Hereditas最新文献

{"title":"Genetic overlap between sarcoidosis and lung cancer: a combined in silico and in vitro approach.","authors":"Sanjukta Dasgupta, Moupiya Ghosh, Subhendu Chakrabarty, Gopal Chakrabarti, Amlan Das","doi":"10.1186/s41065-025-00503-7","DOIUrl":"10.1186/s41065-025-00503-7","url":null,"abstract":"<p><p>Sarcoidosis patients exhibit an elevated risk of developing lung cancer (LC), suggesting shared genetic and molecular mechanisms between these conditions. This study aimed to identify common differentially expressed genes (DEGs) in sarcoidosis and LC and to evaluate the therapeutic potential of a repurposable drug targeting these shared genes. Gene expression datasets (GSE157671 and GSE229253) were analyzed to identify overlapping DEGs, with validation performed using additional GEO datasets and the GEPIA tool. Functional enrichment and protein-protein interaction (PPI) analyses were conducted using Enrichr and STRING, while associated miRNAs and transcription factors were identified via miRNet. Twelve DEGs-SALL4, WNT10A, RASAL1, CAMK2B, GADD45B, KLF4, OLR1, CSF3, WIF1, RAMP3, AGER, and PRKAG3-were consistently dysregulated in both diseases. These genes were significantly associated with epithelial cell enrichment and the Wnt signaling pathway. Drug-gene interaction analysis using DGIdb prioritized metformin as a candidate drug targeting PRKAG3. Its structural integrity was confirmed via X-ray diffraction (XRD) and Rietveld refinement. In vitro validation using MTT assays revealed that metformin selectively reduced viability in A549 (adenocarcinoma human alveolar basal epithelial cells) and HeLa (a widely used epithelial cancer cell line), with minimal cytotoxicity in WI38 normal lung fibroblasts. Colony formation assays further demonstrated dose-dependent, long-term growth inhibition in cancer cells, corroborated by observable morphological alterations. Overall, this study highlights shared pathogenic signatures between sarcoidosis and LC and proposes metformin as a promising therapeutic candidate. These findings support the rationale for drug repurposing and the development of targeted therapies for patients with overlapping disease profiles or those at increased risk of LC progression from sarcoidosis.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"155"},"PeriodicalIF":2.5,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating bioinformatics analysis, machine learning, and experimental validation to identify pyroptosis-related genes in the diagnosis of sepsis combined with acute liver failure.","authors":"Jing Yan, Yifeng Pan, Chaoqi Chen, Lijian Liu, Jinjing Tan, Juan Li, Liqun Li, Sheng Xie","doi":"10.1186/s41065-025-00522-4","DOIUrl":"10.1186/s41065-025-00522-4","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is frequently combined with acute liver failure (ALF), a critical determinant in the mortality of septic patients. Pyroptosis is a significant form of programmed cell death that plays an important role in the inflammatory response. Research has been conducted to elucidate the relationship between pyroptosis, sepsis, and ALF, but the mechanism of action remains unclear.</p><p><strong>Methods: </strong>Datasets relating to sepsis and ALF were obtained from the Gene Expression Omnibus (GEO). The intersection of differentially expressed genes (DEGs) and pyroptosis-related genes for sepsis and ALF was identified. Simultaneously, a gene diagnosis model for sepsis and ALF was developed using machine learning, and the model's accuracy was assessed through the plotting of the ROC curves and confusion matrix. The Hub genes identified by the model with an area under the curve (AUC) value ≥ 0.7 were used for the investigation of immune cell infiltration to explain the molecular mechanism of sepsis combined with ALF. The precise mechanism of action of these model genes in sepsis combined with ALF was evaluated through animal experiments.</p><p><strong>Results: </strong>Machine learning revealed that GABARAP and ITCH may serve as diagnostic biomarkers for pyroptosis in sepsis combined with ALF. The examination of immune cell infiltration indicated that immune dysregulation is present in both sepsis and ALF and preliminarily suggested that GABARAP and ITCH may be pivotal in cellular immunity responses, particularly those mediated by T cells. Animal experiments further validated that in the process of sepsis combined with ALF, the expression level of GABARAP is elevated, while the expression level of ITCH is diminished.</p><p><strong>Conclusions: </strong>We found GABARAP and ITCH may serve as diagnostic biomarkers for pyroptosis in sepsis combined with ALF, suggesting their potential involvement in the initiation and advancement of sepsis combined with ALF through cellular immunomodulatory pathways.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"153"},"PeriodicalIF":2.