Journal of Molecular Histology最新文献

{"title":"Correction: Upregulation of NR4A3 increases sensitivity to niraparib in ovarian cancer cells resistant to this drug","authors":"Jianwei Wang, Yu Wei, Benjun Chen","doi":"10.1007/s10735-026-10725-2","DOIUrl":"10.1007/s10735-026-10725-2","url":null,"abstract":"","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117337","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":"Maternal high-fat diet and its multigenerational impact on hypertension and metabolic alterations in Wistar rat offspring","authors":"Maghawry Hegazy,&nbsp;Mahmoud Mohamed Mokhtar,&nbsp;Elsayed G. E. Elsakka,&nbsp;Hesham A. El-Mahdy,&nbsp;Samy Y. Elkhawaga,&nbsp;Mohamed A. Elkady,&nbsp;Amr Mohamed Yehia,&nbsp;Ahmed Aglan,&nbsp;Ahmed M. Mansour,&nbsp;Salama Abdo Salama,&nbsp;Hamada Ahmed Mokhlis,&nbsp;Hesham Fathy Hassan,&nbsp;Adel I. Abdelaziz,&nbsp;Maher Hassan Gomaa,&nbsp;Ahmed A. El-Husseiny,&nbsp;Mahmoud Eldeib,&nbsp;Hesham Shaaban,&nbsp;Rasha M. Alnefaie,&nbsp;Ahmed Ismail","doi":"10.1007/s10735-025-10693-z","DOIUrl":"10.1007/s10735-025-10693-z","url":null,"abstract":"<div><p>This study investigates the impact of maternal high-fat diet (HFD) on the development of hypertension and associated metabolic changes in offspring across multiple generations of Wistar rats. Pregnant female rats were assigned to either a normal standard diet or a HFD during gestation. We assessed body weight, heart weight, systolic blood pressure (SBP), catechol-O-methyl transferase (COMT), and vanillyl mandelic acid (VMA) in first, second, and third-generation offspring. Our findings revealed that HFD offspring exhibited significantly elevated SBP compared to controls in all generations, with the most pronounced increase in F1. In addition, plasma EP, NE, and urinary VMA were markedly increased in F1, attenuated in F2, and remained elevated though less pronounced in F3. Also, the cardiac COMT expression was downregulated in all HFD offspring, most strongly in F1. Furthermore, the body weights were significantly higher in F1 compared to controls, whereas differences were minimal in F2 and F3. Moreover, dyslipidemia (elevated TC, TG, LDL; reduced HDL) was observed in F1 and partially persisted in F2 and F3. Finally, histopathological analysis revealed cardiac hypertrophy, cytoplasmic vacuolation, and pyknotic nuclei in F1, with milder alterations in F2 and F3. These results suggest that maternal HFD during pregnancy might affect the offspring cardiovascular health, potentially mediated by alterations in catecholamine dynamics. The study underscores the importance of maternal nutrition in the context of fetal programming and its implications for the prevention of hypertension and related metabolic disorders in future generations.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117283","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 effects of BAIBA and thymoquinone in type 1 diabetic nephropathy: modulation of Irisin, NF-κB, and Caspase-3 expression","authors":"Merve Pekince Özöner,&nbsp;Fatih Mehmet Gür,&nbsp;Ibrahim Aktas,&nbsp;Özgür Özöner,&nbsp;Sema Timurkaan","doi":"10.1007/s10735-026-10719-0","DOIUrl":"10.1007/s10735-026-10719-0","url":null,"abstract":"<div><p>Diabetes is closely related to increased production of reactive oxygen species, which leads to oxidative stress, chronic inflammation, and increased apoptosis, especially in kidney tissues. Irisin is a recently discovered myokine with the potential to offer hope for the treatment of many metabolic diseases, while BAIBA is also a newly identified endogenous protective myokine. In this study, the effects of thymoquinone (TIM), known for its antioxidant activity, as well as the possible agonistic interaction between irisin and BAIBA on cellular stress and apoptosis occurring in diabetic kidneys were investigated using immunohistochemical methods. In this study, 35 Sprague Dawley rats were equally separated into five groups: Control, STZ, TIM, BAIBA and STZ + TIM + BAIBA. Type 1 diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ, 50 mg/kg). The same protocol was applied to induce diabetes in the TIM and BAIBA groups. Following induction, TIM (20 mg/kg) and BAIBA (100 mg/kg) were administered daily via gavage for five weeks. In the STZ + TIM + BAIBA group, diabetes was induced similarly, followed by daily oral administration of a combination of TIM and BAIBA at the