat, and metabolite‑mediated cell-cell communication (mCCC) was assessed with MEBOCOST. Mitoxyperilysis activity was scored via AUCell and AddModuleScore. Eleven machine learning classifiers identified transcriptomic signatures distinguishing MASH from controls, and key regulators were subjected to in silico knockout (scTenifoldKnk). A choline‑deficient, L‑amino acid‑defined high‑fat diet (CDAHFD) mouse model was used for in vivo validation.</p><p><strong>Results: </strong>Single‑cell profiling revealed that mitoxyperilysis activity was highly enriched in myeloid cells, particularly monocyte‑derived macrophages (Mo‑Macrophages) and neutrophils, and was strongly induced by high‑fat high‑sucrose diet. CellChat and mCCC analyses demonstrated that Mo‑Macrophages served as central hubs of rewired inflammatory and metabolic crosstalk in MASH. Spatial transcriptomics confirmed the expansion of pro‑inflammatory hepatocyte subsets and conserved upregulation of mitoxyperilysis components (e.g. BAX, TLR4, NINJ1) in both mouse and human MASH. Cross‑species profiling across mouse, rat, hamster, non‑human primate, and human datasets demonstrated evolutionarily conserved activation of the entire mitoxyperilysis pathway. Machine learning identified Bax as the sole overlapping driver gene linking diet‑induced transcriptomic signatures to mitoxyperilysis. In silico Bax ablation perturbed lipid metabolism and immune pathways. In CDAHFD-induced MASH mice with typical pathological phenotypes, core mitoxyperilysis genes were transcriptionally upregulated, and Bax/Bid/Bak1 upregulation was validated at the protein level. While RhoA mRNA increased, total RhoA protein remained stable, with its ubiquitination elevated and activity suppressed.</p><p><strong>Conclusions: </strong>Mitoxyperilysis is an evolutionarily conserved, myeloid‑enriched pathway activated in MASH. Bax acts as a critical regulatory node, while RhoA is modulated via ubiquitination and functional suppression. Targeting this axis may provide a novel therapeutic strategy for MASH.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13688918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149236898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZRANB1-mediated EZH2 stabilization drives S100B/S100A4 transcriptional activation and corneal neovascularization in alkali burns.","authors":"Fangyuan Liu, Ying Xiao, Yeping Huang, Yang Liu, Zhiyou Peng, Yulin Wang","doi":"10.1186/s13062-026-00892-3","DOIUrl":"10.1186/s13062-026-00892-3","url":null,"abstract":"<p><p>Alkali burn is one of the main causes of corneal injury. Corneal neovascularization caused by alkali burns aggravates corneal damage, resulting in aberrant vascular proliferation and consequent visual impairment. The present study investigated the role of enhancer of zeste homolog 2 (EZH2) in alkali burn‑induced corneal neovascularization. Through integrated bioinformatics and experimental approaches, we identified S100B, S100A4 and PI3K/AKT pathway activation as key drivers of alkali-induced corneal injury. In corneal alkali burn mice, knockdown of S100B or S100A4 attenuated corneal neovascularization and suppressed PI3K/AKT/FoxO3a pathway. EZH2 was upregulated in alkali-burn models and transcriptionally activated S100B and S100A4 via direct promoter binding. The deubiquitinase ZRANB1 was identified to stabilize EZH2 protein through deubiquitination, thereby amplifying its transcriptional activity. In alkali-injured human corneal epithelial cells, EZH2 overexpression enhanced cell viability, angiogenic capacity, migration and invasion ability, which was reversed by S100B or S100A4 knockdown. In vivo, EZH2 overexpression exacerbated PI3K/AKT/FoxO3a pathway activation and corneal neovascularization via regulating S100B or S100A4. Collectively, this study demonstrated that ZRANB1-mediated stabilization of EZH2 drove pathological corneal angiogenesis in corneal alkali burns by activating S100B/S100A4-PI3K/AKT/FoxO3a axis. These findings provided novel therapeutic targets for corneal alkali burns.