南方医科大学学报杂志最新文献

{"title":"A multi-constraint representation learning model for identification of ovarian cancer with missing laboratory indicators.","authors":"Zihan Lu, Fangjun Huang, Guangyao Cai, Jihong Liu, Xin Zhen","doi":"10.12122/j.issn.1673-4254.2025.01.20","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2025.01.20","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the performance of a multi-constraint representation learning classification model for identifying ovarian cancer with missing laboratory indicators.</p><p><strong>Methods: </strong>Tabular data with missing laboratory indicators were collected from 393 patients with ovarian cancer and 1951 control patients. The missing ovarian cancer laboratory indicator features were projected to the latent space to obtain a classification model using the representational learning classification model based on discriminative learning and mutual information coupled with feature projection significance score consistency and missing location estimation. The proposed constraint term was ablated experimentally to assess the feasibility and validity of the constraint term by accuracy, area under the ROC curve (AUC), sensitivity, and specificity. Cross-validation methods and accuracy, AUC, sensitivity and specificity were also used to evaluate the discriminative performance of this classification model in comparison with other interpolation methods for processing of the missing data.</p><p><strong>Results: </strong>The results of the ablation experiments showed good compatibility among the constraints, and each constraint had good robustness. The cross-validation experiment showed that for identification of ovarian cancer with missing laboratory indicators, the AUC, accuracy, sensitivity and specificity of the proposed multi-constraints representation-based learning classification model was 0.915, 0.888, 0.774, and 0.910, respectively, and its AUC and sensitivity were superior to those of other interpolation methods.</p><p><strong>Conclusions: </strong>The proposed model has excellent discriminatory ability with better performance than other missing data interpolation methods for identification of ovarian cancer with missing laboratory indicators.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 1","pages":"170-178"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008691","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>Yiqi Yangyin Huazhuo Tongluo</i> Formula alleviates diabetic podocyte injury by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.","authors":"Kelei Guo, Yingli Li, Chenguang Xuan, Zijun Hou, Songshan Ye, Linyun Li, Liping Chen, Li Han, Hua Bian","doi":"10.12122/j.issn.1673-4254.2025.01.04","DOIUrl":"10.12122/j.issn.1673-4254.2025.01.04","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the protective effect of <i>Yiqi Yangyin Huazhuo Tongluo</i> Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism.</p><p><strong>Methods: </strong>Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting. Autophagic activity in the cells were evaluated with MDC staining. The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay.</p><p><strong>Results: </strong>MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression, lowered expressions of FoxO1, PINK1, and Parkin1 mRNAs, and reduced levels of FoxO1, PINK1, parkin, nephrin, and podocin proteins and autophagic activity. Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin, inhibited the expression of miR-21a-5p, increased the mRNA and protein expressions of FoxO1, PINK1 and Parkin, and upregulated autophagic activity of the cells. Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells, and these effects were obviously attenuated by treatment with YYHT-medicated sera.</p><p><strong>Conclusions: </strong>YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 1","pages":"27-34"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008674","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":"CXCL12 is a potential therapeutic target for type 2 diabetes mellitus complicated by chronic obstructive pulmonary disease.","authors":"Huaiwen Xu, Li Weng, Hong Xue","doi":"10.12122/j.issn.1673-4254.2025.01.13","DOIUrl":"10.12122/j.issn.1673-4254.2025.01.13","url":null,"abstract":"<p><strong>Objectives: </strong>To identify the key genes and immunological pathways shared by type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) and explore the potential therapeutic targets of T2DM complicated by COPD.