Current gene therapy最新文献

{"title":"APOL3 Orchestrates Metastasis and Enzalutamide Resistance via STAT3-DAB2IP Signaling in Prostate Cancer.","authors":"Quanxin Wang, Songlin Zuo, Lin Chen, Fangning Wan, Zhe Hong, Wenhao Xu, Wenting Hou, Dingwei Ye","doi":"10.2174/0115665232490462260522095123","DOIUrl":"https://doi.org/10.2174/0115665232490462260522095123","url":null,"abstract":"<p><strong>Background: </strong>In advanced Prostate Cancer (PCa), metastatic spread and the inevitable emergence of enzalutamide resistance represent major clinical hurdles. Although apolipoprotein L3 (APOL3) is linked to oncogenesis, its precise mechanistic role in PCa progression and antiandrogen resistance, particularly its regulation of the STAT3-DAB2IP axis, remains largely unexplored.</p><p><strong>Methods: </strong>Publicly available clinical datasets were analyzed to evaluate APOL3 expression and its prognostic value. The functional consequences of modulating APOL3 and DAB2IP levels were assessed using in vitro and in vivo PCa models, including an established enzalutamide-resistant cell line (C4-2R). Mechanistic insights into cellular proliferation, motility, angiogenesis, and drug response were derived from RNA sequencing, reciprocal co-immunoprecipitation (Co-IP), and dual-targeting phenotypic assays.</p><p><strong>Results: </strong>APOL3 is significantly upregulated in PCa, strongly correlating with elevated Gleason scores, advanced stage, TP53 mutational status, and poor prognosis. Functionally, APOL3 promotes PCa proliferation, metastasis, and angiogenesis. Mechanistically, APOL3 sustains STAT3 phosphorylation and suppresses the tumor suppressor DAB2IP. Notably, Co-IP assays revealed a direct, bidirectional physical interaction between APOL3 and DAB2IP. Furthermore, we discovered that elevated APOL3 drives enzalutamide resistance not by enhancing classical Androgen Receptor (AR) activity, but by directly binding the Glucocorticoid Receptor (GR). This APOL3-GR complex activates a bypass signaling pathway entirely independent of the AR. While restoring DAB2IP resensitized cells to enzalutamide, it triggered a compensatory upregulation of APOL3. Consequently, concurrent APOL3 knockdown and DAB2IP overexpression yielded a powerful synergistic effect, profoundly dismantling malignant phenotypes, suppressing pro-metastatic markers (p-STAT3, VEGF, SNAIL, MMP2), and restoring enzalutamide sensitivity.</p><p><strong>Discussion: </strong>These findings establish APOL3 as a central driver of prostate cancer metastasis and enzalutamide resistance. APOL3 drives these aggressive phenotypes by directly binding and suppressing DAB2IP to sustain oncogenic STAT3 signaling, and by activating an AR-independent bypass pathway through its physical interaction with the Glucocorticoid Receptor (GR). The enrichment of APOL3 in TP53-mutated and resistant tumors underscores its critical role in tumor plasticity. Consequently, synergistically co-targeting APOL3 alongside DAB2IP restoration represents a highly promising therapeutic strategy to overcome adaptive antiandrogen resistance and halt metastatic progression.</p><p><strong>Conclusion: </strong>APOL3 is a central driver of PCa aggressiveness and enzalutamide resistance, functioning via the direct modulation of the DAB2IP/STAT3 axis and the activation of the GR bypass pathway. Cotargeting APOL3 alongside ","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148136815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HOXC4 Is Associated with the Prognosis and Immune Cell Infiltration in the Progression of Prostate Cancer.","authors":"Zhenhong Chen, Dujuan Wang, Yongkang Xie, Zhongjin Fang, Jianjing Wang, Zhaocun Yu, Zaoqing Chen, Yanhui Zou, Zhongning Chen, Qianhai Liu, Huasheng Huang","doi":"10.2174/0115665232480070260518114905","DOIUrl":"https://doi.org/10.2174/0115665232480070260518114905","url":null,"abstract":"<p><strong>Introduction: </strong>Members of the Homeobox (HOX) gene family, particularly HOXCs, may be implicated in the development and prognosis of prostate cancer (PCa), but the specific mechanisms remain unclear.</p><p><strong>Methods: </strong>The clinical and transcriptomic data from TCGA-PRAD and GSE70770 were collected to examine the impact of HOXC family members on progression-free survival (PFS) in PCa. Meanwhile, the mechanisms of HOXC family members in PCa and their relationship with patients' prognosis were systematically investigated by performing survival analysis, enrichment analysis, and COX regression analysis. This study also developed a prognostic model. Additionally, a qPCR assay was conducted to determine the mRNA level of HOXC family members in PCa cells.