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SLC7A11 suppresses paclitaxel resistance and improves survival via the KLF2 regulatory axis associated with autophagy in ovarian cancer.","authors":"Xiaoying Chen, Yao Ke, Shanzhou Xie, Yulin Guo, Yuting Su, Xuemei Sun, Lizhou Shi, Yue Yu, Shunmei Lei, Dan Wei, Han Zhang, Fuqiang Yin, Xia Liu","doi":"10.1186/s13062-026-00909-x","DOIUrl":"10.1186/s13062-026-00909-x","url":null,"abstract":"<p><strong>Background: </strong>SLC7A11 is well-established as a key mediator of ferroptosis. However, its functional role in regulating autophagy, particularly in the context of ovarian cancer (OC) chemoresistance, remains poorly characterized. Our preliminary results suggested that low SLC7A11 expression is associated with paclitaxel resistance in OC, likely through inhibition of autophagy. Despite this initial observation, systematic functional investigations into the role of SLC7A11 in autophagy regulation and OC chemoresistance are lacking, and the underlying molecular mechanisms remain unclear. Therefore, this study aims to elucidate how SLC7A11 mediates chemoresistance in OC through the regulation of autophagy.</p><p><strong>Methods: </strong>The effects of SLC7A11 modulation were assessed in paclitaxel-resistant and parental OC cells using functional assays. Autophagy was evaluated via transmission electron microscopy, immunofluorescence, and Western blotting. Autophagy was inhibited using 3-methyladenine or LC3B knockdown. A subcutaneous xenograft model was used for in vivo validation. Clinical relevance was analyzed using patient tissues. Proteomics, bioinformatics, molecular, and CCK-8 assays were integrated to investigate the SLC7A11/KLF2-autophagy axis.</p><p><strong>Results: </strong>SLC7A11 knockdown enhanced the viability of paclitaxel-resistant OC cells (HeyA8-R) following paclitaxel treatment. In contrast, SLC7A11 overexpression sensitized both HeyA8-R cells and their parental HeyA8 cells to paclitaxel, as evidenced by reduced viability, increased intracellular paclitaxel accumulation, and elevated DNA damage. Moreover, SLC7A11 overexpression augmented autophagy-associated activity, and inhibition of autophagy partially attenuated SLC7A11-mediated sensitization to paclitaxel. In vivo studies showed that SLC7A11 suppressed tumor growth and overcame paclitaxel resistance in OC, accompanied by upregulated autophagy-related markers (LC3B, LC3B-II/I, and LAMP1). Mechanistically, SLC7A11 negatively regulated KLF2, a key oncogenic autophagy regulator, and the SLC7A11/KLF2 regulatory axis was associated with LC3B expression and autophagy-associated activity, which may contribute to paclitaxel sensitivity in OC. Clinically, low SLC7A11 expression correlated with chemoresistance and shorter survival in OC.</p><p><strong>Conclusions: </strong>Our findings underscore the significance of the SLC7A11/KLF2-autophagy regulatory axis in OC paclitaxel resistance. They also suggest that SLC7A11 may serve as a prognostic biomarker and therapeutic target for overcoming OC chemoresistance.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing reveals that TAF7 promotes colorectal cancer stemness by targeting SOX2.","authors":"Xiaohui Ai, Yupei Jiang, Xiaoqing Huang, Haitao Ning, Shaojun Wang, Fang Li, Shulin Wu, Jun Mo","doi":"10.1186/s13062-026-00910-4","DOIUrl":"10.1186/s13062-026-00910-4","url":null,"abstract":"<p><strong>Background: </strong>Cancer cell stemness plays a decisive role in tumor metastasis and recurrence. TATA-box binding protein-associated factor 7 (TAF7), which is highly expressed in multiple cancers and critical for metastasis, has not been clearly linked to stemness characteristics in colorectal cancer (CRC). Therefore, this study aimed to investigate the role of TAF7 in CRC stemness.</p><p><strong>Methods: </strong>Differential gene expression and associated signaling pathways were screened using single-cell transcriptomic data from CRC and adjacent normal tissues obtained from the GEO database and validated in CRC cells. A TAF7-knockdown CRC cell line was established to assess the impact of TAF7 on tumor cell stemness. The molecular mechanism of TAF7 in regulating CRC stemness was explored through bioinformatics analysis combined with chromatin immunoprecipitation and dual-luciferase reporter assays and validated by rescue experiments. Finally, a CRC xenograft mouse model was established to examine the effect of targeting TAF7 on tumor cell stemness and epithelial-mesenchymal transition (EMT).