{"title":"[METTL3-mediated m<sup>6</sup>A 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":"https://doi.org/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 m<sup>6</sup>A-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 m<sup>6</sup>A 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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
南方医科大学学报杂志Pub Date : 2025-03-20DOI: 10.12122/j.issn.1673-4254.2025.03.02
Qi Chen, Tiantian Xia, Yongqiang Zhou, Mingyang Chang, Nan Hu, Yanmei Yang, Zhong Li, Yue Gao, Bin Gu
{"title":"[<i>Prevotella nigrescens</i> exacerbates periodontal inflammation and impairs cognitive function in mice].","authors":"Qi Chen, Tiantian Xia, Yongqiang Zhou, Mingyang Chang, Nan Hu, Yanmei Yang, Zhong Li, Yue Gao, Bin Gu","doi":"10.12122/j.issn.1673-4254.2025.03.02","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2025.03.02","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effects of periodontitis induced by <i>Prevotella nigrescens</i> (Pn) combined with ligation on cognitive functions in mice.</p><p><strong>Methods: </strong>Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining.</p><p><strong>Results: </strong>After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups.</p><p><strong>Conclusions: </strong>Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"453-460"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
南方医科大学学报杂志Pub Date : 2025-03-20DOI: 10.12122/j.issn.1673-4254.2025.03.13
Jiachun Luo, Sodnomjamts Batzaya, Xuefeng Gao, Jingyu Chen, Zhengying Yu, Shasha Xiong, Hong Cao
{"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":"https://doi.org/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 (2×10<sup>8</sup> 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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
南方医科大学学报杂志Pub Date : 2025-03-20DOI: 10.12122/j.issn.1673-4254.2025.03.06
Ying Wang, Wengyang Deng, Chaomei Wu, Shihuan Tian, Hua Li
{"title":"[Effects of larval feeding amount on development and deltamethrin resistance in <i>Aedes albopictus</i>].","authors":"Ying Wang, Wengyang Deng, Chaomei Wu, Shihuan Tian, Hua Li","doi":"10.12122/j.issn.1673-4254.2025.03.06","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2025.03.06","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate how larval feeding regimens influence development and deltamethrin resistance of <i>Aedes albopictus</i> to provide evidence for standardizing larval feeding protocols in studies of insecticide resistance.</p><p><strong>Methods: </strong><i>Aedes albopictus</i> larvae of a laboratory resistant strain were divided into 3 groups (<i>n</i>=500) and reared with high, medium, and low food availability (100, 50, or 25 mg daily for the 1st and 2nd instars, and 500 mg 250, or 125 mg daily for 3rd and 4th instars). The developmental time, pupation rate, adult emergence rate, adult body weight, and wing length were recorded in each group, and deltamethrin resistance of the mosquitoes was assessed using larval bioassays and contact tube tests for adults.</p><p><strong>Results: </strong>Significant developmental differences were observed across the 3 feeding groups. Larval development time decreased as the food availability increased, and both high- and low-food groups showed reduced pupation rates (χ²=16.282, 7.440) and emergence rates (χ²=4.093, 6.977) compared to the medium-food group. Adult body weight and wing length were positively correlated with the amount of larval food intake (<i>P</i><0.05). In high, medium and low food intake groups, larval LC<sub>50</sub> values for deltamethrin were 0.110, 0.072 and 0.064 mg/L, adult KDT50 values were 97.404, 68.964 and 65.005 min, and adult mosquitoe mortality rates at 24 h after deltamethrin exposure were 12%, 16% and 19%, respectively.</p><p><strong>Conclusions: </strong>The feeding amount during larval stage significantly impacts the development and deltamethrin resistance of <i>Aedes albopictus</i>, suggesting the importance of standardization of larval nutrition for ensuring comparability of resistance test data across laboratories.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"488-493"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
南方医科大学学报杂志Pub Date : 2025-03-20DOI: 10.12122/j.issn.1673-4254.2025.03.21
Jinyu Liu, Shujun Liang, Yu Zhang
