Journal of Molecular Histology最新文献

{"title":"Exosomal cytokine profile on lipopolysaccharide-induced acute lung injury in mice","authors":"Jie Liang,&nbsp;Yaowei He,&nbsp;Xiaoxuan Chen,&nbsp;Lizhen Wang,&nbsp;Shaoxi Cai","doi":"10.1007/s10735-025-10610-4","DOIUrl":"10.1007/s10735-025-10610-4","url":null,"abstract":"<div><p>Acute lung injury (ALI) is a severe inflammatory condition marked by alveolar damage and cytokine dysregulation. Exosomes, as carriers of bioactive molecules, regulate immune responses through intercellular communication. However, the cytokine profile of serum-derived exosomes during ALI remains unclear, and their functional role in modulating inflammation is poorly defined. A murine model of ALI was established via intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg), and samples were collected at 2 h and 8 h post-injection. Lung injury severity was assessed using hematoxylin and eosin staining and lung W/D weight ratio. Serum-derived exosomes were isolated using the ExoQuick precipitation method and characterized by transmission electron microscopy and western blotting. Cytokine and chemokine profiles were quantified using a 32-plex Luminex xMAP assay. Exosome-mediated immune modulation was evaluated through a scratch migration assay in RAW264.7 macrophages. LPS treatment led to increased pulmonary edema and histopathological damage, which were more pronounced at 8 h. A total of 14 cytokines in the serum, including IL-6, TNF-α, and MCP-1, were significantly elevated at either 2–8 h compared to the control group. However, chemokines such as IP-10, G-CSF, and MIP-1β were markedly upregulated in serum-derived exosomes from ALI mice. Functional assays demonstrated that exosomes from ALI mice significantly enhanced the migratory capacity of RAW264.7 macrophages. This study demonstrates that serum-derived exosomes from ALI mice are enriched in specific chemokines and promote macrophage migration in vitro. These findings suggest that exosomes may participate in inflammatory cell recruitment during ALI and hold potential as biomarkers or modulators in the inflammatory response.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the persistent renal impact of intrauterine growth restriction and catch-up growth: integrating morphological insights with metabolomic profiling","authors":"Mukaddes Esrefoğlu,&nbsp;Fatmanur Koktasoglu,&nbsp;Nihan Bayindir,&nbsp;Fatma Bedia Karakaya Cimen,&nbsp;Seda Kirmizikan,&nbsp;Emine Rumeysa Hekimoglu,&nbsp;Somer Bekiroglu,&nbsp;Sahabettin Selek","doi":"10.1007/s10735-025-10616-y","DOIUrl":"10.1007/s10735-025-10616-y","url":null,"abstract":"<div><p>The study aimed to investigate the long-term effects of IUGR and consequent catch-up growth on metabolic health by using a comprehensive approach that included histopathological, immunohistochemical, biochemical, and metabolomics analyses. Sprague–Dawley pregnant rats either undergo bilateral uterine artery ligation or a sham surgery on the 19th day of gestation. The offspring reached catch-up growth, kidney samples were collected at postnatal weeks 2, 4, and 8 for analysis. IUGR rats exhibited a spectrum of changes including reduced glomeruli number, proliferating cell number, altered oxidative stress markers, various enzymes involved in Krebs cycle, mitochondrial dynamics, and energy metabolism. Examination of the 8-week-old cohort identified a broader spectrum of metabolic alterations, notably in the biosynthesis of phenylalanine, tyrosine, and tryptophan, phenylalanine, tyrosine, glyoxylate, dicarboxylate, pyruvate, alanine, aspartate, and glutamate metabolism, glycolysis/gluconeogenesis and citrate (TCA) cycle. Our metabolomics analysis provides insights into the potential disease susceptibility of individuals born with IUGR, including obesity, diabetes, hypertriglyceridemia, cardiovascular diseases, and mental retardation. These findings underscore the intricate interplay between intrauterine conditions and long-term metabolic health outcomes, highlighting the need for further investigation into preventive and therapeutic strategies to mitigate the risk of metabolic diseases in individuals with a history of IUGR.