Life sciences最新文献

{"title":"Ambroxol alleviates hippocampus injury after BRIR through suppression of the IRE1α/TRAF2 signaling pathway","authors":"Noha F. Elshazly ,&nbsp;Marwa E. Elsherbiny ,&nbsp;Azza S. Awad ,&nbsp;Ahmed F. Mohamed ,&nbsp;Nesrine S. El Sayed ,&nbsp;Yasmin S. Mohamed","doi":"10.1016/j.lfs.2025.123875","DOIUrl":"10.1016/j.lfs.2025.123875","url":null,"abstract":"<div><div>Acute kidney injury(AKI) is commonly linked to cognitive and neurological impairments. The study aims to investigate the relationship between bilateral renal ischemia reperfusion (BRIR) and hippocampal damage and evaluates the effects of ambroxol against BRIR-induced hippocampal injury and neuroinflammation.</div><div>Thirty adult male rats were randomly assigned to three groups: control (laparotomy without renal occlusion), BRIR model (bilateral renal ischemia was induced by clamping both renal pedicles for 60 min, followed by 3 days of reperfusion), and ambroxol treatment (70 mg/kg, I.P., once daily during reperfusion). Hippocampal injury was assessed through biochemical (ELISA, Western blot, and PCR), histopathological, and behavioral analysis.</div><div>Compared to the control group, BRIR significantly increased serum Cr, BUN, and renal injury markers (MDA, MCP-1, KIM-1) (<em>p</em> &lt; 0.0001), along with notable renal tubular degeneration and necrosis. In the hippocampus, BRIR elevated inflammatory markers (NF-κB, TNF-α, MCP-1, IL-1β, G-CSF), reduced antioxidants (SOD, GSH), and altered apoptotic markers (increased Bax, decreased Bcl-2) (all p &lt; 0.0001). Behavioral tests revealed impairments in learning, memory, and locomotor activity. Histology showed degeneration of pyramidal neurons in the CA1 region.</div><div>Ambroxol treatment significantly ameliorated these effects, preserving CA1 neuronal structure, restoring blood-brain barrier (BBB) integrity (via Occludin and Claudin-5), enhancing BDNF and IBA-1 expression, and modulating MAPK/NF-κB and IRE1α/TRAF2 signaling pathways.</div><div>Finally, BRIR induces both renal and hippocampal injury. Ambroxol mitigates this damage by reducing oxidative stress and inflammation, repairing BBB components, and regulating endoplasmic reticulum stress pathways (ERS).</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"379 ","pages":"Article 123875"},"PeriodicalIF":5.2,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144670977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted bilirubin metabolism and gut microbiome dysregulation: A link to cardio-renal-hepatic-metabolic health in obstructive sleep apnea.","authors":"Mohit, Jayhind Maury, Jyot Bajpai, Sheetal Verma","doi":"10.1016/j.lfs.2025.123872","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.123872","url":null,"abstract":"<p><p>Obstructive Sleep Apnea (OSA) is no longer viewed solely as a sleep related respiratory disorder but as a systemic disease intricately linked to Cardio-Renal-Hepatic-Metabolic (CRHM) axis. Chronic intermittent hypoxia (CIH), oxidative stress, and sympathetic overactivation in OSA lead to endothelial dysfunction, inflammation, and metabolic imbalance. Emerging evidence highlights the gut microbiome as a key mediator in OSA-related metabolic disturbances, where hypoxia-induced dysbiosis reduces microbial diversity and promotes systemic inflammation via endotoxemia and toll-like receptor (TLR) activation. Bilirubin metabolism, traditionally associated with jaundice, has gained recognition for its antioxidant, anti-inflammatory, and metabolic regulatory roles. The gut microbiota, particularly BilR-expressing bacteria, plays a crucial role in bilirubin catabolism, converting it into urobilinogen and urobilin. Disruptions in this pathway may contribute to hypobilirubinemia, exacerbating metabolic dysfunction. Urobilin, a downstream metabolite, has emerged as a potential biomarker for OSA severity and metabolic impairment, reflecting gut-liver axis dysregulation. Therapeutic strategies should be focused on targeting bilirubin-microbiome-metabolism axis including microbiome modulation, dietary antioxidants, and novel interventions such as BilR inhibitors to preserve bilirubin's protective effects. We promote future research should focus on multi-omics approaches to unravel these complex interactions, paving the way for precision medicine in OSA associated metabolic diseases.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123872"},"PeriodicalIF":5.