南方医科大学学报杂志最新文献

{"title":"[<i>Didang</i> Decoction-medicated serum enhances autophagy in high glucose-induced rat glomerular endothelial cells <i>via</i> the PI3K/Akt/mTOR signaling pathway].","authors":"Yanyan Dong, Kejing Zhang, Jun Chu, Quangen Chu","doi":"10.12122/j.issn.1673-4254.2025.03.03","DOIUrl":"10.12122/j.issn.1673-4254.2025.03.03","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effect of <i>Didang</i> Decoction-medicated serum on autophagy in high glucose (HG)-induced rat glomerular endothelial cells (RGECs) and explore the pathway that mediates its effect.</p><p><strong>Methods: </strong>Primary RGECs were isolated and cultured using sequential sieving combined with collagenase digestion, followed by identification using immunofluorescence assay for factor VIII. High glucose medium was used to induce RGECs to simulate a diabetic environment, and the effects of <i>Didang</i> Decoction-medicated serum and 3-MA (an autophagy inhibitor), either alone or in combination, on autophagy of HG-exposed cells were evaluated by observing autophagic vacuoles using monodansylcadaverine (MDC) staining. RT-qPCR and Western blotting were employed to measure mRNA and protein expression levels of Beclin-1, p62, LC3B, p-PI3K, p-Akt, and p-mTOR.</p><p><strong>Results: </strong>Compared with the control cells, the HG-exposed RGECs showed significantly reduced autophagic fluorescence intensity, decreased Beclin-1 mRNA expression, increased p62 mRNA expression, downregulated Beclin-1 protein and LC3-II/I ratio, and upregulated p62, p-PI3K, p-Akt, and p-mTOR protein levels. <i>Didang</i> Decoction-medicated serum significantly enhanced autophagic fluorescence intensity in HG-exposed cells, increased Beclin-1 mRNA expression, decreased p62 mRNA expression, upregulated Beclin-1 protein, and downregulated p62, p-PI3K, p-Akt, and p-mTOR protein levels.</p><p><strong>Conclusions: </strong><i>Didang</i> Decoction-medicated serum enhances autophagy in HG-exposed RGECs by regulating the PI3K/Akt/mTOR signaling pathway, which sheds light on a new therapeutic strategy for diabetic nephropathy.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"461-469"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753635","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 hexokinase 2 promotes proliferation, migration and invasion of colorectal cancer cells by activating the JAK/STAT pathway and regulating tumor immune microenvironment].","authors":"Shunjie Qing, Zhiyong Shen","doi":"10.12122/j.issn.1673-4254.2025.03.12","DOIUrl":"10.12122/j.issn.1673-4254.2025.03.12","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the expression of hexokinase 2 (HK2) in colorectal cancer (CRC) and its possible mechanisms for regulating tumor cell behaviors and tumor immune microenvironment.</p><p><strong>Methods: </strong>We analyzed HK2 expression in CRC and its impact on patient prognosis and tumor immune microenvironment using public databases. HK2 expression was also examined in 8 CRC and paired adjacent tissues using immunohistochemistry, Western blotting and RT-qPCR. In cultured CRC cell lines CT26 and HCT116 with low HK2 expression, the effects of lentivirus-mediated HK2 overexpression and JAK/STAT3 inhibitors on cell proliferation, migration, and invasion were assessed using CCK-8 assay, colony formation assay and Transwell assay and in a subcutaneous tumor-bearing mouse model; the changes were also observed in MC38 and CACO2 cells with high HK2 expressions following treatment with HK2 inhibitor 3-BP. Western blotting was performed to verify the relationship between HK2 and JAK/STAT signaling pathway protein expressions.</p><p><strong>Results: </strong>Informatics analyses suggested that HK2 expression was significantly higher in CRC tissues than in adjacent tissues (<i>P</i><0.001), and patients with high HK2 expressions had worse prognosis (<i>P</i>=0.09). In the 8 clinical CRC tissues, HK2 expressions were significantly higher in the tumor tissues than in the adjacent tissues (<i>P</i><0.01). In CT26 and HCT116 cells, HK2 overexpression significantly enhanced cell proliferation, migration and invasion, while in HK2-overexpressing MC38 and CACO2 cells, inhibiting HK2 with 3-BP strongly suppressed these changes. HK2 overexpression promoted STAT3 phosphorylation, and JAK/STAT3 inhibitors effectively suppressed tumor cell proliferation, migration and invasion. TIMER and MCPcounter analyses indicated correlations between HK2 and immune cells, and TCGA and GEO analyses suggested significant positive correlations between HK2 and the immune checkpoints including PDCD1.