{"title":"[A multi-scale supervision and residual feedback optimization algorithm for improving optic chiasm and optic nerve segmentation accuracy in nasopharyngeal carcinoma CT images].","authors":"Jinyu Liu, Shujun Liang, Yu Zhang","doi":"10.12122/j.issn.1673-4254.2025.03.21","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2025.03.21","url":null,"abstract":"<p><strong>Objectives: </strong>We propose a novel deep learning segmentation algorithm (DSRF) based on multi-scale supervision and residual feedback strategy for precise segmentation of the optic chiasm and optic nerves in CT images of nasopharyngeal carcinoma (NPC) patients.</p><p><strong>Methods: </strong>We collected 212 NPC CT images and their ground truth labels from SegRap2023, StructSeg2019 and HaN-Seg2023 datasets. Based on a hybrid pooling strategy, we designed a decoder (HPS) to reduce small organ feature loss during pooling in convolutional neural networks. This decoder uses adaptive and average pooling to refine high-level semantic features, which are integrated with primary semantic features to enable network learning of finer feature details. We employed multi-scale deep supervision layers to learn rich multi-scale and multi-level semantic features under deep supervision, thereby enhancing boundary identification of the optic chiasm and optic nerves. A residual feedback module that enables multiple iterations of the network was designed for contrast enhancement of the optic chiasm and optic nerves in CT images by utilizing information from fuzzy boundaries and easily confused regions to iteratively refine segmentation results under supervision. The entire segmentation framework was optimized with the loss from each iteration to enhance segmentation accuracy and boundary clarity. Ablation experiments and comparative experiments were conducted to evaluate the effectiveness of each component and the performance of the proposed model.</p><p><strong>Results: </strong>The DSRF algorithm could effectively enhance feature representation of small organs to achieve accurate segmentation of the optic chiasm and optic nerves with an average DSC of 0.837 and an ASSD of 0.351. Ablation experiments further verified the contributions of each component in the DSRF method.</p><p><strong>Conclusions: </strong>The proposed deep learning segmentation algorithm can effectively enhance feature representation to achieve accurate segmentation of the optic chiasm and optic nerves in CT images of NPC.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"632-642"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Cimifugin ameliorates Crohn's disease-like colitis in mice by modulating Th-cell immune balance <i>via</i> inhibiting the MAPK pathway].","authors":"Lixia Yin, Minzhu Niu, Keni Zhang, Zhijun Geng, Jianguo Hu, Jiangyan Li, Jing Li","doi":"10.12122/j.issn.1673-4254.2025.03.17","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2025.03.17","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the therapeutic effects of cimifugin on Crohn's disease (CD)-like colitis in mice and its possible mechanism.</p><p><strong>Methods: </strong>Thirty adult male C57BL/6 mice were randomized equally into control group, 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced CD-like colitis model group, and cimifugin treatment (daily gavage at 12.5 mg/kg) group. The therapeutic effect of cimifugin was evaluated by observing changes in body weight, disease activity index (DAI) scores, colon length, histopathological inflammation scores, and inflammatory cytokine levels in the colonic mucosa. Intestinal barrier integrity in the mice was assessed using immunofluorescence assay and Western blotting for claudin-1 and ZO-1; T-helper (Th) cell subset ratios in the mesenteric lymph nodes were analyzed with flow cytometry. Network pharmacology, KEGG enrichment analysis and molecular docking were used to predict the targets of cimifugin and analyze the key pathways and cimifugin-MAPK protein interactions, which were validated by Western blotting in the mouse models.</p><p><strong>Results: </strong>In mice with TNBS-induced colitis, cimifugin treatment significantly attenuated body weight loss and colon shortening, lowered DAI and histopathological scores, decreased IFN-γ and IL-17 levels, and increased IL-4 and IL-10 levels in the colonic mucosa. Cimifugin treatment also significantly improved TNBS-induced claudin-1 dislocation and reduction of goblet cells, upregulated claudin-1 and ZO-1 expressions, reduced Th1 and Th17 cell percentages, and increased Th2 and Treg cell percentages in the colonic mucosa of the mice. KEGG analysis suggested a possible connection between the effect of cimifugin and MAPK signaling, and molecular docking showed strong binding affinity between cimifugin and MAPK core proteins. Western blotting demonstrated significantly decreased phosphorylation levels of JNK, ERK, and p38 in the colonic mucosa of cimifugin-treated mouse models.</p><p><strong>Conclusions: </strong>Cimifugin alleviates TNBS-induced CD-like colitis by repairing intestinal barrier damage and restoring Th1/Th2 and Th17/Treg balance via suppressing MAPK pathway activation.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"595-602"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Hypericin ameliorates stress-induced depressive-like behaviors in mice by modulating the CN-NFAT calcium signaling pathway in microglia].","authors":"Zhengtao Gao, Pingyan Lin, Bingcan Zhou, Mingheng Chen, Erqi Liu, Tianxiang Lei, Huixin Ni, Haixin Liu, Yao Lin, Qian Xu","doi":"10.12122/j.issn.1673-4254.2025.03.08","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2025.03.08","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the role of the calcium/calmodulin (CaM)-mediated activation of calcineurin (CN)-nuclear factor of activated T cells (NFAT) signaling pathway in mediating the regulatory effect of hyperforin (HY) on stress-induced depression-like disorder (DP) in mice.