南方医科大学学报杂志最新文献

{"title":"HDAC1 overexpression inhibits steroid-induced apoptosis of mouse osteocyte-like MLO-Y4 cells by inducing SP1 deacetylation.","authors":"Shenyao Zhang, Min Lu, Gaoyan Kuang, Xiaotong Xu, Jun Fu, Churan Zeng","doi":"10.12122/j.issn.1673-4254.2025.01.02","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2025.01.02","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the mechanism by which histone deacetylase 1 (HDAC1) regulates steroid-induced apoptosis of mouse osteocyte-like MLO-Y4 cells.</p><p><strong>Methods: </strong>MLY-O4 cells were treated with 400 nmol/L trichostatin A (TSA) or 1 mmol/L dexamethasone for 24 h or transfected with a HDAC1-overexpressing vector prior to TSA or dexamethasone treatment. The changes in the expressions of HDAC1, SP1, cleaved caspase-3 and Bax, SP1 acetylation level, cell proliferation, and cell apoptosis were examined. The interaction between HDAC1 and SP1 was determined with immunoprecipitation assay and Western blotting.</p><p><strong>Results: </strong>Treatment with dexamethasone significantly increased cell apoptosis, enhanced the expressions of cleaved caspase-3 and Bax, reduced HDAC1 expression, and suppressed proliferation of MLO-Y4 cells. Both TSA and dexamethasone obviously increased SP1 acetylation level and the expression of SP1 in MLO-Y4 cells. HDAC1 overexpression in the cells significantly attenuated the effect of TSA and dexamethasone, promoted cell proliferation, lowered the expressions of SP1, cleaved caspase-3 and Bax, and inhibited dexamethasone-induced cell apoptosis. Immunoprecipitation assay and Western blotting demonstrated the interaction between HDAC1 and SP1 in the cells.</p><p><strong>Conclusions: </strong>HDAC1 inhibits dexamethasone-induced apoptosis and promotes proliferation of cultured mouse osteocytes by suppressing SP1 expression via promoting its deacetylation.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 1","pages":"10-17"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High glucose induces pro-inflammatory polarization of macrophages by inhibiting immune-responsive gene 1 expression.","authors":"Wei Luo, Yuhang Wang, Yansong Liu, Yuanyuan Wang, Lei Ai","doi":"10.12122/j.issn.1673-4254.2025.01.01","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2025.01.01","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effect of high glucose on macrophage polarization and the role of immune-responsive gene 1 (IRG1) in mediating its effect.</p><p><strong>Methods: </strong>RAW264.7 cells were transfected with IRG1-overexpressing plasmid or IRG1 siRNA via electroporation and cultured in either normal or high glucose for 72 h to observe the changes in cell viability and morphology using CCK-8 assay and phase contrast microscopy. The protein levels of IRG1, iNOS, Arg-1, IL-1β and IL-10 in the treated cells were detected with Western blotting, and the fluorescence intensities of iNOS and Arg-1 were detected using immunofluorescence assay. The protein levels of IL-1β and IL-10 in the culture medium were determined with ELISA.</p><p><strong>Results: </strong>High glucose exposure significantly reduced IRG1 and Arg-1 expressions, increased iNOS and IL-1β expressions and IL-1β secretion, and decreased IL-10 level in RAW264.7 cells. Transfection with the IRG1-overexpressing plasmid provided the cells with obvious resistance to high glucose-induced changes in iNOS, Arg-1, IL-1β and IL-10, whereas IRG1 knockdown further enhanced the effects of high glucose exposure on Arg-1 expression and the expression and secretion of IL-10.</p><p><strong>Conclusions: </strong>High glucose promotes M1 polarization of the macrophages possibly through a mechanism to inhibit the expression of IRG1 protein, thus leading to chronic inflammatory response.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-acetylneuraminic acid promotes ferroptosis of H9C2 cardiomyocytes with hypoxia/reoxygenation injury by inhibiting the Nrf2 axis.","authors":"Chunfei Ji, Zongchao Zuo, Jun Wang, Miaonan Li","doi":"10.12122/j.issn.1673-4254.2025.01.10","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2025.01.10","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the mechanism through which N-acetylneuraminic acid (Neu5Ac) exacerbates hypoxia/reoxygenation (H/R) injury in rat cardiomyocytes (H9C2 cells).