Journal of Molecular Histology最新文献

{"title":"Immunohistochemical and ultrastructural analysis of macrophages during cyclic corpus luteum formation and regression in Indian Buffalo","authors":"Kritima Kapoor,&nbsp;Opinder Singh,&nbsp;Devendra Pathak","doi":"10.1007/s10735-025-10573-6","DOIUrl":"10.1007/s10735-025-10573-6","url":null,"abstract":"<div>\u0000 \u0000 <p>The present research was conducted on corpora lutea (CL) samples of healthy buffaloes (<i>n</i> = 24) with the aim to localize presence of immune cell macrophage, immunohistochemically and ultrastructurally. The collected CL were categorized into four different stages i.e., early (stage I, 1 to 5 days, <i>n</i> = 6), mid (stage II, 6 to 11 days, <i>n</i> = 6), late luteal phase (stage III, 12 to 16 days, <i>n</i> = 6) and regressing phase (stage IV, 17 to 20 days, <i>n</i> = 6), based on their gross morphology. The macrophages were observed occasionally throughout the luteal parenchyma of early and mid-luteal CL. However, their number was lowest during early and mid-luteal phases being 7.7 ± 0.98 (Mean ± S.E) and 6.37 ± 0.79 per unit area, respectively. The number was considerably higher in regressing phases i.e., late luteal phase (60.45 ± 4.39 per unit area) and corpus albicans (108.25 ± 6.35 per unit area). Ultrastructurally as well, their presence was observed to be higher in the regressing phases as cells with filopdia for the process of phagocytosis. These findings concluded that the presence of macrophages, although lower in early and mid-luteal phases of CL formation, indicated their probable role in promoting angiogenesis and thus proliferation of buffalo CL during its formation. However, their considerable higher presence during late and regressing phases of CL led to increased phagocytosis of degraded luteal cells that thereby promoted its structural luteolysis.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037365","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":"Myogenic induced adipose-derived stem cells sheets combined with electrospun scaffolds of silk fibroin and poly(lactide-co-glycolide) for stress urinary incontinence treatment","authors":"Ming Liu,&nbsp;Yongwei Li,&nbsp;Yining Zhao,&nbsp;Fengze Sun,&nbsp;Youyi Lu,&nbsp;Jitao Wu,&nbsp;Qingsong Zou","doi":"10.1007/s10735-025-10531-2","DOIUrl":"10.1007/s10735-025-10531-2","url":null,"abstract":"<div><p>The stress urinary incontinence (SUI) is a difficulty in urology and current sub-urethral sling treatments are associated with inflamation and recurrence. In this study, we developed a novel tissue-engineered sling with myogenic induced adiposederived stem cells (MI-ADSCs) sheets induced by 5-Aza and combined with electrospun scaffolds of silk fibroin and poly(lactide-co-glycolide) (SF/PLGA) for the treatment of stress urinary incontinence. MI-ADSCs increased α-SMA, MyoD and Desmin the mRNA and protein expression. ICG001, a specific inhibitor of β-catenin signaling pathway, could inhibit 5-Aza-induced expression of myoblast genes and proteins. Electrospun scaffolds of SF/PLGA (50/50) showed favorable mechanical properties and the biocompatibility. The MI-ADSCs sheets was combined with electrospun scaffolds of SF/PLGA (50/50) to form a novel tissue-engineered sling. The tissue-engineered sling was transplanted into female SUI rats to evaluate the feasibility and effcacy for the treatment of SUI. The tissue-engineered sling with MI-ADSCs sheets combined with SF/PLGA can restore leak point pressure (LPP) in the model of SUI steadily. It is of great potential to be a novel tissue-engineered sling in the treatment of SUI.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145021538","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":"Tongxinluo alleviates myocardial ischemia–reperfusion injury by inhibiting the pyroptosis of endothelial cells via the NLRP3/Caspase-1/GSDMD signaling pathway","authors":"Xuan Wu,&nbsp;Yun-long Hou,&nbsp;Tong-xing Wang,&nbsp;Li-ping Chang,&nbsp;Hong-ru Zhou,&nbsp;Ming-ye Wang,&nbsp;Yi-ling Wu","doi":"10.1007/s10735-025-10585-2","DOIUrl":"10.1007/s10735-025-10585-2","url":null,"abstract":"<div><p>Numerous people experiencing acute myocardial infarction are also experiencing myocardial ischemia–reperfusion injury (MIRI). Pyroptosis is a core mechanism in MIRI. Tongxinluo (TXL) has a significant protective effect on endothelial cell function. This study utilized network pharmacology to investigate how