</p><p><strong>Methods: </strong>C57BL/6J mice were randomly divided into control group, DP model group, and hyperforin treatment group (<i>n=</i>15). Behavioral changes of the mice were assessed using open field test (OFT), sucrose preference test (SPT), tail suspension test (TST), light/dark box test (LDB), and novel object suppression test (NSFT). Immunohistochemistry was used to detect tyrosine hydroxylase (TH) expression in the CA1 region of the hippocampus, and serum serotonin (5-HT) and norepinephrine (NA) levels were detected with ELISA. Western blotting was used to analyze the expressions of TNF-α, IL-1β, IL-2, and CN-NFAT pathway proteins. In cultured BV-2 microglial cells with lipopolysaccharide (LPS) stimulation, the effects of hyperforin and CN inhibitor (CNIS) on expressions of ionized calcium-binding adapter molecule 1 (IBA-1), 5-HT, NA, inflammatory cytokines and CN-NFAT pathway proteins were examined using immunofluorescence assay, ELISA or Western blotting.</p><p><strong>Results: </strong>Compared with the control mice, the mice in DP group showed significantly reduced activity in OFT, decreased sucrose consumption in SPT, reduced shuttle crossing in LDB, and lowered food intake in NSFT with significantly increased immobility in TST. The mice with DP showed significantly decreased TH-positive neurons, lowered 5-HT and NA levels, and increased expressions of TNF-α, IL-1β, IL-2 and CaM-CN-NFAT pathway proteins. In cultured BV-2 cells, LPS stimulation strongly increased cellular IBA-1 expression, decreased the levels of neurotransmitters (5-HT and NA), and increased the levels of inflammatory cytokines and CN-NFAT signaling, and these changes were effectively reversed by treatment with hyperforin or CNIS.</p><p><strong>Conclusions: </strong>Hyperforin improves stress-induced depression-like behaviors in mice and activated BV-2 cells by targeting the CN-NFAT signaling pathway.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"506-513"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
南方医科大学学报杂志Pub Date : 2025-03-20DOI: 10.12122/j.issn.1673-4254.2025.03.15
Zehan Li, Meng Liang, Gencheng Han, Xuewu Zhang
{"title":"[Therapeutic effects of inulin-type oligosaccharides of <i>Morinda officinalis</i> on <i>Streptococcus pneumoniae</i> meningitis in mice].","authors":"Zehan Li, Meng Liang, Gencheng Han, Xuewu Zhang","doi":"10.12122/j.issn.1673-4254.2025.03.15","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2025.03.15","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the therapeutic effects of inulin-type oligosaccharides of <i>Morinda officinalis</i> (IOMO) in a murine model of <i>Streptococcus pneumoniae</i> meningitis (SPM) and explore its possible mechanisms.</p><p><strong>Methods: </strong>A total of 120 male C57BL/6J mice were randomly assigned into Sham, SPM+Saline, SPM+IOMO (25 mg/kg), and SPM+IOMO (50 mg/kg) groups. After modeling, the mice received daily gavage of saline or IOMO at the indicated doses for 7 consecutive days, and the changes in symptom scores and mortality of the mice were monitored. Brain pathology and neuronal injury of the mice were assessed using HE and Nissl staining, and qRT-PCR was performed to detect mRNA levels of the inflammatory mediators. Brain edema and blood-brain barrier (BBB) permeability of the mice were evaluated by measuring brain water content and Evans blue (EB) staining; Western blotting was used to analyze the expressions of BBB-associated proteins, and flow cytometry was employed to detect IFN‑γ expression level in the infiltrating lymphocytes. Open-field test (OFT) and novel object recognition test (NORT) were conducted to assess learning and memory ability of the mice on day 21 after modeling.</p><p><strong>Results: </strong>IOMO treatment at 50 mg/kg significantly reduced the symptom scores and mortality rate of SPM mice, alleviated brain damage, and downregulated mRNA levels of IL-6, TNF‑α, IL-1β, IL-18, IFN‑γ, iNOS, NLRP3, ASC, caspase-1 and GSDMD in the brain tissue. IOMO treatment also decreased brain water content and EB leakage, upregulated VE-cadherin and occludin expressions, and suppressed AQP4, iNOS, and IFN‑γ levels of the mice. IOMO-treated mice exhibited improved learning and memory compared with the saline-treated mice on day 21 after SPM modeling.</p><p><strong>Conclusions: </strong>IOMO alleviates SPM symptoms, reduces mortality, and mitigates cognitive deficits in mice possibly by suppressing cerebral inflammation and protecting BBB functions.