</p><p><strong>Conclusions: </strong>HK2 is upregulated in CRC to promote tumor cell proliferation, migration and invasion possibly by activating the JAK-STAT signaling pathway and modulating tumor immune microenvironment.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"542-553"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753673","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":"[Quercetin ameliorates myocardial injury in diabetic rats by regulating L-type calcium channels].","authors":"Hongyan Sun, Guoqing Lu, Chengwen Fu, Mengwen Xu, Xiaoyi Zhu, Guoquan Xing, Leqiang Liu, Yufei Ke, Lemei Cui, Ruiyang Chen, Lei Wang, Pinfang Kang, Bi Tang","doi":"10.12122/j.issn.1673-4254.2025.03.11","DOIUrl":"10.12122/j.issn.1673-4254.2025.03.11","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats.</p><p><strong>Methods: </strong>Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (<i>n</i>=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique.</p><p><strong>Results: </strong>The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin.</p><p><strong>Conclusions: </strong>Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"531-541"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955902/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753687","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":"[Synchronized neural rhythms in rat hippocampal CA1 region and orbitofrontal cortex are involved in learning and memory consolidation in spatial goal-directed tasks].","authors":"Lingwei Tang, Jiasong Li, Haibing Xu","doi":"10.12122/j.issn.1673-4254.2025.03.05","DOIUrl":"10.12122/j.issn.1673-4254.2025.03.05","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the neural mechanisms of rhythmic activity in the hippocampal CA1 region and orbitofrontal cortex (OFC) during a spatial goal-directed task.</p><p><strong>Methods: </strong>Four long-Evans rats were trained to perform a spatial goal-directed task in a land-based water maze (Cheese-board maze). The task was divided into 5 periods: Pre-test, Pre-sleep, Learning, Post-sleep, and Post-test. During the Learning phase, the task was split into two goal navigation and two reward acquisition processes with a total of 8 learning stages. Local field potentials (LFP) from the CA1 and the OFC were recorded, and power spectral density analysis was performed on Theta (6-12 Hz), Beta (15-30 Hz), Low gamma (30-60 Hz), and High gamma (60-90 Hz) bands. Coherence, phase-locking value (PLV), and phase-amplitude cross coupling (PAC) were used to assess the interactions between the CA1 and the OFC during learning and memory.</p><p><strong>Results: </strong>During the task training, the rats showed consistent rhythms of OFC neural activity across the task states (<i>P</i>>0.05) while exhibiting significant changes in Beta and High gamma rhythms in the CA1 region (<i>P</i><0.05). Coherence and PLV between the CA1 and the OFC were higher during goal navigation, especially in the stable learning phase (Stage 8 <i>vs</i> Stage 1, <i>P</i><0.01). The rats showed stronger cross-frequency coupling between CA1-Theta and OFC-Low gamma in the Post-test phase than in the Pre-test phase (<i>P</i><0.05).</p><p><strong>Conclusions: </strong>Learning and memory consolidation in goal-directed tasks involve synchronized activity between the CA1 region and the OFC, and cross-frequency coupling plays a key role in maintaining short-term memory of reward locations in rats.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"479-487"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752768","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":"[Dexmedetomidine attenuates heat stress-induced oncosis in human skeletal muscle cells by activating the Nrf2/Ho-1 pathway].","authors":"Yang Liu, Yiqing Jia, Chengcheng Li, Handing Mao, Shuyuan Liu, Yi Shan","doi":"10.12122/j.issn.1673-4254.2025.03.18","DOIUrl":"10.12122/j.issn.1673-4254.2025.03.18","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the protective effects of dexmedetomidine (DEX) against heat stress (HS)-induced oncosis in human skeletal muscle cells (HSKMCs) and its underlying mechanisms.</p><p><strong>Methods: </strong>A HSKMC model of HS-induced oncosis were established by 43 ℃ water bath for 4 h, and the effects of treatments with 30 μmol/L DEX, ML385 (a Nrf2 inhibitor) +DEX, si-Nrf2+HS, and si-Nrf2+DEX prior to modeling on cell viability was assessed using CCK-8 assay. Oncosis characteristics were evaluated using transmission electron microscopy and Annexin V-FITC/PI flow cytometry. The oxidative stress markers (GSH, GSH-Px, MDA, SOD and ROS), mitochondrial membrane potential, energy metabolism, and inflammatory cytokines (TNF-α, IL-6 and IL-1β) in the cells were quantified using standard kits, and the expressions of porimin, caspase-3 and Nrf2 pathway proteins were analyzed using Western blotting and qRT-PCR.