TXL improves ischemia/reperfusion injury through targeting dysfunction of endothelial cells. Network pharmacology analysis identified 40 key targets through which TXL improves I/R by regulating endothelial dysfunction. We administered TXL (1.5 g/kg/d, oral gavage) to C57BL/6 mice for 7 days before inducing I/R injury, and used 400 μg/ml TXL for in vitro H/R injury in HUVECs. We extensively investigated the effects of TXL on pyroptosis in heart tissue and explored the underlying mechanism through biochemical assays, histopathology, and Western blot analysis. Network pharmacology analysis revealed that TXL targets primarily act on pyroptosis and inflammatory pathways. TXL pretreatment significantly improved cardiac function with increased EF% and decreased LVESV and LVEDV compared to the model group. Myocardial enzymes (CK, CKMB, LDH, cTnI) were markedly reduced by TXL pretreatment. TXL significantly decreased IL-18 and IL-1β levels in serum and reduced neutrophil infiltration in the ischemic area. TXL administration notably downregulated the expression of pyroptosis-related factors (NF-κB, NLRP3, cleaved-Caspase1, GSDMD) in both MIRI mouse model and H/R-treated HUVECs. Molecular docking showed that ginsenoside Rg3, a key TXL component, can directly interact with NLRP3 and GSDMD. TXL has a significant protective effect on endothelial cell function during I/R injury through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD signaling pathway, preserving microcirculation barrier integrity.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-025-10585-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011712","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":"Effects of Melissa officinalis extract in the expression of NLRP3 gene in testicular tissue and sperm parameters in the male rat model of spinal cord injury","authors":"Maryam Khazaei,&nbsp;Gholamreza Hassanzadeh,&nbsp;Maryam Azizi,&nbsp;Simin Fazelipour","doi":"10.1007/s10735-025-10590-5","DOIUrl":"10.1007/s10735-025-10590-5","url":null,"abstract":"<div>\u0000 \u0000 <p>Spinal cord injury (SCI) is a severe condition of the central nervous system that can significantly impact multiple physiological functions, including the male reproductive system. The study aimed to investigate the effects of hydroalcoholic extract of the plant <i>Melissa officinalis</i> (MO) on testicular structure and sperm parameters in a male rat model of spinal cord injury. Thirty-six male Wistar rats, weighing between 225 and 250 g, were used in this study. The animals were randomly divided into four groups: 1-Control group (Co): Underwent laminectomy without spinal cord injury. 2-Vehicle group (V): Received normal saline (equal volume of drugs, daily). 2-Treatment group 1 (MO1): Received hydroalcoholic extract of <i>Melissa officinalis</i> (100 mg/kg, daily). 4-Treatment group 2 (MO2): Received hydroalcoholic extract of <i>Melissa officinalis</i> (150 mg/kg, daily). All injections were administered intraperitoneally 24 h after SCI for 52 days. SCI was induced using an aneurysm clip applied at the T10 vertebral level for 1 min. Twenty-four hours after the surgery, the Basso Beattie Bresnahan (BBB) and Open Field (OFT) behavioral tests were performed every three days until day 52. Afterward, the rats were sacrificed, and the testes, along with the right epididymis were collected for analysis. Sperm parameters (quantity, motility, and morphology) were assessed. The expression levels of Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) genes were evaluated using real-time PCR. Malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) activity were measured by ELISA. In the MO treatment group, compared to the vehicle group, inflammatory markers, including TNF-α, IL-1β, lipid peroxidation (<i>P</i> = 0.0001), and NLRP3 gene expression were significantly reduced (<i>P</i> &lt; 0.05). The diameter and germinal epithelium thickness of the seminiferous tubules, as well as sperm count, were significantly increased in the treatment groups compared to the vehicle group (<i>P</i> &lt; 0.05). Motor function and antioxidant enzyme levels also showed a significant increase following treatment (<i>P</i> &lt; 0.05). MO treatment can significantly mitigate the secondary effects of spinal cord injury on testicular tissue.