</p><p><strong>Results: </strong>Re-analysis of single-cell transcriptomics data identified a TAF7⁺ epithelial cell subpopulation that is highly expressed in CRC and characteristically expresses the stemness marker SOX2. In vitro experiments demonstrated that high TAF7 expression promotes CRC stemness, primarily by enhancing the transcriptional activation of SOX2. Rescue experiments confirmed that targeting the TAF7/SOX2 axis suppresses CRC stemness and EMT. Furthermore, in vivo experiments showed that TAF7 targeting inhibits tumor growth and CRC stemness in mice.</p><p><strong>Conclusion: </strong>Our integrated single-cell transcriptomic and functional analyses reveal that TAF7 promotes CRC stemness and EMT progression via transcriptional activation of the stemness marker SOX2.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":"21 1","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"4-phenylbutyric acid-loaded mesoporous silica nanoparticles alleviate endoplasmic reticulum stress and reduce intraocular pressure in glaucoma model.","authors":"Xuejing Yan, Wu Qin, Xiaoming Gan, Yingyan Mao, Shen Wu, Shipeng Wen, Jingxue Zhang","doi":"10.1186/s13062-026-00907-z","DOIUrl":"10.1186/s13062-026-00907-z","url":null,"abstract":"<p><strong>Purpose: </strong>To develop a mesoporous silica nanoparticle-based delivery system for 4-phenylbutyric acid (4-PBA) and evaluate its potential to alleviate endoplasmic reticulum (ER) stress and improve mutant myocilin (MYOC)-associated glaucoma.</p><p><strong>Materials and methods: </strong>We synthesized hollow/snowflake-like mesoporous silica nanoparticles loaded with 4-PBA (mSiO₂-PBA) for drug loading and release. Cellular uptake and cytotoxicity were evaluated in human corneal epithelial cells (HCECs) and human trabecular meshwork cells (HTMCs). The effects of mSiO₂-PBA on mutant MYOC secretion and ER stress-associated proteins were assessed by Western blot analysis. In Tg-MYOC^N450Y mice, ocular distribution of mSiO₂-PBA was examined by fluorescence imaging and high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Therapeutic efficacy was evaluated by intraocular pressure (IOP) measurements, immunofluorescence analysis of MYOC accumulation and ER stress-associated markers in trabecular meshwork tissue, and transmission electron microscopy (TEM).</p><p><strong>Results: </strong>mSiO₂-PBA exhibited efficient cellular uptake and favorable biocompatibility in vitro. Treatment with mSiO₂-PBA enhanced mutant MYOC secretion and reduced ER stress-associated KDEL-positive proteins in HTMCs. Following topical administration, mSiO₂-PBA achieved ocular penetration and exposure in trabecular meshwork tissue. In Tg-MYOC^N450Y mice, mSiO₂-PBA significantly reduced IOP, decreased mutant MYOC accumulation, and improved ER ultrastructural abnormalities in trabecular meshwork cells.</p><p><strong>Conclusions: </strong>mSiO₂-PBA represents a promising nanoparticle-based delivery platform for 4-PBA in MYOC-associated glaucoma. By promoting mutant MYOC secretion and alleviating ER stress, mSiO₂-PBA demonstrated therapeutic efficacy in vitro and in vivo, supporting its potential as a nanotherapeutic strategy for MYOC-associated glaucoma.