</p><p><strong>Results: </strong>HS induced typical oncotic features in HSKMCs including organelle swelling and cytoplasmic vacuolization. DEX pretreatment significantly attenuated these changes, reduced Annexin V⁺/PI⁺ cell ratio and cellular porimin expression, and lowered the levels of ROS and MDA while restoring GSH and SOD levels. DEX pretreatment also significantly increased the mitochondrial membrane potential and ATP level, upregulated the expressions of Nrf2, p-Nrf2, HO-1 and NQO1, and suppressed the expressions of TNF-α, IL-6 and IL-1β. The protective effects of DEX were obviously attenuated by interventions with ML385 or si-Nrf2.</p><p><strong>Conclusions: </strong>DEX mitigates HS-induced HSKMC oncosis by activating the Nrf2/HO-1 pathway to relieve oxidative stress, mitochondrial dysfunction, and inflammatory responses.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"603-613"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955895/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753669","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":"[Epidemiological survey of osteoporosis in Beijing over the past decade: a single-center analysis of dual-energy X-ray absorptiometry scans from 30 599 individuals].","authors":"Ying Zhou, Danyang Zhang, Lifan Wu, Guishan Wang, Jiedan Mu, Chengwen Cui, Xiuxiu Shi, Jige Dong, Yu Wang, Wangli Xu, Xiao Li","doi":"10.12122/j.issn.1673-4254.2025.03.01","DOIUrl":"10.12122/j.issn.1673-4254.2025.03.01","url":null,"abstract":"<p><strong>Objectives: </strong>To analyze bone mass distribution and the factors affecting bone mass in a general Chinese Han cohort undergoing physical examinations at our center.</p><p><strong>Methods: </strong>We retrospectively collected the data of bone mineral density (BMD) measurements from 30 599 healthy Han Chinese adults (age≥20 years) who underwent dual-energy X-ray absorptiometry scans at our hospital from July, 2013 to July, 2023. Basic parameters including height, body weight, and gender were recorded, and descriptive statistics and correlation analyses were performed using R software.</p><p><strong>Results: </strong>In this cohort, the male individuals had a mean peak BMD of 1.00±0.12 g/cm² in the lumbar vertebrae, 0.94±0.14 g/cm² in the femoral neck, and 0.99±0.13 g/cm² in the total hip, significantly higher than the values in the female individuals [0.99±0.12 g/cm² in the lumbar vertebrae (<i>P</i>=0.022), 0.79±0.11 g/cm² in the femoral neck (<i>P</i><0.001), and 0.88±0.11 g/cm² in the total hip (<i>P</i><0.001)]. In the overall cohort, the BMD values of the lumbar spine and femur decreased with age after reaching their peak levels. There was a positive correlation between BMD value and body mass index (BMI) in both male and female individuals. The 2013-2014 period recorded the lowest BMD values in the lumbar, hip, and femoral neck, which tended to increase steadily in the following years (2015-2023).</p><p><strong>Conclusions: </strong>Our data suggest that the BMD values vary among different populations, and future multi-center studies using more accurate BMD detection technology are warranted to capture the variation patterns of BMD with demographic characteristics of specific populations.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"443-452"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753671","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":"[Risk factors for malnutrition in ulcerative colitis complicated with pyoderma gangrenosum and construction of a lasso regression-based prediction model].","authors":"Lin Shen, Cuihao Song, Congmin Wang, Xi Gao, Junhong An, Chengxin Li, Bin Liang, Xia Li","doi":"10.12122/j.issn.1673-4254.2025.03.09","DOIUrl":"10.12122/j.issn.1673-4254.2025.03.09","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the risk factors for malnutrition in patients with ulcerative colitis complicated with pyoderma gangrenosum and establish a nutritional risk prediction model for these patients.