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"577-586"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[A lightweight classification network for single-lead atrial fibrillation based on depthwise separable convolution and attention mechanism].","authors":"Yong Hong, Xin Zhang, Mingjun Lin, Qiucen Wu, Chaomin Chen","doi":"10.12122/j.issn.1673-4254.2025.03.23","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2025.03.23","url":null,"abstract":"<p><strong>Objectives: </strong>To design a deep learning model that balances model complexity and performance to enable its integration into wearable ECG monitoring devices for automated diagnosis of atrial fibrillation.</p><p><strong>Methods: </strong>This study was performed based on data from 84 patients with atrial fibrillation, 25 patients with atrial fibrillation, and 18 subjects without obvious arrhythmia collected from the publicly available datasets LTAFDB, AFDB, and NSRDB, respectively. A lightweight attention network based on depthwise separable convolution and fusion of channel-spatial information, namely DSC-AttNet, was proposed. Depthwise separable convolution was introduced to replace standard convolution and reduce model parameters and computational complexity to realize high efficiency and light weight of the model. The multilayer hybrid attention mechanism was embedded to compute the attentional weights of the channels and spatial information at different scales to improve the feature expression ability of the model. Ten-fold cross-validation was performed on LTAFDB, and external independent testing was conducted on AFDB and NSRDB datasets.</p><p><strong>Results: </strong>DSC-AttNet achieved a ten-fold average accuracy of 97.33% and a precision of 97.30% on the test set, both of which outperformed the other 4 comparison models as well as the 3 classical models. The accuracy of the model on the external test set reached 92.78%, better than those of the 3 classical models. The number of parameters of DSC-AttNet was 1.01M, and the computational volume was 27.19G, both smaller than the 3 classical models.</p><p><strong>Conclusions: </strong>This proposed method has a smaller complexity, achieves better classification performance, and has a better generalization ability for atrial fibrillation classification.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"650-660"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
南方医科大学学报杂志Pub Date : 2025-03-20DOI: 10.12122/j.issn.1673-4254.2025.03.07
Yan Huang, Xi Chen, Mengchen Qin, Lei Gao
{"title":"[Core targets and immune regulatory mechanisms of <i>Huoluo Xiaoling</i> Pellet for promoting zebrafish fin regeneration].","authors":"Yan Huang, Xi Chen, Mengchen Qin, Lei Gao","doi":"10.12122/j.issn.1673-4254.2025.03.07","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2025.03.07","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the core targets and immunomodulatory mechanisms of <i>Huoluo Xiaoling</i> Pellet (HLXLP) for promoting tissue repair.</p><p><strong>Methods: </strong>Network pharmacology and protein-protein interaction network were used to screen active components in HLXLP, the disease-related targets and the core targets, followed by GO and KEGG enrichment analyses and molecular docking to predict the pharmacological mechanisms. The toxicity of HLXLP was evaluated in zebrafish, and in a tissue regeneration model established in 3 dpf zebrafish larvae by amputating 95% of the tail fin, the effects of a formulated zebrafish embryo culture medium and 10, 20, and 40 μg/mL of aqueous extract of HLXLP on tissue regeneration was evaluated; RT-qPCR was performed to detect mRNA expressions of tissue regeneration marker genes and the core target genes. Transgenic zebrafish with fluorescently labeled macrophages and neutrophils were used to observe immune cell migration during tissue regeneration, and macrophage polarization at different stages was assessed with RT-qPCR.</p><p><strong>Results: </strong>We identified a total of 149 intersected targets between HLXLP active components and tissue repair and 5 core targets (AKT1, IL-6, TNF-α, EGFR and STAT3). GO and KEGG analyses suggested that the effects of HLXLP were mediated primarily through the JAK-STAT pathway, adhesion junctions and positive regulation of cell migration. HLXLP was minimally toxic below 40 μg/mL and lethal at 320 μg/mL in zebrafish, and caused renal and pericardial edema and vascular defects above 80 μg/mL. In zebrafish with tail fin amputation, HLXLP significantly promoted tissue regeneration, reduced <i>IL-6</i> and <i>TNF-α</i> and enhanced <i>AKT1</i>, <i>EGFR</i> and <i>STAT3</i> mRNA expressions, modulated neutrophil and macrophage recruitment to the injury sites, and regulated M1/M2 macrophage polarization during tissue regeneration.</p><p><strong>Conclusions: </strong>HLXLP promotes zebrafish tail fin regeneration through multiple active components, targets and pathways for immunomodulation of immune cell migration and macrophage polarization to suppress inflammation and accelerate healing.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 3","pages":"494-505"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}