Biology Direct最新文献

{"title":"CD13 identifies S100A4⁺ immunosuppressive monocytes and predicts temozolomide benefit in glioblastoma.","authors":"Dong Yu, Ruiyao Hu, Qing Zhu, Xiao Wang","doi":"10.1186/s13062-026-00889-y","DOIUrl":"10.1186/s13062-026-00889-y","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is an immunologically \"cold\" tumor in which S100A4-driven immunosuppressive myeloid cells promote progression and resistance. However, the specific immune subpopulation that intrinsically expresses S100A4 and the corresponding cell surface targets remain poorly defined.</p><p><strong>Materials and methods: </strong>S100A4 expression was profiled across immune subsets in healthy human bone marrow and peripheral blood by flow cytometry. TCGA GBM datasets were used to identify S100A4-correlated surface markers, and CD13 (encoded by ANPEP) was validated across the Human Protein Atlas, Immgen, GEO and single-cell RNA-seq datasets. The functional link between CD13, S100A4, and TGFβ was assessed by network analysis and correlation. Drug response analysis was conducted using GEPIA 3 platform.</p><p><strong>Results: </strong>Monocytes were the predominant S100A4-expressing population in both bone marrow and peripheral blood. CD13 emerged as the surface marker most significantly correlated with S100A4 in GBM. CD13⁺ monocytes co-expressed high levels of S100A4 and were transcriptionally positioned between monocytic and granulocytic lineages. These cells displayed a strong association with TGFβ signaling, suggesting a CD13-TGFβ-S100A4 immunosuppressive axis. Notably, temozolomide conferred a significant survival benefit specifically in CD13-high GBM patients.</p><p><strong>Conclusions: </strong>CD13 marks S100A4-high immunosuppressive monocytes in GBM and represents an accessible surface target for monitoring and potentially depleting this pathogenic population. The CD13-S100A4-TGFβ axis and the predictive value of CD13 for temozolomide response offer a translational framework for advancing GBM immunotherapy.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403562","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":"ALDH18A1 silencing inhibits lung adenocarcinoma progression through mitochondrial dysfunction and PPAR signaling pathway activation.","authors":"Taixu Sun, Jianming Deng, Menglin Yang, Wenjie Wang, Shubin Guan","doi":"10.1186/s13062-026-00882-5","DOIUrl":"10.1186/s13062-026-00882-5","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) remains a prevalent malignant tumor characterized by a dismal prognosis. This study aimed to reveal potential mitochondria-related biomarkers and explore possible mechanisms.</p><p><strong>Methods: </strong>Mitochondria-related differentially expressed genes (mitoDEGs) were identified by intersecting LUAD-associated DEGs with mitochondria-associated genes. Hub mitoDEGs were determined via protein-protein interaction (PPI) network analysis and machine learning. Aldehyde dehydrogenase 18 family member A1 (ALDH18A1) was silenced in LUAD cells to investigate its effects on proliferation, invasion, migration, and mitochondrial function. The potential involvement of the peroxisome proliferator-activated receptor (PPAR) signaling pathway in ALDH18A1-associated effects was evaluated in LUAD cells and tumor-bearing mice using the PPARγ antagonist GW9662.</p><p><strong>Results: </strong>ALDH18A1 was identified as a hub mitoDEG and was highly expressed in LUAD.ALDH18A1 silencing promoted apoptosis, suppressed invasion and migration, and inhibited the proliferation of A549 cells. ALDH18A1 silencing induced mitochondrial dysfunction, as evidenced by elevated reactive oxygen species (ROS), diminished mitochondrial membrane potential, decreased ATP production, increased dynamin related protein 1 (DRP1) and mitofusin 2 (MFN2) expression, and decreased optic atrophy 1 (OPA1) in vitro and in vivo. ALDH18A1 silencing increased PPARγ and fatty acid-binding protein 4 (FABP4) expression, whereas GW9662 notably attenuated the antitumor and mitochondrial dysfunction-related effects of ALDH18A1 knockdown.</p><p><strong>Conclusion: </strong>ALDH18A1 silencing inhibited LUAD progression and induced mitochondrial dysfunction, which may be partly associated with activation of the PPAR signaling pathway. These findings suggest that ALDH18A1 may serve as a candidate mitochondria-related molecular target for LUAD.