Genes & genomicsPub Date : 2025-05-01Epub Date: 2025-03-24DOI: 10.1007/s13258-025-01635-w
Haesoo Jung, Yong-Eun Kim, Eun-Mi Kim, Kee K Kim
{"title":"Alternative splicing of CHI3L1 regulates protein secretion through conformational changes.","authors":"Haesoo Jung, Yong-Eun Kim, Eun-Mi Kim, Kee K Kim","doi":"10.1007/s13258-025-01635-w","DOIUrl":"10.1007/s13258-025-01635-w","url":null,"abstract":"<p><strong>Background: </strong>Alternative splicing (AS) plays a crucial role in regulating protein function through the generation of structurally distinct isoforms.</p><p><strong>Objective: </strong>We identify a novel splicing event in Chitinase 3-like 1 (CHI3L1) that modulates its secretion through conformational changes.</p><p><strong>Methods: </strong>CHI3L1 alternative splicing was analyzed using the GTEx dataset. The regulation of CHI3L1 splicing was examined in response to THP-1 and BEAS-2B cells using RT-PCR. Structural modeling of CHI3L1 isoforms was conducted with AlphaFold to predict conformational changes caused by exon 8 exclusion. Protein expression and secretion levels of CHI3L1 isoforms were analyzed by Western blotting.</p><p><strong>Results: </strong>Analysis of the GTEx dataset revealed tissue-specific regulation of CHI3L1 exon 8, with pronounced exclusion in lung tissue. The splicing pattern of CHI3L1 was dynamically regulated during THP-1 macrophage differentiation and by cell density in lung-derived epithelial BEAS-2B cells, suggesting its responsiveness to cellular context. While both full-length and exon 8-excluded CHI3L1 proteins showed cytoplasmic localization, structural analysis using AlphaFold revealed that exon 8 exclusion significantly altered the orientation of the signal peptide. Consequently, exon 8-excluded CHI3L1 exhibited minimal secretion into the culture medium compared to the full-length protein.</p><p><strong>Conclusion: </strong>These findings demonstrate that alternative splicing-mediated exclusion of exon 8 serves as a novel regulatory mechanism controlling CHI3L1 secretion through conformational changes, providing new insights into the post-transcriptional regulation of secreted proteins.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"571-579"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700370","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":"Whole transcriptome profiling of cardiac injury: insights from a neonatal mouse sepsis model.","authors":"Wenjin Feng, Huanqi Tang, Chengshuai Li, Xiaohui Kong, Xueyun Ren, Huabin Wang","doi":"10.1007/s13258-025-01632-z","DOIUrl":"10.1007/s13258-025-01632-z","url":null,"abstract":"<p><strong>Background: </strong>Neonatal sepsis is characterized by an excessive immune response, often leading to multiple organ failure, including cardiac injury, and is a major cause of morbidity and mortality in newborns. Understanding the molecular mechanisms of sepsis-induced cardiac injury is crucial for developing therapeutic strategies.</p><p><strong>Objective: </strong>To investigate transcriptomic changes and identify potential altered genes associated with cardiac injury in a neonatal sepsis model.</p><p><strong>Methods: </strong>A neonatal sepsis model was established by cecal slurry injection. RNA sequencing analysis was performed on cardiac tissues from sepsis and control groups, followed by functional enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Interaction networks among mRNA, lncRNA, circRNA, and miRNA were constructed, and key regulatory genes were identified through protein-protein interaction (PPI) analysis.</p><p><strong>Results: </strong>A total of 1537 differentially expressed mRNAs, 287 lncRNAs, and 730 circRNAs were identified. Functional analysis revealed significant involvement in immune response and inflammatory regulation. PPI network analysis identified six key genes-Ccl5, Il-6, Pole, Mcm2, Mcm5, Mcm10-that were significantly expressed in sepsis-induced cardiac tissue. Additionally, lncRNAs and circRNAs were found to participate in myocardial injury by regulating immune and inflammatory pathways.</p><p><strong>Conclusions: </strong>This study identified six key genes involved in immune and inflammatory responses, playing critical roles in sepsis-induced cardiac injury in neonates. These findings provide new insights into the pathogenesis of sepsis-induced cardiac injury and offer potential therapeutic targets.