</p><p><strong>Results: </strong>Upregulated expressions of HOXC4, HOXC5, HOXC12, and HOXC13 in PCa tissues were found to be correlated with a worse prognosis. A prognostic model incorporating HOXC4 expression level, T stage, and Gleason score was constructed, exhibiting excellent performance in predicting 1-, 3-, and 5-year PFS (average AUC > 0.7). Enrichment analysis showed that HOXC4, which was highly expressed in PCa cells, may be involved in the progression and invasion of PCa through pathways such as oxidative phosphorylation, PLK1 signaling, cell cycle, and DNA methylation. Further, ssGSEA showed that HOXC4 may affect immune cell infiltration in PCa tumors.</p><p><strong>Discussion: </strong>HOXC4 was related to immune cell infiltration and pathway activation in PCa and confirmed to be a risk factor for the cancer prognosis. However, the specific molecular mechanisms of HOXC4 in PCa development still require further investigation.</p><p><strong>Conclusion: </strong>The HOXC4-based prognostic model may be an effective tool for assessing the prognosis of PCa patients.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148142973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening and Functional Study of Biomarkers Related to Cell-in-cell Structure in Stomach Adenocarcinoma.","authors":"Xiangjie Fang, Xinyu Gu, Dong Hou, Tao Meng, Zhengjie Gao, Minghui Xue","doi":"10.2174/0115665232478980260511193836","DOIUrl":"https://doi.org/10.2174/0115665232478980260511193836","url":null,"abstract":"<p><strong>Introduction: </strong>A comprehensive study of Cell-In-Cell (CIC) structures in stomach adenocarcinoma (STAD) may facilitate the development of therapeutic strategies.</p><p><strong>Methods: </strong>Enrichment analysis was conducted using ssGSEA. WGCNA was used to identify hub genes, and Differentially Expressed Genes (DEGs) were screened by the DESeq2 package. Gene selected by both LASSO regression (glmnet package) and SVM-RFE algorithms (e1071 package) were intersected to develop a diagnostic model for STAD using the rms package. Immune infiltration of STAD samples was analyzed using CIBERSORT and ESTIMATE algorithms. Single-cell data were processed by Seurat package. Cell subpopulations were identified using the FindClusters function, and their marker genes were subsequently determined by FindAllMarkers, followed by in vitro functional validation.</p><p><strong>Results: </strong>Five genes (MSR1, PDGFRB, COL8A1, PLA2G7, and FCGR3A) with AUC > 0.8 were identified as potential biomarkers for STAD and combined into a five-gene diagnostic model. Immune infiltration analysis showed that these genes were associated with T-cell and macrophage infiltration. Among the ten cell types identified by single-cell analysis, the five biomarkers were found to be highly expressed specifically in macrophages and fibroblasts. In vitro functional assays confirmed that these markers were upregulated in HGC-27 and AGS cells, and that MSR1 regulated STAD cell proliferation, migration, and invasion.</p><p><strong>Discussion: </strong>The five biomarkers, which showed a specifically high expression in macrophages and fibroblasts, were closely associated with heterotypic CIC formation. Further analysis suggested that these biomarkers contributed to STAD pathogenesis, potentially via immune, stromal, and metabolic crosstalk. These findings help clarify the interactions between CIC biology and the STAD tumorimmune microenvironment.</p><p><strong>Conclusions: </strong>The five biomarkers provide valuable insights for the early screening, diagnosis, and treatment of STAD.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Potential Biomarkers in Autism: PRELID2, MYO1B, LRCH2, LIFR, and RERG May Serve as Regulators in Synaptic Membrane-Integrating Interneurons.","authors":"Wei Zhang, Chenyang Wang, Xiaoqian Zhao, Shuo Pang, Zhuoling Zhao, Guojun Zhang, Jun Chen","doi":"10.2174/0115665232499854260512155018","DOIUrl":"https://doi.org/10.2174/0115665232499854260512155018","url":null,"abstract":"<p><strong>Background: </strong>Autism Spectrum Disorder (ASD) is a highly heterogeneous neurodevelopmental condition. Single-cell RNA sequencing (scRNA-seq) has revealed transcriptional disruptions, particularly in interneurons, yet their subtypes and molecular signatures remain poorly understood.</p><p><strong>Methods: </strong>It was analyzed scRNA-seq data from the human Prefrontal Cortex (PFC). Key cell types were identified using Scissor and ROGUE methods, followed by secondary clustering for subtype annotation. A signature matrix was established using CIBERSORTx to deconvolute the bulk transcriptomes and estimate cell type-specific proportions. Differential subtype proportions between ASD and control samples were compared to identify key cell subtypes. Differentially Expressed Genes (DEGs) from both the key subtype and bulk data were intersected to determine subtypespecific biomarkers, which were further assessed via molecular docking.