</p><p><strong>Methods: </strong>A total of 277 patients with ulcerative colitis complicated with pyoderma gangrenosum treated from 2019 to 2024 were divided into malnutrition group (<i>n</i>=185) and normal nutrition group (<i>n</i>=92) according to whether malnutrition occurred. The data of 25 potential related factors pertaining to general demography, living and eating habits, and disease-related data were compared between the two groups. Lasso regression was used to screen the risk factors, and a nomogram model was established based on the screened factors and its prediction performance was assessed.</p><p><strong>Results: </strong>The patients in the malnutrition group and normal nutrition group showed significant differences in 21 factors including gender, age, education level, BMI, place of residence, course of disease, and SAS language score (<i>P</i><0.05). Lasso regression analysis identified 6 factors associated with malnutrition in these patients, namely the duration of ulcerative colitis, activity of ulcerative colitis, duration of pyoderma gangrenosum, number of chronic diseases, SAS score, and sleep quality. The nomogram prediction model established based on these 6 factors had an AUC of 0.992 (95% <i>CI</i>: 0.984-1.000) for predicting malnutrition in these patients, and its application in 14 clinical cases achieved an accuracy rate of 100%.</p><p><strong>Conclusions: </strong>The duration of ulcerative colitis, activity of colitis, duration of pyoderma gangrenosum, number of chronic diseases, anxiety, and sleep quality are closely related with malnutrition in patients with ulcerative colitis complicated by pyoderma gangrenosum, and the nomogram prediction model based on these factors can provide assistance for predicting malnutrition in these patients.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"514-521"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753689","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":"[Advances of low-intensity pulsed ultrasound for treatment of musculoskeletal disorders in the past decade].","authors":"Liping Fu, Lixia Yuan, Jie Wang, Xuelan Chen, Guizhi Ke, Yu Huang, Xinyi Yang, Gang Liu","doi":"10.12122/j.issn.1673-4254.2025.03.24","DOIUrl":"10.12122/j.issn.1673-4254.2025.03.24","url":null,"abstract":"<p><p>Musculoskeletal disorders (MSDs) are characterized by extensive pathological involvement and high prevalence and cause a significant disease burden. Long-term drug administration often causes by adverse effects with poor therapeutic efficacy. Low-intensity pulsed ultrasound (LIPUS), as a specialized therapeutic modality, delivers acoustic energy at a low intensity in a pulsed wave mode, thus ensuring stable energy transmission to the target tissues while minimizing thermal effects. This non-invasive approach has demonstrated significant potential for MSD treatment by delivering effective physical stimulations. Extensive animal and clinical studies have demonstrated the efficacy of LIPUS for accelerating the healing process of fresh fractures and nonunions, promoting soft tissue regeneration and suppressing inflammatory responses. Emerging evidence suggests promising applications of LIPUS in skeletal muscle injury treatment and promoting tissue regeneration and repair. This review outlines the recent advancements and mechanistic studies of LIPUS for treatment of common MSDs including fractures, nonunions, muscle injuries, and osteoarthritis, addressing also the technical parameters of commercially available LIPUS devices, current therapeutic approaches, the existing challenges, and future research directions.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"661-668"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753611","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":"[METTL3-mediated m⁶A modification promotes FOXO3 expression and anthracycline resistance in acute myeloid leukemia cells through autophagy regulation].","authors":"Xiawei Zhang, Jingjing Yang, Yanan Wen, Qingyang Liu, Liping Dou, Chunji Gao","doi":"10.12122/j.issn.1673-4254.2025.03.04","DOIUrl":"10.12122/j.issn.1673-4254.2025.03.04","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the role of METTL3 and FOXO3 in anthracycline resistance in acute myeloid leukemia (AML) cells.</p><p><strong>Methods: </strong>Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptome sequencing (RNA-seq) were performed in anthracycline-resistant and sensitive HL60 and K562 cells with lentivirus-mediated knockdown or overexpression of METTL3 and FOXO3. TCGA and GSE6891 datasets were used for analysis of the clinical and gene expression data of AMI patients. FOXO3 expressions at the mRNA and protein levels in the transfected cells were detected with RT-qPCR and Western blotting, and the changes in cell proliferation and apoptosis were evaluated using CCK8 assay and flow cytometry; the expression of m⁶A-modified mRNA and mRNA stability of FOXO3 was detected analyzed using MeRIP-qPCR and RT-qPCR. Functional enrichment analysis of the differential genes in the transfected cells was performed.