Journal of Molecular Histology最新文献

{"title":"Dysregulated autophagy in periodontal ligament stem cells of individuals with type 2 diabetes mellitus and periodontitis","authors":"Qian-Qian Chen,&nbsp;Jie Huang,&nbsp;Qi Liu,&nbsp;Kun Yang","doi":"10.1007/s10735-025-10455-x","DOIUrl":"10.1007/s10735-025-10455-x","url":null,"abstract":"<div><p>This study aimed to investigate autophagy and its associated mechanisms in periodontal ligament stem cells (PDLSCs) within the inflammatory microenvironment of type 2 diabetes mellitus (T2DM) and periodontitis. Periodontal ligament tissues were obtained from healthy individuals, individuals with T2DM, individuals with chronic periodontitis, and individuals with both T2DM and periodontitis. PDLSCs were isolated, cultured, and treated with the autophagy inhibitor 3-methyladenine (3-MA) and the autophagy activator rapamycin (Rapa). Cell proliferative capacity was evaluated, autophagic activity and organelle damage were assessed using transmission electron microscopy, and the relative expression levels of autophagy-related genes (<i>Beclin-1</i>,<i> LC3 II</i>,<i> P62</i>) were measured using real-time quantitative PCR. Compared to PDLSCs derived from healthy individuals, those from individuals with chronic periodontitis or T2DM exhibited no significant morphological differences but demonstrated reduced proliferative capacity. Treatment with 3-MA and Rapa did not significantly alter proliferative capacity across groups. PDLSCs from individuals with chronic periodontitis and T2DM displayed increased autophagosome formation, more severe organelle damage, and upregulated expression of autophagy-related genes <i>Beclin-1</i> and <i>LC3 II</i>, while P62 expression was downregulated, compared to PDLSCs from healthy individuals. PDLSCs from individuals with T2DM and periodontitis exhibit excessive autophagy and organelle damage. Autophagy dysregulation in PDLSCs within a diabetic and inflammatory microenvironment may contribute to the severity of periodontal destruction observed in individuals with T2DM.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144090974","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 autologous cytokine-rich serum and platelet-rich plasma administration on oxidative status, minerals and proinflammatory cytokines in brain and serum in cyclophosphamide-induced ovarian failure","authors":"Mustafa Ermiş,&nbsp;Erol Karakaş,&nbsp;Hanifi Erol,&nbsp;Gökhan Akcakavak,&nbsp;Recai Aci,&nbsp;Furkan Ümit,&nbsp;Özhan Karatas,&nbsp;Gülay Çiftci","doi":"10.1007/s10735-025-10448-w","DOIUrl":"10.1007/s10735-025-10448-w","url":null,"abstract":"<div><p>Cyclophosphamide (CP) is one of the most commonly used chemotherapy agents and carries a high risk of ovarian damage. This study aimed to evaluate the effects of autologous cytokine-rich serum (ACRS) and platelet-rich plasma (PRP) on brain oxidative status, mineral levels, and proinflammatory cytokines in rats with CP-induced ovarian failure. A total of 42 female Wistar rats (12-weeks-old) were used in the study. Six of these rats were allocated as donors, and the remaining 36 rats were randomly distributed into six groups (n = 6 per group). Group 1 received no treatment. On the 1st and 7th days, 75 mg/kg of CP was administered intraperitoneally to Groups 4, 5, and 6. On day 1, PRP was administered intraovarianly to Groups 2 and 5, while ACRS was administered intraovarianly to Groups 3 and 6. Additionally, PRP and ACRS were administered intraperitoneally to the respective groups on 7th and 14th days.The study was terminated at the end of the 31st day. Brain tissue and blood samples were collected for biochemical analyses and ovarian tissue samples were collected for histomorphological examinations. Morphological analysis using Hematoxylin–Eosin (HE) staining and immunohistochemical evaluation for AMH, α-SMA, and IL-1β were conducted on the ovaries. Proinflammatory cytokines and insulin levels were measured using ELISA test kits. TAS/TOS levels were assessed using Relassay Diagnostic kits. Biochemical parameters and mineral levels were measured using autoanalyzer. Histopathological evaluation revealed that follicular degeneration, congestion, hemorrhage, edema, and inflammatory cell infiltration, as well as the number of atretic follicles and IL-1β immunoreactivity, were observed at the highest levels in the CP group (Group 4). In contrast, the numbers