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening, identification, and experimental validation of SUMOylation biomarkers in Parkinson's disease.","authors":"Yifo Wei, Xinning Zhang, Rui Zuo, Wenxin Dang, Lu Chen, Fan Liu, Jia Yao, Weizheng Ran, Zhigang Chen, Xiaoyan Wang, Furong Lv, Yue Yu","doi":"10.1186/s41065-025-00525-1","DOIUrl":"10.1186/s41065-025-00525-1","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease (PD) is a common neurodegenerative disorder. The role of protein post-translational modifications (PTMs), especially small ubiquitin-like modifier (SUMO) conjugation (SUMOylation), in PD pathogenesis remains unclear. This study aimed to investigate the relationship between SUMOylation and PD.</p><p><strong>Methods: </strong>The analysis included the GSE22491 dataset, GSE18838 dataset, and 189 SUMO related genes. Differentially expressed genes (DEGs) between the PD group and the control group were identified in GSE22491; these were then intersected with SUMO related genes to identify candidate genes. Machine learning was used to select biomarkers consistent across both datasets, which were validated in GSE6631. Further analyses included back propagation (BP) neural network analysis, enrichment analysis, immune infiltration analysis, regulatory network construction, drug prediction, and molecular docking. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate the biomarkers.</p><p><strong>Results: </strong>An overlap analysis of 3,222 DEGs and 189 SUMO related genes identified 25 candidate genes. Subsequent validation using the GSE22491 and GSE18838 datasets narrowed these biomarkers down to SUMO3 and SEH1L, which are involved in pathways (such as the nuclear pore pathway) associated with PD. Significant positive correlations were observed between specific immune cell subtypes and both biomarkers. Based on these correlations, relevant transcription factors (ZNF394, IRF4, FOXM1, EGR1) and drugs (Cianidanol, Methylmethanesulfonate, Valproic acid) were predicted. Additionally, RT-qPCR results confirmed that SUMO3 is significantly downregulated in PD.</p><p><strong>Conclusion: </strong>SUMO3 and SEH1L were identified as novel biomarkers for PD, offering potential targets for early diagnosis and therapy in PD.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"154"},"PeriodicalIF":2.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144803972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated analysis of gene networks and cellular functions identifies novel heart failure biomarkers.","authors":"Jiang Juncheng, Chen Lei, Lin Hao, Liang Fei","doi":"10.1186/s41065-025-00521-5","DOIUrl":"10.1186/s41065-025-00521-5","url":null,"abstract":"<p><strong>Introduction: </strong>Heart failure (HF) is a complex clinical condition characterized by impaired cardiac function and progressive structural remodeling. To elucidate the molecular mechanisms driving HF, this study aimed to identify key regulatory hub genes, explore their functional relevance, and assess their diagnostic and therapeutic potential.</p><p><strong>Methods: </strong>Four public microarray datasets (GSE161472, GSE147236, GSE116250, and GSE46224) were retrieved from the Gene Expression Omnibus (GEO) database. Differential expression analysis using the limma package in R identified Differentially expressed genes (DEGs), which were further analyzed via Venn diagrams, STRING PPI networks, and Cytoscape's CytoHubba plugin to determine top hub genes. RT-qPCR and Western blotting were used to validate gene expression in HF and normal cardiomyocyte cell lines. Functional assays (proliferation, colony formation, and wound healing) were conducted following overexpression of COL9A1 and MTIF3. miRNA regulation and immune cell infiltration were analyzed using TargetScan and CIBERSORT, respectively. Enrichment analysis was performed via DAVID, and drug prediction was conducted using DGIdb.</p><p><strong>Results: </strong>Four hub genes-COL9A1, MTIF3, MRPS25, and HMGN1-were consistently downregulated in HF and exhibited high diagnostic potential (AUC > 0.8). Overexpression of COL9A1 and MTIF3 significantly reduced cell proliferation, colony formation, and migration in HF cell lines. Immune infiltration analysis revealed strong negative correlations between hub gene expression and various immune cell types. Drug prediction identified Milrinone as a potential therapeutic candidate targeting COL9A1.</p><p><strong>Conclusion: </strong>COL9A1, MTIF3, MRPS25, and HMGN1 emerge as critical biomarkers and regulators in HF, offering promising avenues for diagnosis, mechanistic understanding, and targeted therapy development.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"152"},"PeriodicalIF":2.