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LOXL1-AS1 suppresses ferroptosis in cervical cancer through m6A-dependent regulation of TFRC","authors":"Hongyou Wang,&nbsp;Jianbo Zhou,&nbsp;Jianfeng Zhang,&nbsp;Wenlei Yao,&nbsp;Haiyang Li,&nbsp;Kangjie Xu,&nbsp;Hui Cheng","doi":"10.1007/s10735-025-10603-3","DOIUrl":"10.1007/s10735-025-10603-3","url":null,"abstract":"<div><p>Transferrin receptor (TFRC) is essential for iron uptake and may regulate ferroptosis, a form of iron-dependent cell death implicated in cervical cancer (CC). Bioinformatic analyses (GEPIA, UALCAN, SRAMP, starBase) were combined with in vitro and in vivo experiments. CC cell lines were transfected with shRNAs or overexpression plasmids targeting TFRC and LOXL1-AS1. Proliferation was assessed by colony formation, EdU staining, and Ki-67 immunostaining. Ferroptosis was evaluated by measuring malondialdehyde (MDA), lipid ROS, Fe²⁺, and ferroptosis-related proteins. RNA pull-down, RIP, and MeRIP assays were used to explore m6A-dependent regulation, and actinomycin D assays assessed mRNA stability. TFRC and LOXL1-AS1 were upregulated in CC and associated with poor prognosis. TFRC promoted CC cell proliferation and inhibited ferroptosis. LOXL1-AS1 positively regulated TFRC by stabilizing its mRNA via an m6A-IGF2BP2-dependent mechanism. Rescue experiments confirmed that TFRC overexpression reversed the effects of LOXL1-AS1 knockdown. In vivo, LOXL1-AS1 depletion suppressed tumor growth and enhanced ferroptosis. LOXL1-AS1 promoted CC progression by stabilizing TFRC mRNA through m6A-IGF2BP2 interaction, suppressing ferroptosis. Targeting the LOXL1-AS1/IGF2BP2/TFRC axis may offer a potential therapeutic strategy for CC.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrine architecture of caprine pancreas: a histomorphochemical and ultrastructural study","authors":"Kapil Dharmesh,&nbsp;Varinder Uppal,&nbsp;Anuradha Gupta,&nbsp;Devendra Pathak,&nbsp;Neelam Bansal","doi":"10.1007/s10735-025-10605-1","DOIUrl":"10.1007/s10735-025-10605-1","url":null,"abstract":"<div><p>This study aimed to study architecture of pancreatic islets by histological, ultrastructural, histochemical, and immunohistochemical investigations in male and female goats. The tissues were collected from different lobes of pancreas from local slaughterhouses and processed for paraffin sectioning. The sections were stained with different histomorphological, histochemical and immunohistochemical staining. For electron microscopy standard protocols were used. The study revealed no morphological differences in islets of male and female pancreas, however significantly larger (<i>p</i> &lt; 0.05) islets were observed in male animals. Among the different lobes larger islets were observed in left lobe in both the sexes. Immunohistochemically, number of insulin positive cells were more in female than male and number of glucagon cells were more in male than female but the difference was non significant (<i>p</i> &gt; 0.05). Low to moderate PCNA expression in both the sexes indicative of cellular proliferation within islets, while strong VEGF reactivity suggested its role in islet vascularization. This study has provided a baseline anatomical and immunohistochemical data for comparative endocrinology and disease models studies across species, especially in ruminants or domestic animals. Future study can help in early identification of sex-specific susceptibility to metabolic or endocrine disorders in goats (e.g., diabetes-like conditions).