{"title":"Significance feature of saffron on testicular histomorphometry and expression profile of antioxidant enzymes in mice with induced multiple sclerosis: an in-vivo study.","authors":"Arezoo Teymoori, Farzaneh Fesahat, Maryam Yadegari, Morteza Anvari, Majid Pourentezari","doi":"10.1007/s10735-025-10444-0","DOIUrl":"https://doi.org/10.1007/s10735-025-10444-0","url":null,"abstract":"<p><p>Multiple sclerosis (MS), a chronic autoimmune disease of the central nervous system (CNS), is characterized by demyelination and oxidative stress. Given the established link between MS and impaired reproductive function, the potential protective role of Crocus sativus (saffron) against testicular damage warrants investigation. This study aimed to assess the effects of saffron on testicular histomorphology and the expression of antioxidant enzymes in a cuprizone-induced MS mouse model. Forty adult male mice were randomly assigned to four groups (n = 6 per group) of the control group; saff group with an intraperitoneal injection of 50 mg/kg saff for 35 days; Cpz + saff group with intraperitoneally injected with 50 mg/kg saff and feeding with 0.2% of Cpz daily, 35 days;and Cpz group feeding with 0.2% of Cpz daily for 35 days. Testicular tissue was collected for histological evaluation by stereological methods as well as analysis of the gene expression of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), Bcl-2, and Bax using real-time PCR. Enzymatic activity of SOD, GPx, and CAT was also assessed. Histopathological analysis revealed significant testicular atrophy and degenerative changes in the MS group, accompanied by reduced seminiferous tubule diameter and epithelial thickness. Saffron administration improved these parameters, preserved testicular architecture, and increased the number of spermatogenic cells. Moreover, saffron treatment significantly upregulated the mRNA expression and activity of antioxidant enzymes (SOD, GPx, and CAT), increased Bcl-2 expression, and downregulated Bax expression. Saffron exhibits protective effects against MS-induced testicular damage by enhancing antioxidant defenses and modulating apoptosis-related gene expression. These findings suggest the potential therapeutic role of saffron in preserving male reproductive function in the context of MS.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":"181"},"PeriodicalIF":2.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197984","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":"Helicobacter pylori VacA-induced gastric mucosal atrophy: a comparative analysis with other forms of atrophic gastritis.","authors":"Yang-Kun Wang, Wen-Rui Chen, Ling-Yan Lu, Ying-Ying Li, Rui-Kun Qiu, Chao-Ya Zhu, Fa-Shun Zhang, Su-Nan Wang, Si-Liang Xu","doi":"10.1007/s10735-025-10469-5","DOIUrl":"https://doi.org/10.1007/s10735-025-10469-5","url":null,"abstract":"<p><p>This study aimed to evaluate the atrophic changes induced by Helicobacter pylori VacA and compare them with other forms of atrophic gastritis.A comprehensive histomorphological analysis and immunohistochemical evaluation were performed on 984 endoscopic gastric mucosal biopsy samples from patients with endoscopically confirmed atrophic gastritis. H. pylori primarily adheres to surface mucus cells, where it proliferates and produces the vacuolating cytotoxin VacA. The underlying mechanism involves VacA inducing the upward migration and compensatory proliferation of cells located in the deeper regions of gastric pits, the isthmus of gastric glands, and the neck mucous cells, ultimately leading to gastric atrophy. In this study, a comparative analysis was performed with autoimmune atrophy, degenerative denaturation atrophy, drug-induced atrophy, and non-specific atrophy. Both clinical and histological characteristics were evaluated, and pathological diagnostic criteria for mucosal atrophy were proposed for the first time. Of the 984 cases examined, H. pylori-induced atrophic gastritis was identified in 648 cases, accounting for 65.9% (648/984); autoimmune atrophy in 34 cases, representing 3.5% (34/984); degenerative denaturation atrophy in 59 cases, representing 6.0% (59/984); drug-induced atrophy in 72 cases, making up 7.3% (72/984); and non-specific atrophy in 171 cases, accounting for 17.4% (171/984). H. pylori infection was found to be associated with a high prevalence of infectious atrophy, accompanied by active epithelial cell proliferation, intraepithelial neoplasia, early changes in mucosa-associated lymphoid tissue lymphoma, and cell proliferation outside the lymphatic follicular mantle. The comparative analysis of gastric mucosal atrophy induced by H. pylori VacA, in comparison to other forms of atrophic gastritis, is crucial for understanding the pathogenesis of gastric cancer and improving management strategies for its prevention and progression.