of primordial, primary, secondary, and tertiary follicles, along with AMH and α-SMA immunoreactivity levels, were found to be the lowest in this group. However, positive therapeutic effects were observed in the CP-treated groups (Groups 5 and 6). In the serum, increased levels of AST, ALT, creatinine, glucose, LDL, TOS, Ca, Fe, Mg, IL-1β, IL-1α, TNF-α, and NF-kB were detected in the CP groups (G4, G5, G6) compared to the control groups (G1, G2, and G3). In brain tissue, a decrease of total protein and total cholesterol levels were observed in the CP groups (G4, G5, G6) compared to the control groups, while increases in Na, Cl, Fe, IL-1β, IL-1α, TNF-α, and NF-kB levels were detected. In conclusion, PRP and ACRS therapies from the patient's own blood have a potential as supportive or chemopreventive strategies with reduced side effects and treatment costs.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084810","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":"Activation of Hippo/YAP signaling pathway exacerbates vascular remodeling and aggravates hypertension by upregulating Foxm1","authors":"Jing Bai,&nbsp;Yujuan Yang","doi":"10.1007/s10735-025-10443-1","DOIUrl":"10.1007/s10735-025-10443-1","url":null,"abstract":"<div><p>The Hippo/YAP signaling pathway is closely related to the occurrence and development of cardiovascular diseases. However, it’s still unclear whether this pathway plays a certain role in hypertension. In this study, aortic morphology and function in spontaneously hypertensive rats (SHR) were comprehensively evaluated using Wistar-Kyoto rats (WKY) as controls. Results indicated that the aorta of SHRs have distinct changes in pathological structure. Furthermore, the proliferative activity of vascular smooth muscle cells (VSMCs) was enhanced, with vascular fibrosis being aggravated. Immunohistochemical analysis revealed that SHRs exhibited high expression of Yes-Associated Protein (YAP). Western Blot analysis showed that cytoplasmic YAP and TAZ expression decreased in hypertensive rats, indicating that YAP/TAZ nuclear transfer increased and Hippo/YAP signaling pathway had been activated. The cell function experiments of VSMCs extracted from rat aorta showed that the cell viability and proliferation ability of VSMCs in SHRs were enhanced, the expression of Fibronectin and collagen I was increased, and vascular fibrosis was aggravated. siRNA-YAP (si-YAP) can reverse the above phenomenon in VSMCs. Knockdown of YAP can inhibit Foxm1 expression. As an inhibitor of large tumor suppressor kinases LAST1/2, GA-107 can inhibit the phosphorylation level of YAP, increase blood pressure, aggravate aortic pathomorphological changes, promote VSMCs proliferation and vascular fibrosis, and thus aggravate hypertension symptoms in SHRs. However, these effects of GA-107 can be antagonized by inhibiting Foxm1 with thiosulfathiazole (Thio). Conclusively, Hippo/YAP signaling pathway promotes vascular remodeling through the regulation of Foxm1 and causes hypertension.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084808","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":"Evaluation of the protective effects of raw and roasted pumpkin (Cucurbita pepo L.) seed-supplemented diets on cisplatin-induced cardiotoxicity in rats","authors":"Seun Funmilola Akomolafe,&nbsp;Moses Orimoloye Akinjiyan,&nbsp;Nnaemeka Tobechukwu Asogwa,&nbsp;Olusola Olalekan Elekofehinti","doi":"10.1007/s10735-025-10432-4","DOIUrl":"10.1007/s10735-025-10432-4","url":null,"abstract":"<div><p>Cardiovascular diseases are among the top killer diseases globally. This work assessed the cardioprotective ability of raw and roasted pumpkin (<i>Cucurbita pepo</i> L.) seed-supplemented diets on cisplatin-induced heart damage in rats. The cardiotoxicity was induced with cisplatin (7 mg/kg) intraperitoneally. The rats’ six groups were treated for 14 days: control rats fed a normal diet; group 2: cisplatin-induced (CIS) untreated; groups 3 and 4: CIS + 5% raw pumpkin seed (RW) and CIS + 10% RW; groups 5 and 6: CIS + 5% and 10% roasted pumpkin seed (RT). The biochemical assays were done using standard procedures, and Schrödinger suites were used for in silico studies of <i>C. pepo</i> phytocompounds with phosphodiesterase 5. There was a significant (<i>p</i> &lt; 0.05) elevation in arginase, phosphodiesterase-5, adenosine deaminase, acetylcholinesterase, and butyrylcholinesterase