Journal of Molecular Histology最新文献

{"title":"Therapeutic effects of Euphorbia altissima on excisional wound model: role of apoptosis, oxidative stress, and inflammatory molecules.","authors":"Hanan Ibrahim Althagbi, Khalid M Alqaisi, Noralhuda Ayad Ibrahim, Parween Abdul-Samad Ismail, Ahmed A J Jabbar, Rawaz Rizgar Hassan, Muzhda Haydar Saber, Ahmed Hameed Al-Dabhawi, Goran Noori Saleh, Talal Salem Al-Qaisi","doi":"10.1007/s10735-025-10519-y","DOIUrl":"https://doi.org/10.1007/s10735-025-10519-y","url":null,"abstract":"<p><p>Euphorbia Altissima (E. altissima) is a traditional medicinal herb used for many inflammatory-related health disorders, including skin problems. The study estimates the phytochemicals, acute toxicity, and wound-healing action of methanolic extracts of Euphorbia Altissima (MEEA) in excisional rat models. Twenty-four Sprague Dawley rats were excised at their dorsal neck and were addressed with either positive control, intrasite gel, or MEEA (250 and 500 mg/kg) for a two-week trial. Phytochemical, histopathological, and immunohistochemical assays were employed to depict wound healing potentials. Phytochemical profiling showed the increased total phenolic (283.10 mg GAE/g) and flavonoid contents (211.5 mg rutin/g) in methanolic extracts of E. altissima. MEEA supplementation did not cause any observable toxic damage, with the absence of any morbidity or mortality in rats ingested with up to 5 g/kg. MEEA addressing resulted in the acceleration indicated by closer and smaller wounds in a dose-dependent manner compared to positive control rats. Histological analysis demonstrated fewer inflammatory cells, more fibroblasts, and higher collagen deposition in skin tissues treated with MEEA than in positive controls. MEEA addressing caused significant modulation of tissue immunohistochemical (decreased Bax and increased HSP 70) proteins and serum inflammatory (reduced TNF-α, IL-6, and magnified IL-10) chemicals, aiding in faster wound recovery. Moreover, hydroxyproline and endogenous antioxidants were higher, and MDA contents were lower in skin tissues addressed with MEEA. This study elucidates MEEA as an efficient wound healer, supporting its folkloric use and providing scientific evidence for future exploration, including molecular identification and isolation as viable sources of therapeutic formulation.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":"232"},"PeriodicalIF":2.9,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666806","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":"Epstein-Barr virus modulates iron metabolism and ferritin expression to promote tumorigenesis in gastric cancer.","authors":"Xia Zhao, Duo Shi, Lingling Sun, Zhiyuan Gong, Wen Liu, Yan Zhang, Bing Luo","doi":"10.1007/s10735-025-10515-2","DOIUrl":"https://doi.org/10.1007/s10735-025-10515-2","url":null,"abstract":"<p><p>Iron is crucial for cell survival and maintaining normal physiological functions. Viral infections can disrupt cellular iron metabolism, leading to inflammation and cancer. Ferritin, a key iron-binding protein, consists of ferritin heavy chain 1 (FTH1) and ferritin light chain (FTL) and helps regulate systemic iron balance, both implicated in various tumor developments. Epstein-Barr virus (EBV), the first oncogenic virus discovered in humans, can induce the development of EBV-associated gastric cancer (EBVaGC). However, the regulatory mechanisms and functions of FTH1 and FTL in EBVaGC are poorly understood. This study aimed to investigate how EBV regulates FTH1 and FTL and their roles in the development of EBVaGC. We show that EBV is able to remodel intracellular iron metabolism, affecting the expression of FTH1 and FTL. EBV-encoded LMP2A promotes the expression of FTH1 and FTL by up-regulating p62 and blocking the autophagy degradation pathway, thus participating in the occurrence and development of EBVaGC. Knocking down FTL inhibits cell migration and proliferation, and promotes apoptosis, whereas FTH1 knockdown has negligible effects on these cellular functions. Additionally, we found that ferritin enhanced the inflammatory state of gastric cancer cells. Overall, our findings highlight the significant impact of EBV on ferritin, underscoring a previously unrecognized role of ferritin in the progression of EBVaGC. This novel pathway could offer new therapeutic targets for the treatment of EBVaGC.