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":"180"},"PeriodicalIF":2.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197981","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":"Porphyromonas gingivalis induced DNA oxidative stress damage by iron overload to deplete CTCF expression and prevent osteogenic differentiation of periodontal ligament stem cells.","authors":"Ying Zhang, Chenchen Si, Changyi Yang, Aijuan Wang, Bohan Yu","doi":"10.1007/s10735-025-10467-7","DOIUrl":"https://doi.org/10.1007/s10735-025-10467-7","url":null,"abstract":"<p><p>We aimed to investigate the effects of Porphyromonas gingivalis (P. gingivalis) on DNA oxidative damage and osteogenic differentiation of periodontal ligament stem cells (PDLSCs) mediated by iron overload, with special attention to the role of CCCTC-binding factor (CTCF). PDLSCs were co-cultured with different concentrations of P. gingivalis-derived LPS. In addition, deferoxamine (DFO, an iron chelator) or recombinant CTCF protein were used to co-treat PDLSCs. Western blot, immunofluorescence staining, flow cytometry and transmission electron microscopy (TEM) were used to observe the iron overload mediated DNA oxidative damage in PDLSCs. Osteogenic differentiation was assessed based on alkaline phosphatase (ALP) activity, mineralization nodule formation, and bone-related protein expression. CTCF was down-regulated in the gingival tissue of periodontitis patients. P. gingivalis-derived LPS significantly decreased the viability of PDLSCs and suppressed CTCF protein expression, particularly at high concentrations (1 μg/mL 10 μg/mL P. gingivalis-derived LPS). However, co-treatment with DFO alleviated these effects by up-regulating CTCF expression and reducing intracellular iron levels, lipid peroxidation, and DNA damage. Furthermore, P. gingivalis-derived LPS inhibited osteogenic differentiation by decreasing ALP activity, mineralization, and expression levels of bone-associated proteins Runx2, BMP2, BMP4, OPN, and OCN. However, this inhibition was significantly reversed by recombinant CTCF treatment. Our findings underscore the detrimental impact of P. gingivalis on PDLSCs through the suppression of CTCF and highlight the potential therapeutic role of DFO and CTCF in preserving PDLSC function and osteogenic potential.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":"182"},"PeriodicalIF":2.9,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197983","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":"Histological study of the therapeutic effect of valerian extract alone or in combination with co-enzyme Q10 on experimentally induced gastric ulcers in adult albino rats: a light and scanning electron microscopic study.","authors":"Heba G Ibrahim, Ghada A Meheissen, Amira M Omar","doi":"10.1007/s10735-025-10466-8","DOIUrl":"https://doi.org/10.1007/s10735-025-10466-8","url":null,"abstract":"<p><p>Gastric ulcer, affecting 10% of the global population, can lead to severe complications as perforation, bleeding, and fatal outcomes. Valerian extract and coenzyme Q10 show a potential as therapeutic agents that decrease inflammation and protect against oxidative damage. To evaluate the therapeutic effect of the co-administration of valerian extract and coenzyme Q10 versus the administration of each of them alone in ameliorating experimentally induced gastric ulcer. Rats were randomly assigned into the following groups: the control, the ulcer-induced, the treated groups: valerian extract, coenzyme Q10, and both treatments, all administered orally one hour after orally ingestion of ethanol, and finally untreated group. After the rats were sacrificed, their stomachs were analyzed macroscopically, histologically, and immunohistochemically. The ulcer-induced group demonstrated severe gastric damage with hyperemia and brownish hemorrhagic spots macroscopically, along with various histological changes, including deep gastric ulcers and multiple erosions. There was complete destruction of the fundic glands and their lining cells, areas of hemorrhage, loss of mucopolysaccharide content, and fibrosis which were confirmed by morphometrical studies. Scanning electron microscopy revealed wide ulcers and complete shedding of surface mucous epithelial cells. Valerian extract and coenzyme Q10 groups showed partial improvement with an increased rate of proliferation detected by immunohistochemical study. The combination of both drugs provided restoration of the gastric mucosa to a nearly control-like appearance. Combined treatment with valerian and Coenzyme Q10 was more effective than either alone in restoring the mucous barrier, regenerating epithelial cells, and reducing inflammation.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":"176"},"PeriodicalIF":2.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155470","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}
