Genes & genomics最新文献

{"title":"DKK1 activated the NF-κB pathway by binding with CKAP4 to induce PASMC oxidative stress and promote pulmonary arterial hypertension.","authors":"Shaojin Wang, Xiuyan Wang, Lili Miao, Yating Zhang, Peng Zhang","doi":"10.1007/s13258-026-01773-9","DOIUrl":"10.1007/s13258-026-01773-9","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary arterial hypertension (PAH) is a hemodynamic disorder that can progress to right heart failure and result in death.</p><p><strong>Objective: </strong>This study investigated the molecular mechanisms underlying the onset and progression of PAH to identify potential therapeutic targets.</p><p><strong>Methods: </strong>Peripheral blood samples from PAH patients were analyzed to assess serum levels of DKK1 and CKAP4, as well as NF-κB pathway activation. Supernatants from hypoxia-treated pulmonary artery endothelial cells (PAECs), plasmid-transfected cells, and SC75741-treated cells were used to modulate pulmonary artery smooth muscle cells (PASMCs). RT-qPCR, Western blot, and ELISA were employed to quantify DKK1 and CKAP4 expression and evaluate NF-κB pathway activation in PASMCs. EdU staining and CCK-8 viability assay were performed to assess cell proliferation, while DCFH-DA staining and ELISA were used to measure ROS, SOD, and MDA levels.</p><p><strong>Results: </strong>DKK1 and CKAP4 expression were positively correlated, and both were upregulated with increasing pulmonary artery systolic pressure (PASP) in PAH patients. The supernatant from hypoxia-exposed PAECs induced NF-κB pathway activation, cell proliferation, and oxidative stress in PASMCs, effects that were inhibited by siDKK1, siCKAP4, and SC75741.</p><p><strong>Conclusions: </strong>Hypoxia stimulated PAECs to secrete DKK1, which in turn upregulated CKAP4 expression and activated the NF-κB pathway in PASMCs, promoting cell proliferation and oxidative stress.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1117-1130"},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148294661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TSTA3 promotes the malignant progression of bladder cancer by regulating LAMP2 and MAPK signaling pathway-mediated epithelial-mesenchymal transition.","authors":"Nihao Cao, Fei Cheng","doi":"10.1007/s13258-025-01724-w","DOIUrl":"10.1007/s13258-025-01724-w","url":null,"abstract":"<p><strong>Background: </strong>Bladder cancer (BCa) is the most frequently seen malignancy of the urinary tract. However, its molecular mechanisms and therapeutic targets are not well established.</p><p><strong>Objective: </strong>This study aims to investigate the mechanism by which tissue specific transplantation antigen P35B (TSTA3) mediates the suppression of epithelial-mesenchymal transition (EMT) in BCa through targeted regulation of lysosome-associated membrane protein 2 (LAMP2) expression via the mitogen-activated protein kinase (MAPK) signaling pathway.</p><p><strong>Methods: </strong>Public datasets were analyzed to predict TSTA3 expression and prognosis in BCa. TSTA3 and LAMP2 expression levels were examined in 30 paired BCa and adjacent normal tissues, followed by Pearson correlation analysis of their mRNA levels. TSTA3 expression was quantified in T24, BIU-87 and simian virus 40-immortalized human urothelial cell line-1 (SV-HUC-1). T24 and BIU-87 cells were subjected to TSTA3 knockdown or overexpression. Cell proliferation, migration/invasion (Transwell), apoptosis (flow cytometry), EMT markers (immunofluorescence), and LAMP2/MAPK pathway proteins were evaluated.</p><p><strong>Results: </strong>TSTA3 upregulation was demonstrated in public databases, BCa patient tissues, and cell strains. TSTA3 knockdown in T24 cells substantially suppressed proliferation, colony formation, invasion, migration, and apoptosis while increasing E-cadherin and decreasing Vimentin expression, whereas TSTA3 overexpression in BIU-87 cells promoted malignant phenotypes. TSTA3 and LAMP2 mRNA levels showed a strongly negative correlation in BCa patients. LAMP2 knockdown reversed the tumor-suppressive effects of TSTA3 silencing. Inhibition of the MAPK pathway rescued the functional deterioration of T24 cells caused by TSTA3 overexpression.</p><p><strong>Conclusions: </strong>TSTA3 promotes BCa proliferation, migration, invasion, and EMT by regulating LAMP2 to activate the MAPK pathway.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1101-1116"},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-omics analysis of a succinylation-associated gene-expression signature in clear cell renal cell carcinoma: prognostic significance and the immune-metabolic microenvironment.","authors":"Yang Zhou, Donghua Liu, Huiming Jiang","doi":"10.1007/s13258-026-01785-5","DOIUrl":"10.1007/s13258-026-01785-5","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC) exhibits significant metabolic alterations. Protein succinylation, a metabolite-induced post-translational modification, plays a vital role in cellular metabolism and tumor biology.</p><p><strong>Objective: </strong>To characterize the succinylation-associated transcriptional signature and its clinical relevance in ccRCC.