</p><p><strong>Results: </strong>Differential gene analysis in anthracycline-resistant versus sensitive AML cells and in cells with METTL3 knockdown revealed the enrichment in FoxO and autophagy pathways (<i>P</i><0.05), and the anthracycline-resistant cells showed significantly increased m⁶A modification of FOXO3. FOXO3 expression was positively correlated with METTL3 expression. METTL3 knockdown significantly reduced FOXO3 mRNA stability and its protein levels in anthracycline-resistant AML cells, which exhibited higher m6A-modified FOXO3 expression levels than their sensitive counterparts. Database analysis, Kaplan-Meier analysis and RT-qPCR results suggested that a high FOXO3 expression was associated with a poor prognosis of AML patients. In anthracycline-resistant AML cells expressing higher FOXO3 levels than the sensitive cells, lentivirus-mediated overexpression of FOXO3 significantly enhanced cell proliferation and suppressed cell apoptosis. Inhibiting autophagy using an autophagy inhibitor (Baf.A1) obviously enhanced the inhibitory effect of adriamycin on resistant AMI cells and cells overexpressing FOXO3.</p><p><strong>Conclusions: </strong>METTL3 promotes FOXO3 expression via m6A modification, and FOXO3-driven autophagy contributes to anthracycline resistance in AML cells by enhancing cell proliferation and suppressing cell apoptosis.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"470-478"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753679","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>Akkermansia muciniphila</i> gavage improves gut-brain interaction disorders in gp120 transgenic mice].","authors":"Jiachun Luo, Sodnomjamts Batzaya, Xuefeng Gao, Jingyu Chen, Zhengying Yu, Shasha Xiong, Hong Cao","doi":"10.12122/j.issn.1673-4254.2025.03.13","DOIUrl":"10.12122/j.issn.1673-4254.2025.03.13","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the effect of <i>A. muciniphila</i> gavage on intestinal microbiota and gut-brain interaction disorders (DGBIs) in gp120tg transgenic mouse models of HIV-associated neurocognitive disorder (HAND).</p><p><strong>Methods: </strong>Intestinal microbiota was detected by 16S rRNA gene sequencing in 6-, 9-, and 12-month-old wild-type (WT) mice and gp120tg transgenic mice. The 12-month-old WT and transgenic mice were divided into 2 groups for daily treatment with PBS or <i>A.muciniphila</i> gavage (2×10⁸ CFU/mouse) for 6 weeks. After the treatment, immunohistochemistry, ELISA and qPCR were used to detect changes in colonic expression levels of glycosylated mucins, MBP and IL-1β, eosinophil infiltration, serum lipopolysaccharide (LPS) levels, and colonic expressions of occludin, ZO-1, IL-10, TNF-α and INF-γ mRNA. Morris water maze test and immunofluorescence assay were used to assess learning and spatial memory abilities and neuronal damage of the mice.</p><p><strong>Results: </strong>Compared with WT mice, the transgenic mice exhibited significantly lowered Simpson's diversity of the intestinal microbiota with reduced abundance of <i>Akkermansia</i> genus, increased serum LPS levels and decreased colonic expression of glycosylated mucin. <i>A.muciniphila</i> gavage obviously ameliorated the reduction of glycosylated mucin in the transgenic mice without causing significant changes in body weight. The 12-month-old gp120tg mice had significantly decreased cdonic expressions of Occludin and ZO-1 with increased eosinophil infiltration and TNF-β, INF-γ and IL-1β levels and obviously lowered IL-10 level; all these changes were significantly mitigated by <i>A.muciniphila</i> gavage, which also improved cognitive impairment and neuronal loss in the hippocampus and cortex of the transgenic mice.</p><p><strong>Conclusions: </strong>The gp120tg mice have lower intestinal microbiota richness and diversity than WT mice. The 12-month-old gp120tg mice have significantly reduced <i>Akkermansia</i> abundance with distinct DGBIs-related indexes, and <i>A. muciniphila</i> gavage can reduce intestinal barrier injury, colonic inflammation and eosinophil activation, cognitive impairment and brain neuron injury in these mice.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"554-565"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753632","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}