Liujia Sun, Xiaoqi Hong, Qi Zhu, Yu Xiang, Cen Xu, Lingling Weng, Jieyu Cai, Na Liang, Mingrui Xue, Hongshan Ge
{"title":"Dietary intervention enhances fertility in obese male mice by regulating SLC2As.","authors":"Liujia Sun, Xiaoqi Hong, Qi Zhu, Yu Xiang, Cen Xu, Lingling Weng, Jieyu Cai, Na Liang, Mingrui Xue, Hongshan Ge","doi":"10.1007/s10735-025-10470-y","DOIUrl":"https://doi.org/10.1007/s10735-025-10470-y","url":null,"abstract":"<p><p>Research has demonstrated that obesity can affect male fertility and reproductive potential, but the underlying mechanism remains unclear. This study aimed to investigate the effects of a high-fat diet (HFD) and dietary intervention on reproductive function, glucose metabolism, and related SLC2As in male mice. Forty 4-week-old male ICR mice were randomly divided into the normal diet (ND) group (group N, n = 15) and the HFD group (group F, n = 25). After 12 weeks, the mice were further divided into the following groups: ND maintenance group (NN group, n = 10), HFD maintenance group (FF group, n = 10), and transition to ND group (FN group, n = 10) through dietary intervention for 8 weeks. Intraperitoneal glucose tolerance test (IPGTT) was performed, and parameters including fasting blood glucose, body weight, sperm count, sperm motility, and testis and epididymis measurements were recorded. Testicular morphology was observed through hematoxylin-eosin staining. Western blot and immunofluorescence were used to detect the protein expression and localisation of SLC2As in the testis. Long-term HFD consumption resulted in increased body and testicular weights, decreased testicular and epididymal organ coefficients, reduced sperm motility rate, and increased area under the curve in the IPGTT test. After dietary intervention, compared to the NN group, the FF and FN groups exhibited increased testis weight, decreased testicular and epididymal organ coefficients, decreased sperm motility rate, reduced SLC2A3 and SLC2A8 protein expression levels in the FF group, and decreased SLC2A8 protein expression in the FN group. Obesity induced by HFD caused damage to the reproductive system of male mice and affected testicular glucose metabolism and the expression of sugar transporter SLC2As. Transitioning from HFD to ND can improve reproductive dysfunction caused by dietary obesity and its impact on sugar transporter protein expression to a certain extent.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":"174"},"PeriodicalIF":2.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155461","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}
Waseem Ali, Atique Ahmed Behan, Yonggang Ma, Yan Chen, Hao Zheng, Zongping Liu, Hui Zou
{"title":"Cadmium-induced disruption of exosomal secretion and cellular pathways in leydig cells.","authors":"Waseem Ali, Atique Ahmed Behan, Yonggang Ma, Yan Chen, Hao Zheng, Zongping Liu, Hui Zou","doi":"10.1007/s10735-025-10463-x","DOIUrl":"https://doi.org/10.1007/s10735-025-10463-x","url":null,"abstract":"<p><p>Cadmium is a toxic heavy metal, disrupts different cellular secretions and induce pathological changes in the male reproductive system. However, cadmium-induced disruption of exosomal secretion and cellular pathways in Leydig cells is largely unknown. In this study, 30 C57BL/6 male mice were divided into two groups: one receiving purified water and the other 50 mg/L CdCl2 for three months. This is a first report, both in vivo and in vitro analyses showed that the control group exhibited strong immunoreactivity and immunosignaling with high secretion of exosomal proteins CD63 and multivesicular bodies (MVBs) through immunohistochemistry, immunofluorescence, and transmission electron microscopy. Leydig cells in the control group maintained a normal steroidogenic pathway, supporting the production of healthy, motile spermatozoa. Conversely, the cadmium-treated group showed irregularly dispersed Leydig cells with condensed nuclei and vacuolated mitochondria. Cadmium exposure led to reduced immunoreactivity, immunosignaling, and expression of CD63 in Leydig cells, with a noticeable lack of MVBs secretion. Additionally, cadmium significantly down-regulated the Steroidogenesis regulatory proteins STAR, CYP11A1, CYP17A1, 3BHSD1, 17BHSD1 and AR of Leydig cells. It also disrupted autophagic flux evidenced by increased expression of ATG5, ATG7, LC3, P62, and LAMP2 proteins. Furthermore, cadmium up-regulated apoptotic proteins (Caspase-3, Caspase-8, and Bax) and down-regulated the anti-apoptotic protein Bcl-2. This study provides novel insights into the detrimental effects of cadmium on Leydig cells' secretory pathways, highlighting disruptions in exosomal-MVBs secretion, autophagy and apoptosis, thereby posing significant risks to male fertility.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":"177"},"PeriodicalIF":2.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155458","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}