</p><p><strong>Methods: </strong>We developed a succinylation-associated transcriptional score based on a literature-curated 20-gene panel using the TCGA-KIRC RNA-seq dataset, with prognostic validation in two independent cohorts (E-MTAB-1980 and CPTAC). The tumor immune microenvironment was analyzed via ESTIMATE, CIBERSORT, and ssGSEA. Cellular localization of the score was investigated using single-cell and spatial transcriptomics. Functional enrichment, drug response analyses, and qPCR validation were also performed.</p><p><strong>Results: </strong>Tumor tissues demonstrated significantly reduced succinylation-associated transcriptional scores compared to normal counterparts, with higher scores correlating with improved clinical outcomes. Multivariate analyses supported the independent prognostic value of the succinylation-associated transcriptional score for overall survival in the TCGA and validation datasets. Interestingly, low-score tumors exhibited a transcriptionally \"immune-hot\" phenotype, characterized by enhanced immune cell infiltration and elevated immune checkpoint expression. Single-cell and spatial transcriptomic analyses suggested that tumor cells primarily contributed to the succinylation-associated transcriptional score. Functional assessments revealed that high scores were associated with oxidative phosphorylation and fatty acid metabolism, while low scores correlated with pro-tumorigenic signaling pathways. Computational drug sensitivity analysis identified exploratory associations that may inform future therapy stratification based on succinylation profiles.</p><p><strong>Conclusion: </strong>The succinylation-associated transcriptional score represents a promising biomarker candidate in ccRCC, showing associations with prognosis and key metabolic-immune features. Our study underscores the role of succinylation in ccRCC biology and provides a framework for metabolic subtyping that may inform future biological and clinical stratification studies.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1087-1099"},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148198711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Anti-inflammatory activity and antioxidant capacity of Clerodendrum japonicum (Thunb.) sweet extract in LPS-stimulated macrophages.","authors":"Jeongeun Noh, Kyeoungtae Park, Fred Pitisopa, Myknee Qusa Sirikolo, Jung Jin Kim, Sung-Suk Suh, Jong Bae Seo","doi":"10.1007/s13258-026-01784-6","DOIUrl":"10.1007/s13258-026-01784-6","url":null,"abstract":"","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1173"},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular and neural mechanisms of sodium sensation.","authors":"Nabin Rana, Youngseok Lee","doi":"10.1007/s13258-026-01782-8","DOIUrl":"10.1007/s13258-026-01782-8","url":null,"abstract":"<p><strong>Background: </strong>Sodium (NaCl) is essential for neuronal excitability, muscle contraction, and osmotic balance, yet excessive intake causes cellular stress and dehydration, requiring tight homeostatic control. Drosophila melanogaster provides a genetically tractable system to dissect salt sensing and regulation.</p><p><strong>Objective: </strong>To summarize current understanding of concentration-dependent salt taste coding and systemic sodium homeostasis in flies.</p><p><strong>Methods: </strong>This review integrates genetic, behavioral, electrophysiological, and physiological studies describing (1) peripheral taste receptor neurons mediating differential responses to low- versus high-salt, (2) neural circuits for appetitive versus aversive behaviors, (3) state-dependent plasticity of salt preference, and (4) post-prandial ion balancing in the gut and malpighian tubules.</p><p><strong>Results: </strong>Flies exhibit a biphasic behavioral response to salt: low concentrations promote feeding, whereas high concentrations induce aversion. Distinct classes of gustatory receptor neurons encode these opposing valences. Salt preference is further modulated by internal physiological state, integrating sensory detection with systemic ion balance.</p><p><strong>Conclusion: </strong>Coordinated sensory, neural, and excretory mechanisms govern ionic homeostasis in Drosophila melanogaster, thereby providing an evolutionarily conserved framework for investigating sodium balance across species.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1045-1055"},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148137850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polytrichastrum alpinum methanol extract induces cell cycle arrest and apoptosis in mammary tumor cells of companion dogs.","authors":"Minseo Kim, Hyunsoo Lee, Minseo Yang, Kim-Hoa Phi, Ui Joung Youn, Yeong-Bin Baek, Sang-Ik Park, Sung-Suk Suh, Jong-Bae Seo, Sung-Hak Kim","doi":"10.1007/s13258-026-01780-w","DOIUrl":"10.1007/s13258-026-01780-w","url":null,"abstract":"<p><strong>Background: </strong>Mammary tumor is one of the most prevalent cancers in female companion dogs. Current chemotherapeutic treatments are often limited by high toxicity and financial burden, highlighting the need for safer and more accessible therapeutic alternatives.