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"599-613"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669634","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":"Report of two coinfections of human adenovirus and sapovirus in patients with acute gastroenteritis from China.","authors":"Xin Wang, Yaqing He, Mingda Hu, Wanqiu Liu, Kexin Li, Qiao Li, Shaofu Qiu, Lianqun Jin, Hailong Zhang, Boqian Wang, Chuanfu Zhang, Zhixi Peng, Long Chen, Xiaofeng Hu, Hongguang Ren, Hongbin Song","doi":"10.1007/s13258-025-01637-8","DOIUrl":"10.1007/s13258-025-01637-8","url":null,"abstract":"<p><strong>Background: </strong>Coinfections involving multiple diarrheal viruses have gained increasing recognition as a significant cause of acute gastroenteritis in recent years. Understanding the genetic diversity and evolutionary relationships of these viruses is crucial for effective outbreak identification and tracking.</p><p><strong>Objective: </strong>To report two cases of HAdV and SaV coinfections and elucidate the genetic diversity and evolutionary patterns of these viruses through whole-genome sequencing (WGS) and phylogenetic analysis.</p><p><strong>Methods: </strong>A total of 873 diarrheal stool samples were collected from sentinel hospitals in Shenzhen, China, in 2021. The collected stool samples were identified using RT-PCR and positive samples were subjected to WGS on the NovaSeq platform. phylogenetic trees were constructed using MEGA to analyze genetic relationships.</p><p><strong>Results: </strong>The sequencing results showed that both samples were human adenovirus type 41, which clustered in two distinct evolutionary clades. Additionally, we also retrieved the complete genome of sapovirus (GI.1 genotype) from the same sample. Phylogenetic analysis revealed that they were similar to previously reported strains, belonging to the clade predominating in China.</p><p><strong>Conclusions: </strong>This study reveals the genetic diversity of epidemic strains involved in coinfections of human adenovirus and sapovirus. The findings establish a groundwork for the identification and traces of acute gastroenteritis outbreaks.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"581-586"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735758","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}
Genes & genomicsPub Date : 2025-05-01Epub Date: 2025-03-20DOI: 10.1007/s13258-025-01634-x
Yeseul Choi, Jinuk Jeong, Minseo Kim, Seunghee Cha, Kyudong Han
{"title":"Backtracking identification techniques for predicting unclear bacterial taxonomy at species level: molecular diagnosis-based bacterial classification.","authors":"Yeseul Choi, Jinuk Jeong, Minseo Kim, Seunghee Cha, Kyudong Han","doi":"10.1007/s13258-025-01634-x","DOIUrl":"10.1007/s13258-025-01634-x","url":null,"abstract":"<p><p>Bacterial 16S rRNA genes are widely used to classify bacterial communities within interesting environments (e.g., plants, water, human body) because they contain nine hyper-variable regions (V1-V9) reflecting a large number of sequence variation sites between species. Short-read sequencing platform (targeting partial region of 16S rRNA gene; approximately 150-500 bp) commonly used in the 16S-based microbiome study is favored by many researchers because it is economical and can generate highthroughput sequencing data faster than long-read sequencing platforms. However, this sequencing platform has technical limitations in that it cannot clarify bacterial classification at the species level compared to long-read sequencing technology, which can cover the unclassification issue due to sequence similarity between species by targeting the 16S full-length region. In recent microbiome research-related industries, species-level high-resolution microbial classification is considered a key challenge to secure microbial resources among institutions in the field. However, the long-read sequencing platforms currently offered are still under price adjustment (demanding higher cost than short-read sequencing platforms) and have the disadvantage of low base-calling accuracy compared to short-read sequencing platforms. Therefore, this brief communication introduces the'Molecular diagnosis-based bacterial classification' technology to predict candidate species by backtracking for unclassified bacterial taxonomy at the species level in the NGS-based 16S microbiome study.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"503-508"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669545","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}