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13628846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148403499","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":"LINC00324 induces nucleus pulposus cell apoptosis in intervertebral disc degeneration via miR-143-3p targeted TRAIL/DR4/DR5 axis.","authors":"Jialin Zhang, Min Zhao, Zewei Shan, Yueliang Chang, Yaqin He","doi":"10.1186/s13062-026-00879-0","DOIUrl":"10.1186/s13062-026-00879-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Intervertebral disc degeneration (IDD) serves as a predominant pathogenic driver of spinal degenerative diseases and low back pain. Long non-coding RNAs (lncRNAs) have emerged as important regulators involved in the pathogenesis of IDD. Despite this, the specific contributions of LINC00324, a particular lncRNA, to the advancement of IDD are not yet well understood. The study seeks to elucidate the functional role and explore the potential molecular mechanisms of LINC00324 in IDD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;RT-qPCR was employed to analyze LINC00324, miR-143-3p, and TRAIL levels in intervertebral disc (IVD) tissues from IDD patients and control subjects, followed by correlation analysis. Bioinformatics tools, dual-luciferase reporter assays, and RNA pull-down experiments were conducted to validate the regulatory interactions within LINC00324/miR-143-3p/TRAIL in nucleus pulposus cells (NPCs). In vitro, NPCs were stimulated with lipopolysaccharide (LPS) to construct an IDD cell model. RT-qPCR, western blot, CCK-8 assay, and flow cytometry were utilized to evaluate the effects on the levels of LINC00324/miR-143-3p/TRAIL/DR4/DR5, as well as the proliferation and apoptosis of NPCs. Additionally, extracellular matrix (ECM)-related proteins and inflammatory factors were detected by western blot and ELISA, respectively. In vivo, a rat IDD model was established through fibroannular puncture. Radiological analysis (X-ray), HE staining, TUNEL staining, and western blot were used to assess disc structural changes, NPC apoptosis, and the levels of miR-143-3p/TRAIL/DR4/DR5 and apoptosis-related proteins.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Clinical evidence showed that LINC00324 and TRAIL levels were increased, and miR-143-3p was decreased in IDD samples. miR-143-3p had the negative correlation coefficient with TRAIL and LINC00324. Furthermore, LINC00324 acted as a sponge for miR-143-3p, and miR-143-3p specifically attenuated the downstream of TRAIL level. In vitro, the LPS-induced IDD model showed decreased NPC viability, increased apoptosis, disrupted ECM metabolism (downregulated Collagen II and Aggrecan, upregulated MMP13), elevated inflammatory factors, and activated TRAIL/DR4/DR5 axis. Silencing LINC00324 or overexpressing miR-143-3p alleviated these pathological changes. Furthermore, miR-143-3p partially counteracted the promoting influences of LINC00324 overexpression on NPC apoptosis, ECM degradation, inflammatory response, and TRAIL/DR4/DR5 axis activation in the IDD model. In vivo, LINC00324 overexpression exacerbated IDD in rats (decreased disc height index, disrupted NPC tissue structure, enhanced NPC apoptosis, aggravated ECM degradation, inhibited miR-143-3p expression, and activated TRAIL/DR4/DR5 axis), while LINC00324 knockdown attenuated these degenerative changes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In conclusion, LINC00324 promotes IDD progression by inducing NPC apoptosis, disrupting ECM metabolism, and enhan","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387415","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":"MLKL confers ferroptosis resistance in colorectal cancer cells via impaired ESCRT-III-mediated membrane repair.","authors":"Sasiprapa Sonkaew, Nattaya Duangthim, Chutikarn Butkinaree, Yodying Yingchutrakul, Swati Choksi, Zheng-Gang Liu, Siriporn Jitkaew","doi":"10.1186/s13062-026-00887-0","DOIUrl":"10.1186/s13062-026-00887-0","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis resistance is a major challenge in cancer therapy, contributing to poor prognosis and unsatisfactory treatment outcomes. Thus, identifying key regulators of ferroptosis is essential for developing strategies to overcome this limitation. Mixed lineage kinase domain-like protein (MLKL) is well established as the executioner of necroptosis, but emerging evidence suggests broader functions beyond necroptosis. A previous study demonstrated that MLKL regulates ferroptosis in an acute kidney injury model. However, its role in ferroptosis regulation in cancer remains largely unexplored.