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":"231"},"PeriodicalIF":2.9,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144658041","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":"Pannexin1 via P2rx7/amphiregulin contributes to cardiac fibrosis post myocardial infarction.","authors":"Na Deng, Liwei You, Haijun Guo, Yingying Wei, Fujia Xu, Dandan Chen, Sihan Luo, Surong Huang, Siying Zuo, Wei Li, Xiaoyun Si","doi":"10.1007/s10735-025-10517-0","DOIUrl":"https://doi.org/10.1007/s10735-025-10517-0","url":null,"abstract":"<p><p>The primary pathological mechanism underlying ventricular remodeling and cardiac dysfunction following myocardial infarction (MI) is predominantly mediated by cardiomyocyte apoptosis. Pannexin1 (PANX1) channels, which open during apoptosis, facilitate the release of ATP from dying cells. However, the functional significance of PANX1 in mediating cardiomyocyte apoptosis and its contribution to myocardial infarction progression remain to be fully elucidated. To investigate the regulatory role of PANX1 in cardiomyocyte apoptosis following MI and elucidate its underlying molecular mechanisms. We conducted both in vivo and vitro studies. In vivo, we observed a significant elevation of PANX1 expression levels in post-MI mice, which facilitated macrophage recruitment and subsequently triggered upregulation of amphiregulin(AREG). In vitro, HL-1 cells exposure to hypoxia/reoxygenation (H/R) induced apoptosis, accompanying with the upregulation of PANX1, enhanced extracellular ATP release. And these alterations promoted the recruitment of RAW264.7 cells, subsequently elevating AREG levels. These effects were mitigated by the knockdown of PANX1. To confirm PANX1's role in MI hearts, AAV-9-PANX1-RNAi and negative control vectors were administered into the hearts of mice. Over 28 days post-MI, PANX1 knockdown significantly enhanced cardiac function and attenuated myocardial fibrosis. Our findings reveal that PANX1 plays a crucial role in facilitating a link between apoptotic cardiomyocyte and macrophage, contributing to modulate myocardial fibrosis and cardiac dysfunctional recovery post-MI via the AREG. Furthermore, the PANX1/P2rx7/AREG pathway is essential for facilitating a link between apoptotic cardiomyocytes and macrophages in mice following MI.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":"230"},"PeriodicalIF":2.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641366","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":"Does Moringa oleifera leaf extract protect the brain against 3-acetylpyridine-induced cerebellar ataxia in rat?","authors":"Doaa Mohamad Hassan, Nourhan Tharwat Sabra, Maha Eid Farghaly, Ahmed Yahia Sedeak","doi":"10.1007/s10735-025-10511-6","DOIUrl":"https://doi.org/10.1007/s10735-025-10511-6","url":null,"abstract":"<p><p>There is no treatment for some neurological conditions, like cerebellar ataxia (CA). Moringa Oleifera (MO) has been revealed to have neuroprotective properties, but little is known about how it could protect against CA. In this study, we studied the neuroprotective effects of MO in an animal model of CA induced by 3-acetylpyridine (3-AP), which showed deficits in balance and motor coordination. Although cerebellar neuroinflammatory responses are evident in CA, it is yet unclear how neuroinflammation might influence CA. Here, we investigate whether MO, which has anti-inflammatory, antioxidant, and neuroprotective qualities, can help with cerebellar neurodegeneration and locomotor activity deficits. We divided 24 adult male rats into four equal groups. The control group received saline orally, the MO group received MO extract orally, the 3-AP group was injected with 3-AP, and the 3-AP + MO combined group received both 3-AP and MO for four weeks. The animals underwent a motor coordination test on the experiment's first and last days. At the end of the experiment, the animals were euthanized, the cerebellums were dissected, and they were then subjected to standard biochemical, histological, and immunohistochemical studies. The combined group showed remarkable improvement in the CA. The cerebellar neurodegeneration and declination of locomotor activity had improved. Our findings imply that MO may protect against the CA degenerative condition and improve cerebellar function.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":"227"},"PeriodicalIF":2.