</p><p><strong>Results: </strong>Interneurons were identified as the most heterogeneous cell population in ASD-affected PFC and were further categorized into five subtypes. A signature matrix was then developed with CIBERSORTx to reflect the proportion of each cell type and subtype. Among the cell subtypes, synaptic membrane-integrating interneurons (SMI-IN) emerged as the key subtypes, which exhibited notable distinctions between the ASD and control samples. Furthermore, five potential biomarkers (PRELID2, MYO1B, LRCH2, LIFR, and RERG) were identified from the SMI-IN subtype. Finally, quercetin and coumestrol were predicted as potential therapeutic compounds targeting these biomarkers. Nevertheless, as all findings were obtained via computational analysis, further cellular and clinical experiments are required to validate these identified biomarkers and candidate compounds.</p><p><strong>Discussion: </strong>This study focused on interneurons and identified SMI-IN as a key cell subtype and its potential biomarkers (PRELID2, MYO1B, LRCH2, LIFR, and RERG).</p><p><strong>Conclusion: </strong>The present findings provided new insights for ASD intervention.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Complement and Coagulation Cascade-Related Prognostic Signature Predicts Survival and Immune Landscape in Lung Adenocarcinoma.","authors":"Binbin He, Rangfei Zhu, Na Li, Wei Li","doi":"10.2174/0115665232473551260504092329","DOIUrl":"https://doi.org/10.2174/0115665232473551260504092329","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the prognostic value of complement and coagulation cascades (CCC) in lung adenocarcinoma (LUAD).</p><p><strong>Methods: </strong>Transcriptomic and clinical data of LUAD were retrieved from public databases. Differentially Expressed Genes (DEGs) were identified via the limma R package, and WGCNA was used to screen gene modules strongly correlated with CCC enrichment scores. Functional enrichment analysis was conducted with clusterProfiler. Univariate and LASSO Cox regression analyses were applied to build a CCC-related prognostic risk model, and its performance was validated using Kaplan-Meier survival analysis and ROC curves. ESTIMATE, MCPcounter, GSVA, and pRRophetic algorithms assessed immune infiltration and drug sensitivity, while CCK-8, Transwell, and scratch-healing assays verified the regulatory effects of biomarkers on cancer cells.</p><p><strong>Results: </strong>WGCNA identified brown modules that were significantly correlated with CCC scores; enrichment analysis showed that these genes mainly participated in NF-κB, B-cell receptor signaling, and T-cell differentiation pathways. Six key genes (CPS1, EPHB2, LARGE2, MS4A1, OAS3, S100P) were selected to construct the risk model, with the high-risk group exhibiting poorer overall survival and lower T/B-cell infiltration. Risk scores were positively correlated with Rapamycin and Phenformin IC50s but negatively correlated with FTI-277, BMS-509744, etc. EPHB2 inhibition suppressed lung cancer cell viability, migration, and invasion.</p><p><strong>Discussion: </strong>This study systematically characterized the molecular features and prognostic significance of CCC-associated genes in LUAD, established a CCC-related risk model, and confirmed their tight association with immune infiltration and drug sensitivity.</p><p><strong>Conclusion: </strong>The findings provide a theoretical foundation for precise prognostic evaluation and personalized treatment of LUAD.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage-related Genes were Discovered by Applying Highdimensional Weighted Gene Co-expression Network Analysis as Biomarkers for Esophageal Squamous Cell Carcinoma.","authors":"Jingrong Yang, Chuxun Zhou, Wencui Kong, Li Yi, Zhiyong Zeng, Yu Wang, Bo Wu","doi":"10.2174/0115665232428966260215221222","DOIUrl":"https://doi.org/10.2174/0115665232428966260215221222","url":null,"abstract":"<p><strong>Introduction: </strong>Esophageal squamous cell carcinoma (ESCC) lacks effective early diagnostic markers. High-dimensional WGCNA (hdWGCNA) enables the systematic identification of macrophage-related signatures from single-cell data, offering a novel approach to discovering potential biomarkers for ESCC.