</p><p><strong>Methods: </strong>H9C2 cells were cultured in hypoxia and glucose deprivation for 8 h followed by reoxygenation for different durations to determine the optimal reoxygenation time. Under the optimal H/R protocol, the cells were treated with 0, 5, 10, 20, 30, 40, 50, and 60 mmol/L Neu5Ac during reoxygenation to explore the optimal drug concentration. The cells were then subjected to H/R injury followed by treatment with Neu5Ac, Fer-1 (a ferroptosis inhibitor), or both. The changes in SOD activity, intracellular Fe²⁺ and lipid ROS levels in the cells were evaluated, and the cellular expressions of Nrf2, GPX4, HO-1, FSP1, and xCT proteins were detected using Western blotting.</p><p><strong>Results: </strong>Following hypoxia and glucose deprivation for 8 h, the cells with reoxygenation for 6 h, as compared with other time lengths of reoxygenation except for 9 h, showed the lowest expression levels of Nrf2, GPX4, HO-1, and FSP1 proteins (<i>P</i><0.001). Neu5Ac treatment of dose-dependently decreased the viability of the cells with H/R injury with an IC₅₀ of 30.07 mmol/L. Reoxygenation for 3 h with normal glucose supplementation and a Neu5Ac concentration of 30 mmol/L were selected as the optimal conditions in the subsequent experiments. The results showed that Neu5Ac could significantly increase SOD activity, Fe²⁺ and lipid ROS levels and reduce Nrf2, GPX4, HO-1, and FSP1 protein expressions in H9C2 cells with H/R injury, but its effects were significantly attenuated by treatment with Fer-1.</p><p><strong>Conclusions: </strong>Neu5Ac exacerbates ferroptosis of myocardial cells with H/R injury by inhibiting the Nrf2 axis to promote the production of ROS and lipid ROS.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 1","pages":"72-79"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Relationship between traditional Chinese cultural beliefs and suicide risk among Chinese medical postgraduate students].","authors":"Kailu Chen, Rong Xiao","doi":"10.12122/j.issn.1673-4254.2024.12.14","DOIUrl":"10.12122/j.issn.1673-4254.2024.12.14","url":null,"abstract":"<p><strong>Objectives: </strong>To study the relationship between traditional Chinese cultural beliefs and suicide risk in Chinese medical postgraduate students.</p><p><strong>Methods: </strong>The Chinese Traditional Cultural Belief Scale (CTCBS) and Suicidal Behavior Questionnaire (SBQ-R) were used to investigate 541 medical postgraduate students in a medical university.</p><p><strong>Results: </strong>The total score of traditional Chinese cultural belief of the medical postgraduate students was 49.68±6.85, and 66.9% of them had a clear cultural belief. The detection rate of suicide risk among the medical postgraduates was 15.7%, and 20.1% of them reported suicidal ideation within the past year. Traditional Chinese cultural belief was negatively correlated with suicide risk among the medical postgraduates (<i>r</i>=-0.210, <i>P</i><0.001), and those with higher levels of cultural belief had lower SBQ-R scores (<i>F</i>=6.255, <i>P</i><0.01). The medical postgraduates with lower cultural beliefs had a higher detection rate of suicide risk (28.6% <i>vs</i> 21.2% <i>vs</i> 12.7%). The students with high suicide risks had significantly lower total scores and all the dimension scores of CTCBS (<i>P</i><0.001).</p><p><strong>Conclusions: </strong>Most medical postgraduates have clear traditional Chinese cultural beliefs, which can be beneficial to reduce suicide risk among the students.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"44 12","pages":"2382-2387"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[<i>Danshen</i> Injection inhibits peritoneal dialysis fluid-induced endothelial-mesenchymal transition in HMrSV5 cells by regulating the TGF-β/Smad signaling pathway].","authors":"Lihua Yu, Jingya Li, Xiaoqi Wang, Li Li, Ya Chen, Feiyu Wang, Kun Zhang, Tongsheng Wang","doi":"10.12122/j.issn.1673-4254.2024.12.02","DOIUrl":"10.12122/j.issn.1673-4254.2024.12.02","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the inhibitory effect of Danshen Injection on endothelial-mesenchymal transition (EndMT) induced by peritoneal dialysis fluid in HMrSV5 cells and the role of the TGF‑β/Smad signaling pathway in mediating this effect.</p><p><strong>Methods: </strong>HMrSV5 cells cultured in 40% peritoneal dialysis solution for 72 h to induce EndMT were treated with 0.05%, 0.1% and 0.5% Danshen Injection. CCK-8 assay was used to assess the changes in viability of the treated cells, and the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and vascular endothelial growth factor (VEGF) in the cell supernatant were detected using ELISA; Western blotting was performed to detect the protein expressions of E-cadherin, α-smooth muscle actin (α-SMA), p-Smad 2/3, and Smad 7 in the cells.