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking necroptosis with liver aging and chronic inflammation in hepatic pathology.","authors":"Bhagyalakshmi Nair, Anjana Menon, Marva Abdul Khader, Gautam Sethi, Lekshmi R Nath","doi":"10.1016/j.lfs.2025.123871","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.123871","url":null,"abstract":"<p><p>Necroptosis, a regulated form of cell death distinct from apoptosis and necrosis, is increasingly recognized for its role in chronic inflammation and tissue damage within the liver. It is mainly associated with upregulation of necroptotic factors like phosphorylated MLKL (Mixed lineage kinase domain-like protein), Receptor Interacting Kinase 1 (RIPK1), and Receptor Interacting Kinase 3 (RIPK3). The regulation of necroptotic signaling becomes increasingly impaired as liver age progresses, promoting a pro-inflammatory hepatic environment that contributes to the onset and development of age-related liver pathologies such as steatosis, fibrosis, and hepatocellular carcinoma (HCC). The chronic low-grade inflammation associated with aging, often termed \"inflammaging,\" further amplifies necroptosis-mediated damage, establishing a vicious cycle of cell death and inflammatory signaling. Thus, understanding the mechanisms of necroptosis in the aging liver highlights new potential therapeutic targets to alleviate liver diseases. Current therapeutic strategies include the development of small molecule inhibitors that target crucial components of the necroptotic pathway, such as inhibitors of RIPK1 (e.g., Necrostatin-1), RIPK3, and MLKL blockers. Limited articles are seen on aspects of the liver aging and disease progression, necroptosis and liver disorders. No reviews are available relating the three aspects together as the role of necroptosis in liver aging with respect to chronic liver disease. The present review delves into the complex role of necroptosis in liver aging and chronic liver diseases, detailing the underlying mechanisms and the latest treatment approaches, and underscores the critical need for extensive research in the area.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123871"},"PeriodicalIF":5.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTEN-L dephosphorylates Parkin and Ub Ser65 to aggravate mitophagy dysfunction in prion disease cell models.","authors":"Xueyuan Li, Jie Li, Fengting Gou, Yuexin Dai, Mengyang Zhao, Dongdong Wang, Zhixin Sun, Pei Wen, Jingjing Wang, Qing Fan, Tianying Ma, Xiaoyu Wang, Deming Zhao, Lifeng Yang","doi":"10.1016/j.lfs.2025.123860","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.123860","url":null,"abstract":"<p><p>PINK1-Parkin-dependent mitophagy dysfunction is a critical contributor to the accumulation of damaged mitochondria in prion disease, leading to impaired autophagy and neurons apoptosis. However, the specific molecular mechanisms underlying mitophagy dysfunction in prion disease remain unclear. Phosphorylation of Parkin at Ser65 (pSer65-Parkin) is a key determinant for the initiation of PINK1-Parkin-mediated mitophagy. In the prion disease cell model, we observed a significant reduction in pSer65-Parkin and pSer65-Ub expression. PTEN-L, an isoform of the PTEN family, has been implicated in the regulation of PINK1-Parkin-mediated mitophagy. Here, we demonstrate that PTEN-L acts as a phosphatase for Parkin and Ub, exerting a regulatory role in mitophagy in prion disease. We found that PTEN-L expression and mitochondrial translocation were elevated in PrP^106-126-treated SH-SY5Y cells. Increased PTEN-L dephosphorylates pSer65-Parkin pSer65-Ub, leading to reduced pSer65-Parkin and pSer65-Ub, then impaired mitophagy initiation. Overexpression of PTEN-L in SH-SY5Y cells mimicked the effects of PrP^106-126 treatment, reducing Parkin mitochondrial translocation and pSer65-Parkin levels. PTEN-L knockout alleviates these deficits, restoring Parkin and ubiquitin recruitment to mitochondria and increasing Ser65 phosphorylation in prion disease cell models. Furthermore, PTEN-L deficiency mitigated mitophagy dysfunction and apoptosis in neurons exposed by PrP^106-126. These findings suggest that PrP^106-126 upregulates PTEN-L, enhancing dephosphorylation of pSer65-Parkin and pSer65-Ub, thereby impairing mitophagy initiation. Targeting PTEN-L expression or activity may represent a novel therapeutic strategy for prion disease.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123860"},"PeriodicalIF":5.