</p><p><strong>Methods: </strong>This study analyzed bulk transcriptomic datasets and a single‑cell RNA‑seq dataset from the Gene Expression Omnibus (GEO) database. Specifically, the GSE53625 dataset (179 ESCC and 179 matched normal samples) was a training cohort, while GSE20347 (17 ESCC and 17 normal samples) was an independent validation set. The single‑cell dataset GSE196756 (3 ESCC and 3 adjacent normal tissues) was processed to construct a cellular atlas. The CellChat package was used to assess the communication between macrophages and other cell subpopulations. Macrophage‑associated co‑expression modules were identified by hdWGCNA. Differentially expressed genes (DEGs) were screened with the limma package, and the intersection of DEGs and hub genes from hdWGCNA was further refined via LASSO and SVM-RFE algorithms to obtain candidate genes. Functional enrichment, immune infiltration, drug prediction, and molecular docking were subsequently performed. In vitro experiments were carried out to validate the expression and functional role of candidate genes in ESCC cell lines.</p><p><strong>Results: </strong>Four macrophage‑related gene models consisting of TGFBI, FTL, GPNMB, and APOE were created and validated. These genes were significantly overexpressed in ESCC tissues and exhibited high diagnostic accuracy, reaching an AUC value >0.8 in both the training and independent validation cohorts. In vitro functional assays confirmed that silencing TGFBI suppressed ESCC cell proliferation, migration, and invasion. Enrichment analysis linked these genes to neutrophil activation and apoptosis pathways, and immune infiltration analysis further revealed their correlation with immunosuppressive cell subsets. Drug prediction yielded 190 candidate compounds, and molecular docking suggested potential binding of retinoic acid, rosiglitazone, and GDC‑0941 to the corresponding targets in ESCC.</p><p><strong>Discussion: </strong>In this study, four characteristic genes (TGFBI, FTL, GPNMB, and APOE) were identified for the diagnosis of ESCC, contributing to the improvement of early detection of the cancer.</p><p><strong>Conclusion: </strong>The present findings contributed to the pathogenesis research, detection, and management of ESCC.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147940505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Epithelial-Mesenchymal Transition-Based Prognostic Model for Survival Prediction in Lung Adenocarcinoma: COL5A2 and ZEB2.","authors":"Peng Zhang, Pan Zhang, Chao Tao, Min Li, Zhixu Guo, Zongyang Yu, Yanhua Wang","doi":"10.2174/0115665232432935260223045202","DOIUrl":"https://doi.org/10.2174/0115665232432935260223045202","url":null,"abstract":"<p><strong>Introduction: </strong>High heterogeneity and complex molecular mechanisms of lung adenocarcinoma (LUAD) lead to significant variability in patient prognosis. Epithelial-mesenchymal transition (EMT) is decisive to treatment response and tumor prognosis, which suggests that developing an EMT-related gene model might facilitate the prognostic management of LUAD.</p><p><strong>Methods: </strong>The RNA-seq, clinical information, and imaging data of LUAD patients were collected from public databases. EMT-related modules were clustered by performing WGCNA with the \"WGCNA\" package. Differentially expressed genes (DEGs) were identified using the \"DESeq2\" package. A RiskScore model was constructed via uni/multivariate Cox regression analyses and Lasso regression, implemented with the \"survival\" and \"glmnet\" packages. The prognostic performance was evaluated using the Receiver Operating Characteristic (ROC) curve with the \"timeROC\" package. The CIBERSORT algorithm was utilized to conduct immune infiltration analysis. Drug sensitivity analysis was performed with the \"oncoPredict\" R package, followed by employing GSEA_4.4.0 software to conduct GSEA. A nomogram model was developed utilizing the \"rms\" package. Finally, the expression and potential functions of the selected key genes were validated through cellular assays.</p><p><strong>Results: </strong>A prognostic RiskScore model was developed based on two EMT-related genes (COL5A2 and ZEB2), which were identified through WGCNA and differential expression analysis. This model effectively classified LUAD patients into low- and high-risk categories, where those in the highrisk subgroup exhibited markedly reduced overall survival. Tumor immune microenvironment analysis revealed distinct infiltration patterns between the two risk groups. Notably, high-risk LUAD patients exhibited enrichment of oncogenic pathways, including EMT and E2F targets. Computational assessments further indicated that the high-risk group was associated with an increased possibility of immune evasion and lower sensitivity to certain chemotherapeutic agents. Additionally, a radiomics-based nomogram incorporating two CT features exhibited promising diagnostic performance. Finally, in vitro experiments demonstrated that silencing COL5A2 suppressed LUAD cell proliferation, migration, and invasion, confirming its oncogenic role in LUAD.