Journal of Gene Medicine最新文献

{"title":"Anti-Glutamic Acid Decarboxylase 65 (GAD65) Antibodies and Neurological Syndromes","authors":"Omid Mohammadzadeh,&nbsp;Nafise Fahimzadeh,&nbsp;Fateme Elhami,&nbsp;Saeideh Sadat Shobeiri","doi":"10.1002/jgm.70039","DOIUrl":"10.1002/jgm.70039","url":null,"abstract":"<div>\u0000 \u0000 <p>Various neurological disorders have been linked to the presence of serum antibodies targeting glutamic acid decarboxylase (GAD), a key enzyme in the production of γ-aminobutyric acid (GABA). Associated conditions include stiff-person syndrome (SPS) (classic and variant forms), cerebellar ataxia, limbic or extra-limbic encephalitis, nystagmus issues, drug-resistant epilepsy, paraneoplastic SPS, and progressive encephalopathy with rigidity and myoclonus (PERM). Although PERM and paraneoplastic SPS are mainly associated with antibodies targeting glycine receptors and amphiphysin, GAD antibodies might also be detected. Despite evidence of autoimmune activity and GABAergic dysfunction in some cases, the direct pathological role of GAD antibodies remains uncertain and debated. Diagnosis relies on clinical evaluation combined with detecting GAD antibodies in serum and cerebrospinal fluid (CSF), alongside confirmation of intrathecal antibody production. While GAD antibodies are not always required for diagnoses like SPS, they are essential for confirming cerebellar ataxia, encephalitis, or epilepsy. Treatment typically involves immunotherapy, with first-line options including intravenous immunoglobulins, steroids, or plasma exchange to induce remission. Long-term immunosuppression is often necessary. Symptomatic therapies (e.g., for muscle spasms, seizures, or delirium) are also recommended. The prognosis can differ, but it is typically positioned at an intermediate level between neurological syndromes associated with antibodies that target neural membrane antigens and those linked to onconeural antibodies. This review aims to further investigate the pathogenic role of these antibodies to improve predictions and select more appropriate treatment strategies.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 10","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214488","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":"DSCC1 as a Novel Biomarker in Hepatocellular Carcinoma: Diagnostic Potential, Prognostic Impact, Correlation With Key Pathways, and Association With the Immune Landscape","authors":"Abdul Jamil Khan,&nbsp;Shad Man,&nbsp;Shahid Ullah Khan","doi":"10.1002/jgm.70045","DOIUrl":"10.1002/jgm.70045","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;DSCC1, a key subunit of the alternative RFC complex, is essential for DNA replication and genome stability. While its role in cancers like breast cancer is documented, its function in LIHC remains largely unexplored. This study comprehensively examines DSCC1's involvement in LIHC.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;DSCC1 expression in tumor versus normal at the mRNA and protein levels was assessed using UALCAN, GEPIA, OncoDB, HPA, and TIMER databases. Prognostic significance was evaluated via Kaplan–Meier Plotter, PrognoScan, and validated through UALCAN, cBioPortal, TIMER, HPA, and TISIDB. Genomic alterations were analyzed across TCGA cohorts using cBioPortal. Drug sensitivity data were retrieved from GDSC, and pathway activities were explored to elucidate DSCC1's functional impact. Immune cell infiltration and modulatory interactions were examined using TIMER and TISIDB. Functional roles and interaction networks were assessed using GeneMANIA (PPI), SRplot (GO/KEGG), and Spearman correlation. Associations with key oncogenic pathways including cell cycle, EMT, DNA replication, lipogenesis, and glycolysis were explored via cBioPortal.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;DSCC1 was significantly overexpressed at both mRNA and protein levels in LIHC across various stages, grades, lymph node statuses, and molecular subtypes. High DSCC1 expression was consistently associated with poor overall survival. Genomic analysis revealed frequent alterations, with amplification observed in up to 31% of LIHC patients. Pathway activity profiling showed strong activation of the cell cycle, apoptosis, and EMT pathways, alongside suppression of RAS/MAPK and RTK signaling. DSCC1 expression positively correlated with immune infiltration, including CD4&lt;sup&gt;+&lt;/sup&gt;/CD8&lt;sup&gt;+&lt;/sup&gt; T cells, macrophages, neutrophils, dendritic cells, and various immune modulators. Functional enrichment and coexpression analyses revealed involvement in DNA replication, chromosome segregation, and mitotic spindle assembly, suggesting a role in promoting genomic instability. DSCC1 was implicated in metabolism, metastasis, and immune-related pathways. Additionally, DSCC1 expression correlated with resistance to drugs such as 17-AAG and Trametinib, and increased sensitivity to PI-103 and Vorinostat.