Toxicology and applied pharmacology最新文献

{"title":"Human umbilical cord mesenchymal stem cells-derived exosomes restore lung architecture and reduce the susceptibility to asthma of offspring in maternal asthma","authors":"Xin Li ,&nbsp;Yueting Wu ,&nbsp;Min Mao ,&nbsp;Hong Xu ,&nbsp;Caijun Liu ,&nbsp;Yang Liu ,&nbsp;Haiyang Zhang ,&nbsp;Hanmin Liu","doi":"10.1016/j.taap.2026.117746","DOIUrl":"10.1016/j.taap.2026.117746","url":null,"abstract":"<div><div>Asthma is a heterogeneous disorder driven by inflammatory processes that promote pathogenic airway remodeling. Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exos) emerge as a compelling therapeutic candidate to disrupt this disease cycle, with potential intergenerational benefits. In a chronic OVA-induced asthma model using C57BL/6 mice, hucMSC-Exos were delivered via serial injections during the sensitization phase. Airway structural changes were evaluated through histological analysis (H&amp;E staining, Masson's trichrome) and immunofluorescence for key remodeling markers including α-SMA, CC-10, and the proliferation marker Ki67. Molecular pathway analyses specifically targeted the TGF-β/Smad and STAT6 signaling cascades. We found that hucMSC-Exos intervention effectively ameliorated the core pathological features of asthma-induced lung injury and significantly reduced the levels of IL-6 and TNF-α in bronchoalveolar lavage fluid (BALF) in a dose-dependent manner. Additionally, this treatment reduced asthma susceptibility in offspring of mothers with chronic asthma. Compared to the OVA group, the Exos group showed restored CC-10 expression and decreased pulmonary Ki67 levels. In offspring, Hopx (but not SPC) expression was significantly elevated at PN1 and PN4 relative to the OVA group, though these differences lost statistical significance at PN14, consistent with Western blotting (WB) validation. Notably, unlike maternal findings, both CC-10 and Ki67 expression in the lungs of treated offspring were lower than in controls. Furthermore, we observed that OVA-induced activation of PECAM-1, α-SMA, p-ROCK1, and Caspase-8 was attenuated by hucMSC-Exos treatment. RNA sequencing of hucMSC-Exos identified asthma-associated miRNAs, including let7a-5p and miR-125a-5p. The therapeutic efficacy of hucMSC-Exos against asthma was partially abolished when these miRNA inhibitors were applied, underscoring their critical regulatory role in exosome-based asthma therapy. In conclusion, hucMSC-Exos have demonstrated significant efficacy in the treatment of asthma, capable of alleviating airway remodeling and related symptoms. What is particularly important is that they have a cross-generational protective effect, which can reduce the asthma susceptibility of children born to asthmatic mothers. Mechanistically, this benefit may be achieved through the transfer of asthma-related miRNAs. These findings elucidate the key molecular pathways of the cross-generational therapeutic effect mediated by hucMSC-Exos, providing a scientific basis for their clinical application in the management of maternal and offspring asthma.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"509 ","pages":"Article 117746"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of key targets and mechanisms of isoorientin in osteoporosis treatment through integrated network pharmacology and experimental validation","authors":"Jinku Guo ,&nbsp;Jun Xie ,&nbsp;Ankai Xu ,&nbsp;Wei Wang ,&nbsp;Zhiqiang Fu ,&nbsp;Kening Zhou ,&nbsp;Shengkun Hong","doi":"10.1016/j.taap.2026.117733","DOIUrl":"10.1016/j.taap.2026.117733","url":null,"abstract":"<div><div>Osteoporosis is a prevalent metabolic bone disorder characterized by diminished bone mineral density and elevated fracture susceptibility. Although isoorientin (ISO) has emerged as a promising candidate for osteoporosis treatment, its molecular mechanisms remain unclear. In this study, a comprehensive network pharmacology approach was employed to identify potential therapeutic targets by systematically mining the GeneCards and DisGeNET databases. ISO-target interactions were predicted through an integrated analysis of multiple chemoinformatic platforms, including Super-Pred, SwissTargetPrediction, PharmMapper, and ChemMapper. Hub targets were identified via