same doses for five weeks. At the conclusion of the study, kidney samples were obtained and analysed using both histochemical and immunohistochemical methods. Results demonstrated that TIM significantly reduced intersitial fibrosis by 55% in the kidneys. It is revealed that both TIM and BAIBA reduced NF-κB immunointensity by 63% and when used simultaneously by %48. Caspase3 immunointensity was reduced by 38%, 46% and 26% following TIM, BAIBA and TIM + BAIBA administration respectively. Also both TIM and BAIBA was observed to cause positive up-regulation on irisin expression. The findings of this study demonstrated that TIM and BAIBA effectively prevented renal fibrosis and apoptosis in STZ-induced diabetic rats, particularly through the downregulation of NF-κB.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117302","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":"Morin induces ferroptosis in endometrial cancer cells by down-regulating FTH1","authors":"Nie Hua,&nbsp;Shu Zhan,&nbsp;Chen Yu","doi":"10.1007/s10735-025-10663-5","DOIUrl":"10.1007/s10735-025-10663-5","url":null,"abstract":"<div><p>Ferritin heavy chain 1 (FTH1) is abnormally expressed in various cancers, but its role and mechanism in endometrial cancer (EC) remain unclear. This study aims to explore the clinical significance, biological functions and potential inhibitor of FTH1 in EC. The expression, prognosis and clinical correlation of FTH1 in EC were analyzed using TIMER, GEO, kaplan–meier plotter and UALCAN databases. Virtual screening and molecular docking were conducted for identifying potential inhibitors of FTH1. In vitro experiments were conducted using human EC cells HEC-1A and RL95-2. Cell proliferation, cell cycle and apoptosis were detected by CCK-8 assay and flow cytometry. The level of reactive oxygen species (ROS) was detected by using the DCFH-DA probe. The levels of malondialdehyde (MDA) and glutathione (GSH) were detected using the corresponding test kits. Western blot was used to detect the expression level of FTH1, AKT and p-AKT. FTH1 was highly expressed in EC tissues and was associated with a shorter overall survival time of patients. Functional enrichment analysis revealed that FTH1 was mainly involved in the iron homeostasis and ferroptosis pathways. FTH1 knockdown inhibits the proliferation of EC cells, induces cell cycle arrest at the G0/G1 phase and triggers cell apoptosis. In EC cells with FTH1 knockdown, the levels of ROS and MDA were significantly increased, accompanied by a decrease in GSH levels. Furthermore, morin had a high binding affinity with FTH1, which also inhibited the malignant phenotypes of EC cells. Morin triggered ferroptosis of EC cells by down-regulating FTH1 expression and inhibiting the PI3K/AKT pathway. FTH1 is a potential prognostic biomarker and therapeutic target for EC. Morin induces ferroptosis of EC cells by regulating FTH1-PI3K/AKT axis, providing a new candidate drug and theoretical basis for the treatment of EC.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117328","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":"Therapeutic effect of naringenin against fenamiphos‑induced testicular damage in male rats: a histological and biochemical study","authors":"Eray Demirkol,&nbsp;Fatma Gokce Apaydin","doi":"10.1007/s10735-026-10728-z","DOIUrl":"10.1007/s10735-026-10728-z","url":null,"abstract":"<div>\u0000 \u0000 <p>Fenamiphos (FNP) is an organophosphate compound used to control many agricultural pests. Naringenin (NAR) is a compound that has been recognized as a having physiologically potent antioxidant activity. This study was made to detect the possible therapeutic effects of NAR in preventing fenamiphos-induced reproductive toxicity. For this purpose, rats were treated with Fenamiphos (FNP) and Naringenin (NAR) for 4 weeks. This study was conducted on a total of 24 adult male albino rats. The rats were divided in an equally random manner into four groups: Group 1 was determined as the control group; group II received a dose of 50 mg/kg naringenin orally; group III received fenamiphos in a dose of 0.76 mg/kg/day orally; group IV received both naringenin and fenamiphos in the same stated doses. The results obtained in the testis showed a significant increase in the malondialdehyde, 8-OHdG, IL-17, and a significant decrease in superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, acetylcholine