</p><p><strong>Results: </strong>Bioinformatics analyses revealed that MLKL expression positively correlates with glutathione metabolism-related genes in colorectal cancer (CRC) patients and with reduced sensitivity to GPX4 inhibitors across pan-cancer cell lines. Functional studies demonstrated that MLKL depletion sensitizes not only CRC cells but also multiple cancer cell types to ferroptosis induced by GPX4 inhibitors. Mechanistically, MLKL-deficient CRC cells exhibited reduced intracellular glutathione levels and dysregulation of the NRF2/KEAP1/SLC7A11 antioxidant axis. However, KEAP1 knockdown in MLKL-depleted cells partially reduced ferroptosis sensitivity, indicating that additional mechanisms are involved. Proteomic analysis identified CHMP5, a component of the ESCRT-III membrane repair machinery, as a key downstream effector associated with MLKL. MLKL depletion suppressed CHMP5 expression and impaired its translocation to the plasma membrane during ferroptosis induction. Consistent with defective membrane repair, MLKL-knockdown CRC cells exhibited increased HMGB1 release following GPX4 inhibitor treatment, indicating enhanced membrane damage. Notably, CHMP5 overexpression reduced ferroptosis in MLKL-knockdown cells, highlighting that MLKL regulates ferroptosis susceptibility in part through CHMP5-dependent ESCRT-III signaling.</p><p><strong>Conclusions: </strong>This study reveals a previously unrecognized role for MLKL in ferroptosis regulation through coordinating NRF2/KEAP1/SLC7A11-mediated glutathione metabolism and ESCRT-III-dependent membrane repair. These findings identify MLKL as a potential regulator of ferroptosis resistance and warrant further studies to evaluate the therapeutic relevance of MLKL-targeting strategies in colorectal cancer.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387463","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":"Epicatechin suppresses cancer stem-like cell phenotype and radioresistance in non-small cell lung cancer via targeting CXCL8.","authors":"Tianqian Li, Hongmei Han, Meiyan Liu, Yongmei He, Sihan Zhou, Youchuan Xiao, Nan Huang, Na Peng, Chongxin Li, Hongying Xu, Jie Xia, Zengbo Lv, Yao Wu, Meifang Huang","doi":"10.1186/s13062-026-00881-6","DOIUrl":"10.1186/s13062-026-00881-6","url":null,"abstract":"<p><strong>Background: </strong>Radiotherapy remains a cornerstone for non‑small cell lung cancer (NSCLC). However, its efficacy is frequently limited by radioresistance, a phenomenon closely associated with cancer stem-like cells (CSCs). Although our previous work demonstrated that epicatechin (EC) sensitizes NSCLC cells to ionizing radiation (IR), whether this effect involves modulation of CSCs and the underlying mechanisms remain to be elucidated.</p><p><strong>Methods: </strong>A radioresistant NSCLC cell line (A549RR) was established via fractionated irradiation and employed in both in vitro assays and murine xenograft models. To assess its radiosensitizing potential, EC was administered prior to IR exposure. Cell viability and colony formation capacity were measured to evaluate radiosensitivity. Putative targets of EC were predicted using network pharmacology and validated through molecular docking. The direct interaction between EC and CXCL8 was examined by cellular thermal shift assay (CETSA). The functional relevance of CXCL8 in EC-mediated effects was assessed through both loss-of-function (shRNA-mediated knockdown) and gain-of-function (CXCL8 overexpression) approaches. CSC properties were evaluated by tumor sphere formation assays and immunoblotting for stemness markers.</p><p><strong>Results: </strong>EC significantly enhanced NSCLC radiosensitivity both in vitro and in vivo, concomitant with marked suppression of CSC stemness. CXCL8 was identified as a direct functional target of EC: its expression was substantially upregulated in radioresistant cells but downregulated upon EC treatment. CETSA confirmed a direct interaction between EC and CXCL8 in cells. Functionally, CXCL8 knockdown suppressed cell viability, colony formation capacity, and CSC properties in A549RR cells. Conversely, overexpression of CXCL8 abrogated EC-induced radiosensitization and restored CSC phenotypes in both cellular and xenograft models.