activities, ROS and TBARS in cisplatin-induced rats relative to control. Cisplatin-induced rats also have their nitric oxide, antioxidant (catalase, GST, and GSH) levels reduced, and the heart’s histoarchitectural structure degenerated relative to control. These conditions were reversed upon treatment with raw and roasted pumpkin seeds (5% and 10%). Molecular docking of <i>C. pepo</i> phytocompounds like chlorogenic acid (-11.4 kcal/mol), beta-sitosterol (-11.013 kcal/mol), quercetin (-10.323 kcal/mol), and epicatechin (-10.168 kcal/mol) suggests that they are potent inhibitors of phosphodiesterase 5, better than standard drug pravastatin (-9.809 kcal/mol), with a good pharmacotoxicity profile. The study suggests that the cardioprotective effect of raw and roasted pumpkin seeds could be via their ability to inhibit phosphodiesterase 5, improve vasodilation, increase antioxidant levels, and alleviate oxidative stress.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084809","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":"Field Marigold (Calendula arvensis L.) accelerates wound-healing in vivo: role of transforming growth factor-beta1 (TGF-β1), inflammatory, and biochemical molecules","authors":"Safwan Mahmoud Al-Adwan,&nbsp;Talal Salem Al-Qaisi,&nbsp;Ahmed A.j. Jabbar,&nbsp;Kamaran Younis M. Amin,&nbsp;Hawri Fatih Sami,&nbsp;Hanan Ibrahim Althagbi,&nbsp;Ahmed Hameed Al-Dabhawi,&nbsp;Bassam Ali Abed Wahab,&nbsp;Rawaz Rizgar Hassan,&nbsp;Mahmood Ameen Abdulla,&nbsp;Musher Ismael Saleh","doi":"10.1007/s10735-025-10433-3","DOIUrl":"10.1007/s10735-025-10433-3","url":null,"abstract":"<div><p>Medicinal plants are major sources of natural products, which have gained a renewed interest in recent years because of drawbacks associated with synthetic ones used for human health disorders. <i>Calendula arvensis</i> L. is a traditional medicinal plant used for many inflammatory-related diseases. The study explores the acute toxicity and wound-healing effects of methanolic extracts of <i>Calendula arvensis</i> L. aerial parts (MECAA) on excisional neck injury in rats. A two-week acute toxicity procedure was applied to find the safety of MECAA in animal models. For the wound-healing experiment, a uniform dorsal neck injury was created for twenty-four Sprague–Dawley rats, which were aligned arbitrarily into 4 groups and received topical treatments; group A rats addressed with normal saline; group B rats had intrasite gel; groups C and D rats had 0.2 ml of 250 and 500 mg/kg of MECAA, respectively. There was no toxicity nor mortality in rats supplemented orally with up to 5 g/kg MECAA. MECAA topical addressing accelerated wound contraction represented by higher deposition of fibroblast and keratinocytes, angiogenic factors, and reduced inflammatory cells. MECAA treatment up-regulated tissue antioxidants (SOD and CAT), transforming growth factor-β 1, and hydroxyproline (collagen) contents while lowering MDA and serum inflammatory mediators (TNF-α and IL-6). The outcomes can serve as scientific evidence for the traditional use of <i>Calendula arvensis</i> as a wound healer, which requires further molecular isolation and identification as a viable source of a potent drug formulation.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074025","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":"Downregulation of MPC1 promotes HCC cell proliferation and metastasis via the STAT3 pathway","authors":"Dandan Shan,&nbsp;Qiuxian Zheng,&nbsp;Zhi Chen","doi":"10.1007/s10735-025-10435-1","DOIUrl":"10.1007/s10735-025-10435-1","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) is prevalent globally, and the discovery of new targets is vital for the treatment of HCC. Mitochondrial pyruvate carrier 1 (MPC1) has been found to exhibit reduced expression and promote tumour progression in some cancers, although its role in HCC needs to be explored. Using GEO datasets and Kaplan‒Meier plotter, the clinicopathological features and patient prognosis were analysed by assessing the expression levels of MPC1 in HCC tissues. After MPC1-knockdown and MPC1-overexpressing cell lines were constructed, the effects of modulating MPC1 expression on the malignant phenotype of HCC cells were tested via CCK8, colony formation, and scratch assays and flow cytometry. The effects of MPC1 on HCC cells and mitochondria were examined via MitoTracker Red CMXRos staining, cytoskeleton staining and cellular energy metabolism assays. MPC1 expression was found to be reduced in HCC patients and correlated with prognosis and clinicopathological features. It was found that low expression of MPC1 promotes the malignant phenotype of HCC cells and affects the mitochondrial energy metabolism of HCC cells to support the tumour microenvironment, and that MPC1 may act through signal transducer and activator of transcription 3 (STAT3). MPC1 might play a tumor-suppressing role in HCC through its interaction with STAT3, and this discovery could offer novel perspectives for HCC treatment.