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Overall, this study suggests that DSCC1 may function as a valuable prognostic biomarker, an early diagnostic indicator, and a potential therapeutic target in LIHC, given its diverse involvement in tumor progression, drug responsiveness, immune regulation, and genomic instabil","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 10","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214544","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":"Prime Editing: The Next Frontier in Precision Gene Therapy","authors":"Melike Aliciaslan,&nbsp;Ezgi Erbasan,&nbsp;Fulya Erendor,&nbsp;Salih Sanlioglu","doi":"10.1002/jgm.70040","DOIUrl":"10.1002/jgm.70040","url":null,"abstract":"<div>\u0000 \u0000 <p>Prime editing (PE) represents a significant advancement in genome editing, offering high precision for diverse genetic modifications without inducing double-strand breaks or requiring exogenous donor DNA templates. This “search-and-replace” technology employs a Cas9 nickase–reverse transcriptase fusion protein, guided by a PE guide RNA (pegRNA), to directly install specified edits including all 12 base-to-base conversions and targeted insertions/deletions with high fidelity. Since its introduction, PE systems have undergone rapid evolution (e.g., PE2-PE6, PEmax), markedly improving editing efficiency, product purity, and targeting scope. Although PE efficacy is context dependent, influenced by pegRNA design, cellular milieu, and DNA repair pathway engagement, ongoing research focuses on comprehensive system optimization. These efforts include engineering the Cas9 nickase and reverse transcriptase components for enhanced performance and processivity, alongside developing improved pegRNA architectures and chemical modifications to increase their stability and editing efficiency. Furthermore, strategies to modulate the cellular environment, such as transiently altering DNA repair pathway activities, particularly mismatch repair, are being explored to boost the accuracy and yield of precise edits. PE holds substantial promise for basic research, including precise disease modeling, and has demonstrated successful correction of pathogenic mutations in preclinical models of various genetic disorders like sickle cell disease, cystic fibrosis, and inherited retinal diseases. A significant milestone was the US Food and Drug Administration's granting of Investigational New Drug (IND) clearance for the first clinical trial of PM359, a therapeutic based on PE. This agent employs an ex vivo strategy, correcting the <i>NCF1</i> gene in patient-derived hematopoietic stem cells for the treatment of chronic granulomatous disease. Despite considerable progress, unlocking the complete therapeutic promise of PE requires overcoming significant hurdles, particularly in developing effective in vivo delivery systems for its sizable components, with ongoing research actively investigating diverse viral and nonviral approaches. The translation of this versatile platform into transformative precision gene therapies is critically dependent upon its continued responsible advancement under robust ethical and regulatory oversight.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 10","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214514","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":"Tele-Genetic Versus Onsite Counseling for APOE Disclosure: A 6-Month Study of Empowerment, Psychological Distress, and Behavioral Outcomes in Cognitively Diverse Individuals","authors":"Marina Makri,&nbsp;Ioanna Antigoni Angelidou,&nbsp;Despoina Moraitou,&nbsp;Liana Fidani,&nbsp;Thomas Tegos,&nbsp;Vasileios Kimiskidis,&nbsp;Magdalini Tsolaki","doi":"10.1002/jgm.70041","DOIUrl":"https://doi.org/10.1002/jgm.70041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>With the increasing demand for clinical genetic services and the lack of clinical geneticists, tele-genetics is utilized in clinical genetics to improve cost efficiency and equitable access to health services. But is tele-genetic counseling (GC) for APOE genotype disclosure for Alzheimer's disease (<span>ad</span>) risk as effective as onsite interventions?</p>\u0000 \u0000 <p>This study examines behavioral, psychological, empowerment, and risk recall responses following the disclosure of genetic results of AD risk to first-degree relatives of people with AD (PwAD) in Greece.