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635861","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":"SOX4 promotes triple-negative breast cancer progression by promoting SRPX2 transcription to regulate AKR1C1.","authors":"Weiwei Ge, Chao Shi, Chun Ge, Siyun Zhang, Shuhua Chen, Jinfeng Qian","doi":"10.1007/s10735-025-10468-6","DOIUrl":"https://doi.org/10.1007/s10735-025-10468-6","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer that poses a serious threat to women's health. The aldo-keto reductase type 1 C (AKR1C) family serves as a crucial ferroptosis defense system, catalyzing the conversion of aldehydes and ketones into their corresponding alcohols. SRY-Box4 (SOX4), a transcription factor of the SOX (sry-related HMG-box) family, is important in regulating tumor progression. This study aims to investigate the mechanism through which AKR1C1 mediates the growth, invasion, and ferroptosis of triple-negative breast cancer cells. SRPX2 was highly expressed in TNBC tissues and cells and was detrimental to patient prognosis. SRPX2 knockdown inhibited TNBC cell viability, invasion, and Stemness of tumor while promoting TNBC cell apoptosis and ferroptosis. SOX4 could bind to SRPX2 and was highly expressed in TNBC tissues and cells, down-regulation of SOX4 could inhibit the expression of SRPX2. Silencing SRPX2 inhibited the expression of AKR1C1. Up-regulating AKR1C1 reversed the inhibitory effect of SRPX2 knockdown on cell viability, invasion, and sphere formation abilities, and also reversed the promotive effect on apoptosis in TNBC cells. In vivo, SRPX2 knockdown suppressed tumor growth and expression of Ki67 and AKR1C1 via down-regulated AKR1C1. SOX4 facilitates triple-negative breast cancer progression via promoting SRPX2 transcription to regulate AKR1C. This study is expected to explore potential therapeutic targets and strategies for the treatment of TNBC.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":"226"},"PeriodicalIF":2.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635863","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":"Regulatory effects of head acupuncture on the GABAergic system and Wnt7a/β-catenin pathway in post-stroke spasticity rats.","authors":"Xingyu Kang, Siyu Chen, Le Ma, Ying Kong, Ying Huang, Shuai Shi","doi":"10.1007/s10735-025-10505-4","DOIUrl":"10.1007/s10735-025-10505-4","url":null,"abstract":"<p><p>To investigate the regulation of the GABAergic system and Wnt/β-catenin signaling pathway in rats with limb spasticity after stroke by Head Acupuncture therapy and its potential mechanism. A middle cerebral artery occlusion (MCAO) model was established by the thread bolus method, and randomly grouped into a blank group, a model group, and a needling group, the latter of which received the intervention of needling at the points of \"Hundred Houses\" and \"Rate Valley\" for 30 min a day for 7 consecutive days. The neurological deficits and muscle tone of rats were assessed by Zeo Longa score and modified Ashworth score, and the expression levels of key proteins of the GABAergic system (GAD65, GAD67, GABA-T, GAT-3, NKCC1) and Wnt/β-catenin signaling pathway were detected by immunohistochemistry, real-time fluorescence quantitative PCR and Western blot and Wnt/β-catenin signaling pathway key protein expression levels. Head Acupuncture significantly improved the neurological deficit score and muscle tone of rats in the model group, decreased the mRNA and protein expression levels of GABA-T and NKCC1, and significantly up-regulated the expression of GAD65, GAD67, and GAT-3. In addition, acupuncture promoted the expression of Wnt7a and β-catenin, and the effect of 7 days of treatment was better than that of 1 day. Head Acupuncture therapy may exert a therapeutic effect on limb spasticity after stroke by regulating the balance of the GABAergic system and activating the Wnt/β-catenin signaling pathway. This provides a new experimental basis for the application of acupuncture in post-stroke sequelae.Clinical trial number: 2024062814.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":"228"},"PeriodicalIF":2.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12263488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A combined in vitro, in vivo and in silico approach for the discovery of bioactive molecules from Corchorus olitorius L as pancreatic lipase inhibitors, interleukin-6 and tumor necrosis factor alpha TNF-α.","authors":"Fatima Zohra Djeziri, Meriem Ghalem, Fouzia Mesli, Nassima Benzazoua, Nabila Yelles, Said Ghalem","doi":"10.1007/s10735-025-10514-3","DOIUrl":"https://doi.org/10.1007/s10735-025-10514-3","url":null,"abstract":"<p><p>This study aimed to evaluate the antioxidant, anti-inflammatory, and anti-obesity effects of bioactive compounds derived from Corchorus olitorius L., using a combined in vitro, in vivo, and in silico approach. The in vitro phase involved polyphenol extraction and antioxidant activity assays. The in vivo phase used a high-fat diet (HFD)-induced obesity model in Wistar rats divided into four groups: standard diet (STD), high-fat diet (HFD), STD with C. olitorius extract (STD + C. olitorius), and HFD with C. olitorius extract (HFD + C. olitorius). Rats received a daily oral administration of C. olitorius extract (100 mg/kg) throughout a 9-week treatment period. Plasma biochemical parameters and adipose tissue histology were assessed. The in silico phase involved molecular docking of previously identified and synthesized C. olitorius compounds against obesity- and inflammation-related targets (TNF-α, IL-6, PL), followed by ADMET predictions and analog design via bioisosteric replacement. C. olitorius treatment reduced body weight gain, visceral fat accumulation, and lipid parameters in HFD-fed rats. Histological analysis showed decreased fibrosis and inflammatory cell infiltration in adipose tissue, supporting its anti-inflammatory and anti-fibrotic effects. Molecular docking revealed that key compounds-particularly L7 (methyl-1,4,5-tri-O-caffeoylquinic acid) and L2 (3,5-dicaffeoylquinic acid)-demonstrated strong binding affinities to proinflammatory cytokines and pancreatic lipase. Analog compounds designed via bioisosteric modification retained favorable biological activity. ADME analysis indicated that the principal compounds possess favorable oral absorption properties and align with drug-likeness criteria. Compared to orlistat, these natural compounds offer a safer profile with reduced toxicity risks. This study highlights the multi-target therapeutic potential of C. olitorius derived compounds-particularly L7 and its analogs-as promising candidates for natural anti-obesity drug development. To fully establish their therapeutic value, comprehensive preclinical and clinical investigations are necessary to evaluate both efficacy and safety. Nonetheless, the current study is limited by the need for mechanistic validation and long-term toxicity assessments.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":"229"},"PeriodicalIF":2.9,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635860","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":"The effect of chitosan/alginate hydrogel loaded quercetin on wound healing in diabetic rat model.","authors":"Ghazaleh Larijani, Abolfazl Lotfi, Shirin Barati, Atousa Janzadeh, Saeid Abediankenari, Faezeh Faghihi, Naser Amini","doi":"10.1007/s10735-025-10508-1","DOIUrl":"https://doi.org/10.1007/s10735-025-10508-1","url":null,"abstract":"<p><p>Diabetic ulcers often result from a combination of ischemia and oxidative stress, which are exacerbated by inflammation in the wound. Quercetin (3,3',4',5,7-pentahydroxyflavone), a flavonoid with well-documented antioxidant and anti-inflammatory properties, has garnered significant attention in the field of skin regeneration. In addition, chitosan/alginate (C/A) wound dressings have been shown to create a conducive environment for wound healing, leveraging the antimicrobial and anti-inflammatory properties of chitosan, as well as the hydrogel and water-absorbing properties of alginate. Thus, the development of a biologic scaffold, such as quercetin-loaded C/A, may offer a promising alternative for diabetic wound treatment, providing a dermal structure that supports wound healing. In this study, a chitosan-alginate hydrogel was prepared and loaded with varying concentrations of quercetin (0.03%, 0.1%, and 0.3% w/v). Following in vitro evaluation using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), MTT assay, and swelling and degradation tests, the prepared dressings were applied to rats with diabetic wounds, and the resulting scars were analyzed histologically after a 2-week period. The FTIR spectra of the C/A hydrogels revealed characteristic absorption bands corresponding to specific functional groups, including hydroxyl (O-H), amine (N-H), and alkene (C=C) groups. Scanning electron microscopy (SEM) analysis demonstrated successful blending of the hydrogels and adequate cell adhesion. The MTT assay results indicated no significant differences in cellular metabolic activity among the groups. The water uptake levels reached a plateau after 240 min across all experimental groups, suggesting a saturation point in water absorption capacity. The degradation rate of the hydrogel increased substantially from day 1 to day 7, with no significant differences observed among the groups, regardless of quercetin loading. A marked increase in re-epithelialization and collagen deposition was observed across all groups at day 14 compared to day 7, although no significant differences were detected between the quercetin-treated groups and the control or C/A groups. The reduction in wound diameter was significantly greater in the quercetin-treated groups compared to the control and C/A groups at day 14 (p < 0.05). Although our quercetin-loaded chitosan/alginate (2:1) wound dressing did not exhibit significant benefits in terms of re-epithelialization or collagen deposition, it did demonstrate efficacy in reducing wound diameter in diabetic rats.