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The NADPH oxidase NOX2 mediates isoflurane-induced lung cell injury in vitro and in vivo.","authors":"Pedro Alves Machado-Junior, Maria Laura da Cruz Castro, Wellington Carvalho Malta, Ramony Gonzaga Vieira, Vitória Louise Teixeira E Silva, Jorge Lucas Nascimento Souza, Getúlio Mota E Silva-Junior, Breno de Mello Silva, Laser Antônio Machado de Oliveira, Silvia Paula-Gomes, André Talvani, Daniela Caldeira Costa, Remo Castro Russo, Frank Silva Bezerra","doi":"10.1016/j.lfs.2025.123861","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.123861","url":null,"abstract":"<p><strong>Background: </strong>Isoflurane is a widely used inhaled anesthetic, but its administration has been linked to increased reactive oxygen species (ROS) and pro-inflammatory cytokines. NADPH oxidases are suggested as the primary ROS source. This study aimed to evaluate the mechanisms by which isoflurane induces ROS and reactive nitrogen species (RNS) in vitro in human and murine cells and in vivo using wild-type (WT) and NOX2 knockout (NOX2^-/-) mice.</p><p><strong>Methods: </strong>J774A.1 macrophages and MRC-5 fibroblast were exposed to 2 % isoflurane or ambient air for 3 or 6 h. In vivo, 28 mice (WT and NOX2^-/-) were divided into four groups (n = 7/group) and exposed to 2 % isoflurane for 3 h.</p><p><strong>Results: </strong>Isoflurane significantly altered cell metabolism and increased ROS production. In vivo, ISOWT (12.42 ± 4.44); (10.19 ± 3.44) mice showed greater leukocyte and macrophage influx in bronchoalveolar lavage fluid (BALF) than WT controls (p < 0.05). Superoxide dismutase, catalase activity, and the expression of iNOS, IL-1β, NF-κB, and Nrf2 were significantly elevated in ISOWT mice compared to the control (p < 0.0411). Levels of CCL2, IL-1β, and IL-6 also increased in ISOWT compared to WT (p < 0.0391). However, no significant differences were found between NOX2^-/-isoflurane-exposed mice and their controls.</p><p><strong>Conclusion: </strong>These findings demonstrate that the NADPH oxidase NOX2 plays a key role in oxidative stress and inflammation in the lungs of healthy mice exposed to isoflurane.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123861"},"PeriodicalIF":5.2,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tamsulosin regulates antifibrotic effects in thioacetamide-induced liver damage and ameliorates portal hypertension","authors":"Mariana Yazmin Medina-Pizaño ,&nbsp;Leonel Alejandro Gómez Llanos-Angulo ,&nbsp;Javier Ventura-Juárez ,&nbsp;Andrés Quintanar-Stephano ,&nbsp;Odila Saucedo-Cárdenas ,&nbsp;Roberto Montes de Oca-Luna ,&nbsp;María de Jesús Loera-Arias ,&nbsp;Martín Humberto Muñoz-Ortega","doi":"10.1016/j.lfs.2025.123859","DOIUrl":"10.1016/j.lfs.2025.123859","url":null,"abstract":"<div><div>Liver cirrhosis is one of the leading causes of mortality worldwide, with portal hypertension being the initial sign of decompensation. Recent studies in animal models of liver fibrosis have proposed various treatments that reduce stellate cell activity, with adrenergic antagonists having an impact. This study evaluated the effect of tamsulosin as a potential treatment to reduce fibrosis and portal hypertension in a rat model of cirrhosis, without affecting the regenerative capacity of hepatocytes. <em>In vitro</em>, viability, morphological, and molecular techniques analyzed the challenge between the activation of hepatic LX2 stellate cells with noradrenaline and the possible reduction of this activation with tamsulosin and carvedilol treatments. <em>In vivo,</em> male Wistar rats were intoxicated with thioacetamide for 4 weeks to induce liver fibrosis, then treated orally with carvedilol and tamsulosin for 4 weeks. Hepatic function, histological, and molecular evaluation were made. <em>In-situ</em> perfusion was used to evaluate portal pressure. Norepinephrine (NE) induced increasing collagen-1 and α-SMA genes expression, while reducing PPAR-γ. Tamsulosin inhibited NE-induced proliferation, migration, and activation of HSCs, otherwise carvedilol showed partial effects. <em>In vivo,</em> tamsulosin treatment improved liver fibrosis, reduced collagen I levels, and normalized liver function. Additionally, in a thioacetamide-induced cirrhosis rat model, tamsulosin treatment prevented development of portal hypertension or arterial hypotension. Our results demonstrate that NE promotes hepatic stellate cell activation and fibrosis, while tamsulosin and carvedilol effectively reduce these effects <em>in vitro</em> and <em>in vivo,</em> without affecting the regenerative capacity of hepatocytes. In addition, the treatment also alleviates portal hypertension without causing systemic hypotension.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"379 ","pages":"Article 123859"},"PeriodicalIF":5.