</p><p><strong>Conclusion: </strong>EC overcomes NSCLC radioresistance by directly targeting CXCL8, thereby disrupting CSC-like traits.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13621744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387424","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":"Contactin-2 mitigates heart failure and cardiac remodeling via regulation of NUPR1 and ferroptosis.","authors":"Yu-Dong Fei, Zhi-Xing Wei, Tai-Zhong Chen, Liu-Hui Zhang, Yi-Chao Zhang, Jian-Wen Hou, Qian Wang, Xing-Xing Cai, Mu Chen, Yu-Li Yang, Peng-Cheng Yao, Zhen-Tao Fei, Yangjinming Bai, Ting-Ting Zhao, Ji Yan, Wei Li, Mei Yang, Rui Zhang, Xiang-Dong Liu, Ming-Zhe Zhao, Xiao-Lei Xu, Jian Sun, Yue-Peng Wang, Yi-Gang Li","doi":"10.1186/s13062-026-00890-5","DOIUrl":"10.1186/s13062-026-00890-5","url":null,"abstract":"<p><strong>Background: </strong>The roles of Contactin-2 (CNTN2) and ferroptosis in heart failure and cardiac remodeling remain incompletely understood.</p><p><strong>Results: </strong>CNTN2 was significantly upregulated in hypertrophic cardiomyopathy patients and heart failure mice. In cardiomyocyte specific CNTN2 conditional knockout (CNTN2 cKO) mice, transverse aortic constriction (TAC) induced markedly exacerbated heart failure, cardiac remodeling and ferroptosis compared to control mice. Ferroptosis inhibition substantially attenuated heart failure in CNTN2 cKO mice subjected to TAC, indicating that enhanced ferroptosis contributes to the detrimental effects of CNTN2 deficiency. RNA sequencing identified NUPR1, a ferroptosis repressor, as a downstream molecule of CNTN2. Mechanistically, CNTN2 activated the Lyn/eIF2α/ATF4 pathway to regulate NUPR1. CNTN2 overexpression attenuated Angiotensin II-induced cardiomyocyte ferroptosis and pathological remodeling, whereas these protective effects were abolished by Lyn or NUPR1 inhibitors. We further revealed CNTN2 and Lyn interacted with each other, and that CNTN2 interacted with Lyn through its 1-328aa domain. In vivo NUPR1 overexpression via AAV9 significantly mitigated TAC-induced heart failure and cardiac remodeling in CNTN2 cKO mice.</p><p><strong>Conclusions: </strong>Our study demonstrates that CNTN2 protects against pressure overload induced heart failure and cardiac remodeling by regulating ferroptosis through the Lyn/eIF2α/ATF4/NUPR1 pathway, suggesting CNTN2 as a potential therapeutic target.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13386709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387472","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 lipid metabolism disorders in the retina in spontaneous high myopia.","authors":"Bo Bao, Jinpeng Liu, Yunxiao Xie, Ruofan Xi, Yuecong Sun, Jingzhe Yan, Jizhao Xin, Zhaohui Yang, Xuewei Yin, Dadong Guo, Hongsheng Bi","doi":"10.1186/s13062-026-00884-3","DOIUrl":"10.1186/s13062-026-00884-3","url":null,"abstract":"<p><strong>Background: </strong>Myopia is one of the most common eye diseases affecting children and adolescents, with its etiology often attributed to a combination of genetic and environmental factors. This study utilized single-cell RNA sequencing (scRNA-seq) technology to investigate gene expression differences between guinea pigs with spontaneous high myopia (SHM) and those with normal vision.</p><p><strong>Results: </strong>Lens-induced myopia (LIM) and SHM guinea pigs exhibit significant retinal structural abnormalities and functional impairments, characterized by reduced retinal thickness and abnormal electroretinogram (ERG) responses, indicating progressive retinal dysfunction during myopia development. scRNA-seq and molecular experiments revealed that the ceramide synthase 5 (CERS5) / ceramide synthase 6 (CERS6) / alkaline ceramidase 3 (ACER3) / phospholipid phosphatase 1 (PLPP1) / prosaposin (PSAP) / UDP-glucose ceramide glucosyltransferase (UGCG) signaling axis is significantly activated in the retinas of myopic guinea pigs, suggesting dysregulation of sphingolipid metabolism. These changes were associated with an increased expression of SPHK1 and a shift in receptor expression from S1PR1 to S1PR2, indicating a transition in lipid signaling from a physiological state to a stress-related pathological state. Additionally, the activation of the P62/NRF2/KEAP1 pathway confirmed enhanced oxidative stress in the myopic retina. This study demonstrates that the CERS5/CERS6/ACER3/PLPP1/PSAP/UGCG signaling axis mediates disruption of sphingolipid metabolism and oxidative stress in the myopic guinea pig retina.