中南大学学报(医学版)最新文献

{"title":"Expression of transcription factors in polycystic ovary syndrome.","authors":"Qi Zhang, Shujuan Zhu, Bin Jiang","doi":"10.11817/j.issn.1672-7347.2025.240631","DOIUrl":"https://doi.org/10.11817/j.issn.1672-7347.2025.240631","url":null,"abstract":"<p><strong>Objectives: </strong>Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women's health. This study aims to investigate gene and transcription factor (TF) expression differences between PCOS patients and healthy individuals using bioinformatics approaches, and to verify the function of key transcription factors, with the goal of providing new insights into the pathogenesis of PCOS.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) and differentially expressed transcription factors (DETFs) between PCOS patients and controls were identified from the RNA sequencing dataset GSE168404 using bioinformatics methods. Functional enrichment analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The expression and function of core transcription factors were further validated in ovarian tissues of PCOS model mice and control mice using Western blotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>A total of 332 DEGs were identified between PCOS patients and controls, including 259 upregulated and 73 downregulated genes in the PCOS group. 19 DETFs were further screened, of which 16 were upregulated and 3 were downregulated in PCOS. The upregulated DETFs (including <i>TFCP2L1</i>, <i>DACH1</i>, <i>ESR2</i>, <i>AFF3</i>, <i>SMAD9</i>, <i>ZNF331</i>, <i>HOPX,</i><i>ATOH8</i>, <i>HIF3α</i>, <i>DPF3</i>, <i>HOXC4</i>, <i>HES1</i>, <i>ID1</i>, <i>JDP2</i>, <i>SOX4</i>, and <i>ID3</i>) were primarily associated with lipid metabolism, development, and cell adhesion. Protein and mRNA expression analysis in PCOS model mice revealed significantly decreased levels of hypoxia-inducible factor (<i>HIF</i>) <i>1α</i> and <i>HIF2α</i>, and significantly increased expression of <i>HIF3α</i> compared to control mice (all <i>P</i><0.001).</p><p><strong>Conclusions: </strong>Significant differences in gene and TF expression exist between PCOS patients and healthy individuals. HIF-3α may play a crucial role in PCOS and could serve as a novel biomarker for diagnosis and a potential therapeutic target.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"50 3","pages":"447-456"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592584","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":"Expression of WNT10A in papillary thyroid carcinoma and its effect on cell proliferation, invasion, and metastasis.","authors":"Li Yuan, Ping Zhou, Yongfeng Zhao, Jiale Li, Yan Zhang, Wengang Liu","doi":"10.11817/j.issn.1672-7347.2025.240237","DOIUrl":"https://doi.org/10.11817/j.issn.1672-7347.2025.240237","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;Lymph node metastasis in papillary thyroid cancer (PTC) is closely associated with tumor recurrence and patient survival. However, current technologies have limited sensitivity in detecting occult cervical lymph node metastases. Identifying accurate molecular markers for predicting PTC metastasis holds significant clinical value. This study aims to analyze WNT10A expression in PTC and its clinical significance, and to explore the role of &lt;i&gt;WNT10A&lt;/i&gt; gene knockdown in PTC cell proliferation, invasion, and metastasis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The expression of &lt;i&gt;WNT10A&lt;/i&gt; in thyroid carcinoma was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) and University of Alabama at Birminghara Cancer data analysis Portal (UALCAN) databases. Real-time RT-PCR was used to measure &lt;i&gt;WNT10A&lt;/i&gt; mRNA levels in tumor and adjacent normal tissues from 32 PTC patients. Immunohistochemistry was conducted on 158 PTC specimens to assess WNT10A protein expression and its correlation with clinicopathological features. In vitro experiments were performed using K1 and TPC-1 cell lines. Cell proliferation was assessed using the Celigo system and methyl thiazolyl tetrazolium (MTT) assays; apoptosis was measured via flow cytometry; invasion and metastasis were evaluated using scratch and Transwell assays. A xenograft model was established in nude mice to observe tumor growth, and tumor weight and volume were compared between cell lines. Differentially expressed genes regulated by &lt;i&gt;WNT10A&lt;/i&gt; were identified via mRNA sequencing, followed by Gene Ontology (GO) and ingenuity pathway analysis (IPA). Real-time PCR and Western blotting were used to validate the effects of WNT10A on key downstream mRNA and protein in the Tec kinase signaling pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;&lt;i&gt;WNT10A&lt;/i&gt; mRNA expression was significantly higher in thyroid cancer tissues compared to adjacent normal tissues according to GEPIA and UALCAN (both &lt;i&gt;P&lt;/i&gt;&lt;0.01). The real-time RT-PCR result showed that &lt;i&gt;WNT10A&lt;/i&gt; mRNA expression in PTC tissues was high than that in adjacent tissues (&lt;i&gt;P&lt;/i&gt;&lt;0.01). Immunohistochemistry revealed significantly higher WNT10A protein expression in PTC tissues compared to adjacent tissues (&lt;i&gt;P&lt;/i&gt;&lt;0.01), and its expression correlated with multifocality, extrathyroidal invasion, and lymph node metastasis. &lt;i&gt;WNT10A&lt;/i&gt; knockdown significantly inhibited proliferation, altered cell cycle distribution, and increased apoptosis in K1 and TPC-1 cells (all &lt;i&gt;P&lt;/i&gt;&lt;0.01). &lt;i&gt;WNT10A&lt;/i&gt; silencing also reduced migration and invasion abilities in both cell lines. In vivo, &lt;i&gt;WNT10A&lt;/i&gt; knockdown in TPC-1 cells suppressed tumor formation in nude mice. GO analysis and IPA suggested that the Tec kinase signaling pathway was a key downstream target of WNT10A. RT-PCR and Western blotting confirmed that &lt;i&gt;WNT10A&lt;/i&gt; knockdown downregulated the expression of key genes (&lt;i&gt;STAT3&lt;/i&gt;, &lt;i&gt;MAPK8&lt;/i&gt;, &lt;i&gt;TNFRSF21&lt;/i&gt;, ","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"50 3","pages":"402-415"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592585","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":"Optimization of flow rate and orientation of outflow graft at implantation for patients with left ventricular assist device.","authors":"Yongyi Wang, Li Shi, Shijun Hu, Xiao Tan, Tianli Zhao","doi":"10.11817/j.issn.1672-7347.2025.240244","DOIUrl":"https://doi.org/10.11817/j.issn.1672-7347.2025.240244","url":null,"abstract":"<p><strong>Objectives: </strong>A ventricular assist device (VAD) is an electromechanical device used to assist cardiac blood circulation, which can be employed for the treatment of end-stage heart failure and is most commonly placed in the left ventricle. Despite enhancing perfusion performance, the implantation of left ventricular assist device (LVAD) transforms the local intraventricular flow and thus may increase the risk of thrombogenesis. This study aims to investigate fluid-particle interactions and thromboembolic risk under different LVAD configurations using three-dimensional (3D) reconstruction models, focusing on the effects of outflow tract orientation and blood flow rates.</p><p><strong>Methods: </strong>A patient-specific end-diastolic 3D reconstruction model was initially constructed in stereo lithography (STL) format using Mimics software based on CT images. Transient numerical simulations were performed to analyze fluid-particle interactions and thromboembolic risks for LVAD with varying outflow tract orientations under 2 flow rates (4 L/min and 5 L/min), using particles of uniform size (2 mm), and a blood flow rate optimization protocol was implemented for this patient.</p><p><strong>Results: </strong>When the LVAD flow rate was 5 L/min, helicity and flow stagnation of the blood flow increased the particle residence time (RT) and the risk of thrombogenesis of the aortic root. The percentage of particles traveling toward the brachiocephalic trunk was up to 20.33%. When the LVAD flow rate was 4 L/min, blood turbulence in the aorta was reduced, the RT of blood particles was shortened, and then the percentage of particles traveling toward the brachiocephalic trunk decreased to 10.54%. When the LVAD blood flow rate was 5 L/min and the direction of the outflow pipe was optimal, the RT of blood particles was shortened, and then the percentage of particles traveling toward the brachiocephalic trunk decreased to 11.22%. A 18-month follow-up observation of the patient revealed that the LVAD was in good working order and the patient had no complications related to the implantation of LVAD.</p><p><strong>Conclusions: </strong>Implantation of LVAD results in a higher risk of cerebral infarction; When implanting LVAD with the same outflow tract direction, optimizing flow velocity and outflow tract can reduce the risk of cerebral infarction occurrence.