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Participants (<i>N</i> = 93) were randomly assigned to one of two GC interventions. Additional grouping variables included the cognitive status (healthy relatives of PwAD or people with mild cognitive impairment [MCI]) and the genetic test result (ε4-positive or not). Throughout the three time points (baseline/before GC, 3 and 6 months post-disclosure), participants completed questionnaires for psychological well-being, empowerment, risk recall, and behavioral adaptations. Repeated-measures ANOVA, Mann–Whitney <i>U</i> tests, logistic regression, Friedman test, and <i>χ</i>² tests were used to examine changes in different scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Ninety-three adults (mean age 64.77 years, years of education 13.72, 61% female) were randomly assigned to online (46 participants) and onsite (47 participants) groups. There were no statistically significant differences between the two intervention groups in psychological and empowerment scores. However, people with MCI have substantially lower odds of recalling risk after 6 months and lower empowerment scores. People with ε4 were much more likely to endorse behavior change and indicated higher distress scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Tele-GC can serve as an effective intervention for APOE disclosure for healthy relatives of PwAD and people with MCI.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 10","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.70041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145196315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Potential Hub Genes and Molecular Mechanisms Linking Cardia Carcinoma With Sjögren's Syndrome Based on Comprehensive Bioinformatics Analysis and Machine Learning","authors":"Meng Qian,&nbsp;Ying Chen,&nbsp;Zhenxiang Wang,&nbsp;Ye Chen,&nbsp;Yan Zhang,&nbsp;Xiaofen Wu,&nbsp;Huihui Sun,&nbsp;Shuchang Xu","doi":"10.1002/jgm.70044","DOIUrl":"https://doi.org/10.1002/jgm.70044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cardia carcinoma (CC) is a highly heterogeneous cancer with an increasing incidence worldwide. Gastroesophageal reflux disease has been identified as a risk factor for CC, and patients with Sjögren's syndrome (SS) are often reported to have esophageal motility disorders. This study aimed to identify potential hub genes and molecular processes for CC with SS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) analysis and weighted gene coexpression network analysis (WGCNA) were conducted to identify shared genes between CC and SS. Functional enrichment analysis and protein–protein interaction (PPI) network construction were performed on these genes. Four machine learning algorithms, including random forest (RF), least absolute shrinkage and selection operator (LASSO), support vector machine–recursive feature elimination (SVM-RFE), and extreme gradient boosting (XGBoost), were applied to screen hub genes. Then, a nomogram predicting the risk of CC in SS patients was constructed and validated by the receiver operating characteristic (ROC) curve and calibration curve. Additionally, we analyzed the transcriptional regulatory relationships, coexpression networks, and correlations between the hub genes and immune infiltration.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>By intersecting DEGs and module genes identified by WGCNA, we screened 60 shared genes that were mainly enriched in cell cycle, response to xenobiotic stimulus, and p53 signaling pathways. Based on machine learning algorithms, three hub genes were identified and used to construct a nomogram with high predictive performance (the AUC for the training cohort and validation cohort were 0.991 and 0.978, respectively). Furthermore, the immune infiltration results suggested that T cells, mast cells, macrophages, and B cells play an important role in both diseases, and the hub genes were significantly associated with T cells and B cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study identified three hub genes (E2F3, CHIA, and SCNN1B) and established a nomogram that could effectively predict the risk of CC. The unbalanced immune response may be the common pathogenesis of these two diseases, which provides novel insights into the diagnosis and therapy of CC with SS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 9","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146351","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":"Multi-Omics Integrated Analysis of the Protective Effect of Tertiary Lymphoid Structures and Associated Key Regulatory Genes in Human Gallbladder Cancer","authors":"Xiaolong Chen,&nbsp;Yimin Nong,&nbsp;Ming Zhang,&nbsp;Chengyou Du","doi":"10.1002/jgm.70037","DOIUrl":"https://doi.org/10.1002/jgm.70037","url":null,"abstract":"<div>\u0000 \u0000 <p>Tertiary lymphoid structures (TLSs) are lymphoid structures found in non-lymphoid tissues, which have been involved in the pathogenesis of multiple chronic diseases including tumors. TLSs are associated with better prognosis and response to immunotherapy in most types of tumors. However, what their associations with prognosis and the exact roles of TLS-related genes in gallbladder cancer (GBC) are still unclear. Here, we investigated the associations of TLS with the prognosis in 85 patients with GBC. Our results showed that the presence