protein-protein interaction (PPI) network analysis, complemented by functional enrichment assessments and molecular docking simulations. The computational findings were experimentally validated using an ovariectomy (OVX)-induced osteoporotic murine model. Network pharmacological analysis revealed 332 putative ISO targets, 45 of which significantly overlapped with 610 osteoporosis-associated targets. Functional enrichment analysis highlighted the critical involvement of these genes in hormone-mediated signaling pathways and cellular responses to nutrient levels. KEGG pathway analysis further implicated these targets in key regulatory cascades, including the MAPK, relaxin signaling, and lipid metabolism-associated atherosclerosis pathways. Molecular docking simulations demonstrated strong binding affinities between ISO and pivotal targets, including MAPK14, TLR4, and ESR1. In vivo validation using OVX mice confirmed ISO's capacity to attenuate bone loss by suppressing osteoclast activation, as evidenced by micro-CT analysis and histomorphometric quantification. Further in vitro studies demonstrated that ISO inhibits RANKL-induced osteoclastogenesis via suppression of the MAPK pathway. This study elucidates the key targets and pathways through which ISO exerts anti-osteoporotic effects, highlighting its therapeutic potential in osteoporosis management.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"509 ","pages":"Article 117733"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics reveal the key role of gut microbiota metabolism in adenine-induced chronic kidney disease","authors":"Yijing Xin ,&nbsp;Hui Ma ,&nbsp;Xiang Li ,&nbsp;Ruiyang Sun ,&nbsp;Luo Fang ,&nbsp;Libin Pan","doi":"10.1016/j.taap.2026.117754","DOIUrl":"10.1016/j.taap.2026.117754","url":null,"abstract":"<div><div>The gut microbiota plays a crucial role in the progression of chronic kidney disease (CKD). The adenine-induced CKD mouse model is widely employed in preclinical research, yet the effects of adenine on the composition and metabolic function of the gut microbiota remain to be elucidated. This study aimed to test the hypothesis that adenine-induced alterations in the structure and function of the gut microbiota are significantly associated with the onset and progression of CKD. To this end, a mouse CKD model was established by alternating feeding with 0.15% and 0.20% adenine for 7 weeks. Multi-omics analysis (untargeted metabolomics, metagenomics, and spatial metabolomics) was performed to compare the adenine-induced CKD group with a standard diet-fed normal control group. Integrated analysis of plasma metabolomics and intestinal content metabolomics identified 94 differentially co-regulated metabolites: among these, indolelactic acid was significantly upregulated, while indole-3-propionic acid was significantly downregulated. The bile acid metabolic pathway also underwent marked perturbations: taurochenodeoxycholic acid and tauro-β-muricholic acid (two taurine-conjugated bile acids) were significantly elevated, whereas nordeoxycholic acid and norcholic acid were notably reduced. Integrated metabolomics-metagenomics analysis further demonstrated that <em>Lactobacillus</em> exhibited a significant positive correlation with a subset of upregulated metabolites (including indolelactic acid), while <em>Taurinivorans muris</em> showed a strong negative correlation with the taurine-conjugated bile acids. Additionally, renal spatial metabolomics revealed that phospholipid metabolic disorders in the adenine-induced CKD group directly contributed to the aggravation of renal inflammatory responses. Collectively, these findings reveal a gut microbiota-metabolite-kidney axis perturbed by adenine, providing novel insights into the pathogenesis of CKD and potential targets for metabolic intervention.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"509 ","pages":"Article 117754"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term exposure to Di(2-ethylhexyl) phthalate induced uterine histopathologic alterations in female mice","authors":"Je Yeon Lee ,&nbsp;Jin Su Kim ,&nbsp;Javeria Zaheer ,&nbsp;Sun Hee Chang ,&nbsp;Kyungho Choi ,&nbsp;Dong Won Hwang ,&nbsp;Jisun Lee ,&nbsp;Young Ah. Kim ,&nbsp;Yoon Hee Cho","doi":"10.1016/j.taap.2026.117738","DOIUrl":"10.1016/j.taap.2026.117738","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the effects of long-term Di(2-ethylhexyl) phthalate (DEHP) exposure on the female reproductive system, employing different dosages and durations of exposure.