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12333206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic value of Linc00662/miR-16-5p/FASN in cervical cancer and regulation of tumor progression.","authors":"Yu Yang, Zhanping Guo","doi":"10.1186/s41065-025-00520-6","DOIUrl":"10.1186/s41065-025-00520-6","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer (CC) is the world's single most frequent gynecological cancer, is more than 500,000 new annual cases globally, and is a serious threat to women's reproductive health. LncRNAs have significant effects on human diseases; nevertheless, the expression of Linc00662 in CC and its mechanism of action are not yet entirely clear. The goal of the work was to investigate the expression, prognostic value and biological utility of Linc00662 in CC progression and to identify its underlying mechanisms in molecular terms.</p><p><strong>Methods: </strong>Expression levels of Linc00662, miR-16-5p and FASN in CC tissues and cells were detected through real-time quantitative PCR. Determination of cell proliferative capacity by CCK-8. Cell migration and invasion were assessed through Transwell assay. Binding of Linc00662 to miR-16-5p was mediated through a dual-luciferase reporter gene test was validated.</p><p><strong>Results: </strong>Linc00662 expression levels were significantly elevated in CC. High Linc00662 expression was strongly linked to increased tumor size, later FIGO staging, poorer tumor differentiation, mesenchymal infiltration, and lymph node metastasis, and high Linc00662 expression predicted a poor prognosis. Silencing Linc00662 reduced the proliferation, migration, and invasion of CC cells. Furthermore, Linc00662 negatively regulated miR-16-5p and indirectly regulated the upregulation of FASN expression.</p><p><strong>Conclusions: </strong>Linc00662 positively regulates FASN expression through targeting miR-16-5p and facilitates CC cell proliferation, migration and invasion, promoting CC progression.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"151"},"PeriodicalIF":2.5,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12326733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and validation of ANXA3 and SOCS3 as biomarkers for acute myocardial infarction related to sphingolipid metabolism.","authors":"Ling Sun, Lingyan He, Hai-Hua Pan, Chang-Lin Zhai","doi":"10.1186/s41065-025-00515-3","DOIUrl":"10.1186/s41065-025-00515-3","url":null,"abstract":"<p><strong>Background: </strong>Sphingolipid metabolism (SM) is linked to acute myocardial infarction (AMI), but its role remains unclear. This study explored SM-related genes (SMRGs) in AMI to support clinical diagnosis.</p><p><strong>Methods: </strong>We analyzed datasets GSE48060 and GSE123342 to identify differentially expressed genes (DEGs) and key module genes. Protein-protein interaction (PPI) network analysis and machine learning were used to screen potential biomarkers, which were validated via receiver operating characteristic (ROC) curves and expression assessment. Further analyses included artificial neural networks (ANN), enrichment analysis, immune infiltration, drug prediction, and molecular docking. Single-cell RNA sequencing (scRNA-seq) identified key cell types and their functions. Biomarkers were validated via reverse transcription quantitative polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>Intersection of 95 DEGs and 2,196 module genes yielded 20 genes, with ANXA3 and SOCS3 identified as biomarkers. The ANN model showed superior diagnostic performance compared to individual markers. Biomarkers were enriched in the toll-like receptor (TLR) signaling pathway. Immune infiltration analysis revealed differences in five immune cell types between AMI and control groups. ANXA3 correlated positively with neutrophils and negatively with resting memory CD4 T cells. Drugs targeting ANXA3 included ethanolamine, difluocortolone, and fluocinolone acetonide, with strong binding affinity. scRNA-seq identified B cells and monocytes as key cells; ANXA3 and SOCS3 expression increased during monocyte differentiation before decreasing, while B cells showed no significant changes.</p><p><strong>Conclusion: </strong>ANXA3 and SOCS3 were identified as SM-related biomarkers in AMI, providing insights for clinical diagnosis.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"150"},"PeriodicalIF":2.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and functional assessment of TBX20 gene variants in pediatric ventricular septal defect.","authors":"Zhenzhen Qin, Caixia Liu, Jie Wang, Yanmei Jin","doi":"10.1186/s41065-025-00513-5","DOIUrl":"10.1186/s41065-025-00513-5","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to investigate the potential role of TBX20 gene variants in the molecular pathogenesis of congenital ventricular septal defect (VSD) in pediatric patients.