</p><p><strong>Methods: </strong>GEO database was used for analyzing the gene expression profiles in T2DM and COPD to identify the common differentially expressed genes (DEGs) in the two diseases. A protein-protein interaction network was constructed to identify the candidate hub genes, which were validated in datasets and disease sets to obtain the target genes. The diagnostic accuracy of these target genes was assessed with ROC analysis, and their expression levels and association with pulmonary functions were investigated using clinical data and blood samples of patients with T2DM and COPD. The abundance of 22 immune cells was analyzed with CIBERSORT algorithm, and their relationship with the target genes was examined using correlation analysis. DGIdb database was used for analyzing the drug-gene interactions and the druggable genes followed by gene set enrichment analysis.</p><p><strong>Results: </strong>We identified a total of 175 common DEGs in T2DM and COPD, mainly enriched in immune- and inflammation-related pathways. Among these genes, CXCL12 was identified as the final target gene, whose expression was elevated in both T2DM and COPD (<i>P</i><0.05) and showed good diagnostic efficacy. Immune cell infiltration correlation analysis showed significant correlations of CXCL12 with various immune cells (<i>P</i><0.01). GESA analysis showed that high CXCL12 expression was significantly correlated with \"cytokine-cytokine receptor interaction\". Drug-gene analysis showed that most of CXCL12-related drugs were not targeted drugs with significant cytotoxicity.</p><p><strong>Conclusions: </strong>CXCL12 is a potential common key pathogenic gene of COPD and T2DM, and small-molecule targeted drugs against CXCL12 can provide a new strategy for treatment T2DM complicated by COPD.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 1","pages":"100-109"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008696","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>Buyang Huanwu</i> Decoction reduces mitochondrial autophagy in rheumatoid arthritis synovial fibroblasts in hypoxic culture by inhibiting the BNIP3-PI3K/Akt pathway.","authors":"Junping Zhan, Shuo Huang, Qingliang Meng, Wei Fan, Huimin Gu, Jiakang Cui, Huilian Wang","doi":"10.12122/j.issn.1673-4254.2025.01.05","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2025.01.05","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the role of the BNIP3-PI3K/Akt signaling pathway in mediating the inhibitory effect of <i>Buyang Huanwu</i> Decoction (BYHWT) on mitochondrial autophagy in human synovial fibroblasts from rheumatoid arthritis patients (FLS-RA) cultured under a hypoxic condition.</p><p><strong>Methods: </strong>Forty normal Wistar rats were randomized into two groups (<i>n</i>=20) for daily gavage of BYHWT or distilled water for 7 days to prepare BYHWT-medicated or control sera. FLS-RA were cultured in routine condition or exposed to hypoxia (10% O₂) for 24 h wigh subsequent treatment with IL-1β, followed by treatment with diluted BYHWT-medicated serum (5%, 10% and 20%) or control serum. AnnexinV-APC/7-AAD double staining and T-AOC kit were used for detecting apoptosis and total antioxidant capacity of the cells, and the changes in ROS, ATP level, mitochondrial membrane potential and Ca²⁺ homeostasis were analyzed. The changes in mRNA and protein expressions of BNIP3, PI3K and AKT and mRNA expressions of LC3, Beclin-1 and P62 were detected using RT-qPCR and Western blotting.</p><p><strong>Results: </strong>Treatment with BYHWT-medicated serum dose-dependently lowered apoptosis rate of IL-1β-induced FLS-RA with hypoxic exposure. The treatment significantly decreased T-AOC concentration, increased ROS production, autophagosome formation and ATPase levels, and lowered mitochondrial membrane potential and Ca²⁺ level in the cells. In IL-1β-induced FLS-RA with hypoxic exposure, treatment with BYHWT-medicated serum significantly increased BNIP3 protein expression, decreased the protein expressions of PI3K and AKT, increased the mRNA expressions of BNIP3 and P62, and lowered the mRNA expressions of PI3K, AKT, LC3 and Beclin-1 without significantly affecting Beclin-1 protein expression. The cells treated with 5% and 10% BYHWT-medicated serum showed no significant changes in LC3 expression.