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":"225"},"PeriodicalIF":2.9,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615702","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":"miR-429 suppresses progression and metastasis of salivary adenoid cystic carcinoma by targeting ZEB1.","authors":"Juan Li, Hongwei Zhao","doi":"10.1007/s10735-025-10504-5","DOIUrl":"https://doi.org/10.1007/s10735-025-10504-5","url":null,"abstract":"<p><p>miR-429 is a tumor suppressor that has been observed in various cancers. The exact mechanism by which miR-429 affects salivary adenoid cystic carcinoma(SACC) is not fully understood. Initially, the expression of miR-429 and zinc finger E-box-binding homeobox 1 (ZEB1) in tumor tissues and matched adjacent non-tumor tissues of SACC patients were inspected by quantitative real-time polymerase chain reaction. Next, CCK-8, wound healing, transwell, and dorsal root ganglion (DRG) co-culture models were used to explore the effects of miR-429 on SACC cell proliferation, migration, invasion, and perineural invasion (PNI). Finally, the downstream target genes of miR-429 were screened and validated through bioinformatics analysis and dual-luciferase reporter analysis, and the regulatory role of miR-429 on epithelial-mesenchymal transition (EMT) in SACC cells was explored. miR-429 was poorly expressed while ZEB1 was substantially expressed in SACC tumor tissues. Elevated levels of miR-429 led to a significant suppression of SACC cell of proliferation, migration, invasion, and PNI. ZEB1 was screened and validated as a downstream target gene of miR-429. High concentrations of miR-429 also markedly lowered the expression of ZEB1 in SACC cells, thereby inhibiting EMT. These results suggest that miR-429 is lowly expressed in SACC, may suppress progression and metastasis of SACC cells, and is associated with ZEB1 and the EMT pathway.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":"224"},"PeriodicalIF":2.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590184","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":"CYP2E1 overexpression in hepatocellular carcinoma modulates tumor invasion and migration via Wnt/β-catenin signaling pathway.","authors":"Sharmeen Ishteyaque, Karan Singh Yadav, Shobhit Verma, Arpon Biswas, Rabi Sankar Bhatta, Madhav Nilakanth Mugale","doi":"10.1007/s10735-025-10500-9","DOIUrl":"https://doi.org/10.1007/s10735-025-10500-9","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the primary cause of cancer-related mortality in the world. Cytochrome P450 2E1 (CYP2E1) plays a key role in metabolizing xenobiotics and toxic substances. The attempts to target CYP2E1 with inhibitors have yielded limited success in cancer treatment. Loss and gain-of-function experiments were performed to investigate the effects of CYP2E1 on HepG2 and Hepa 1-6 cells. Migration, invasion, intracellular reactive oxygen species (ROS) accumulation, and mitochondrial membrane potential were assessed in HepG2 cells. In vivo histopathological alterations were studied in DEN-administered rat models. Western blotting was performed to evaluate the mechanistic activation of the Wnt/β-catenin signaling pathway. In our pursuit, to elucidate the impact of CYP2E1 in carcinogenesis we revealed that in vitro, overexpression of CYP2E1 enhances the migration, invasion, increases the accumulation of intracellular ROS, and reduces the loss of mitochondrial membrane potential of HepG2 cells. In contrast, siRNA-mediated silencing of CYP2E1 produced the opposite effects. Histopathological analysis of liver sections showed pathological features such as clear cell foci, bile duct proliferation, inflammatory cell infiltration and nodule formation. In vitro and in vivo, mechanistic analysis demonstrated that CYP2E1 overexpression significantly activated the Wnt/β-catenin signaling pathway in HCC cells, as evidenced by increased protein levels of β-catenin, LEF, Cyclin D1 and survivin in immunoblot study. In vivo increased β catenin, LEF and GPC3 enhance the carcinogenicity as revealed in immunohistochemistry results. Altogether, the above findings indicates that CYP2E1 has a pivotal role in the pathogenesis and progression of HCC identifying it as a potential target for liver cancer treatment.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 4","pages":"218"},"PeriodicalIF":2.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590181","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}