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949654","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":"Oleuropein attenuates cardiac and lung injury induced by 5-fluorouracil via modulating oxidative stress and TNF-α/IL-6 signaling pathway","authors":"Shokofeh Banaei,&nbsp;Vahid Asghariazar,&nbsp;Faraz Mahdizadeh,&nbsp;Mohammad Ghasem Golmohammadi,&nbsp;Elham Safarzadeh","doi":"10.1007/s10735-025-10437-z","DOIUrl":"10.1007/s10735-025-10437-z","url":null,"abstract":"<div><p>The cardiac and lung damage are considered a serious risk associated with the administration of chemotherapy agents like 5-fluorouracil (5-FU). Oleuropein (OLE) is valuable medicinal plant that has diverse pharmacological properties with remarkable antioxidant activities. This research aimed to evaluate the impact of OLE on cardiac and pulmonary toxicity induced by 5-FU. 24 adult rats were randomly assigned to four groups (N = 6), which included a control group, a group receiving 5-FU at a dosage of 100 mg/kg, a group administered OLE at 200 mg/kg, and a group treated with both 5-FU and OLE (5-FU + OLE). Following the treatment, blood samples were obtained for the assessment of biochemical parameters, and the cardiac and pulmonary tissues were removed for the measurement of oxidative stress and inflammatory cytokines and histological alterations. 5-FU elevated lipid profiles (triglyceride, low-density lipoprotein (LDL), and cholesterol), glucose serum levels, and myocardial injury markers (CK-MB and LDH), malondialdehyde (MDA), interleukin‐6 (IL-6) and tumor necrosis factor alpha (TNF-α) expression. Additionally, the histopathological analysis of 5-FU revealed dystrophic calcification (DC) in the cardiac tissues and neutrophil infiltration in the lung tissues. However, the administration of OLE reduced lipid profiles, glucose, lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB) levels and inflammation, improved antioxidant capacity, and pathological alterations. It seems that OLE exerts cardio-pulmonary protective effects against 5-FU toxicity through the decrease of oxidative stress and inflammatory cytokines.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925681","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 effects of the GLP1 analog liraglutide on allodynia and motor coordination in peripheral neuropathy induced by a chemotherapeutic agent, cisplatin","authors":"Fikriye Yasemin Ozatik,&nbsp;Yasemin Teksen,&nbsp;Orhan Ozatik,&nbsp;Cigdem Çengelli Unel,&nbsp;Suna Karadeniz Saygili","doi":"10.1007/s10735-025-10440-4","DOIUrl":"10.1007/s10735-025-10440-4","url":null,"abstract":"<div><p>Peripheral neuropathy is one of the dose-limiting side effects of cisplatin (CIS) and still has no effective treatment. In this study, we aimed to investigate the potential protective effects of liraglutide, a Glucagon-like peptide-1 (GLP-1) analogue against CIS-induced peripheral neuropathy. For this purpose, female Sprague Dawley rats (<i>n</i> = 32) were randomly allocated into 4 groups: control, CIS, CIS + liraglutide (once weekly) and CIS + liraglutide (daily). Neuropathic pain was induced by CIS 3 mg/kg/week for 5 weeks. The potential effects of liraglutide were investigated by behavior tests (von Frey, tail flick and footprint analysis), biochemical analysis and histopathological analyses of sciatic nerves and dorsal root ganglions. In the von Frey and tail flick tests, liraglutide demonstrated anti-neuropathic effects. Liraglutide also ameliorated motor coordination which was impaired by CIS. Liraglutide was shown to have beneficial effects against CIS-induced peripheral neuropathy by parameters demonstrating reduction of histopathological damage (stained by toluidine blue) of the sciatic nerves and dorsal root ganglions, suppression of oxidative stress parameters (SOD, CAT and GPx), and inflammatory load (NO, IL-6 and IL-10). Weekly dosing regimen was more effective than daily administration of liraglutide in this study. As a result, liraglutide seems to be the candidate agent for the effective treatment of CIS-induced peripheral neuropathy.