</p><p><strong>Conclusions: </strong>The present study demonstrates that the CERS5/CERS6/ACER3/PLPP1/PSAP/UGCG signaling axis mediates sphingolipid metabolic dysregulation and oxidative stress in the retinas of myopic guinea pigs. Mechanistically, the abnormal activation of the SPHK1-S1P signaling pathway, the shift in receptors from S1PR1 to S1PR2, and the subsequent activation of the P62/KEAP1/NRF2 pathway collectively led to changes in retinal morphology (such as reduced thickness) and functional impairment. These findings establish a mechanistic link between lipid metabolic imbalance and retinal pathology in myopia offering potential therapeutic targets for preventing retinal damage associated with myopia.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148374602","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":"The PTHR1/PKA/CREB1 axis promotes osteosarcoma progression by activating the PVT1/miR-590-3p/AXIN2 ceRNA network to induce epithelial-mesenchymal transition.","authors":"Jiaming Zhang, Weishang Li, Fei Liu, Hui Zhang, Wei Wang","doi":"10.1186/s13062-026-00849-6","DOIUrl":"10.1186/s13062-026-00849-6","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma (OS) remains a clinically challenging primary bone tumor because of its strong metastatic potential and unsatisfactory outcomes in advanced cases. Parathyroid hormone receptor 1 (PTHR1), a receptor closely associated with bone-related signaling, has not been fully characterized in OS. This study explored whether PTHR1 contributes to OS progression and clarified the downstream regulatory mechanism involved.</p><p><strong>Methods: </strong>Public GEO datasets, clinical OS specimens, and cultured OS cells were used to assess PTHR1 expression. Stable PTHR1 knockdown and overexpression OS cell models were established using lentiviral vectors. Cell growth, apoptosis, motility, invasiveness, EMT, and tumor growth were evaluated by CCK-8, flow cytometry, Transwell, Western blot, and xenograft assays. The underlying mechanism was explored using dual-luciferase reporter assays, ChIP-qPCR, pathway intervention, and rescue experiments.</p><p><strong>Results: </strong>PTHR1 was significantly upregulated in OS tissues and cells. PTHR1 overexpression promoted OS cell proliferation, migration, invasion, EMT, and xenograft tumor growth while suppressing apoptosis, whereas PTHR1 knockdown exerted the opposite effects. Mechanistically, PTHR1 activated the cAMP/PKA/CREB1 pathway, leading to transcriptional upregulation of lncRNA PVT1. PVT1 functioned as a competing endogenous RNA by sponging miR-590-3p, thereby relieving miR-590-3p-mediated repression of AXIN2. AXIN2 further promoted EMT and malignant progression, and AXIN2 overexpression partially reversed the inhibitory effects of PTHR1 knockdown.</p><p><strong>Conclusion: </strong>PTHR1 promotes OS progression by activating the CREB1/PVT1/miR-590-3p/AXIN2 regulatory axis and enhancing EMT. This five-component signaling cascade may provide potential biomarkers and therapeutic targets for OS.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350766","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":"Running exercise alleviates chronic heart failure by promoting cardiomyocyte autophagic flux through the NEAT1-QKI affecting Beclin1/LC3B mRNA stability.","authors":"Ying Zhang, Rui Song, Lei Zhuang, Ying Zhao, Zhuo Chen, Yongjie Wang, Shouling Mi, Jiaxin Liu, Wenlin Tai","doi":"10.1186/s13062-026-00880-7","DOIUrl":"10.1186/s13062-026-00880-7","url":null,"abstract":"<p><p>As the end-stage manifestation of cardiovascular diseases (CVDs), chronic heart failure (CHF) is associated with high morbidity and mortality. Our previous study showed that Running exercise could improve CHF by inducing autophagy, but the underlying mechanisms and applicability remain unclear. This study investigated the roles of NEAT1 and RNA-binding protein Quaking (QKI) in the cardioprotective effects of running exercise initiated during the early