</p><p><strong>Results: </strong>Culture in 40% peritoneal dialysis fluid for 72 induced significant EndMT in HMrSV5 cells, which exhibited obviously lowered cell viability. Danshen Injection within the concentration range of 0.025%-1.5% did not significantly affect the viability of the cells. Exposure of HMrSV5 cells to peritoneal dialysis fluid for 72 h significantly increased the production of IL-6, TNF‑α, TGF‑β and VEGF, upregulated the protein expressions of α‑SMA and p-Smad 2/3, and lowered the expressions of E-cadherin and Smad7 proteins. Treatment of the exposed cells with Danshen injection significantly increased cell viability and cellular expressions of E-cadherin and Smad 7 proteins and reduced the production of IL-6, TNF-α, TGF-β and VEGF and the protein expressions of α‑SMA and p-Smad 2/3.</p><p><strong>Conclusions: </strong>Danshen Injection can suppress peritoneal dialysis fluid-induced EndMT in HMrSV5 cells possibly by regulating the TGF-β/Smad signaling pathway.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"44 12","pages":"2276-2282"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[MiR-139-5p regulates the Notch/RBP-J/Hes1 axis to promote homing of bone mesenchymal stem cells in bronchial asthma].","authors":"Kun Wang, Haoxiang Fang, Xiaomei Cao, Ziheng Zhu","doi":"10.12122/j.issn.1673-4254.2024.12.03","DOIUrl":"10.12122/j.issn.1673-4254.2024.12.03","url":null,"abstract":"<p><strong>Objectives: </strong>To observe the role of miR-139-5p and Notch1 signaling pathway in regulation of homing of bone mesenchymal stem cells (BMSCs) of asthmatic rats.</p><p><strong>Methods: </strong>Normal rat BMSCs were co-cultured with bronchial epithelial cells from normal or asthmatic rats, followed by transfection with miR-139-5p mimics or a negative control sequence. The changes in cell viability and cell cycle were analyzed, and the cellular expressions of CXCR4 and SDF-1 were detected using immunofluorescence staining. The changes of BMSC homing after the transfection were observed, and the expressions of Notch1, RBP-J, and Hes1 mRNAs and proteins and Th1/Th2 cytokines were detected with RT-qPCR, Western blotting or ELISA.</p><p><strong>Results: </strong>The co-cultures of BMSCs and asthmatic bronchial epithelial cells showed significantly decreased expressions of miR-139-5p, IL-2 and IL-12 and increased expressions of CXCR4, SDF-1, IL-5, IL-9, Notch1, RBP-J, and Hes1. Transfection with miR-139-5p mimics significantly increased the expressions of miR-139-5p, IL-2, CXCR4 and SDF-1 and lowered the expression levels of IL-5, IL-9, Notch1, activated Notch1, and Hes1 in the co-cultured cells. Correlation analysis showed that BMSC homing was positively correlated with miR-139-5p and IL-12 and negatively correlated with IL-5 expression. The expression of CXCR4 was negatively correlated with activated Notch1, and SDF-1 was positively correlated with miR-139-5p but negatively correlated with Notch1 expression.</p><p><strong>Conclusions: </strong>High expression of miR-139-5p promotes homing of BMSCs in asthma by targeting the Notch1 signaling pathway to regulate the expressions of Th1/Th2 cytokines, thereby alleviating airway inflammation.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"44 12","pages":"2283-2290"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[GSK484, a PAD4 inhibitor, improves endothelial dysfunction in mice with sepsis-induced lung injury by inhibiting H3Cit expression].","authors":"Xiaofei Su, Lin Li, Jingrong Dai, Bao Xiao, Ziqi Jin, Bin Liu","doi":"10.12122/j.issn.1673-4254.2024.12.16","DOIUrl":"10.12122/j.issn.1673-4254.2024.12.16","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the inhibitory effect of GSK484, a PAD4 inhibitor, on H3Cit expression following sepsis and its effects for improving sepsis-induced endothelial dysfunction.</p><p><strong>Methods: </strong>Eighteen C57BL/6 mice were randomized into sham-operated group, sepsis model group and GSK484 treatment group (<i>n=</i>6), and in the latter two groups, models of sepsis were established by cecal ligation and puncture (CLP). The mice in GSK484 treatment group were given an intraperitoneal injection of GSK484 (4 mg/kg) on the second day following the surgery. Twenty-four hours after the injection, the mice were euthanized for measurement of serum levels of VEGF, ESM-1, IL-6 and IL-1β using ELISA. Lung tissue pathology was observed with HE staining, and pulmonary expressions of F-actin, VE-cadherin, ZO-1 and H3Cit proteins were detected using immunofluorescence staining and Western blotting. In primary cultured of mouse lung microvascular endothelial cells, the effect of stimulation with LPS (10 μg/mL) for 24 h on tube formation, proliferation, apoptosis and expressions of VEGF, ESM-1, IL-6 and IL-1β were assessed using CCK-8 assay, flow cytometry and ELISA.