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor cells escape from therapy-induced senescence: from molecular mechanisms to targeted intervention.","authors":"Yu Han, Lie Ma, Xiangyu Ma","doi":"10.1186/s13062-026-00908-y","DOIUrl":"10.1186/s13062-026-00908-y","url":null,"abstract":"<p><p>Tumor recurrence represents a significant challenge in the field of tumor therapy, severely affecting patients' survival rates and quality of life. Even after standard treatments, many patients still experience tumor recurrence. Traditional radiotherapy, chemotherapy, and targeted therapies can induce tumor cell senescence to suppress tumor growth and dissemination. However, recent studies have shown that therapy-induced senescent tumor cells can re-enter the cell cycle, acting as a key driver of tumor recurrence. Consequently, senescent tumor cells have emerged as a pivotal focus for unraveling the mechanisms underlying tumor recurrence. This review systematically elucidates the multidimensional molecular regulatory networks through which senescent tumor cells promote tumor recurrence, encompassing key processes such as cell cycle reactivation mechanisms, epithelial-mesenchymal transition (EMT), acquisition of stemness phenotypes, formation of polyploid giant cancer cells (PGCCs), fate transition from senescence to pyroptosis, and remodeling of the immune microenvironment. Additionally, it summarizes the latest advances in targeted interventions against senescent tumor cells, including senolytics-mediated clearance of senescent cells and senomorphic modulation of the senescence-associated secretory phenotype (SASP). Furthermore, we propose that, guided by the molecular mechanisms underlying senescent tumor cell-mediated recurrence, the integration of multi-omics analyses to precisely delineate the therapeutic window, combined with artificial intelligence-driven drug screening, holds promise for developing more specific senolytic agents, thereby offering innovative strategies to improve recurrence control rates following cancer therapy.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PAX5 alleviates atherosclerosis by transcriptionally regulating GSDMD and inhibiting STAT3-mediated pyroptosis.","authors":"Xiangkui Wang, Peipei Wu, Yadi Shen, Shiwei Xu, Qi Wan, Qilun Zhang, Ran Lu","doi":"10.1186/s13062-026-00905-1","DOIUrl":"10.1186/s13062-026-00905-1","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to elucidate the role of PAX5 in the pathogenesis of atherosclerosis (AS) and its underlying mechanisms, with a particular focus on the transcriptional regulation of GSDMD and STAT3-mediated pyroptosis.</p><p><strong>Methods: </strong>Serum PAX5 and GSDMD levels were detected in AS patients and healthy controls. In vitro, human umbilical vein endothelial cells (HUVECs) were stimulated with oxidized low-density lipoprotein (ox-LDL) and transfected with PAX5 overexpression vectors, followed by assays for cell viability, tube formation, lipid accumulation, LDH release, and pro-inflammatory cytokine (IL-1β, IL-18) secretion. Immunofluorescence and dual-luciferase reporter assays were performed to verify the co-localization of PAX5 and GSDMD, and the transcriptional interaction between PAX5 and the GSDMD promoter. Co-immunoprecipitation (Co-IP) ubiquitination assays were conducted to determine whether PAX5 promotes GSDMD poly-ubiquitination. In vivo, ApoE⁻/⁻ AS mouse models were treated with AAV-mediated PAX5 overexpression, followed by histopathological assessment of atherosclerotic lesions, lipid metabolism detection, and Western blot analysis of pyroptosis and STAT3 signaling-related proteins.</p><p><strong>Results: </strong>Serum PAX5 was significantly downregulated in AS patients, while GSDMD was upregulated. In vitro, PAX5 overexpression reversed ox-LDL-induced viability reduction, lipid accumulation, LDH release, and IL-1β/IL-18 hypersecretion in HUVECs. Dual-luciferase assay confirmed that PAX5 directly binds to and activates the GSDMD promoter. Ubiquitination assays demonstrated that PAX5 promotes both K48-linked and K63-linked poly-ubiquitination of GSDMD, with the degradation pathway predominating over transcriptional activation, resulting in a net decrease in GSDMD protein abundance. In vivo, PAX5 overexpression reduced atherosclerotic lesion size, lipid deposition, and systemic inflammatory levels, improved serum lipid profiles, and inhibited STAT3 phosphorylation, GSDMD-N generation, and pyroptosis-related protein expression.</p><p><strong>Conclusion: </strong>PAX5 alleviates AS progression through a dual regulatory mechanism involving transcriptional activation and ubiquitin-proteasome-mediated degradation of GSDMD, thereby inhibiting STAT3-associated pyroptosis. PAX5 represents a promising therapeutic target for AS intervention.