</p><p><strong>Objective: </strong>This study aimed to evaluate the anticancer potential of the methanol extract of Polytrichastrum alpinum, a moss species native to Antarctica, in mammary tumor cell lines derived from companion dogs.</p><p><strong>Methods: </strong>Two canine mammary tumor cell lines, MGT316 and MGT612, were treated with various concentrations of Polytrichastrum alpinum methanol extract. Cell viability, colony-forming ability, cell cycle distribution, apoptosis, migration, and invasion were assessed. Cytotoxic effects on normal canine epithelial cells were also evaluated to compare responses between tumor and non-tumorigenic cells.</p><p><strong>Results: </strong>Polytrichastrum alpinum methanol extract significantly reduced cell viability and colony-forming ability in a dose-dependent manner. It induced G0/G1 cell cycle arrest and promoted apoptosis in both tumor cell lines. Additionally, the extract effectively inhibited cell migration and invasion. Notably, minimal cytotoxic effects were observed in normal canine epithelial cells, indicating differential sensitivity between tumor and non-tumorigenic cells.</p><p><strong>Conclusion: </strong>These findings demonstrate that Polytrichastrum alpinum methanol extract exerts antiproliferative, pro-apoptotic, and anti-invasive effects on mammary tumor cells of companion dogs, indicating its potential as a natural therapeutic agent. Furthermore, given the relevance of canine mammary tumors as a comparative model, this study may provide valuable translational insights for human breast cancer research within a One Health framework.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1057-1065"},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148137878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BMP/Ventx1.1 axis modulates the multiciliogenesis in the early Xenopus epidermis.","authors":"Neha Kaushik, Zia Ur Rehman, Soochul Park, Seung-Hwan Lee, Unjoo Lee, Jaebong Kim","doi":"10.1007/s13258-026-01777-5","DOIUrl":"10.1007/s13258-026-01777-5","url":null,"abstract":"<p><strong>Background: </strong>In Xenopus laevis, multiciliated cells (MCCs) in epidermis produce coordinated motile cilia to promote fluid flow across epithelial surfaces. In a previous study, it has been reported that Bmp signaling negatively regulates the multiciliated cell formation. However, Bmp signaling is required for the early ectodermal patterning and epidermal specification.</p><p><strong>Objective: </strong>In the present study, the requirement of Bmp signaling was examined in ectoderm specification including multiciliogenesis of epidermis. Inhibition of Bmp signaling using a dominant-negative Bmp receptor (Dnbr) decreased MCC formation both in animal cap explants and whole embryos.</p><p><strong>Methods: </strong>Differentially expressed MCC-associated transcripts were confirmed by transcriptome and RT-qPCR analysis of Bmp-inhibited and control animal cap explants. The promoters of multicilia-associated genes including mcidas, foxj1, deup1 and ccno were cloned to examine how Bmp signaling regulated MCC gene expression.</p><p><strong>Results: </strong>Dnbr-injected embryos consistently showed the reduced promoter activity. However, a direct target gene of Bmp signaling ventx1.1 restored MCC gene expression and promoter activity as well as epidermal marker expression in Dnbr-injected embryos.</p><p><strong>Conclusion: </strong>Together, the results support a model in which early BMP/Ventx1.1 axis positively modulates epidermal multiciliogenesis at least in part by establishing epidermal competence through ventx1.1 associated transcriptional programs.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1131-1143"},"PeriodicalIF":2.0,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platform-dependent performance of P2A and IRES linkers in multicistronic gene expression.","authors":"Mingyu Ju, Jinju Han","doi":"10.1007/s13258-026-01771-x","DOIUrl":"10.1007/s13258-026-01771-x","url":null,"abstract":"","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"1007-1016"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13314811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of Lcn2 and neuroinflammation in a scopolamine-induced cognitive impairment animal model: implication of the NLRP3 inflammasome pathway.","authors":"Min Yeong Lee, Nicole Bon Campomayor, Bernabe Apare, Ra Eun Park, Doyun Kim, Hee Jin Kim, Mikyung Kim","doi":"10.1007/s13258-026-01765-9","DOIUrl":"10.1007/s13258-026-01765-9","url":null,"abstract":"","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"975-985"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147638607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"5-Aminoimidazole-4-carboxamide riboside, an AMPK activator, enhances TRAIL-mediated apoptosis in human bladder cancer cells in a p38 MAPK-dependent manner.","authors":"Cheol Park, Hyun Hwangbo, Su Hyun Hong, Hyeon Ji Jeong, Seok Joong Yun, Jeong Sook Noh, Sung-Kwon Moon, Wun-Jae Kim, Gi-Young Kim, Yung Hyun Choi","doi":"10.1007/s13258-026-01764-w","DOIUrl":"10.1007/s13258-026-01764-w","url":null,"abstract":"","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"963-974"},"PeriodicalIF":2.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147689626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}