</div></div><div><h3>Methods</h3><div>Pregnant female CD-1 mice (F0) were orally exposed to DEHP at doses of 0, 100, and 500 mg/kg/day during gestation. Following birth, the female offspring (F1) were allocated into three groups as F0 mice. Both F0 and F1 mice were consequently subjected to ongoing DEHP exposure until they were sacrificed. Body weight, anogenital distance, anogenital index (AGI), and histopathologic outcomes of the uterus were examined at 21 and 35 weeks for F0 mice and at 10 and 24 weeks for F1 mice.</div></div><div><h3>Results</h3><div>Both low and high DEHP exposures significantly decreased body weight in F0 at 21 weeks and in F1 at 10 and 24 weeks, while AGI was not significantly changed in response to DEHP exposure in both F0 and F1 mice. DEHP exposure induced endometrial stromal fibrosis, endometrial hyperplasia, and myometrial atrophy in the uterus of F1mice, while cystic hyperplasia and endometrial stromal sarcoma (ESS) were seen in the F0 after DEHP exposure at 35 weeks.</div></div><div><h3>Conclusions</h3><div>Long-term Exposure to DEHP significantly reduced body weight and induced pathological alterations in the uterus of both F0 and F1 mice. Dams exposed to high doses of DEHP developed ESS, suggesting that DEHP may have carcinogenic potential in the uterus. However, further research is necessary to confirm this finding.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"509 ","pages":"Article 117738"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146094287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting aryl hydrocarbon receptor signaling attenuates hypertension programmed by maternal Di-2-ethylhexylphthalate exposure","authors":"Chien-Ning Hsu ,&nbsp;Hsi-Yun Liu ,&nbsp;Chih-Yao Hou ,&nbsp;Yu-Wei Chen ,&nbsp;Guo-Ping Chang-Chien ,&nbsp;Shu-Fen Lin ,&nbsp;You-Lin Tain","doi":"10.1016/j.taap.2026.117751","DOIUrl":"10.1016/j.taap.2026.117751","url":null,"abstract":"<div><div>Adverse early-life conditions can predispose offspring to long-term health risks. Phthalate exposure, particularly to di-2-ethylhexylphthalate (DEHP), during pregnancy and lactation has been implicated in programming offspring hypertension via aryl hydrocarbon receptor (AHR) activation, renin–angiotensin system (RAS) dysregulation, nitric oxide (NO) deficiency, and gut microbiota alterations. Using a maternal DEHP exposure rat model, we investigated whether blockade of AHR signaling—directly with the AHR inhibitor CH223191 or indirectly with the indoleamine 2,3-dioxygenase (IDO) inhibitor INCN-024360—prevents offspring hypertension. Pregnant rats received DEHP (10 mg/kg/day) by oral gavage throughout pregnancy and lactation, with or without CH223191 (10 mg/kg/day) or INCN-024360 (50 mg/kg/day). Maternal DEHP exposure induced sustained systolic hypertension in adult male offspring, accompanied by upregulation of renal AHR signaling and RAS components. This effect was attenuated by the IDO inhibitor (approximately 10 mmHg reduction in systolic blood pressure) and more effectively by the AHR inhibitor (approximately 16 mmHg reduction). Mechanistically, the IDO inhibitor reduced asymmetric dimethylarginine (an endogenous nitric oxide synthase inhibitor), renin, and CYP1A1 expression while increasing angiotensin-converting enzyme 2 (ACE2), whereas the AHR inhibitor suppressed renal AHR, renin, angiotensin-converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R) expression and significantly enhanced short-chain fatty acid receptor expression. Both interventions were associated with distinct alterations in gut microbiota composition. These findings identify AHR as a key mechanistic link between early-life environmental phthalate exposure and programmed hypertension and support early-life AHR blockade as a potential preventive strategy for offspring cardiometabolic–kidney risk.