</p><p><strong>Conclusions: </strong>BYHWT inhibits mitochondrial autophagy in IL-1β-induced FLS-RA with hypoxic exposure possibly by inhibiting BNIP3-mediated PI3K/AKT signaling pathway.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 1","pages":"35-42"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008448","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>Pulsatilla saponin D</i> inhibits invasion and metastasis of triple-negative breast cancer cells through multiple targets and pathways.","authors":"Qiao Chu, Xiaona Wang, Jiaying Xu, Huilin Peng, Yulin Zhao, Jing Zhang, Guoyu Lu, Kai Wang","doi":"10.12122/j.issn.1673-4254.2025.01.18","DOIUrl":"10.12122/j.issn.1673-4254.2025.01.18","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the mechanism by which <i>Pulsatilla saponin D</i> (PSD) inhibits invasion and metastasis of triple-negative breast cancer (TNBC).</p><p><strong>Methods: </strong>The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC. The \"PSD-target-disease\" interaction network was constructed and protein-protein interaction (PPI) analysis was performed to obtain the core targets, which were analyzed for KEGG pathway and GO functional enrichment. Molecular docking study of the core targets and PSD was performed, and the therapeutic effect and mechanism of PSD were verified using Transwell assay and Western blotting in cultured TNBC cells.</p><p><strong>Results: </strong>Network pharmacology analysis identified a total of 285 potential PSD targets and 26 drug-disease intersection core targets. GO analysis yielded 175 entries related to the binding of biomolecules (protein, DNA and RNA), enzyme activities, and regulation of gene transcription. KEGG analysis yielded 46 entries involving pathways in cancer, chemical carcinogenesis-receptor activation, microRNAs in cancer, chemical carcinogenesis-reactive oxygen species, PD-L1 expression and PD-1 checkpoint pathway in cancer. Molecular docking showed high binding affinities of PSD to MTOR, HDAC2, ABL1, CDK1, TLR4, TERT, PIK3R1, NFE2L2 and PTPN1. In cultured TNBC cells, treatment with PSD significantly inhibited cell invasion and migration and lowered the expressions of MMP2, MMP9, N-cadherin and the core proteins p-mTOR, ABL1, TERT, PTPN1, HDAC2, PIK3R1, CDK1, TLR4 as well as NFE2L2 expressionin the cell nuclei.</p><p><strong>Conclusions: </strong>The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 1","pages":"150-161"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008450","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 improves heart failure by inhibiting cardiomyocyte apoptosis <i>via</i> suppressing the MAPK signaling pathway.","authors":"Xiupeng Long, Shun Tao, Shen Yang, Suyun Li, Libing Rao, Li Li, Zhe Zhang","doi":"10.12122/j.issn.1673-4254.2025.01.22","DOIUrl":"10.12122/j.issn.1673-4254.2025.01.22","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the mechanism that mediate the therapeutic effect of quercetin on heart failure.</p><p><strong>Methods: </strong>We searched the TCMSP and Swiss ADME databases for the therapeutic targets of quercetin and retrieved heart failure targets from the Genecards and OMIM databases. The intersecting targets were analyzed with GO and KEGG pathway analysis using DAVID database, and the key genes were identified <i>via</i> PPI analysis. Molecular docking between the core targets and quercetin was performed using PyMOL and AutoDock Tools. In a heart failure model established in H9C2 cardiomyocytes by treatment with isoproterenol, the effect of quercetin on the expressions of the MAPK signaling pathway was tested.</p><p><strong>Results: </strong>A total of 60 intersecting targets were identified. Enrichment analysis revealed that quercetin may inhibit heart failure through the MAPK signaling pathway. The core genes, including AMPK3 and BCL-2, were identified as potential key regulators in quercetin-mediated improvement of heart failure. Cellular experiments demonstrated that quercetin significantly reduced isoproterenol-induced apoptosis of cardiomyocytes in a dose-dependent manner and obviously decreased the Bax/Bcl-2 ratio and the expression levels of caspase-3, ERK and p38 in the cells.