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011714","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":"Synaptotagmin-like 5 is a potential biomarker and correlates with immune infiltrates in thyroid carcinoma","authors":"Xiaohui Zhu,&nbsp;Xia Li,&nbsp;Hengfeng Cui,&nbsp;Haiyan Wu,&nbsp;Dongmei Jiang,&nbsp;Yuying Wang,&nbsp;Fei Hua","doi":"10.1007/s10735-025-10593-2","DOIUrl":"10.1007/s10735-025-10593-2","url":null,"abstract":"<div><p>Thyroid carcinoma (TC) continues to show concerning rates of metastasis and recurrence, despite an overall favorable prognosis. This study aimed to investigate the characteristics and predictive value of synaptotagmin-like 5 (SYTL5) expression and its association with immune infiltration and potential effects on cell apoptosis and proliferation in TC. Messenger ribonucleic acid expression profiles from 45 TC samples and 37 normal samples in The Cancer Genome Atlas database were analysed. The differentially expressed gene SYTL5 was highly expressed in TC tissues and closely associated with the tumour–node–metastasis classification in TC. The receiver operating characteristic curve for predicting TC showed an area under the curve of 0.878. Immune cell expression significantly differed between SYTL5 low- and high-expression groups. Zinc-finger protein 384 (ZNF384) was predicted as the transcription factor of SYTL5 and was found to be underexpressed in TC tissues, showing a negative correlation with SYTL5. Molecular biology experiments demonstrated that SYTL5 expression was elevated in human TC cells and tissues, while SYTL5 knockdown promoted apoptosis and inhibited proliferation in vitro. Zinc-finger protein 384 was shown to bind to the promoter of SYTL5, and overexpression of SYTL5 reversed the effects of ZNF384 overexpression on TC cells. These findings indicate that SYTL5 acts as a potential oncogene in TC and may serve as a biomarker for TC diagnosis. Moreover, this study enhances our understanding of TC’s underlying mechanisms and highlights SYTL5 as a promising target for immunotherapy.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011711","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":"Investigation of survivin and autophagy marker expression in different Indian cancer tissue samples","authors":"Sree Karani Kondapuram,&nbsp;Sagar Puli,&nbsp;Nirupama Murali,&nbsp;Mohane Selvaraj Coumar","doi":"10.1007/s10735-025-10513-4","DOIUrl":"10.1007/s10735-025-10513-4","url":null,"abstract":"<div><p>Survivin, an inhibitor of apoptosis protein, is minimally expressed in normal adult tissues but overexpressed in multiple cancers. This study investigates survivin expression alongside autophagy markers ATG7 and LC3B in seven solid tumor types in Indian patient samples. Immunohistochemical analysis was performed on 48 cancer tissue samples (breast n = 7, buccal n = 6, cervical n = 5, colon n = 8, renal n = 6, liver n = 10, thyroid n = 6) and adjacent normal tissues (n = 9) using anti-human antibodies against survivin, ATG7, and LC3B. Expression levels were semi-quantitatively scored (0–3 +) and statistically analyzed. Survivin demonstrated significant overexpression in cancer tissues compared to normal tissues across all tumor types (<i>p</i> ≤ 0.05–0.0001). Moreover, a statistically significant inverse correlation was observed between survivin and autophagy marker (ATG7/LC3B) expression in 85% of examined samples. Breast, buccal, liver, and kidney cancers showed strong-to-moderate survivin expression in &gt; 50% of cases, while thyroid cancers exhibited predominantly weak survivin expression with strong autophagy marker expression. These findings demonstrate consistent survivin overexpression with concomitant autophagy suppression in Indian cancer patients. The inverse relationship between survivin and autophagy marker expression suggests survivin inhibition as a potential therapeutic strategy to activate autophagic cell death, particularly in breast, buccal, liver, and kidney cancers with high survivin expression. Future large-scale validation studies and mechanistic investigations are warranted to translate these findings into personalized survivin-targeted therapeutic strategies. This study contributes to a better understanding of survivin and its relation to autophagy in various solid tumors, paving the way for novel therapeutics for cancer.