Esraa S Habiba, Mona Hassan Fathelbab, Eman M Omar, Aliaa M T ElAlkamy, Walaa Omar, Sahar A Harby
{"title":"Capsaicin counteracts dexamethasone-induced osteoporosis and metabolic disturbances in rats: role of AMPK/SIRT1/β-catenin/RUNX2 pathway.","authors":"Esraa S Habiba, Mona Hassan Fathelbab, Eman M Omar, Aliaa M T ElAlkamy, Walaa Omar, Sahar A Harby","doi":"10.1007/s10735-025-10460-0","DOIUrl":"https://doi.org/10.1007/s10735-025-10460-0","url":null,"abstract":"<p><p>Given their potent immunosuppressive and anti-inflammatory effects, long-term glucocorticoid therapy (GCs) is a common cause of bone fractures and secondary osteoporosis. Transient receptor potential vanilloid 1 (TRPV1) has been shown to play a role in preserving bone homeostasis and preventing bone disorders. The chili pepper is a naturally occurring source of capsaicin, a TRPV1 agonist. For this reason, this study compared the anti-resorptive properties of capsaicin with alendronate, the conventional treatment for osteoporosis, using a rat model of osteoporosis induced by dexamethasone (Dexa). Over six weeks, five groups of rats received the vehicle, Dexa alone (0.1 mg/kg, Sc), or Dexa plus either alendronate (1 mg/kg, orally) or capsaicin (1 or 2.5 mg/kg, orally). After the experiment, osteocalcin, RANKL, phosphorus, calcium, alkaline phosphatase (ALP), and metabolic parameters were measured. Furthermore, AMPK levels and the relative expression of Bax, Bcl-2, SIRT1, β-catenin, and RUNX2 were assessed in bone, and tissues from the femur were evaluated histologically. Capsaicin's effectiveness in alleviating the bone-damaging effect of dexamethasone was evident through a dose-dependent reduction in ALP, RANKL, and Bax, a rise in osteocalcin and Bcl-2, and a higher expression of AMPK, SIRT1, β-catenin, and RUNX2. Additionally, capsaicin improved bone architecture and effectively mitigated Dexa's detrimental metabolic impact on blood glucose and lipid profile. By upregulating the AMPK/SIRT1/β-catenin/RUNX2 pathway, capsaicin exhibits dose-dependent bone-stimulant effects in a dexamethasone-induced osteoporosis model in rats.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":"175"},"PeriodicalIF":2.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155459","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}
Hülya Çetin, İlknur Lafcı, Yeliz Arman Karakaya, Buket Er Urgancı, Özlem Koşar Can
{"title":"Investigation of TIGIT, PVRIG, CD112 and CD155 expression in early and late onset preeclampsia.","authors":"Hülya Çetin, İlknur Lafcı, Yeliz Arman Karakaya, Buket Er Urgancı, Özlem Koşar Can","doi":"10.1007/s10735-025-10459-7","DOIUrl":"https://doi.org/10.1007/s10735-025-10459-7","url":null,"abstract":"<p><p>Preeclampsia is characterized by hypertension and proteinuria after the 20th week of pregnancy. The disease is divided into early and late onset according to the time of diagnosis. Early onset preeclampsia (EOP) develops after the 20th week of pregnancy. The late-onset form usually occurs after the 34th week of pregnancy. TIGIT and PVRIG are immune checkpoint inhibitor receptors. PVRIG binds only to the PVRL2 (nectin-2, CD112). TIGIT binds to both CD112 and CD155. In our study, the control group consisted of placentas from healthy pregnant women, the early onset preeclampsia group (EOP) consisted of patients diagnosed before the 34th week, and the late-onset preeclampsia group (LOP) consisted of placentas from patients diagnosed at or after the 34th week. TIGIT, PVRIG, CD155, and CD112 expression in placental materials was evaluated both immunohistochemically and by RT-PCR. As a result of H scoring of immunohistochemical expression, it was observed that CD112 and CD155 expression decreased and PVRIG expression increased when the EOP and LOP groups were compared with the control group. In the early onset preeclampsia group, CD112, CD155, TIGIT, and PVRIG gene expression increased twofold compared to that in the control group. In the late-onset preeclampsia group, the expression of all the genes decreased to one-third. The results of our study revealed that these genes may serve as biomarkers for early- and late-onset preeclampsia. Detailed studies are required to determine the use of these receptors in the diagnosis and treatment of the disease.