</p><p><strong>Discussion: </strong>The present work discovered and systematically validated the potential regulatory roles of COL5A2 and ZEB2 in LUAD progression. However, future prospective studies and experimental validations are still needed to confirm the clinical utility of the model.</p><p><strong>Conclusion: </strong>We developed an EMT-related prognostic model and a non-invasive assessment nomogram for LUAD patients, hoping to facilitate personalized therapy for LUAD.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hutchinson-Gilford Progeria Syndrome: Genetic Insights, Clinical Challenges, and Innovative Therapeutic Approaches.","authors":"R Pruthvi Raj, B R Swetha, Jincy Thomas","doi":"10.2174/0115665232415170251130041834","DOIUrl":"https://doi.org/10.2174/0115665232415170251130041834","url":null,"abstract":"<p><p>Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare genetic disorder caused by a de novo point mutation in the LMNA gene, resulting in progerin, an abnormal form of lamin A. Progerin disrupts the nuclear architecture, impairs DNA repair, and alters gene expression, collectively leading to systemic premature aging. Diagnosis involves a clinical evaluation, along with genetic and radiological tests, for skeletal and cardiovascular abnormalities. To provide an overview of current and emerging therapeutic strategies for HGPS, with a focus on pharmacological, genetic, and interventional approaches aimed at mitigating disease progression and improving survival outcomes. Current treatment focuses on symptom relief and extending lifespan. Emerging therapies include gene editing, antisense oligonucleotides, ICMT inhibitors, and high-risk cardiovascular interventions. Recent studies highlight angiopoietin-2 as a potential target. Symptomatic management remains the mainstay of care, with lonafarnib, an FDA-approved farnesyltransferase inhibitor, demonstrating modest benefits in reducing progerin accumulation and improving survival. Novel approaches under investigation include gene editing techniques, antisense oligonucleotides, and inhibitors of isoprenylcysteine carboxyl methyltransferase (ICMT). Cardiovascular interventions such as transcatheter aortic valve replacement and ascending aortic constriction are being explored for high-risk patients. Recent studies also identify angiopoietin-2 modulation as a potential therapeutic avenue for vascular and skeletal repair. While lonafarnib provides modest clinical benefit, long-term management of HGPS will likely depend on advances in gene editing, RNA-based therapies, and targeted pharmacological strategies to reduce progerin toxicity. Further research is needed to enhance precision and safety in gene therapies and to explore new molecular targets for broader therapeutic impact.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of a Vasculogenic Mimicry-related RiskScore Model to Assess Patient Prognosis and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.","authors":"Yujia Zhai, Xinyu Gu, Di Huang, Miaomiao Xue","doi":"10.2174/0115665232450562260311121959","DOIUrl":"https://doi.org/10.2174/0115665232450562260311121959","url":null,"abstract":"<p><strong>Introduction: </strong>Vasculogenic mimicry (VM) plays vital roles in tumor development that are closely relevant to patient adverse outcomes and chemoresistance. This study aimed to identify a novel VM-associated signature to forecast the prognosis and immunotherapy response of head and neck squamous cell carcinoma (HNSC) patients.</p><p><strong>Materials and methods: </strong>HNSC samples were derived from TCGA and GEO databases. VM-related genes (VMGs) were acquired from previous literature. VMGs' score was estimated using the \"GSVA\" package. The critical gene module was recognized by the \"WGCNA\" package. Differentially expressed genes (DEGs) were determined utilizing the \"limma\" package, and functional enrichment analysis was conducted by the \"clusterProfiler\" package. Hereafter, employing univariate Cox, lasso Cox, and multivariate stepwise regression analysis, the independent prognostic VMGs were identified to develop the RiskScore model and verify their predictive performance. Moreover, the immune infiltration, immunotherapy response, and drug sensitivity were analyzed. Finally, the expression of the selected key genes was evaluated in vitro using qRT-PCR in HNSC lines.</p><p><strong>Results: </strong>The tumor group showed a higher VMGs score than the normal group. 