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ovarian cancer-derived ADAMTS2 promotes the omental pre-metastatic niche formation through remodeling collagen I.","authors":"Jing Guo, Xinyi Wu, Qiulei Wu, Lin Huang, Wenhan Li, Yan Wei, Le Chen, Feiquan Ying","doi":"10.1186/s13062-026-00903-3","DOIUrl":"10.1186/s13062-026-00903-3","url":null,"abstract":"<p><strong>Background: </strong>Epithelial ovarian cancer (EOC) frequently metastasizes to the omentum, yet the mechanisms driving this site-specific dissemination remain incompletely understood. Through transcriptomic profiling, we previously identified ADAMTS2 (A disintegrin and metalloproteinase with thrombospondin type 1 motifs 2) as the most upregulated gene in highly metastatic EOC (EOC-HM) cells. Here, we investigated the functional role of ADAMTS2 in orchestrating the omental metastatic niche.</p><p><strong>Results: </strong>In orthotopic mouse models, silencing ADAMTS2 in EOC-HM cells significantly suppressed spontaneous intraperitoneal metastasis and extended survival. Mechanistically, we observed a negative correlation between tumoral ADAMTS2 expression and omental collagen deposition in both murine models and patient samples, as visualized by polarized picrosirius red staining. Furthermore, EOC-HM cells secreted elevated levels of ADAMTS2 compared to parental lines, and intraperitoneal injection of this ADAMTS2-rich supernatant was sufficient to reduce omental collagen density in vivo. In vitro assays confirmed that ADAMTS2 knockdown impaired the invasive capacity of EOC cells through collagen I matrices and diminished the collagenolytic activity of their conditioned media.</p><p><strong>Conclusions: </strong>These findings identify tumor-derived ADAMTS2 as a key initiator of extracellular matrix remodeling in the omentum that facilitates subsequent metastatic colonization, providing mechanistic insight into premetastatic niche formation and suggesting ADAMTS2 as a potential therapeutic target in EOC.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A senescence-associated gene signature predicts radiotherapy prognosis in non-small cell lung cancer and identifies CSF1 as a target to potentiate radioimmunotherapy.","authors":"Shaochuan Liu, Yuhan Zhang, Liuze Li, Huanhuan Wang, Hao Yuan, Deyi Zhang, Donghe Zhao, Yong Guan, Zhiyong Yuan","doi":"10.1186/s13062-026-00901-5","DOIUrl":"10.1186/s13062-026-00901-5","url":null,"abstract":"<p><p>The role of cellular senescence as a tumor-associated hallmark and therapeutic target in influencing radiotherapy or radioimmunotherapy outcomes remains incompletely understood. To address this, we developed a senescence-associated gene signature to predict prognosis in non‑small cell lung cancer (NSCLC) patients treated with radiotherapy. A risk model based on nine genes-including COL4A1 and CSF1-effectively stratified patients into high‑ and low‑risk groups. High‑risk patients exhibited significantly poorer overall survival and a tumor microenvironment characterized by reduced immune infiltration and an immune‑excluded phenotype. CSF1 was identified as a pivotal gene within this signature. Mechanistically, radiotherapy induces the expansion of a CSF1‑high‑expressing exhausted T‑cell population, which exhibits characteristics of both exhausted and senescent T cells and forms a positive feedback loop with M2‑like macrophages, thereby reinforcing the immunosuppressive microenvironment. Preclinical studies demonstrated that combining a CSF1‑neutralizing antibody with radiotherapy and anti‑PD‑1 therapy effectively reduced exhausted T cells and M2 macrophages, leading to a significant enhancement in therapeutic efficacy. Taken together, our work establishes a nine‑gene signature for risk stratification in NSCLC and provides proof‑of‑concept that targeting CSF1 can potentiate radioimmunotherapy, offering a novel translational strategy for improving patient survival.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}