</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium benzoate exposure disrupts HPG-axis in male rats: insights into oxidative stress, hormonal dysregulation, histopathology and kisspeptin/RFRP-3 expression","authors":"Safdar Khan,&nbsp;Mohammad Attaullah,&nbsp;Sarwat Jahan,&nbsp;Rahmat Ali,&nbsp;Hira Zubair,&nbsp;Naila Hamayoun","doi":"10.1007/s10735-025-10611-3","DOIUrl":"10.1007/s10735-025-10611-3","url":null,"abstract":"<div><p>The reproductive effects related to sodium benzoate (SB) are increasingly recognized as concerns for public health. To elucidate the underlying mechanistic pathway in SB-induced reproductive impairment, we evaluated its dose-dependent effects by assessing the key elements of HPG- axis, encompassing wide range of doses from dietary to presumably harmful levels. Thirty-five adult male rats (Sprague-Dawley) split into seven groups (<i>n</i> = 5/group); control, SB10, SB50, SB100, SB500, SB1000mg/kg and the co-treated group (SB + EB). SB and distilled water were gavage for 90 consecutive days. The co-treated group received SB500 from day one, while estradiol benzoate (EB; 40 µg/kg) was given at mid-study onward till completion of experiment. Biochemical parameters, sperm parameters, reproductive hormones, gonadal histopathology, hypothalamic kisspeptin and RFRP-3 expression were assessed. SB produced a concentration-dependent reduction in the testis, accessary sex organs weight, antioxidant activities (SOD, POD, CAT and GSH), testosterone and FSH levels. Testicular ROS, TBARs and plasma LH levels were significantly raised compared to control. Fertility parameters underwent a significant decline in SB rats. Notably, kisspeptin showed dose-related decline, while RFRP-3 upregulated in SB rats. Morphometric indices of seminiferous tubules highlighted apparent alterations and marked traces of histopathology were noticed in test groups. EB treatment restored kisspeptin hence stabilized hormones and improved fertility parameters were seen in co-treated rats. SB exposure significantly disrupts HPG-axis via neuroendocrine dysregulation and inducing testicular cytotoxicity, with oxidative stress serve as the key mediator of these effects. It underscores the dire need for careful usage and future studies of its long-term reproductive safety.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repurposing disulfiram: targeting Zeb1 to attenuate paraquat-induced pulmonary fibrosis in rats","authors":"Fatemeh Karimzadeh,&nbsp;Abdolreza Daraei,&nbsp;Ebrahim Zabihi-Neyshaburi,&nbsp;Farideh Feizi,&nbsp;Mohammad Ranaee,&nbsp;Soraya Khafri,&nbsp;Zohre Esmaeili,&nbsp;Zahra Babazadeh","doi":"10.1007/s10735-025-10613-1","DOIUrl":"10.1007/s10735-025-10613-1","url":null,"abstract":"<p>Pulmonary fibrosis is a fatal condition marked by excessive extracellular matrix deposition and myofibroblast activation, with paraquat (PQ) being a potent inducer via oxidative stress and profibrotic signaling. This study evaluated the antifibrotic effects of disulfiram (DSF), an FDA-approved medication, in rats with PQ-induced pulmonary fibrosis. Forty male Wistar rats were divided into eight groups receiving PQ (40 mg/kg) and DSF (1, 10, 100 mg/kg) for 21 days. Lung tissues were analyzed histopathologically (H&amp;E, Mallory’s trichrome) for inflammation, alveolar septal thickening, vascular congestion, and fibrosis, while <i>Zeb1</i> gene expression was assessed by real-time PCR. PQ exposure led to severe lung injury, collagen deposition, and significant upregulation of <i>Zeb1</i> (<i>p</i> = 0.0022). DSF at 10 mg/kg provided the most effective protection, significantly reducing histopathological damage and <i>Zeb1</i> expression (<i>p</i> &lt; 0.001). The 1 mg/kg dose showed moderate efficacy, and the 100 mg/kg dose had limited benefits, suggesting a dose-dependent toxicity. These findings indicate that DSF at 10 mg/kg attenuates PQ-induced pulmonary fibrosis by reducing inflammation, collagen accumulation, and <i>Zeb1</i>-mediated profibrotic signaling, supporting DSF as a potential repurposed antifibrotic therapy for PQ-induced and possibly idiopathic pulmonary fibrosis.