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"509 ","pages":"Article 117751"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146126493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of Florfenicol against DSS-induced ulcerative colitis by inhibiting cellular senescence and reducing inflammation via the AMPK signaling pathway","authors":"Wei Lian ,&nbsp;Qinran Hou ,&nbsp;Jinchan Liu ,&nbsp;Cui Chen ,&nbsp;Zhiwei Wang ,&nbsp;Shujia Song ,&nbsp;Min Zhou ,&nbsp;Fei He ,&nbsp;Xiaobo Wang","doi":"10.1016/j.taap.2026.117755","DOIUrl":"10.1016/j.taap.2026.117755","url":null,"abstract":"<div><div>Ulcerative colitis (UC) is a chronic inflammatory disorder of unclear etiology. Senescence-related signs have been detected in the intestinal tissue of UC patients. Senescence is known to amplify the body's inflammatory response, potentially accelerating UC progression. However, the precise relationship between UC and senescence remains elusive. Florfenicol (FLO) is a broad-spectrum antibiotic characterized by potent antibacterial activity and low toxicity. To date, no studies have reported on the potential of FLO in mitigating intestinal damage and senescence. In this study, we discovered that DSS can induce cellular and colon tissue senescence. Interestingly, we found that FLO can effectively counteract DSS-induced cellular senescence and alleviate DSS-induced ulcerative colitis and colon senescence in C57BL/6j mice. Moreover, we provide strong evidence that FLO effectively inhibits colon senescence and treats DSS-induced colitis by activating the AMPK signaling pathway. Consequently, FLO's anti-senescence properties may represent a novel therapeutic approach for UC management.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"509 ","pages":"Article 117755"},"PeriodicalIF":3.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of drug transporters in human allogenic transplanted kidneys in acute rejection","authors":"J. Łapczuk-Romańska ,&nbsp;J. Hybiak ,&nbsp;K. Piotrowska ,&nbsp;M. Marchelek-Myśliwiec ,&nbsp;A. Wilk ,&nbsp;M. Słojewski ,&nbsp;E. Urasińska ,&nbsp;M. Droździk","doi":"10.1016/j.taap.2026.117735","DOIUrl":"10.1016/j.taap.2026.117735","url":null,"abstract":"<div><div>Kidney drug transporters, primarily located in the basolateral and apical membranes of proximal tubule cells, play a key role in the secretion and reabsorption of drugs and endogenous compounds. Recent studies have demonstrated that kidney diseases can alter transporter expression; however, the expression of these transporters in human transplanted kidneys, with and without rejection, remains unclear. Therefore, the aim of this study was to investigate the mRNA expression (qRT-PCR) and immunolocalization (via immunohistochemistry) of key ABC (ATP-binding cassette) (<em>n</em> = 14) and SLC (solute carriers) (<em>n</em> = 33) transporters in glomeruli and proximal tubule cells from human normal kidney (CTRL, <em>n</em> = 8), non-rejected transplanted kidney (AR-0, <em>n</em> = 7) and transplanted kidney under rejection process (AR-I, n = 8) from patients receiving immunosuppressive drugs. Our study shows that mRNA expression level of <em>SLC22A4</em>, <em>SLC22A6</em>, <em>SLC22A7</em>, <em>SLC22A8</em>, <em>SLC28A1</em>, <em>SLC47A1</em>, <em>SLC22A11</em>, <em>SLC15A2</em>, <em>SLC16A1</em>, <em>ABCC2</em>, <em>ABCC5</em> and <em>ABCC6</em> are statistically significantly downregulated, while <em>SLC22A2</em>, <em>SLCO4A1</em> and <em>ABCB1</em> are statistically upregulated in proximal tubule cells from rejected transplanted kidneys compared to controls. Immunohistochemistry revealed that OAT1, OAT3, OCT2, MATE1, MRP2, MRP6 and P-gp were primarily expressed in proximal tubule cells, with significantly lower protein expression of OAT1, OAT3, P-gp in AR-I and AR-0 biopsies compared to CTRL sections. These preliminary data suggest that the expression profile of kidney transporters may be altered in transplanted kidneys from patients treated with immunosuppressive drugs.