</p><p><strong>Methods: </strong>Genetic sequencing and variant detection were performed for the TBX20 gene, a T-box transcription factor, in a cohort of 150 pediatric patients diagnosed with VSD, recruited from the Department of Cardiothoracic Surgery at Shanxi Children's Hospital. Functional characterization of newly identified variants was conducted using homology-based protein structural modeling, dual-luciferase reporter assays, and quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><strong>Results: </strong>Two variants within the highly conserved T-box DNA-binding domain were identified in five children: a synonymous variant c.576C > T (p.Thr192Thr) and a missense variant c.577G > A (p.Gly193Ser). Structural modeling predicted that the p.Gly193Ser substitution destabilized the TBX20 protein by altering its conformation and increasing its potential energy state. Functional assays demonstrated that this variant reduced TBX20 mRNA expression and significantly attenuated transactivation of the downstream target gene ANF. Bioinformatic analysis supported the deleterious functional impact of the p.Gly193Ser variant and its potential contribution to VSD pathogenesis. In contrast, the synonymous p.Thr192Thr variant was associated with increased transcriptional activity of TBX20 and enhanced regulation of ANF. qRT-PCR data indicated significantly reduced TBX20-G193S mRNA levels compared to wild-type (WT) when expressed independently (p < 0.01), but elevated levels in the presence of GATA4 and NKX2-5 (p < 0.001). Despite this, ANF transactivation remained significantly lower than WT, suggesting impaired functional capacity. These alterations may influence translational efficiency and contribute to abnormal cardiac septation.</p><p><strong>Conclusion: </strong>The findings underscore the involvement of TBX20 gene variants in the etiology of pediatric VSD and provide mechanistic insights that may inform future clinical research and the development of targeted therapeutic strategies.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"149"},"PeriodicalIF":2.5,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12323031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144784074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro activity of Houttuynia cordata against bacteria isolated from diabetic foot.","authors":"Chong Geng, Liuxuan An, Lin Niu, Xiaona Cui, Shulan Zhang, Xueqin Yuan, Qian Ma","doi":"10.1186/s41065-025-00505-5","DOIUrl":"10.1186/s41065-025-00505-5","url":null,"abstract":"<p><strong>Background: </strong>Misuse of antibiotics makes it very easy for bacteria to become resistant to drugs. Houttuynia cordata (HC) has antibacterial, antiviral, analgesic, antioxidant, diuretic, hypoglycemic, and immune-enhancing properties.</p><p><strong>Aim: </strong>To study the inhibitory effect of HC on Staphylococcus aureus and Pseudomonas aeruginosa isolated from tissue or pus specimens from patients with diabetic foot ulcers.</p><p><strong>Materials and methods: </strong>Seventy-two patients with DFU were randomly divided into three groups and given treatment with methicillin (Met), meropenem (Mer), and HC, respectively. Analysis and identification of clinical isolates of Staphylococcus aureus and Pseudomonas aeruginosa using the Orbitrap Exploris™ 480. The drug susceptibility of four isolates to HC was studied by bacteriostatic test. The MIC and MBC of Houttuynia cordata against four isolates were determined using the broth microdilution method. The growth and time-kill curves of the bacteria were studied by bacterial inhibition experiments.The effect of Houttuynia cordata on the viability of H6C7 cells was examined by MTT assay.</p><p><strong>Results: </strong>HC treatment improved clinical parameters of DFUs patients. The inhibition zone of S08 (MSSA) was 15.45 ± 0.12 mm, which was highly sensitive to Houttuynia cordata. The inhibition zone sizes of R11 (MRSA), P10 (CRPA) and D22 (MDRPA) were 12.64 ± 0.09 mm,13.42 ± 0.11 mm and 11.23 ± 0.08 mm, respectively. All of them were moderately sensitive to Houttuynia cordata. The MIC of S08,R11,P10 and D22 were 31.25,62.5,62.5 and 125 µg/mL, respectively. The MBCS of S08,R11,P10 and D22 were 500,1000,1000 and 1000 µg/mLrespectively.Bacterial growth curves and time-kill curves demonstrated that Houttuynia cordata significantly inhibited the growth of both bacteria. Cytotoxicity assay showed that Houttuynia cordata effectively inhibited bacteria without cytotoxicity to eukaryotic cells.</p><p><strong>Conclusion: </strong>Houttuynia cordata exhibits promising antibacterial activity against both Staphylococcus aureus and Pseudomonas aeruginosa, including drug-resistant strains, without cytotoxic effects on eukaryotic cells. These findings support its potential as an alternative therapeutic agent for DFU-associated infections.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"147"},"PeriodicalIF":2.