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011841","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":"High-intensity interval training (HIIT) ameliorates cardiac hypertrophy and fibrosis in diabetic rats: the role of P53 and SIRT1","authors":"Mohammad Rami,&nbsp;Samaneh Rahdar,&nbsp;Hamid Aghili Nasab,&nbsp;Roya Adelnia,&nbsp;Mohammad Amin Rajizadeh","doi":"10.1007/s10735-025-10596-z","DOIUrl":"10.1007/s10735-025-10596-z","url":null,"abstract":"<div><p>One of the most prevalent metabolic diseases in recent years, type 2 diabetes is now one of the top causes of death globally and a significant risk factor for cardiovascular diseases. Therefore, the goal of this study is to investigate the impact of HIIT exercises on the levels of specific proteins associated with mitochondrial biogenesis and apoptosis in the heart tissue of male Wistar rats with type 2 diabetes. Animals in diabetic groups were given a high-fat diet and an intraperitoneal injection of STZ to cause diabetes. Following confirmation of the induction of diabetes, the exercise groups engaged in an 8-week HIIT exercise program. The current study’s findings show that in the heart tissue of diabetic rats, the creation of diabetes significantly raised P53 protein levels and significantly decreased SIRT1 protein levels. On the other hand, HIIT decreased P53 expression and raised SIRT1.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011710","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":"Robinin decreases myocardial ischemia/reperfusion injury via Nrf2 anti-oxidative effects mediated by Akt/GSK3β/Fyn in hypercholesterolemic rats","authors":"XiBao Shen,&nbsp;AiJun Liu,&nbsp;LiuGen Li,&nbsp;JianFang Zhu,&nbsp;JianHai Yuan,&nbsp;Liming Wu,&nbsp;Xuehong Zhang","doi":"10.1007/s10735-025-10563-8","DOIUrl":"10.1007/s10735-025-10563-8","url":null,"abstract":"<div><p>Robinin (RB) is an accepted antioxidant herbal product with known cardio-protective activity. To explore the anti-oxidative potential of RB in treating myocardial ischemia or reperfusion (MI/RI) damage in rats after inducing hypercholesterolemia (HC). HC was induced by administering cholesterol (2%) to rats for eight weeks. The rats were given RB (50 mg/kg bw) for the last two weeks. The rats were arbitrarily divided into four groups: (Group I) normal control, (Group II) hypercholesterolemic (HC) alone, (Group III) HC + RB (50 mg/kg body weight), and (Group IV) RB alone (50 mg/kg body weight). LV-developed pressure (LVDP), and left ventricular end-diastolic pressure (LVEDP) were recorded during the perfusion process. Histopathology staining was used to analyze liver and kidney damage in heart tissue (H&amp;E, MT, and PAS stains), and in silico techniques, such as molecular docking and MD simulation, were employed. Results revealed that RB administration reduced MI/RI in HC rats due to Akt/GSK3β/Fyn-as facilitated Nrf2 anti-oxidative function. Administering RB to HC rats resulted in increased expression of Akt, whereas it reduced the Fyn and GSK3β levels, which activated Nrf2 activity. When RB is administered to HC rats. Glide (a Schrodinger module) was used to dock RB with NQO1, Nrf-2, HO-1, GSK-3β, and Akt to select the best interacting drug action on inflammatory markers for the therapeutic action of RB and followed OH-1 and Nrf2 MD simulation study were carried out. These results highlight how Nrf2 antioxidative effects are mediated by Akt/GSK3β/Fyn are enhanced by RB, protecting the HC heart from MI/RI.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-025-10563-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011842","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":"Berberine contributes to protecting against the cadmium-induced pancreatic damage: role of intestinal microbiome modulation and barrier function","authors":"Abdulaziz Q. Ali,&nbsp;Ezat A. Mersal,&nbsp;Rastam Samer,&nbsp;Samaa A. Alhjmohammad,&nbsp;Zainab H. Alabdrabalridha,&nbsp;Fatimah Y. Alseeni,&nbsp;Amal F. Dawood,&nbsp;Marwa Omar Abdel All,&nbsp;Ahmed M. Abdelmoneim,&nbsp;Tamer M. Shawky","doi":"10.1007/s10735-025-10591-4","DOIUrl":"10.1007/s10735-025-10591-4","url":null,"abstract":"<div><p>Cadmium (Cad) is a worldwide heavy metal pollutant associated with global health challenges. Alteration of the intestinal microbiome, due to chemicals’ exposure, plays a vital role in the pathogenesis of gastrointestinal diseases such as pancreatic disorders. Hence, modulation of the gut microbiota might be a targeted approach to manage pancreatic diseases. Using murine modeling, this study consisted of two dependent experiments to investigate the curative potential of