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"50 3","pages":"457-468"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592589","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":"Role of acitretin in regulating glucose and lipid homeostasis in an imiquimod-induced psoriasis model mouse.","authors":"Kexin Long, Wangqing Chen, Manyun Mao, Wu Zhu","doi":"10.11817/j.issn.1672-7347.2025.240619","DOIUrl":"https://doi.org/10.11817/j.issn.1672-7347.2025.240619","url":null,"abstract":"<p><strong>Objectives: </strong>Psoriasis is a chronic inflammatory skin disease often accompanied by comorbidities such as hyperglycemia, insulin resistance, and obesity. Acitretin, as a second-generation retinoid, is used in the treatment of psoriasis. This study aims to explore the role of acitretin on glucose and lipid metabolism in psoriasis.</p><p><strong>Methods: </strong>HepG2 cells were treated with acitretin under high- or low-glucose conditions. mRNA and protein expression levels of glucose transport-related genes were evaluated using real-time reverse transcription PCR (real-time RT-PCR) and Western blotting. Glucose uptake was analyzed by flow cytometry, and intracellular lipid droplet formation was assessed via Oil Red O staining. Healthy adult female BALB/C mice were randomly divided into 3 groups: a control group, an imiquimod (IMQ)-induced psoriasis model group (IMQ group), and an acitretin treatment group. Skin lesions and inflammatory markers were examined, along with changes in body weight, plasma glucose/lipid levels, and transcription of metabolic genes. Islets were isolated from normal and psoriasis-induced mice, and the effect of acitretin on insulin secretion was evaluated in vitro.</p><p><strong>Results: </strong>Acitretin treatment increased glucose uptake and lipid droplet synthesis of HepG2 in high-glucose environment, with elevated transcription levels of glucose transport-related genes <i>GLUT1</i> and <i>GLUT4</i>. Transcription of gluconeogenesis-related gene <i>G6pase</i> decreased, while transcription levels of glycogen synthesis-related genes <i>AKT1</i> and <i>GSY2</i> increased (all <i>P</i><0.05), while acitretin inhibits glucose uptake and promotes gluconeogenesis in low-glucose environment. In vivo experiments revealed that compared with the control group, the blood glucose level in the IMQ group was significantly decreased (<i>P</i><0.05), while acitretin treatment partially restored glucose homeostasis and alleviated weight loss. Ex vivo culture of islets from psoriatic mice revealed that acitretin reduced elevated insulin secretion and downregulated <i>PDX-1</i> expression, while upregulating glucose homeostasis gene <i>SIRT1</i> and insulin sensitivity gene <i>PPARγ</i> (all <i>P</i><0.05). These findings suggest that acitretin plays a critical role in improving islet function and restoring islet homeostasis.</p><p><strong>Conclusions: </strong>Acitretin helps maintain the balance between hepatic glycogenesis and gluconeogenesis, enhances insulin sensitivity, and improves pancreatic islet function, thereby promoting systemic and cellular glucose homeostasis.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"50 3","pages":"344-357"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592592","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":"Characteristics of the amygdala and its subregions in premenstrual syndrome/premenstrual dysphoric disorder patients.","authors":"Ming Cheng, Baoyi Li, Zhen Zhang, Zhaoshu Jiang, Jie Yang, Peng Jiang, Zhonghao Yuan","doi":"10.11817/j.issn.1672-7347.2025.240526","DOIUrl":"https://doi.org/10.11817/j.issn.1672-7347.2025.240526","url":null,"abstract":"<p><p>Premenstrual dysphoric disorder (PMDD) is considered a severe form of premenstrual syndrome (PMS). As a key brain region involved in emotional regulation and stress responses, the amygdala has been implicated in the pathogenesis of PMS/PMDD. The amygdala is composed of multiple subregions, each playing distinct roles in emotion, memory, and stress responses, and forms complex brain areas. Summarizing the interconnections among amygdala, subregions and their connectivity with external areas, and exploringt the neuroimaging characteristics of the amygdala, as well as changes in its neural circuits and brain networks in these patients, will help provide a theoretical foundation for targeted modulation of amygdala function in the treatment of PMS/PMDD.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"50 3","pages":"492-500"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592581","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":"Effect of different surgical approaches for intrauterine adhesions patients on pregnancy outcomes.","authors":"Ping Guo, Meiqin Chen, Shan Liu, Wei Peng, Xingping Zhao, Hualian Chen","doi":"10.11817/j.issn.1672-7347.2025.240529","DOIUrl":"https://doi.org/10.11817/j.issn.1672-7347.2025.240529","url":null,"abstract":"<p><strong>Objectives: </strong>Transcervical resection of adhesions (TCRA) under hysteroscopy is the mainstay treatment for intrauterine adhesions (IUA), but its effectiveness varies depending on the surgical approach. This study aims to investigate the impact of different surgical techniques on endometrial repair and pregnancy outcomes in patients with secondary infertility and moderate-to-severe IUA.