stage after abdominal aortic coarctation (AAC) surgery. NEAT1 and QKI were overexpressed in vivo or NEAT1 and QKI were knocked down in vitro. The effects of running exercise on the myocardial damage of CHF rats or Ang II-induced cardiomyocyte apoptosis, autophagic flux, autophagy-related protein expression, and the expression of the PI3K/ AKT pathway by regulating NEAT1 and QKI were assessed using echocardiography, tissue staining, immunofluorescence, western blotting, and confocal microscopy. Furthermore, RNA immunoprecipitation (RIP), RBPmap prediction, actinomycin D (ActD) chase experiments and Dual-luciferase reporter assays were performed to explore the post-transcriptional regulation of autophagy-related genes by QKI. Running exercise reduced myocardial tissue damage in CHF rats and up-regulated the expression of autophagy-related proteins. NEAT1 was up-regulated in the myocardial tissue of CHF rats, and Ang II-damaged cardiomyocytes. Whereas QKI expression showed the opposite trend. Additionally, running exercise inhibited NEAT1 while restoring QKI expression, particularly during weeks 2-3 of exercise intervention. Mechanistically, NEAT1 directly interacted with QKI and negatively regulated its expression. Simultaneously, QKI bound to the 3'untranslated regions (3'-UTRs) of Beclin1 and LC3B mRNA and enhances the stability of Beclin1 and LC3B transcripts, thereby promoting autophagy. Functionally, NEAT1 inhibition or QKI upregulation suppressed the PI3K/AKT/mTOR signaling pathway, and attenuated cardiomyocyte apoptosis under pathological conditions. Collectively, the current findings revealed the regulatory mechanism by which running exercise alleviates CHF, and clarified that running promotes cardiomyocyte autophagy and alleviates CHF through the NEAT1-QKI-Beclin1/LC3B regulatory axis, highlighting a novel mechanism underlying exercise-mediated cardioprotection. Given that exercise intervention was initiated during the early stage following AAC surgery, the observed benefits may include early remodeling-modifying and disease-progression-modifying effects, rather than solely therapeutic effects on established decompensated CHF.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350753","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":"Bovine lactoferrin induces apoptosis and modulates the transcriptomic landscape of HeLa cervical cancer cells.","authors":"Yu Zhao, Rui Liu, Mengtian Li, Mingzhuang Feng, Yuting Bao, Guoxin Chen, Haixia Zhang","doi":"10.1186/s13062-026-00859-4","DOIUrl":"10.1186/s13062-026-00859-4","url":null,"abstract":"<p><p>Cervical cancer (CC) remains a leading malignancy among women worldwide. Current management strategies, including surgery, radiotherapy, chemotherapy, targeted therapy, and prevention, often cause significant adverse effects and demonstrate limited efficacy in advanced disease. Consequently, identifying novel therapeutic strategies and drug targets, particularly low-toxicity, high-specificity natural agents-constitutes a critical research priority. Bovine lactoferrin (bLF), a multifunctional iron-binding glycoprotein, demonstrates therapeutic potential, though its precise molecular mechanisms in cervical cancer are incompletely understood. This study therefore examined the biochemical and transcriptomic alterations in bLF-treated cervical cancer cells to elucidate its mode of action. bLF suppressed HeLa cell viability in a dose-dependent manner and concurrently promoted apoptosis while inhibiting proliferation and migration. The bLF-induced apoptosis appears to arise from a synergistic multi-mechanistic interplay, potentially involving increased intracellular ROS levels, downregulated mitochondrial membrane potential, or modulated expression of autophagy-related proteins to activate autophagic pathways. RNA sequencing identified substantial transcriptomic changes in cancer-associated pathways, notably affecting cell cycle progression, protein transport, apoptotic processes, and the negative regulation of apoptosis. These results substantiate the potent anticancer activity of bLF and highlight its promise as a therapeutic candidate derived from a natural product.</p>","PeriodicalId":9164,"journal":{"name":"Biology Direct","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148326897","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}