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chinese ginger (Boesenbergia rotunda) mitigates diabetic nephropathy and cardiomyopathy by regulating oxidative inflammatory pathway","authors":"Chunhong Liu,&nbsp;Xiaolei Tang,&nbsp;Min Zhang,&nbsp;Yanhong Wu,&nbsp;Ademola Famurewa,&nbsp;Chitchamai Ovatlarnporn,&nbsp;Opeyemi Joshua Olatunji","doi":"10.1007/s10735-025-10559-4","DOIUrl":"10.1007/s10735-025-10559-4","url":null,"abstract":"<div><p>Chinese ginger (<i>Boesenbergia rotunda</i>) is a culinary and traditional medicinal plant in Southeast Asia and Indo-China regions with several medicinal benefits. This study aims to assess the effectiveness of Chinese ginger extract against diabetic nephropathy and cardiomyopathy and the associated signaling pathways. Animals were randomly assigned to groups; control rats, diabetic rats, diabetic rats treated with 100 and 400 mg/kg of the <i>B. rotunda</i> EtOAc fraction (BRE). Treatment was administered for 5 successive weeks via oral gavage. Thereafter, the rats were evaluated for fasting blood glucose, tumour necrosis factor alpha, interleukin-6, interleukin-1 beta, reduced glutathione, superoxide dismutase, catalase, lipid peroxidation activities. Gene expression levels of nuclear factor erythroid 2-related factor 2, and Kelch-like ECH-associated protein 1 were examined. Cardiorenal histopathological and immunohistochemical were performed to assess tissue damage. BRE administration to diabetic rats notably ameliorated changes in body weight, kidney and heart weight and fasting blood glucose level. Furthermore, in diabetic rats, BRE significantly reduced malonaldehyde, tumour necrosis factor alpha, interleukin-6, interleukin-1 beta levels considerably with increasing activity of antioxidant enzymes in the kidney and cardiac tissues of rats treated with BRE. Diabetic rats treated with BRE showed upregulated mRNA expression levels of nuclear factor erythroid 2-related factor 2, while Kelch-like ECH-associated protein 1 mRNA expression in the kidney and cardiac tissues were downregulated. In addition, BRE treatment significantly reduced the cardiorenal protein expression of Bcl2 and collagen IV in the immunohistochemical analyses. From the results of this study, it can be concluded that <i>B. rotunda</i> exerts cardiorenal protective effect on diabetic rats due to its antidiabetic and antioxidant and may be considered a treatment for T2DM.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of ambroxol on cyclophosphamide-induced intestinal damage: involvement of oxidative stress, inflammation, and Keap-1/Nrf2/HO-1 signaling","authors":"Reem S. Alruhaimi,&nbsp;Sulaiman M. Alnasser,&nbsp;Hanan S. Althagafy,&nbsp;Sherif M. A. Mansour,&nbsp;Omnia A. M. Abd El-Ghafar,&nbsp;Ayman M. Mahmoud,&nbsp;Emad H. M. Hassanein","doi":"10.1007/s10735-025-10599-w","DOIUrl":"10.1007/s10735-025-10599-w","url":null,"abstract":"<div><p>Cyclophosphamide (CP) is an effective chemotherapeutic agent whose clinical efficacy is often limited by toxicity, including intestinal injury. Oxidative stress and inflammation are central to CP-induced tissue damage and represent a valuable target to attenuate intestinal injury. Ambroxol (ABX), a clinically approved mucolytic agent, has demonstrated antioxidant, anti-inflammatory, and mucoregulatory properties that may confer multi-organ protection. This study investigated the protective effects of ABX against CP-induced intestinal injury in rats, exploring the involvement of oxidative stress, inflammation and Keap-1/Nrf2/HO-1 signaling. Adult male rats received ABX (20 mg/kg/day) orally for seven consecutive days, with CP (100 mg/kg, i.p.) administered on the fifth day. CP induced significant intestinal injury manifested by intestinal mucosal atrophy, decreased length of villi and goblet cell depletion. CP triggered oxidative stress characterized by increased MDA and decreased GSH, SOD, and catalase, upregulated NF-κB, IL-6, and TNF-α, and increased caspase-3 expression in the intestine. ABX attenuated histopathological alterations, mitigated oxidative stress, suppressed NF-κB and cytokines, and downregulated caspase-3. In addition, ABX preserved intestinal goblet cells while modulating the Keap-1/Nrf2/HO-1 pathway in intestinal tissue. These findings demonstrate the protective role of ABX against CP-induced intestinal injury via antioxidant, anti-inflammatory, and mucoprotective mechanisms, supporting its potential repurposing as an adjuvant during CP chemotherapy. The protective mechanism of ABX involves its ability to modulate the Keap-1/Nrf2/HO-1 signaling pathway.