590 key module genes were recognized by WGCNA, and then intersected with 6160 DEGs to obtain 293 candidate genes that were mainly involved in the PI3K-Akt and extracellular matrix (ECM)-relevant pathways. Thereafter, 9 independent prognostic VMGs (CHSY1, TNFAIP6, PRELP, HTRA1, RNF144A, COL8A2, DCHS1, FMOD, NOSTRIN) in HNSC were identified and selected to establish a RiskScore model, with good robustness in predicting patient outcomes. Compared with the low-risk group, the high-risk group showed an adverse prognosis, lower immune infiltration, and worse immunotherapy response. Besides, RiskScore was negatively correlated with several chemotherapeutic drugs such as FTI-277, Obatoclax Mesylate, Embelin, etc. Experimental validation using qRT‑PCR confirmed that most of the signature genes (including CHSY1, TNFAIP6, HTRA1, COL8A2, FMOD) were significantly upregulated in an oral squamous cell carcinoma line compared to normal keratinocytes.</p><p><strong>Discussion: </strong>Our present study established a novel 9-VMGs RiskScore to predict the prognosis, immune infiltration features, immunotherapy response, and drug sensitivity for HNSC patients. This study provided a theoretical foundation for further exploration of HNSC pathogenesis, contributing to personalized treatment and drug selection for HNSC.</p><p><strong>Conclusion: </strong>The VM-related RiskScore we developed serves as a reliable prognostic and predictive tool, providing valuable guidance for risk stratification and immunotherapy decision-making in HNSC patients.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sotagliflozin Ameliorates LPS‑Induced Cardiomyocyte Injury by Regulating the PI3K‑Akt and Extracellular Matrix-Related Pathways.","authors":"Junlei Liao, Cheng Wang, Qian Gao, Weike Tian, Houxiang Hu","doi":"10.2174/0115665232484949260423110648","DOIUrl":"https://doi.org/10.2174/0115665232484949260423110648","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aimed to define the protective effects of sotagliflozin against lipopolysaccharide (LPS)-induced injury in H9C2 cardiomyocytes, and map the core molecular pathways driving these effects to support new therapeutic strategies for SRMI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;H9C2 rat cardiomyocytes were divided into a control group, LPS-challenged group, and LPS-challenged groups treated with 10, 20, and 30 μM sotagliflozin. Label-free quantitative Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) proteomics, coupled with bioinformatic analyses, was performed to map the drugregulated molecular network. Cell Counting Kit-8 (CCK-8) assay, biochemical kits, quantitative Real-Time PCR (qRT-PCR), Western blotting, immunofluorescence staining, and JC-1 probe assay were used to assess cell viability, cytotoxicity, oxidative stress markers, expression of inflammatory cytokines and NLRP3 inflammasome-related molecules, and mitochondrial membrane potential, respectively.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Proteomic profiling quantified 10,270 stably expressed proteins across all samples. Principal Component Analysis (PCA) revealed that PC1 and PC2 cumulatively explained 50.33% of intergroup variance, with clear separation between control and LPS groups, a pattern partially reversed by sotagliflozin treatment. In total, 630 differentially expressed proteins (DEPs; 252 upregulated, 378 downregulated) were identified in the LPS vs control comparison, and 210 DEPs (116 upregulated, 94 downregulated) in the sotagliflozin vs LPS comparison, with 49 core overlapping DEPs that were dysregulated by LPS and normalized by sotagliflozin. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that LPS challenge predominantly disrupted pathways, including extracellular matrix organization and the PI3K-Akt signaling cascade, which were targeted and restored by sotagliflozin. Functional validation demonstrated that sotagliflozin mitigated LPS-induced cardiomyocyte injury in a dose-dependent manner: it significantly improved cell viability (20 and 30 μM groups, P&lt;0.01 and P&lt;0.001, respectively), reduced lactate dehydrogenase (LDH) release (P&lt;0.05 and P&lt;0.001), and restored the antioxidant defense markers glutathione (GSH) and superoxide dismutase (SOD) (P&lt;0.01 and P&lt;0.001). Sotagliflozin also markedly downregulated mRNA levels of pro-inflammatory cytokines IL6, TNF, and NLRP3 (P&lt;0.05 and P&lt;0.01), and dose-dependently inhibited the aberrant upregulation of NLRP3 inflammasome activation markers NLRP3, cleaved Caspase-1, and cleaved IL-1β (30 μM group, P &lt; 0.05), a regulatory effect further validated by immunofluorescence staining (P &lt; 0.01). Additionally, sotagliflozin significantly ameliorated LPS-induced mitochondrial membrane potential collapse in cardiomyocytes (30 μM group, P&lt;0.01).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;SRMI is a major driver of adverse clinical outcomes in patients with sepsis,","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}