of intra-tumoral TLS was negatively associated with T stage (<i>p</i> = 0.035) and vascular invasion (<i>p</i> = 0.048) and predicted a higher rate of overall survival (<i>p</i> = 0.004) and a decreased risk of early recurrence (<i>p</i> = 0.002). Moreover, using integrative analysis of single-cell RNA sequencing, bulk RNA sequencing, and deep machine learning, we screened six TLS-related candidate genes in GBC, including CTSG, FLNC, CCNB1, HSPB8, NR4A1, and MYLK. Furthermore, through the evaluation of biofunctions and clinical significance, we found that CTSG, FLNC, CCNB1, and HSPB8 played an important role in immune infiltration, diagnosis, and prognosis of GBC. Finally, cell-based experimental validation indicated that either knockdown of CTSG or overexpression of HSPB8 promoted CD8+ T cell apoptosis and exhaustion. In conclusion, TLS had a protective effect on human GBC, and its related genes, played a potential role in diagnosis, prognosis, immune infiltration, and metastasis of GBC. Our findings provided a new insight for the research on clinical biomarkers of GBC and development of its therapeutic targets.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 9","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146478","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":"Exploring the Protein–Metabolite Interplay to Discover Novel Drug Targets for Alzheimer's Disease","authors":"Kang-Fu Yin,&nbsp;Xiao-Jing Gu,&nbsp;Zheng Jiang,&nbsp;Wei-Ming Su,&nbsp;Qing-Qing Duan,&nbsp;Sheng-Yi He,&nbsp;Bei Cao,&nbsp;Qin Chen,&nbsp;Qin Zhang,&nbsp;Yong-Ping Chen","doi":"10.1002/jgm.70035","DOIUrl":"10.1002/jgm.70035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The protein–metabolite interactions play a pivotal role in the pathogenesis of Alzheimer's disease (<span>AD</span>); however, the causal significance of these interactions in <span>AD</span> pathogenesis remains elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We integrated datasets of protein quantitative trait loci (pQTL), metabolite quantitative trait loci (mQTL), and genome-wide association study (GWAS) for <span>AD</span>. Initially, we performed MR analysis to identify proteins and metabolites causally associated with <span>AD</span> risk. To guarantee the robustness of these findings, Bayesian colocalization analysis was employed to confirm shared genetic signals. Meanwhile, Steiger filtering was utilized to verify the directionality of causal effects. Sensitivity analyses were further carried out to assess potential pleiotropy and bias. Moreover, we employed MR analysis to assess the causal relationships between proteins and metabolites, identifying protein–metabolite pairs that are associated with <span>AD</span>. Finally, we evaluated the druggability of these causal proteins as potential therapeutic targets.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Proteomic and metabolomic MR analyses identified 14 proteins and 50 metabolites causally associated with <span>AD</span>. Among these, five proteins (BIN1, C1R, SHPS1, LILRB1, and TMEM106B) passed Bayesian colocalization analysis (PPH4 ≥ 80%). Notably, LILRB1 exhibited a protective effect against <span>AD</span>, while BIN1, C1R, SHPS1, and TMEM106B were implicated as risk factors for the disease. Of the 50 metabolites, 38 passed sensitivity and Steiger filtering analyses and were utilized for further protein-metabolite pair analysis. Subsequent MR analysis revealed 13 protein–metabolite pairs associated with <span>AD</span>, involving four proteins (BIN1, C1R, SHPS1, and LILRB1) and 12 metabolites. Notably, drugs targeting BIN1, including M344, L-type calcium channel blockers, and BIN1 monoclonal antibodies, have been reported as potential treatments for <span>AD</span>. For the remaining three drug targets, medications used for other diseases were identified as potentially applicable.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings highlight four proteins as potential drug targets for <span>AD</span>, and suggest their corresponding protein–metabolite pairs should be prioritized for analysis of potential mechanistic pathways.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 9","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093163","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":"Marine-Derived Enteromorpha prolifera Polysaccharides Suppress Castration-Resistant Prostate Cancer via Akt1 Inhibition","authors":"Pingfa Lin,&nbsp;Na Yao,&nbsp;Tingting Lin,&nbsp;Yanhui Zou,&nbsp;Weiling Lin,&nbsp;Yong Lin","doi":"10.1002/jgm.70038","DOIUrl":"10.1002/jgm.70038","url":null,"abstract":"<p>Prostate cancer remains a leading cause of cancer-related mortality, with castration-resistant and metastatic forms posing significant therapeutic challenges. Marine-derived polysaccharides from <i>Enteromorpha prolifera</i> (EP) have emerged as promising anticancer agents due to their unique bioactive properties. In