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"508 ","pages":"Article 117735"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Elucidating the distinctive regulatory effects and mechanisms of active compounds in Salvia miltiorrhiza Bunge via network pharmacology: Unveiling their roles in the modulation of platelet activation and thrombus formation” [Toxicology and Applied Pharmacology volume 484, March 2024, 116871]","authors":"Ying Zhang ,&nbsp;Guang Xin ,&nbsp;Qilong Zhou ,&nbsp;Xiuxian Yu,&nbsp;Lijuan Feng,&nbsp;Ao Wen,&nbsp;Kun Zhang,&nbsp;Tingyu Wen,&nbsp;Xiaoli Zhou,&nbsp;Qiuling Wu,&nbsp;Hongchen He,&nbsp;Wen Huang","doi":"10.1016/j.taap.2025.117668","DOIUrl":"10.1016/j.taap.2025.117668","url":null,"abstract":"","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"508 ","pages":"Article 117668"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EP300 promotes cervical cancer progression through a Wnt/β-catenin–dependent HIF-1α signaling axis","authors":"Yue Zhang ,&nbsp;Yongxin Zhang ,&nbsp;Ke Wang","doi":"10.1016/j.taap.2026.117718","DOIUrl":"10.1016/j.taap.2026.117718","url":null,"abstract":"<div><div>This study aimed to investigate the role of EP300 in cervical cancer progression, focusing on its functional effects related to pyroptosis under Wnt/β-catenin–dependent conditions. In SiHa and HeLa cells, EP300 was silenced using lentiviral-mediated knockdown under hypoxic conditions, and subsequent changes in cell proliferation, inflammatory cytokine secretion, and pyroptosis-related protein expression were evaluated. A subcutaneous HeLa xenograft model was established to examine the in vivo effects. Hypoxia-inducible factor 1-alpha (HIF-1α) expression was also analyzed. The results showed that hypoxia significantly increased the expression levels of EP300, β-catenin, and HIF-1α. EP300 knockdown was associated with decreased Wnt/β-catenin signaling and, under Wnt/β-catenin–dependent conditions, resulted in reduced HIF-1α expression and enhanced pyroptosis-related phenotypes. Activation of Wnt/β-catenin signaling by HLY78 partially reversed these alterations. In vivo, silencing EP300 suppressed tumor growth, decreased Ki67 expression, and increased pyroptosis markers, while activation of the Wnt/β-catenin pathway partially restored proliferation and reduced pyroptosis. Taken together, loss of EP300 function impedes cervical cancer progression by affecting the Wnt/β-catenin signaling axis and inducing concomitant changes in HIF-1α expression. This study provides functional evidence supporting the role of EP300 in the progression of cervical cancer under hypoxic conditions.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"508 ","pages":"Article 117718"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146019802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-treatment with sevoflurane alleviates hypoxia-reoxygenation-induced cardiomyocyte damage through PAX8-AS1-targeted miR-145-5p","authors":"Yan Xu ,&nbsp;Xianglong Di ,&nbsp;Ye Cai ,&nbsp;Shilin Hu","doi":"10.1016/j.taap.2026.117705","DOIUrl":"10.1016/j.taap.2026.117705","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the regulatory role of the lncRNA PAX8-AS1/miR-145-5p axis in the mitigation of hypoxia-induced damage to oxygenated myocardial cells by sevoflurane (Sev).</div></div><div><h3>Methods</h3><div>A hypoxic-reoxygenation (HR) in vitro model was established by subjecting cells to 4 h of hypoxia followed by 24 h of aeration. An in vivo MI/RI model was established via ischemia-reperfusion. Gene expression was detected using RT-qPCR. Cell proliferation and apoptosis was assessed using CCK8 and flow cytometry. Expression of myocardial injury markers, inflammatory factors, and oxidative stress markers was measured via ELISA. The targeted relationship between genes was validated using dual luciferase reporter assays and RNA immunoprecipitation.</div></div><div><h3>Results</h3><div>Sev can resist the upregulation of PAX8-AS1 and downregulation of miR-145-5p in HR cardiomyocytes or MI/RI myocardial tissue. PAX8-AS1 overexpression attenuates Sev-induced suppression of cardiomyocyte proliferation and apoptosis inhibition following injury Sev pre-treatment reduced the expression of myocardial cell damage markers, inflammatory factors, and oxidative stress markers, but these markers increased after PAX8-AS1 overexpression and decreased after miR-145-5p analogue transfection.</div></div><div><h3>Conclusion</h3><div>Sev can alleviate HR-induced myocardial cell injury by inhibiting PAX8-AS1 and promoting miR-145-5p expression.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"508 ","pages":"Article 117705"},"PeriodicalIF":3.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}