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EPHX1 enhances drug resistance to regorafenib by activating the JAK/STAT signaling pathway in hepatocellular carcinoma cell lines.","authors":"Bin Xu, Xiangnan Liang, Wuguang Liu, BaiTong Wu, Qiuxiang Wang, Gong Kai, Chun Han, Binwen Sun, Bing Dong, Chengyong Dong, Liming Wang","doi":"10.1186/s41065-025-00517-1","DOIUrl":"10.1186/s41065-025-00517-1","url":null,"abstract":"<p><strong>Background: </strong>Regorafenib serves as a second-line treatment for patients with advanced hepatocellular carcinoma (HCC). Microsomal epoxide hydrolase 1 (EPHX1) is closely associated with tumorigenesis and drug resistance. However, the relationship between EPHX1 and regorafenib resistance, as well as the underlying mechanisms in HCC, remains unclear.</p><p><strong>Objective: </strong>To investigate the role and mechanisms of EPHX1 in mediating regorafenib resistance in HCC.</p><p><strong>Methods: </strong>We assessed the protein expression levels of EPHX1 in human HCC tissues and adjacent non-tumor tissues. Subsequently, we constructed HCC cell lines with EPHX1 overexpression and knockdown using lentiviral vectors and stimulated these cells with varying concentrations of regorafenib. We then measured cell proliferation and apoptosis using flow cytometry and Western blotting. Additionally, we established xenograft tumor models to explore the impact of EPHX1 on the in vivo efficacy of regorafenib. Furthermore, we employed digital gene expression sequencing (DGE-seq) to investigate and validate the specific molecular mechanisms by which EPHX1 mediates regorafenib resistance in HCC cells.</p><p><strong>Results: </strong>We found that EPHX1 protein levels were significantly higher in HCC tissues compared to adjacent non-tumor tissues. EPHX1 inhibited the effects of regorafenib on cell proliferation and apoptosis. Consistently, the efficacy of regorafenib was enhanced in vivo following EPHX1 knockdown. Moreover, KEGG pathway enrichment analysis of DGE-seq data indicated that the JAK/STAT signaling pathway is crucial for EPHX1-induced regorafenib resistance. Finally, EPHX1 suppressed regorafenib-induced inactivation of the JAK/STAT signaling pathway and blocking this pathway with HY-N1447 alleviated EPHX1-induced regorafenib resistance.</p><p><strong>Conclusion: </strong>In summary, we conclude that EPHX1 enhances regorafenib resistance in HCC by activating the JAK/STAT signaling pathway. Our findings suggest that EPHX1 is a key resistance-related gene, which has significant implications for the application of regorafenib in advanced HCC.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"148"},"PeriodicalIF":2.5,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A retrospective study on the efficacy of integrating traditional Chinese medicine with Western medicine in the treatment of adult measles.","authors":"Xiaoyan Liu, Zhongying Bao, Shuhong Duan, Jing Sun, Jie Zhang","doi":"10.1186/s41065-025-00518-0","DOIUrl":"10.1186/s41065-025-00518-0","url":null,"abstract":"<p><strong>Objective: </strong>Measles is a highly contagious, potentially fatal disease, and using western medicine for treating this disease showed some limits including the long period of treatment and some side effects. Of note, traditional Chinese medicine (TCM) exhibited advantages of treating measles in using alone or combing with western medication. However, little information on the clinical study on adjunctive efficacy of TCM on measles. Therefore, the objective of this study is to observe the adjunctive efficacy of TCM in the treatment of adult measles.</p><p><strong>Methods: </strong>Ninety-one patients diagnosed with adult measles in our hospital were enrolled for this study. All of them underwent symptomatic treatment, nutritional support therapy, and ribavirin antiviral therapy. Loxoprofen was added to the treatment regime when the body temperature exceeded 38.5 °C. The patients were stratified into two groups based on the administration of TCM, comprising 49 individuals in the TCM group and 42 individuals in the control group. Patients in the TCM group voluntarily received the following TCM prescriptions: 15 g of Lonicerae Japonica, 15 g of Forsythiae Fructus, 15 g of Arnebiae Radix, 15 g of Cicadae Periostracum, 30 g of Phragmitis Rhizoma, 10 g of Anemarrhenae Rhizoma, 6 g of Glycyrrhizae Radix et Rhizoma and 30 g of Gypsum Fibrosum was administered to patients with high fever. Decoction: 1 dose daily for 5 days. The control group received treatment without the incorporation of TCM.</p><p><strong>Results: </strong>In comparison to the control group, patients in the TCM group experienced a quicker resolution of clinical symptoms (P < 0.05) and a lower complication rate (P < 0.05).</p><p><strong>Conclusion: </strong>The application of TCM in treating adult measles can shorten the duration of the disease, reduce the incidence of complications, and offers promise for wider clinical adoption and utilization.</p>","PeriodicalId":12862,"journal":{"name":"Hereditas","volume":"162 1","pages":"146"},"PeriodicalIF":2.5,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}