berberine (BBR) in a Wistar rat model of Cad-provoked pancreatic toxicity and the possible contribution of gut microbiota to BBR protection. In experiment 1, Cad-induced pancreatic injury was established in rats via 8-week oral gavage of Cad at 4 mg/kg. The treatment group was exposed to BBR at 200 mg/kg body weight, oral gavage for 8 weeks. In experiment 2, transplantation of the fecal microbiome was done, in which the fecal microbiota in each group of experiment 1 was orally gavaged to the healthy rats of each corresponding group in experiment 2, once weekly for 8 weeks. The serum amylase and lipase levels, pancreatic inflammatory and oxidative markers, histological, and immunohistochemical analyses were evaluated. The markers of gut mucosal barrier, and mRNA expression of cell junction proteins were investigated for possible intestinal injury. 16S rRNA sequencing was applied to identify the gut bacterial changes and possible pancreatic bacterial translocation. Cad induced intestinal barrier disruption and elicited a state of pancreatic inflammation and apoptosis as indicated by TGF-β and BAX immunohistochemistry, which were relieved by BBR. A decreased firmicutes/bacteroidetes ratio and microbial migration due to interrupted intestinal mucosal barrier were reported. Furthermore, BBR restored the bacterial richness and proportions in the gut, thereby maintaining the intestinal microbial community, fixing the intestinal mucosal barrier structure, and inhibiting the pathway of bacterial migration. BBR protected against Cad-induced pancreatic damage, mostly through safeguarding the intestinal barrier function. Modulation of the intestinal bacterial community, repairing the gut barrier structure, and interference with the pancreatic bacterial migration and colonization were suggested BBR effects, potentially alleviating Cad-related pancreatic injury.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998561","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":"CSF2RA promotes gastric cancer progression through activation of the JAK2/STAT3 signaling pathway","authors":"Mengjie Li,&nbsp;Qing Cao,&nbsp;Xuzhong Ding,&nbsp;Anning Liu,&nbsp;Yu Xu,&nbsp;Kang Gu,&nbsp;Yin Peng,&nbsp;Peng Li","doi":"10.1007/s10735-025-10588-z","DOIUrl":"10.1007/s10735-025-10588-z","url":null,"abstract":"<div><p>Pseudoautosomal regions (PARs), located at the ends of sex chromosomes, harbor genes that may play a role in tumor pathology by regulating cell proliferation and the immune microenvironment. Gastric cancer (GC) is a prevalent and molecularly heterogeneous malignancy of the digestive system. However, studies on the role of PARs-related genes in GC are limited. This study focuses on the PARs gene CSF2RA and its regulatory role in GC progression through the JAK2/STAT3 signaling pathway. Differentially expressed PARs-related genes associated with GC were identified using multi-omics datasets(including TCGA-STAD and four GEO cohorts). Functional enrichment, immune infiltration, and drug sensitivity analyses, combined with in vitro (using MKN45 and AGS cell lines) and in vivo experiments, were conducted to validate the role of CSF2RA in GC. Additionally, RT-qPCR, Western blot, immunofluorescence, and co-immunoprecipitation assays were performed to investigate the interaction between CSF2RA and JAK2 and their activation of downstream signaling pathways. CSF2RA was found to be highly expressed in GC and associated with poor prognosis. It was significantly enriched in the JAK/STAT signaling pathway and closely related to immune cell infiltration. Furthermore, CSF2RA promoted GC cell proliferation and metastasis by activating the JAK2/STAT3 pathway. The JAK inhibitor Ruxolitinib effectively reversed the tumor-promoting effects of CSF2RA and demonstrated significant inhibitory effects in both in vitro and in vivo experiments. This study is the first to reveal the tumor-promoting mechanism of CSF2RA in GC, demonstrating its role in facilitating tumor progression via the JAK2/STAT3 signaling pathway. The potential therapeutic value of Ruxolitinib was validated in both cell-based and xenograft tumor models. Future research should further explore the upstream regulatory mechanisms of CSF2RA and its dynamic role in the immune microenvironment to advance precision treatment strategies for GC.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998560","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}