esterase activities, testosterone, FSH, and LH contents in the FNP-treated group. Tissue damage induced significant histopathological/immunohistochemical changes following exposure to FNP. Treatment with NAR reduced malondialdehyde, 8-OHdG, and IL-17 contents, and naringenin treatment caused an increase in superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, acetylcholine esterase, testosterone, FSH, and LH parameters compared with the FNP-treated groups. Micrographs of testis sections in FNP plus NAR-treated rats showed fewer histopathological and immunohistochemical changes. Flavonoids could effectively protect against fenamiphos-induced damage, offering a potential solution for pesticide-related toxicity. In this investigation, it was shown that fenamiphos caused testicular toxicity, and naringenin reduced this toxicity.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117308","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":"Exosomal CeRNAs from the tumor microenvironment: hidden drivers of colorectal cancer progression","authors":"Faris Anad Muhammad,&nbsp;Abdulkareem Shareef,&nbsp;S. Renuka Jyothi,&nbsp;Priya Priyadarshini Nayak,&nbsp;J. Bethanney Janney,&nbsp;Gurjant Singh,&nbsp;Aashna Sinha,&nbsp;Nodira Rabbimova,&nbsp;Hayder Naji Sameer,&nbsp;Ahmed Yaseen,&nbsp;Rasim M. Salih,&nbsp;Mohaned Adil","doi":"10.1007/s10735-026-10724-3","DOIUrl":"10.1007/s10735-026-10724-3","url":null,"abstract":"<div><p>Colorectal cancer (CRC) remains a major global health burden, with rising incidence and mortality, particularly in developing countries. The tumor microenvironment (TME) plays a critical role in CRC progression by facilitating angiogenesis, immune evasion, and metastasis through complex intercellular communication. Among the key mediators of this communication are exosomes—nano-sized extracellular vesicles—that transport a variety of bioactive molecules, including competing endogenous RNAs (ceRNAs). These ceRNAs, such as long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and mRNAs, act as molecular sponges for microRNAs (miRNAs), thereby regulating gene expression and influencing cancer-related pathways like Wnt/β-catenin and PI3K/Akt. This review explores the emerging role of exosomal ceRNAs derived from the TME in CRC progression, emphasizing their involvement in promoting tumor cell proliferation, invasion, metastasis, and resistance to therapy. By elucidating the intricate crosstalk between exosomal ceRNAs and the TME, we highlight their potential as novel biomarkers and therapeutic targets, offering new avenues for personalized treatment strategies in colorectal malignancies. Despite growing interest in exosomes and non-coding RNAs in colorectal cancer (CRC), limited attention has been given to the specific role of exosomal ceRNAs derived from the tumor microenvironment (TME). Existing reviews have predominantly addressed broader aspects of exosomal non-coding RNAs (e.g., miRNAs, lncRNAs, and circRNAs in general CRC progression, metastasis, or as biomarkers) or focused on exosomal communication in other malignancies. However, the intricate mechanisms by which TME-derived exosomal ceRNAs establish regulatory networks to drive CRC pathology—particularly through miRNA sponging in stromal-tumor crosstalk—remain underexplored and insufficiently synthesized. This review addresses these critical gaps by uniquely emphasizing exosomal ceRNAs sourced from the TME (including CAFs, macrophages, and other stromal components), elucidating their convergent roles in orchestrating proliferation, invasion, immune evasion, and chemoresistance. By integrating recent evidence into a TME-centric framework, we provide novel insights into potential diagnostic and therapeutic applications, advancing beyond general exosomal RNA overviews toward targeted strategies for CRC.