</p><p><strong>Conclusions: </strong>Quercetin improves heart failure possibly by inhibiting cardiomyocyte apoptosis through the MAPK signaling pathway.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 1","pages":"187-196"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008648","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":"NLRP6 overexpression improves nonalcoholic fatty liver disease by promoting lipid oxidation and decomposition in hepatocytes through the AMPK/CPT1A/PGC1A pathway.","authors":"Qing Shi, Suye Ran, Lingyu Song, Hong Yang, Wenjuan Wang, Hanlin Liu, Qi Liu","doi":"10.12122/j.issn.1673-4254.2025.01.15","DOIUrl":"10.12122/j.issn.1673-4254.2025.01.15","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the regulatory role of nucleotide-bound oligomerized domain-like receptor containing pyrin-domain protein 6 (NLRP6) in liver lipid metabolism and non-alcoholic fatty liver disease (NAFLD).</p><p><strong>Methods: </strong>Mouse models with high-fat diet (HFD) feeding for 16 weeks (<i>n</i>=6) or with methionine choline-deficient diet (MCD) feeding for 8 weeks (<i>n</i>=6) were examined for the development of NAFLD using HE and oil red O staining, and hepatic expressions of NLRP6 were detected with RT-qPCR, Western blotting, and immunohistochemical staining. Cultured human hepatocytes (LO2 cells) with adenovirus-mediated NLRP6 overexpression or knock-down were treated with palmitic acid (PA) in the presence or absence of compound C (an AMPK inhibitor), and the changes in cellular lipid metabolism were examined by measuring triglyceride, ATP and β-hydroxybutyrate levels and using oil red staining, RT-qPCR, and Western blotting.</p><p><strong>Results: </strong>HFD and MCD feeding both resulted in the development of NAFLD in mice, which showed significantly decreased NLRP6 expression in the liver. In PA-treated LO2 cells, NLRP6 overexpression significantly decreased cellular TG content and lipid deposition, while NLRP6 knockdown caused the opposite effects. NLRP6 overexpression in PA-treated LO2 cells also increased mRNA and protein expressions of PGC1A and CPT1A, levels of ATP and β-hydroxybutyrate, and the phosphorylation level of AMPK pathway; the oxidative decomposition of lipids induced by Ad-NLRP6 was inhibited by the use of AMPK inhibitors.</p><p><strong>Conclusions: </strong>NLRP6 overexpression promotes lipid oxidation and decomposition through AMPK/CPT1A/PGC1A to alleviate lipid deposition in hepatocytes.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 1","pages":"118-125"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008727","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":"Overexpression of CHMP2B suppresses proliferation of renal clear cell carcinoma cells.","authors":"Xiaorui Chen, Qingzheng Wei, Zongliang Zhang, Jiangshui Yuan, Weiqing Song","doi":"10.12122/j.issn.1673-4254.2025.01.16","DOIUrl":"10.12122/j.issn.1673-4254.2025.01.16","url":null,"abstract":"<p><strong>Objectives: </strong>To analyze the association of CHMP2B expression level of with clinicopathological characteristics and prognosis of clear cell renal cell carcinoma (CRCC) and the possible role of CHMP2B in tumorigenesis and progression of CRCC.</p><p><strong>Methods: </strong>RNAseq data of CRCC were downloaded from the TCGA database for analysis of CHMP2B expression levels in tumor and adjacent tissues and their correlation with clinicopathological characteristics of the patients. Survival outcomes of the patients with high and low CHMP2B expressions were analyzed using the Kaplan-Meier model, and the COX risk regression model was used for identifying the prognostic factors of the patients. The correlation between CHMP2B expression and immune infiltration, its co-expressed genes, and the effect of CHMP2B gene mutations on immunotherapy responses, and its immunohistochemical expression in CRCC and normal tissues were analyzed. Clinical samples of CRCC were collected to examine CHMP2B expressions using RT-PCR, and cell experiment was carried out to test the effect of CHMP2B overexpression on biological behaviors of CRCC cells.