</p><p><strong>Results: </strong>Compared to the sham-operated mice, the septic mice exhibited significant lung tissue pathologies characterized by vascular congestion, alveolar rupture, edema, and neutrophil infiltration. Serum levels of IL-6, IL-1β, VEGF, and ESM-1 were elevated, pulmonary expressions of F-actin, VE-cadherin, and ZO-1 were decreased, and H3Cit expression was increased significantly in the septic mice. GSK484 treatment effectively mitigated these changes in the septic mice. The LPS-stimulated endothelial cells showed increased productions of IL-6, IL-1β, VEGF and ESM-1, which were significantly reduced after treatment with 2.5 μmol/L GSK484.</p><p><strong>Conclusions: </strong>GSK484 treatment effectively suppresses H3Cit expression in septic mice to ameliorate sepsis-induced endothelial dysfunction.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"44 12","pages":"2396-2403"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[AKBA combined with doxorubicin inhibits proliferation and metastasis of triple-negative breast cancer MDA-MB-231 cells and xenograft growth in nude mice].","authors":"Youqin Zeng, Siyu Chen, Yan Liu, Yitong Liu, Ling Zhang, Jiao Xia, Xinyu Wu, Changyou Wei, Ping Leng","doi":"10.12122/j.issn.1673-4254.2024.12.22","DOIUrl":"10.12122/j.issn.1673-4254.2024.12.22","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the synergistic inhibitory effects of AKBA and doxorubicin on malignant phenotype of triple-negative breast cancer (TNBC) MDA-MB-231 cells.</p><p><strong>Methods: </strong>CCK-8 assay was used to determine the 48-h IC₅₀ of AKBA and doxorubicin in MDA-MB-231 cells, and SynergyFinder was employed to calculate the synergistic index and the optimal concentrations of the two agents. MDA-MB-231 cells treated with AKBA (22.5 μmol/L), doxorubicin (0.84 μmol/L) or their combination were examined for changes in cell proliferation, migration, invasion and apoptosis using Transwell migration, scratch assay, clone generation, RT-qPCR and Western blotting. Network pharmacology analysis was conducted to identify the downstream targets of AKBA in TNBC. In nude mouse models bearing subcutaneous MDA-MB-231 cell xenografts, the effects of normal saline, AKBA (50 mg/kg), doxorubicin (2.5 mg/kg), and AKBA combined with doxorubicin on xenograft growth and histopathology were observed.</p><p><strong>Results: </strong>The IC₅₀ of AKBA and doxorubicin in MDA-MB-231 cells at 48 h was 45.15±0.97 μmol/L and 0.42±0.99 μmol/L, respectively. SynergyFinder confirmed the synergistic effect of AKBA and ADR with a ZIP>10. The combined treatment with AKBA and doxorubicin significantly inhibited the proliferation, migration and invasion, promoted apoptosis of MDA-MB-231 cells, and effectively suppressed xenograft growth in nude mice. Network pharmacology analysis predicted that AKBA affects the progression of TNBC through its downstream target AKBA.</p><p><strong>Conclusions: </strong>AKBA combined with doxorubicin inhibits proliferation, migration and invasion, promotes apoptosis of MDA-MB-231 cells and suppresses MDA-MB-231 cell xenograft growth in nude mice. The combined use of AKBA can attenuate the toxic effects of doxorubicin in nude mice.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"44 12","pages":"2449-2460"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[Asperosaponin VI alleviates TNBS-induced Crohn's disease-like colitis in mice by reducing intestinal epithelial cell apoptosis via inhibiting the PI3K/AKT/NF-κB signaling pathway].","authors":"Minzhu Niu, Lixia Yin, Ting Duan, Ju Huang, Jing Li, Zhijun Geng, Jianguo Hu, Chuanwang Song","doi":"10.12122/j.issn.1673-4254.2024.12.09","DOIUrl":"10.12122/j.issn.1673-4254.2024.12.09","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effects of asperosaponin VI (AVI) on intestinal epithelial cell apoptosis and intestinal barrier function in a mouse model of Crohn's disease (CD)-like colitis and explore its mechanisms.