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 225 patients who underwent TCRA followed by in vitro fertilization and embryo transfer between January 2021 and December 2022. Patients were grouped based on the surgical method: A cold knife group (<i>n</i>=127) and an electrosurgical group (<i>n</i>=98). Adhesions were separated using either cold knife or electrosurgical instruments. Postoperative visualization of uterine angle and tubal ostia, endometrial restoration, vascular endothelial growth factor (VEGF) expression in adhesion tissues, and clinical pregnancy outcomes were compared. Univariate and multivariate Logistic regression analyses were performed to identify factors influencing pregnancy outcomes. A LightGBM model was constructed to predict pregnancy outcomes.</p><p><strong>Results: </strong>Compared with the electrosurgical group, patients in the cold knife group had significantly greater postoperative endometrial thickness [(8.86±0.53) mm vs (8.10±0.87) mm, <i>P</i><0.05], higher live birth rates (64.57% vs 30.61%, <i>P</i><0.05), and lower VEGF expression (1.31±0.09 vs 1.53±0.16, <i>P</i><0.05). Logistic regression analyses identified age, number of visible tubal ostia postoperatively, and surgical method as significant factors affecting pregnancy outcomes (<i>P</i><0.05). The LightGBM model based on surgical method had an area under the curve (AUC) of 0.882 (0.838-0.926), with internal validation AUC of 0.817 (0.790-0.840).</p><p><strong>Conclusions: </strong>Cold knife surgery promotes faster recovery of the endometrial microenvironment and earlier improvement of fertility in patients with secondary infertility and IUA Surgical method is a key factor influencing pregnancy outcomes, and the LightGBM model based on surgical approach shows good predictive performance for pregnancy outcomes in patients with moderate-to-severe IUA.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"50 3","pages":"482-491"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592583","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":"Identification of shared key genes and pathways in osteoarthritis and sarcopenia patients based on bioinformatics analysis.","authors":"Yuyan Sun, Ziyu Luo, Huixian Ling, Sha Wu, Hongwei Shen, Yuanyuan Fu, Thainamanh Ngo, Wen Wang, Ying Kong","doi":"10.11817/j.issn.1672-7347.2025.240669","DOIUrl":"https://doi.org/10.11817/j.issn.1672-7347.2025.240669","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;Osteoarthritis (OA) and sarcopenia are significant health concerns in the elderly, substantially impacting their daily activities and quality of life. However, the relationship between them remains poorly understood. This study aims to uncover common biomarkers and pathways associated with both OA and sarcopenia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Gene expression profiles related to OA and sarcopenia were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between disease and control groups were identified using R software. Common DEGs were extracted via Venn diagram analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify biological processes and pathways associated with shared DEGs. Protein-protein interaction (PPI) networks were constructed, and candidate hub genes were ranked using the maximal clique centrality (MCC) algorithm. Further validation of hub gene expression was performed using 2 independent datasets. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of key genes for OA and sarcopenia. Mouse models of OA and sarcopenia were established. Hematoxylin-eosin and Safranin O/Fast Green staining were used to validate the OA model. The sarcopenia model was validated via rotarod testing and quadriceps muscle mass measurement. Real-time reverse transcription PCR (real-time RT-PCR) was employed to assess the mRNA expression levels of candidate key genes in both models. Gene set enrichment analysis (GSEA) was conducted to identify pathways associated with the selected shared key genes in both diseases.