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time-restricted feeding attenuates hepatic inflammation and enhances muscular endurance of biliary cirrhotic rats","authors":"Hui-Chun Huang ,&nbsp;Chien-Lin Chang ,&nbsp;Shao-Jung Hsu ,&nbsp;Ching-Chih Chang ,&nbsp;Chiao-Lin Chuang ,&nbsp;Jiing-Chyuan Luo ,&nbsp;Ming-Chih Hou ,&nbsp;Fa-Yauh Lee","doi":"10.1016/j.lfs.2025.123856","DOIUrl":"10.1016/j.lfs.2025.123856","url":null,"abstract":"<div><h3>Aims</h3><div>Time-restricted feeding (TRF) influences the metabolism of various nutrients. However, the impact of TRF on liver cirrhosis, sarcopenia and hepatic encephalopathy remains unknown. Herein, we evaluate the effects of TRF on common bile duct ligation (BDL)-induced cirrhotic rats.</div></div><div><h3>Materials and methods</h3><div>A 14-day TRF treatment was conducted from the 15th to 28th day post BDL operation. Then the body weight, muscular change, hemodynamics, biochemistry data, hepatic and muscular histology and protein expressions of various molecules were examined in BDL rats. On the other hand, the effects of TRF treatment on the portal-systemic collaterals, motor activities, and muscular strength and endurance were measured.</div></div><div><h3>Key findings</h3><div>TRF treatment significantly decreased body weight without adverse effects in BDL rats. Meanwhile, TRF treatment reduced cardiac index and portal venous flow, attenuated hepatic inflammation and decreased insulin resistance, reduced oxidized low-density lipoprotein and decreased intrahepatic fat accumulation. The circumference of gastrocnemius muscle did not change despite a significant body weight reduction after TRF. Furthermore, rats' endurance of exercise enhanced after TRF. A 14-day TRF treatment neither ameliorated liver fibrosis nor improved motor activities of BDL rats. In addition, the severity of portal-systemic shunts was not influenced by TRF.</div></div><div><h3>Significance</h3><div>In BDL-induced cirrhotic rats, a 14-day TRF treatment alters hemodynamics, attenuates hepatic inflammation and improves metabolic derangement. Additionally, TRF treatment increases muscular endurance without influencing the circumference of gastrocnemius muscle. However, TRF treatment does not affect liver fibrosis and hepatic encephalopathy.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"379 ","pages":"Article 123856"},"PeriodicalIF":5.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homoyessotoxin alleviates inflammatory responses by regulating the TLR4/MyD88/NFκB and Nrf2/HO-1 pathways","authors":"Xinyu Gao ,&nbsp;Kuilin Chen ,&nbsp;Hanyi Wang ,&nbsp;Yifan Guo ,&nbsp;Ni Zhang ,&nbsp;Wenhui Su ,&nbsp;Jin Zhou ,&nbsp;Weidong Xie","doi":"10.1016/j.lfs.2025.123858","DOIUrl":"10.1016/j.lfs.2025.123858","url":null,"abstract":"<div><h3>Aims</h3><div>To explore the anti-inflammatory mechanisms of homoyessotoxin (hYTXs), a marine polyether toxin, by investigating its effects on key inflammatory signaling pathways and validating its therapeutic potential in vitro and in vivo.</div></div><div><h3>Materials and methods</h3><div>Inflammation-related targets of hYTXs were predicted via network pharmacology, followed by molecular docking and dynamics simulations. LPS-stimulated RAW264.7 macrophages were used to assess cytokine release, ROS production, and protein expression. Anti-inflammatory efficacy was further verified in mouse models of LPS-induced systemic inflammation and xylene-induced ear edema.</div></div><div><h3>Key findings</h3><div>hYTXs exhibited strong binding affinities with inflammatory targets such as TLR4 and NFκB1. In vitro, it significantly reduced IL-6 and TNF-α secretion, suppressed iNOS and COX-2 expression, inhibited LPS-TLR4 interaction and NFκB activation, and activated the Nrf2/HO-1 antioxidant pathway. These effects were partly reversed by HO-1 inhibitor ZnPP IX. In vivo, hYTXs alleviated lung edema, reduced systemic cytokine levels, attenuated immune cell infiltration, and restored vascular integrity. It also reduced swelling and inflammatory protein expression in xylene-induced ear inflammation.</div></div><div><h3>Significance</h3><div>This study is the first to demonstrate the anti-inflammatory potential of hYTXs through dual regulation of the TLR4/MyD88/NFκB and Nrf2/HO-1 pathways. These findings suggest hYTXs as a promising marine-derived compound for treating inflammatory disorders. Further studies are warranted to elucidate its molecular targets and clinical applicability in conditions such as sepsis and sterile inflammation.