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083063","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":"Comparative evaluation of tamoxifen and red clover extract on reproductive and hepatic function in female Trichogaster trichopterus: a translational endocrine toxicology study","authors":"Tahereh Naji,&nbsp;Mahdi Ahmadinia,&nbsp;Mohammad Mehrkar,&nbsp;Homayoun Hosseinzadeh Sahafi","doi":"10.1007/s10735-026-10727-0","DOIUrl":"10.1007/s10735-026-10727-0","url":null,"abstract":"<div><p>Tamoxifen, a selective estrogen receptor modulator (SERM), regulates estrogen signaling in a tissue-dependent manner. Phytoestrogens such as red clover (<i>Trifolium pratense</i>) activate estrogenic pathways through receptor agonism and are increasingly studied for hormone-related conditions. This study compared the endocrine and hepatic effects of tamoxifen and red clover extract in a validated vertebrate model, the female three-spot gourami (<i>Trichogaster trichopterus</i>). A total of 120 adult female gourami were randomly assigned to eight groups, receiving intramuscular (IM) injections of tamoxifen (10, 50, 100 mg/kg), IM injections of red clover extract (25, 75, 150 mg/kg), vehicle, or no treatment over 18 days. Reproductive (GSI, hormone levels, ovarian histology) and hepatic (HSI, ALT/AST levels, liver histology, TEM) parameters were assessed. Tamoxifen induced dose-dependent reductions in GSI at 50 and 100 mg/kg (<i>p</i> = 0.004 and <i>p</i> &lt; 0.001), accompanied by significant decreases in sex hormone levels and elevations in ALT and AST (<i>p</i> &lt; 0.01), along with marked hepatic histopathological changes. In contrast, red clover extract significantly increased GSI at 75 and 150 mg/kg (<i>p</i> = 0.012 and <i>p</i> = 0.001) and enhanced sex hormone levels (<i>p</i> &lt; 0.05) compared with controls. Histological and ultrastructural analyses confirmed arrested ovarian development and hepatic degeneration in tamoxifen-treated fish, while red clover–treated fish showed follicular maturation and preserved liver architecture. The contrasting effects of tamoxifen and red clover reflect their distinct estrogen-modulatory mechanisms. While tamoxifen showed anti-estrogenic and hepatotoxic effects, red clover promoted reproductive activity with preserved hepatic safety, supporting its potential as a safer phytoestrogenic alternative.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146083108","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":"Effect of dual RF-EMF and pulsed magnetic field exposure on eNOS expression and histological integrity in male rat reproductive tissues","authors":"Halil Ascı,&nbsp;Selcuk Comlekcı,&nbsp;Rumeysa Taner,&nbsp;Muhammet Yusuf Tepebası,&nbsp;Orhan Berk Imecı,&nbsp;Esma Selçuk,&nbsp;Rahime Aslankoc,&nbsp;Sinem Gultekın,&nbsp;Coskun Comlekcı,&nbsp;Ozlem Ozmen","doi":"10.1007/s10735-026-10720-7","DOIUrl":"10.1007/s10735-026-10720-7","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigated the molecular and histological responses of male rat reproductive tissues to combined radiofrequency electromagnetic field (RF-EMF) and pulsed magnetic field (PMF) exposure. Sixty adult male Wistar rats were assigned to ten groups and exposed once, twice, or three times daily for 1 day, 1 week, and 1 month. Penile, testicular, prostatic, and renal tissues were analyzed using real-time quantitative polymerase chain reaction (RT-qPCR), histopathology, and immunohistochemistry. Dual-mode electromagnetic exposure produced a marked increase in endothelial nitric oxide synthase (eNOS) mRNA expression, particularly in long-term and higher-frequency groups, whereas vascular endothelial growth factor (VEGF) levels displayed only minimal changes. Tumor necrosis factor-alpha (TNF-α) expression decreased in penile tissue following short-term exposure but showed a mild elevation in the long-term, high-frequency testicular group, indicating localized sensitivity. Histopathological examination revealed preserved tissue architecture in the penis, prostate, and kidneys, with hyperemia being the primary finding in penile sections. Caspase-3 (Cas-3) immunoreactivity remained low across all groups, demonstrating an absence of apoptotic activation. Testicular tissues maintained overall tubular integrity, although a moderate reduction in intratubular spermatozoa was noted in the one-month high-frequency group without accompanying necrosis or apoptosis. These findings indicate that RF-EMF and PMF exposure enhances endothelial activation mainly through eNOS upregulation while maintaining general tissue integrity in male reproductive organs. The mild testicular inflammatory response observed under prolonged exposure underscores the importance of dose-dependent application. Overall, the results support the biological safety and physiological relevance of dual electromagnetic stimulation under controlled experimental conditions.