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 89 common DEGs were identified in the gene expression profiles of OA and sarcopenia, including 76 upregulated and 13 downregulated genes. These 89 DEGs were significantly enriched in protein digestion and absorption, the PI3K-Akt signaling pathway, and extracellular matrix-receptor interaction. PPI network analysis and MCC algorithm analysis of the 89 common DEGs identified the top 17 candidate hub genes. Based on the differential expression analysis of these 17 candidate hub genes in the validation datasets, &lt;i&gt;AEBP1&lt;/i&gt; and &lt;i&gt;COL8A2&lt;/i&gt; were ultimately selected as the common key genes for both diseases, both of which showed a significant upregulation trend in the disease groups (all &lt;i&gt;P&lt;/i&gt;&lt;0.05). The value of area under the curve (AUC) for AEBP1 and COL8A2 in the OA and sarcopenia datasets were all greater than 0.7, indicating that both genes have potential value in predicting OA and sarcopenia. Real-time RT-PCR results showed that the mRNA expression levels of &lt;i&gt;AEBP1&lt;/i&gt; and &lt;i&gt;COL8A2&lt;/i&gt; were significantly upregulated in the disease groups (all &lt;i&gt;P&lt;/i&gt;&lt;0.05), consistent with the results observed in the bioinformatics analysis. GSEA revealed that &lt;i&gt;AEBP1&lt;/i&gt; and &lt;i&gt;COL8A2&lt;/i&gt; were closely related to extrac","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"50 3","pages":"430-446"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592587","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":"TMAO promotes disorders of lipid metabolism in psoriasis.","authors":"Rao Li, Boyan Hu, Manyun Mao, Wangqing Chen, Wu Zhu","doi":"10.11817/j.issn.1672-7347.2024.240663","DOIUrl":"https://doi.org/10.11817/j.issn.1672-7347.2024.240663","url":null,"abstract":"<p><strong>Objectives: </strong>Psoriasis is associated with lipid metabolism disorders, but the underlying mechanisms remain unclear. This study aims to investigate the role of trimethylamine N-oxide (TMAO) in lipid metabolism dysregulation in psoriasis.</p><p><strong>Methods: </strong>An imiquimod (IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters, TMAO levels, and liver flavin monooxygenase 3 (<i>FMO3</i>) mRNA expression. Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles. To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model, exogenous TMAO, choline, or 3,3-dimethyl-1-butanol (DMB) were administered via intraperitoneal injections or diet in IMQ-treated mice. Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways.</p><p><strong>Results: </strong>IMQ-induced psoriatic mice exhibited abnormal glucose, insulin, and lipid levels. IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2 (<i>Glut2</i>) and silence information regulator 1 (<i>Sirt1</i>), while upregulating glucose transporter 4 (<i>Glut4</i>) and peroxisome proliferator-activated receptor gamma (<i>PPARγ</i>). Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice. Additionally, liver <i>FMO3</i> mRNA expression was increased in the psoriatic mouse model. In patients, TMAO levels positively correlated with Psoriasis Area and Severity Index (PASI) scores, serum triglyceride (TG), and total cholesterol (TC) levels. The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice. A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice, whereas DMB treatment alleviated these effects. RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122 (<i>miR-122</i>), which may suppress the expression of gremlin 2 (<i>GREM2</i>), thus contributing to lipid metabolism disorder.</p><p><strong>Conclusions: </strong>TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic <i>miR-122</i>/<i>GREM2</i> pathway.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"50 3","pages":"331-343"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592593","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":"Application and mechanisms of targeting BRD4 in osteosarcoma.","authors":"Ding Chen, Jiaming Tian, Yihe Dong, Zi Li, Jun Huang","doi":"10.11817/j.issn.1672-7347.2025.240628","DOIUrl":"https://doi.org/10.11817/j.issn.1672-7347.2025.240628","url":null,"abstract":"<p><strong>Objectives: </strong>Metastasis is the primary cause of death in osteosarcoma, and current clinical treatments remain limited. BRD4, a key epigenetic regulator, has shown therapeutic promise in various cancers through its inhibition. However, the mechanistic role of BRD4 in osteosarcoma remains poorly understood. This study aims to elucidate the molecular mechanisms by which BRD4 regulate osteosarcoma progression and to explore novel therapeutic strategies.