this study, we investigated the antitumor effects of EP on prostate cancer cells and elucidated its underlying molecular mechanisms. EP demonstrated selective cytotoxicity against aggressive DU145 prostate cancer cells. Mechanistically, EP induced G1/S cell cycle arrest, suppressed DNA synthesis, and inhibited epithelial-mesenchymal transition. Cellular thermal shift assays confirmed EP–Akt1 interaction, increasing the thermal stability of Akt1. These findings establish EP as a novel Akt1-targeting agent that simultaneously blocks proliferative and metastatic pathways in prostate cancer. In conclusion, our results highlight the therapeutic potential of EP as a multitargeted, marine-derived compound for prostate cancer treatment.</p>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 9","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jgm.70038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145093178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miRNA-574-5p and miRNA-522 as Potential Biomarkers in Nonalcoholic Fatty Liver Disease","authors":"Reham Fares,&nbsp;Asmaa Mohammed,&nbsp;Mahmoud A. F. Khalil,&nbsp;Tarek I. Ahmed,&nbsp;Shaimaa A. Fathy,&nbsp;Amira Samy,&nbsp;Ahmed S. Doghish 0000-0002-0136-7096,&nbsp;Randa Erfan","doi":"10.1002/jgm.70042","DOIUrl":"10.1002/jgm.70042","url":null,"abstract":"<div>\u0000 \u0000 <p>Nonalcoholic fatty liver disease (NAFLD) forms a global health burden with prominent incidence rates exceeding 26%, possessing a versatile spectrum of presentations starting from benign liver steatosis and deteriorating to hepatic fibrosis and even cirrhosis. In our study, we aimed to be the first to investigate the serum concentrations of miR-574-5p and miR-522 in individuals with NAFLD and link them to obesity and dyslipidemia. Eighty participants were enrolled in our study and split into two groups: The first group included 40 individuals diagnosed with NAFLD via clinical, imaging, and laboratory procedures (24 males and 16 females). The second group involved 40 healthy controls (22 males and 18 females). Venous blood samples were collected from all subjects. The miR-574-5p and miR-522 serum expressions were evaluated using quantitative real-time PCR (qRT-PCR). Our study data revealed a marked reduction in the mean miR-574 expression levels simultaneous with an increase in the mean level of miR-522 expression in NAFLD cases compared to controls (<i>p</i> &lt; 0.001), as for the specificity and sensitivity tests for the miR-522 and miR-574-5p markers, they revealed sensitivities of 80% and 100%, respectively, along with specificities of 100% and 95%, respectively, at cutoff values of 1.136 and 0.891, respectively. The <i>p</i> value for both markers is less than 0.001. Serum miR-574-5p and miR-522 could serve as promising biomarkers in diagnosing NAFLD.</p>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 9","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088467","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":"Mechanism of Tourette Syndrome Induced by ABGA-Mediated CaMKII-TH Pathway","authors":"Xinnan Wu,&nbsp;Juanjuan Hao,&nbsp;Keyu Jiang,&nbsp;Min Wu,&nbsp;Xin Zhao,&nbsp;Xin Zhang","doi":"10.1002/jgm.70043","DOIUrl":"10.1002/jgm.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In this study, we intend to investigate the mechanism by which anti-basal ganglia antibodies (ABGA) modulate dopamine release through the CaMKII-TH pathway, which leads to the onset of Tourette syndrome (TS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In the clinical experiment, serum samples were collected from 40 TS children and 40 healthy children. ELISA was performed to detect ABGA, anti-streptolysin O (ASO), and anti-deoxyribonuclease B (ADNB) levels in each group. In the animal experiment, the TS group was microinfused with ABGA-positive serum from TS children. The expression levels of striatal pCaMKIIα/CaMKIIα, pTH/TH, Drd1, Drd2, and dopamine (DA) were detected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Clinical experiments showed positive correlation between serum ABGA, ASO, ADNB levels, and YGTSS scores. Animal experiments showed that the stereotype score and the expression levels of striatal pCaMKIIα/CaMKIIα, pTH/TH, Drd1, and DA were increased in the TS group. The expression levels of striatal Drd2 were reduced, accompanied by neuronal loss within the striatum in the TS group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>ABGA may contribute to the development of TS by increasing striatal dopamine levels through the activation of calcium-calmodulin dependent protein kinase II (CaMKIIα) phosphorylation and tyrosine hydroxylase (TH) phosphorylation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":56122,"journal":{"name":"Journal of Gene Medicine","volume":"27 9","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088325","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}