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058397","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":"Effect of metformin on the autophagy process in renal ischemia reperfusion injury","authors":"Mostafa M. Mohammed,&nbsp;Maggie M. Ramzy,&nbsp;Shereen S. Gaber,&nbsp;Sara G. Ahmed,&nbsp;Rabeh Khairy Saleh,&nbsp;Hatem A. Mohamed","doi":"10.1007/s10735-025-10688-w","DOIUrl":"10.1007/s10735-025-10688-w","url":null,"abstract":"<div>\u0000 \u0000 <p>Autophagy refers to the intra-cellular metabolism pathways that deliver cytoplasmic target substances to lysosomes for degradation. When cells are exposed to stress; autophagy is developed and has the ability to maintain an adaptable method to the survival of cells. The AMPK- signaling pathway was considered an essential regulator of the autophagy during energy depletion. Many studies suggest that autophagy protects the I/R-induced renal tubular cell injury via an AMPK-regulated pathway. The aim of the current work is to study the effect of metformin on autophagy process and renal alterations associated with ischemia-reperfusion injury through examining its effect on renal functions, oxidative markers and expression of <i>ATG7</i> and <i>LC3II</i> gene in renal tissue. Sham rats (control, <i>n</i> = 10); the rats in the sham group were pre-treated with saline before laparotomy, Group 2 (Ischemic-reperfusion injury, I/R, <i>n</i> = 20); bilateral renal pedicles were clipped for 45 min, followed by perfusion for 24 h to establish I/R model, Group 3(IR + metformin 300 mg/kg, <i>n</i> = 20), Animals were pre-treated with the metformin (Met) at 300 mg/kg 2 doses 2 h, 12 h prior to 45 min of ischemia. The results showed that there is disturbed renal functions as evidenced by the increase in kidney function parameters. Metformin treatment had a protective effect in group that receive treatment through up-regulation of autophagy markers <i>ATG7</i> and <i>LC3II</i> gene &amp; improve kidney function tests, MDA and histological findings. The results suggest that metformin-induced autophagy through activating the AMPK pathway has protection impact against kidney I/R injury.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058383","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":"Evaluating the implications of K-Ras, KEAP1/NRF2-mediated signaling pathways and metabolic alterations in urethane-induced lung cancer","authors":"Kaveri R. Washimkar,&nbsp;Manendra Singh Tomar,&nbsp;Shobhit Verma,&nbsp;V. M. Prajapati,&nbsp;Ashutosh Shrivastava,&nbsp;Madhav Nilakanth Mugale","doi":"10.1007/s10735-026-10721-6","DOIUrl":"10.1007/s10735-026-10721-6","url":null,"abstract":"<div>\u0000 \u0000 <p>Lung cancer, being an aggressive malignancy, is a leading cause of cancer-related mortality worldwide. Urethane, a genotoxic chemical, is a highly potent carcinogen in the development of lung cancer. Understanding the molecular mechanisms related to oxidative stress and metabolic anomalies involved in lung malignancy caused by urethane is of utmost importance. Male C57BL/6 mice were used to generate a urethane-induced lung cancer model. Urethane-exposed animals demonstrated cancerous lesions, loss of normal pulmonary architecture, and condensed alveolar structure. Urethane exposure upregulated K-Ras and downregulated p53 in the induced group. The induced rats also showed a decrease in Kelch-like ECH-associated protein 1 (KEAP1), Cullin3 (CUL3) and upregulated nuclear factor erythroid 2–related factor 2 (NRF2) and Heme oxygenase-1 (HO-1). Metabolomics studies identified that urethane exposure impacted the citric acid cycle, nucleic acid biosynthesis, amino acid, and sugar and lipid metabolism. Crucial metabolites, such as homocysteine, methylmalonic acid and 5-hydroxytryptamine (5-HT) were found to be upregulated, while tricarboxylic acid (TCA) cycle and fatty acid (FA) cycle metabolites were found to be downregulated in the urethane-induced group. Moreover, a rise in homocysteine was identified in univariate, multivariate, as well as biomarker analysis. Overall, the outcomes of the present study acknowledge the implications of key signaling and metabolic pathway modulations by urethane treatment, whose dysregulation might be associated with lung carcinogenesis.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"57 1","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146058414","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}