</p><p><strong>Methods: </strong>Immunofluorescence was used to assess BRD4 expression levels in a tissue microarray containing 80 osteosarcoma samples from different patients. The Gene Expression Omnibus (GEO) dataset (GSE42352, containing survival data from 88 osteosarcoma patients) was downloaded to perform Kaplan-Meier survival analysis based on BRD4 gene expression levels. In vivo, an orthotopic intramedullary osteosarcoma model was established using HOS cells in C57 mice, followed by treatment with varying doses of the BRD4 inhibitor (+)-JQ1. Micro-CT, 3D reconstruction of bone tissue, and HE staining were employed to evaluate pathological changes in bone and intestinal lymph nodes. In vitro, cell viability was measured using the methyl thiazolyl tetrazolium (MTT) assay, while colony formation and Transwell assays assessed proliferative and invasive capacities. Chromatin-bound BRD4 was analyzed via co-immunoprecipitation combined with mass spectrometry (Co-IP/MS), and O-GlcNAc glycosylation sites and glycan chains of BRD4 were identified using Co-IP with Nano-LC MS/MS. Real-time PCR and Western blotting were used to analyze the relative mRNA and protein expression levels of target genes, respectively.</p><p><strong>Results: </strong>BRD4 was positively expressed in 61.25% (49/80) of osteosarcoma tissues. Patients with high BRD4 expression exhibited significantly shorter survival times (<i>P</i><0.05). In the orthotopic mouse model, intervention with (+)-JQ1, a potent and commonly used BETi, significantly inhibited tumor growth in vivo and reduced bone destruction (<i>P</i><0.05). (+)-JQ1 treatment significantly suppressed the proliferation (<i>P</i><0.001), invasion (<i>P</i><0.001), and migration (<i>P</i><0.05) of HOS cells. In osteosarcoma cells, BRD4 exhibited O-GlcNAc modifications at both N- and C- C-termini, particularly at Thr73, which is essential for protein stability. This modification also contributed to the activation of the EGFR tyrosine kinase inhibitor resistance pathway (KEGG Pathway: hsa01521). (+)-JQ1 treatment displaced BRD4 from enhancers and downregulated the transcription of pathway-related genes, such as <i>EGFR</i> and <i>PDGFC</i>, thereby suppressing the malignant behavior of osteosarcoma cells.</p><p><strong>Conclusions: </strong>BRD4 promotes osteosarcoma progression via O-GlcNAc modification at Thr73 and plays a crucial role in tumor growth and metastasis.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"50 3","pages":"416-429"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592577","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":"Characteristics and differential diagnosis of common verrucous proliferative skin diseases under dermoscopy and reflectance confocal microscopy.","authors":"Lu Zhou, Yule Fu, Jian Huang, Zhen Tang, Jianyun Lu, Lina Tan, Dan Wang, Jinrong Zeng, Jia Wang, Lihua Gao","doi":"10.11817/j.issn.1672-7347.2025.240708","DOIUrl":"https://doi.org/10.11817/j.issn.1672-7347.2025.240708","url":null,"abstract":"<p><strong>Objectives: </strong>Verrucous epidermal nevus (VEN), seborrheic keratosis (SK), verruca plana (VP), verruca vulgaris (VV), and nevus sebaceous (NS) are common verrucous proliferative skin diseases with similar clinical appearances, often posing diagnostic challenges. Dermoscopy and reflectance confocal microscopy (RCM) can aid in their differentiation, yet their specific features under these tools have not been systematically described. This study aims to summarize and analyze the dermoscopic and RCM features of VEN, SK, VP, VV, and NS.</p><p><strong>Methods: </strong>A total of 121 patients with histopathologically confirmed verrucous proliferative skin diseases were enrolled. Dermoscopy and RCM imaging was used to observe and analyze the microscopic features of these conditions.</p><p><strong>Results: </strong>Under dermoscopy, the 5 diseases displayed distinct characteristics: VEN typically showed gyriform structures; SK was characterized by gyriform structures, comedo-like openings, and milia-like cysts; VP and VV featured dotted vessels and frogspawn-like structures; NS presented as brownish-yellow globules. RCM revealed shared features such as hyperkeratosis and acanthosis across all 5 diseases. Specific features included gyriform structures and elongated rete ridges in VEN; pseudocysts and gyriform structures in SK; evenly distributed ring-like structures in VP; vacuolated cells and papillomatous proliferation in VV; and frogspawn-like structures in NS.</p><p><strong>Conclusions: </strong>These 5 verrucous proliferative skin conditions exhibit distinguishable features under both dermoscopy and RCM. The combination of these 2 noninvasive imaging modalities holds significant clinical value for the differential diagnosis of verrucous proliferative skin diseases.</p>","PeriodicalId":39801,"journal":{"name":"中南大学学报(医学版)","volume":"50 3","pages":"358-365"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592580","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}