</p><p><strong>Methods: </strong>Male C57BL/6 mice with TNBS-induced CD-like colitis were treated with saline or AVI (daily dose 150 mg/kg) by gavage for 6 days. The changes in body weight, colon length, DAI scores, and colon pathologies of the mice were observed, and the expressions of inflammatory factors and tight injunction proteins were detected using ELISA and RT-qPCR. The effects of AVI on barrier function and apoptosis of mouse intestinal epithelial cells and TNF‑α‑treated Caco-2 cells were analyzed using immunofluorescence staining, TUNEL assay, and Western blotting. Network pharmacology, TUNEL assay, and Western blotting were performed to explore and validate the therapeutic mechanisms of AVI for CD.</p><p><strong>Results: </strong>In the mouse models of CD-like colitis, AVI significantly improved body weight loss, colon shortening and DAI and tissue inflammation scores, alleviated intestinal villi and goblet cell injuries, and lowered the expressions of inflammatory factors. AVI treatment significantly reduced the loss of tight junction proteins and apoptosis in both mouse intestinal epithelial cells and TNF‑α-stimulated Caco-2 cells. KEGG enrichment pathway analysis suggested that the therapeutic effect of AVI on CD was associated with inhibition of PI3K/AKT/NF-κB pathway activation, which was confirmed by lowered expressions of p-PI3K, p-AKT, and p-p65 in AVI-treated mouse models and Caco-2 cells. In Caco-2 cells, Recilisib significantly blocked the inhibitory effect of AVI on the PI3K/AKT/NF-κB pathway and TNF-α-induced apoptosis, and AKT1 knockdown experiment confirmed the role of the PI3K/AKT pathway for mediating the activation of downstream NF-κB signaling.</p><p><strong>Conclusions: </strong>AVI can improve TNBS-induced CD-like colitis in mice by reducing intestinal epithelial cell apoptosis and intestinal barrier damage via inhibiting the PI3K/AKT/NF-κB signaling pathway.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"44 12","pages":"2335-2346"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"[High expression of CRTAC1 promotes proliferation, migration and immune cell infiltration of gastric cancer by regulating the PI3K/AKT signaling pathway].","authors":"Fuxing Zhang, Guoqing Liu, Rui Dong, Lei Gao, Weichen Lu, Lianxia Gao, Zhongkuo Zhao, Fei Lu, Mulin Liu","doi":"10.12122/j.issn.1673-4254.2024.12.19","DOIUrl":"10.12122/j.issn.1673-4254.2024.12.19","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the expression of cartilage acidic protein 1 (CRTAC1) in gastric cancer (GC) and its effect on biological behaviors and immune cell infiltration of GC.</p><p><strong>Methods: </strong>Transcriptomic, GO and KEGG analyses were conducted to investigate the association of CRTAC1 expression with prognosis of GC patients and its involvement in cell function and signaling pathways. ESTIMATE algorithm was used to analyze the effect of CRTAC1 expression on the tumor microenvironment and the tumor mutation load. In two GC cell clines (HGC-27 and MKN-74), CCK8, EdU and clone formation assays, flow cytometry, and Hoechst staining were used to examine the effects of CRTAC1 knockdown on cell proliferation, cell cycle changes and apoptosis. Wound healing assay, Transwell assay, and Western blotting were performed to analyze the effect of CRTAC1 knockdown on GC cell migration and the underlying mechanism.</p><p><strong>Results: </strong>Bioinformatics analysis showed significantly higher expression of CRTAC1 in GC tissues than in adjacent tissues (<i>P</i><0.05). Age and tumor stage were both prognostic risk factors in GC patients with high CRTAC1 expression (<i>P</i><0.001). Analysis using ESTIMATE algorithm showed that CRTAC1 expression increased immune cell infiltration and decreased tumor mutational load in GC (<i>P</i><0.001). In HGC-27 and MKN-74 cells, CRTAC1 knockdown significantly inhibited cell proliferation and migration and promoted cell apoptosis. Western blotting demonstrated that CRTAC1 knockdown significantly increased E-cadherin expression and reduced the expression levels of vimentin, p-PI3K, AKT2, p-AKT and p-mTOR in GC cells.</p><p><strong>Conclusions: </strong>High expression of CRTAC1 in GC tissues affects immunotherapeutic efficacy and prognosis of the patients, possibly by promoting epithelial-mesenchymal transition <i>via</i> modulating tumor mutational load, tumor microenvironment, and the PI3K/AKT signaling pathway.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"44 12","pages":"2421-2433"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11683341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}