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925680","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":"Autografted hair follicles with dermal papilla removed promote wound repair and regeneration in Bama mini-pigs","authors":"Wenzi Liang,&nbsp;Chang Mai,&nbsp;Yuandong Yuan,&nbsp;Xiuwen Chen,&nbsp;Bozhi Cai,&nbsp;Na Ni,&nbsp;Chutong Zhuang,&nbsp;Changmin Lin,&nbsp;Keng Huang","doi":"10.1007/s10735-025-10420-8","DOIUrl":"10.1007/s10735-025-10420-8","url":null,"abstract":"<div><p>Autologous free flap transplantation is the most economical and effective method for clinical treatment of large-area trauma, but the shortage of flap donors prevents widespread use of this method. Hair follicle stem cells have great potential to repair wounds, but wound repair by hair follicle stem cells has not yet met expectations. We used a wound model of Bama mini-pigs and treated the wound with autologous hair follicles or flaps. The wound healing was observed on days 7, 14, and 21 post-surgery and wound healing rates were analyzed using Image J software. Hematoxylin and eosin staining was performed to evaluate re-epithelialization of the wound. Immunofluorescence staining was used to detect the expression of hair follicle stem cell markers (CK15, Sox9) and explore the mechanism of wound repair. This research found that autologous hair follicles can accelerate wound healing. The efficiency of hair follicles in wound repair is related to their structure. Dermal papilla acts as a biological barrier to hair follicle-mediated wound repair. Dermal papilla removal enhances wound healing efficiency, likely by relieving dermal papilla-imposed restrictions on hair follicle stem cell migration. Autologous hair follicles for wound repair has the advantages of minimal damage, simple fabrication, and abundant source, which may be able to replace the flap transplantation as a therapeutic strategy in the future. This study is helpful to elucidate the regulatory mechanism of hair follicles involved in wound repair, and has important academic and clinical value for solving the problem of shortage flap donor.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925699","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":"Demethylated miR-184 regulates EPB41L5 and downregulates Notch signaling to inhibit metastasis in colorectal cancer","authors":"Yin Shu,&nbsp;Xiaohui Cai,&nbsp;Xinhui Yang,&nbsp;Yuping Yang,&nbsp;Lei Ge","doi":"10.1007/s10735-025-10434-2","DOIUrl":"10.1007/s10735-025-10434-2","url":null,"abstract":"<div><p>Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with metastasis being a major contributor to poor prognosis. MicroRNA-184 (miR-184) has been implicated in the progression of various cancers, but its role in CRC metastasis remains poorly defined. This study investigated the effects of miR-184 promoter demethylation on EPB41L5 expression and Notch signaling in CRC. SW620 human colon carcinoma cells were treated with the DNA methylation inhibitor 5-Aza for 96 h. Methylation status was assessed via bisulfite sequencing, and gene expression was evaluated using qRT-PCR and Western blotting. Functional assays were conducted to assess cell proliferation, apoptosis, migration, and invasion. 5-Aza treatment significantly decreased miR-184 promoter methylation, leading to increased miR-184 expression. This upregulation suppressed CRC cell migration and invasion, induced G2/M cell cycle arrest, and promoted apoptosis. Mechanistically, miR-184 inhibited EPB41L5 expression, thereby downregulating the Notch signaling pathway and modulating epithelial–mesenchymal transition markers. High EPB41L5 expression in CRC tissues was associated with worse prognosis. These findings suggest that demethylated miR-184 inhibits CRC metastasis by targeting the EPB41L5/Notch signaling axis. This regulatory pathway may serve as a novel prognostic biomarker and therapeutic target, with potential clinical implications for the prevention and treatment of metastatic colorectal cancer.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143925700","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}