</p><p><strong>Results: </strong>CHMP2B was significantly under-expressed in renal cancer tissues, and its overexpression obviously inhibited the proliferation of CRCC cells <i>in vitro</i>. CHMP2B expression level was significantly correlated with age, gender, lymph node metastasis, and tumor stage, and the patients with low CHMP2B expression had poor survival outcomes. Enrichment and co-expression gene analyses suggested that CHMP2B was mainly involved in viral outgrowth, necrotic apoptosis, endocytosis, and immune-regulatory processes in kidney cancer.</p><p><strong>Conclusions: </strong>CHMP2B is lowly expressed in renal cancer tissues to affect tumor progression and tumor immune processes, and may serve as a prognostic biomarker and therapeutic target for CRCC.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 1","pages":"126-136"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008730","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":"Differential expressions of exosomal miRNAs in patients with chronic heart failure and hyperuricemia: diagnostic values of miR-27a-5p and miR-139-3p.","authors":"Zhiliang Chen, Yonggang Yang, Xia Huang, Yan Cheng, Yuan Qu, Qiqi Heng, Yujia Fu, Kewei Li, Ning Gu","doi":"10.12122/j.issn.1673-4254.2025.01.06","DOIUrl":"https://doi.org/10.12122/j.issn.1673-4254.2025.01.06","url":null,"abstract":"<p><strong>Objectives: </strong>To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes.</p><p><strong>Methods: </strong>This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment.</p><p><strong>Results: </strong>A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (<i>P</i>=0.000179), and miR-139-3p was significantly downregulated (<i>P</i>=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (<i>P</i>=0.004) and downregulation of miR-139-3p (<i>P</i>=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% <i>CI</i>: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment.</p><p><strong>Conclusions: </strong>Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 1","pages":"43-51"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008698","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>Schistosoma japonicum</i> cystatin has protective effects against \"two-hit\" sepsis in mice by regulating the inflammatory microenvironment.","authors":"Wenjuan Duo, Yixiang Wang, Jiaxing Wang, Xinlong Xu, Linxian Li, Dongchen Yang, Qili Shen, Lichun Yang, Xiaojing Liu, Qiwang Jing, Liang Chu, Xiaodi Yang","doi":"10.12122/j.issn.1673-4254.2025.01.14","DOIUrl":"10.12122/j.issn.1673-4254.2025.01.14","url":null,"abstract":"<p><strong>Objectives: </strong>To evaluate the protective effect of <i>Schistosoma japonicum</i> cystatin (r<i>Sj</i>-Cystatin) in a mouse mode of \"two-hit\" sepsis.</p><p><strong>Methods: </strong>Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, \"two-hit\" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg r<i>Sj</i>-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg r<i>Sj</i>-Cystatin were injected 30 min after CLP. At 12 h after r<i>Sj</i>-Cystatin treatment, 6 mice from each group were sacrificed for detection of TNF-α, IL-6, IL-10, TGF-β, iNOS and Arg-1 in the serum, spleen, liver, lung and kidney tissues using ELISA, for examinations of liver, lung and kidney pathologies with HE staining, and for analysis of CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage in the spleen using flow cytometry. The remaining mice were observed for general condition and 72-h survival.</p><p><strong>Results: </strong>The 72-h survival rates in the 4 groups were 100%, 100%, 0% and 20%, respectively, showing significant differences between the latter two groups. The mouse models of \"two-hit\" sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate, which were significantly ameliorated by r<i>Sj</i>-Cystatin treatment. Treatment with r<i>Sj</i>-Cystatin also increased IL-10 and TGF-β levels and spleen CD3⁺CD4⁺CD25⁺Foxp3⁺ T cell percentage. The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney, and these changes were obviously improved by r<i>Sj</i>-Cystatin treatment.</p><p><strong>Conclusions: </strong>r<i>Sj</i>-Cystatin has a protective effect against \"two-hit\" sepsis in mice by regulating the inflammatory microenvironment.</p>","PeriodicalId":18962,"journal":{"name":"南方医科大学学报杂志","volume":"45 1","pages":"110-117"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008673","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}