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S1PR5 as a prognostic biomarker in colon cancer: insights into efferocytosis-related mechanisms and immune modulation","authors":"Aijie Pei,&nbsp;Ling Lu,&nbsp;Xiaolin Wu","doi":"10.1007/s10735-025-10608-y","DOIUrl":"10.1007/s10735-025-10608-y","url":null,"abstract":"<div><p>Colon cancer remains a major cause of global cancer mortality, characterized by complex interactions between genetic, epigenetic, and immune factors. This study investigates the prognostic value of efferocytosis-related genes and their role in colon cancer progression and immune modulation. A prognostic signature relied on efferocytosis-related genes was developed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Immune infiltration, immune checkpoint expression, and tumor microenvironment characteristics were analyzed using single-sample gene set enrichment analysis (ssGSEA), ESTIMATE, and tumor immunophenotype (TIP) frameworks. S1PR5 was knocked down in SW1116 and SW620 cells. The effect of S1PR5 on colon cancer growth and macrophage regulation in vivo and in vitro. Colon cancer patients were stratified into high- and low-risk groups, with high-risk patients demonstrating significantly worse survival outcomes. S1PR5, a key gene in the model, was markedly overexpressed in colon cancer tumors and correlated with advanced clinical stages, poor survival outcomes, and diminished responses to immunotherapy. Furthermore, S1PR5 knockdown could inhibit colon cancer cell activity and increase macrophage polarization from M0 to M1. Our research developed an efferocytosis-related gene prognostic model and identified S1PR5 as a key biomarker. S1PR5 showed significant associations with advanced clinical stages, immunosuppressive microenvironments, and unfavorable survival outcomes, underscoring its potential as both a prognostic marker and a therapeutic target in colon cancer.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MAO-A inhibition alleviates sepsis-driven lung injury via Nrf2/HO-1 pathway activation and suppression of pyroptosis","authors":"Min Li,&nbsp;Hu Li,&nbsp;Liming Gong,&nbsp;Xinmin Chen,&nbsp;Jincan Dai,&nbsp;Jirong Tian,&nbsp;Xiaochuan Yin,&nbsp;Qinghe Yu","doi":"10.1007/s10735-025-10560-x","DOIUrl":"10.1007/s10735-025-10560-x","url":null,"abstract":"<div><p>Extensive research has highlighted the involvement of excessive oxidative stress and pyroptosis in sepsis-caused acute lung injury (ALI). The present investigation delves into the potential role of Monoamine oxidase A (MAO-A) in this pathological process. Analyzing Gene Expression Omnibus (GEO) datasets alongside clinical samples revealed a significant upregulation of MAO-A in sepsis patients. To further elucidate this, cecal ligation puncture (CLP)-induced ALI were established in C57BL/6 mice. Additionally, human alveolar epithelial cells (HPAEpiC) treated with MAO-A inhibitor RO11-11639 were subjected to lipopolysaccharide (LPS) stimulation in vitro. The <i>in-vivo</i> experiments demonstrated that RO11-11639 mitigated CLP-induced ALI, significantly reducing pulmonary oxidative stress, inflammation and pyroptosis in lung tissue. Biochemical quantification revealed significant suppression of both oxidative stress biomarkers reactive oxygen species (ROS), malondialdehyde (MDA) and key inflammatory markers interleukin (IL)-1β, IL-16. Consistent with these findings, the <i>in-vitro</i> model confirmed that RO11-11639 reduced ROS and MDA accumulation, and inflammation in HPAEpiC, in response to LPS stimulation. Moreover, functional rescue analysis delineated the nuclear factor erythropoietin-2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) pathway as the critical mediator of RO11-11639’s dual antioxidant and anti-pyroptosis activities in HPAEpiC. Mechanistically, MAO-A inhibition promoted the nuclear translocation of Nrf2, thereby activating the downstream regulatory proteins HO-1, quinone oxidoreductase 1 (NQO-1) and glutathione s-transferase (CST). These data cumulatively indicate that pharmacological targeting of MAO-A may offer therapeutic benefits in septic ALI by attenuating pathophysiological processes involving oxidative damage and inflammasome-mediated pyroptosis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}