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"379 ","pages":"Article 123858"},"PeriodicalIF":5.2,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144649859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial p32-mediated regulation of p-TBK1 affects the radiosensitivity of colorectal cancer.","authors":"Yanjin Wu, Haitao Zhou, Jiahui Meng, Wenyue Zhao, Xiaotong Zhao, Yujia Hou, Qin Wang, Feng Wang, Qiang Liu, Yang Liu","doi":"10.1016/j.lfs.2025.123854","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.123854","url":null,"abstract":"<p><strong>Purpose: </strong>Many colorectal cancer (CRC) patients respond poorly to radiotherapy due to radioresistance. Understanding the molecular mechanisms underlying this resistance is crucial. It was demonstrated that p32, a mitochondrial protein translation regulator, is related to cancer development. However, its specific function and mechanism in CRC, has not yet been investigated. This study aims to explore the role of p32 in CRC and its impact on radiotherapy sensitivity.</p><p><strong>Methods: </strong>Cell viability was evaluated by MTT and EdU assay. Mitochondrial DNA (mtDNA) leakage was quantified by RT-qPCR. Radiosensitivity was indicated by cellular phosphorylation of H2AX (γH2AX) foci, phosphorylation of ataxia telangiectasia mutated (p-ATM) and phosphorylation of checkpoint kinase 2 (p-CHK2) levels, as well as by mice tumor model subjected to radiotherapy. Moreover, histological and transcriptomic analysis of p32 expression were performed in CRC patients.</p><p><strong>Results: </strong>In p32-KO cells, we observed reduced cell viability, damaged mitochondria, mtDNA leakage, and increased radiosensitivity. Furthermore, depletion of p32 induced the DNA damage response (DDR) by activating cytoplasmic DNA sensing cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-TANK-binding kinase 1 (TBK1), which was reversed by p32/TBK1 double knockout. Depletion of p32 also induced the mitochondrial fragmentation, induced mtDNA leakage through the mitochondrial permeability transition pore (mPTP), effects that could be mitigated by Mdivi-1 or Cyclosporin A (CsA).</p><p><strong>Conclusions: </strong>Our study demonstrates that inhibiting p32 in CRC enhances radiosensitivity by causing mitochondrial dysfunction, increasing mitochondrial fission, inducing mtDNA leakage and activating the cGAS-STING-TBK1 pathway. These findings provide a potential therapeutic target for overcoming radioresistance in CRC.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123854"},"PeriodicalIF":5.2,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic application of mesenchymal stem cells in endometriosis","authors":"C. Varela-Pombo ,&nbsp;B. López-Viñas ,&nbsp;S. Quintana Tustain ,&nbsp;C. Guillán Maquieira ,&nbsp;J. Mateos ,&nbsp;J. Fafián-Labora ,&nbsp;M.C. Arufe","doi":"10.1016/j.lfs.2025.123851","DOIUrl":"10.1016/j.lfs.2025.123851","url":null,"abstract":"<div><div>Endometriosis is a complex gynaecological condition that remains difficult to treat, largely because of delayed diagnosis and the wide variability of its symptoms. Mesenchymal stem cell (MSC) therapies and their derivatives, such as modified extracellular vesicles and conditioned media, have emerged as promising therapeutic strategies, acting directly on the proliferative and inflammatory processes central to the disease. Understanding current advances in experimental treatments involving stem cells and their derivatives is therefore of critical importance. A comprehensive review of MSC-based therapies in endometriosis is essential not only to consolidate existing knowledge and identify research gaps but also to evaluate the safety and efficacy of these approaches. Such a review may contribute to the development of standardised protocols and regulatory frameworks, supporting the progression from experimental models to clinical application. Ultimately, this could accelerate the development of innovative, disease-modifying therapies, offering hope to those affected by the debilitating impact of endometriosis. This review primarily explores the molecular mechanisms underlying inflammation in endometriosis and highlights experimental therapies involving MSCs and their derivatives. Particular focus is given to the therapeutic potential of MSCs in both cell- and gene-based interventions, with an emphasis on the molecular pathways involved in tissue repair and healing.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"379 ","pages":"Article 123851"},"PeriodicalIF":5.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}