</p>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":"178"},"PeriodicalIF":2.9,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155471","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":"hsa_circ_0001103 correlates with unfavorable MRI features and promotes glioma progression by modulating the miR-375/YAP1 axis","authors":"Yu Hong, Lijun Liu, Yuedong Hai, Liwei Bao","doi":"10.1007/s10735-025-10445-z","DOIUrl":"10.1007/s10735-025-10445-z","url":null,"abstract":"<div><p>To investigate the role of circ_0001103 in glioma and its underlying molecular mechanism. Differentially expressed circRNAs in glioblastoma cells and neural progenitor cells were analyzed with the data of GSE146463. Tissues samples, clinicopathological parameters and MRI characteristics were retrospectively collected. Circ_0001103, miR-375 and YAP1 expression levels were measured by qRT-PCR and Western blot. The relationship between circ_0001103 expression and clinicopathological parameters or MRI features of glioma patients was analyzed by chi-square test. After circ_0001103 or miR-375 was selectively up-regulated or down-regulated, CCK-8 assay, BrdU assay and flow cytometry were used to detect the proliferation and apoptosis of glioma cells. Bioinformatics prediction, dual-luciferase reporter gene assay and RNA immunoprecipitation were executed to verify the targeting relationships among miR-375, circ_0001103 and YAP1 3’ UTR. circ_0001103 was significantly up-regulated in glioma tissues and cell lines, which was positively correlated with the larger tumor size and non-uniform signal in MRI. Overexpression of circ_0001103 promoted glioma cell proliferation and inhibited apoptosis, while knockdown of circ_0001103 worked oppositely. Circ_0001103 negatively regulated miR-375 expression. MiR-375 targeted YAP1, and YAP1 was indirectly and positively modulated by circ_0001103. Circ_0001103 expression was negatively correlated with miR-375 expressions, while positively correlated with YAP1 expression in glioma tissues. Circ_0001103 contributes to glioma progression by regulating miR-375/YAP1 axis.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140124","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-29a-3p compositely regulates the COL6A6/PTEN-PI3K/Akt/CUX1 feedback loop to participate in the proliferation and invasion of pituitary adenomas","authors":"Zhuohui Liu, Xiufu Liao, Hexiang Zhao, Biao Ruan, Fengfeng Jia, Xuzhi He, Ruiqing Long","doi":"10.1007/s10735-025-10436-0","DOIUrl":"10.1007/s10735-025-10436-0","url":null,"abstract":"<div><p>Pituitary adenoma (PA) is one of the most common intracranial tumors, and owing to its special biological morphology and behavior, there is currently no effective treatment. miRNAs play crucial roles as diagnostic indicators and targets for the treatment of numerous cancer types. The objective of this research was to explore how miR-29a-3p influences the development of PA. We collected 25 pairs of PA tissue and normal pituitary tissue, followed by the subcutaneous injection of 5 × 10<sup>7</sup> HP75 cells into the left axilla of nude mice, creating a heterotopic PA xenograft tumor model for experimental study. TtT/GF and HP75 cell proliferation and tumor growth in nude mice were assessed using CCK-8, Transwell, and immunohistochemistry tests. Western blotting, RT‒qPCR and RIP were used to detect the expression and interaction of related proteins and genes. The expression of miR-29a-3p was upregulated in PA. Knockdown of miR-29a-3p can inhibit the proliferation, invasion and migration of TtT/GF and HP75 cells and reduce the epithelial mesenchymal transformation (EMT) of these cells. Furthermore, reducing miR-29a-3p levels suppressed the expression of Ki-67 in the PA tissues of nude mice and slowed tumor growth. From a mechanistic standpoint, miR-29a-3p can target COL6A6 and PTEN. Knockdown of miR-29a-3p inhibits the PI3K/Akt/CUX1 signaling pathway through simultaneously increasing COL6A6 and PTEN expression, thus inhibiting the proliferation, invasion, migration and EMT of PA cells and alleviating the progression of PA. Conversely, CUX1 can promote the expression of miR-29a-3p through a positive feedback loop and accelerate the development of PA. Our study suggests that downregulating the expression of miR-29a-3p may be a new target for the treatment of PA.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-025-10436-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140127","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}