Genes & genomicsPub Date : 2025-05-01Epub Date: 2024-12-06DOI: 10.1007/s13258-024-01596-6
Yun Lei, Dan Shu, Jianyu Xia, Tao Zhang, He Wei
{"title":"Extracellular nicotinamide phosphoribosyltransferase visfatin activates JAK2-STAT3 pathway in cancer-associated fibroblasts to promote colorectal cancer metastasis.","authors":"Yun Lei, Dan Shu, Jianyu Xia, Tao Zhang, He Wei","doi":"10.1007/s13258-024-01596-6","DOIUrl":"10.1007/s13258-024-01596-6","url":null,"abstract":"<p><strong>Background: </strong>Metastasis is one of the major challenges in the treatment of colorectal cancer (CRC), during which cancer-associated fibroblasts (CAFs) in the tumor microenvironment are critically involved.</p><p><strong>Objective: </strong>In this study, we aim to explore the regulatory role of extracellular nicotinamide phosphoribosyltransferase Visfatin and its impact on CRC metastasis.</p><p><strong>Methods: </strong>To examine the effect of visfatin on CAFs, human CRC tissue-derived CAFs were exposed to visfatin, and the expression of inflammatory factors, activation of JAK-STAT pathway and production of ROS in CAFs were assessed. To examine the effect of visfatin-treated CAFs on CRC metastasis, human CRC cell line SW480 or SW620 were cultured with the conditioned medium derived from visfatin-treated CAFs, and the invasion and migration ability of SW480 or SW620 cells were evaluated by transwell migration and matrigel invasion assays.</p><p><strong>Results: </strong>Our previous study found that visfatin, a secreted form of nicotinamide phosphoribosyltransferase that governs the rate-limiting step of NAD synthesis, promoted CRC metastasis. However, little is known about the effect of visfatin on CAFs. The conditioned medium derived from visfatin- treated CAFs promotes the migratory and invasive capability of CRC cells, and enhance lung metastasis in mouse model. Visfatin treatment stimulated the expression of a couple of inflammatory factors in CAFs, which was mediated by visfatin-induced activation of JAK- STAT pathway and accumulation of ROS. Inhibition of JAK-STAT pathway or neutralization of cellular ROS attenuated visfatin-mediated migration and invasion of CRC cells.</p><p><strong>Conclusions: </strong>The present work highlights a critical role of visfatin in the crosstalk between CRC cells and CAFs, which moonlight as a non-metabolic extracellular signal molecule to hijacks JAK-STAT pathway in CAFs to promote CRC metastasis.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"615-624"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791665","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}
Genes & genomicsPub Date : 2025-04-28DOI: 10.1007/s13258-025-01646-7
Jie Yang, Junwei Han
{"title":"Comprehensive analysis based on IFN-γ and SASP related genes, bulk RNA and single-cell sequencing to evaluate the prognosis and immune landscape of stomach adenocarcinoma.","authors":"Jie Yang, Junwei Han","doi":"10.1007/s13258-025-01646-7","DOIUrl":"https://doi.org/10.1007/s13258-025-01646-7","url":null,"abstract":"<p><strong>Background: </strong>Stomach adenocarcinoma (STAD) represents the predominant subtype of gastric cancer, known for its drug resistance, unfavorable prognosis, and low cure rates. IFN-γ serves as a cytokine generated by immune cells, instrumental in tumor immune clearance and essential to the tumor microenvironment. The aging-associated secretory phenotype (SASP) can modify the local tissue environment, facilitating gastric cancer progression and chemotherapy resistance.</p><p><strong>Objective: </strong>This study intends to identify STAD subtypes based on IFN-γ and SASP-related genes and to develop a risk prognostic model for predicting patient survival, tumor immune microenvironment, and responses to drug treatment.</p><p><strong>Methods: </strong>The genomic and clinical datasets originate from the Cancer Genome Atlas (TCGA) database, while the genes associated with IFN-γ and SASP come from pertinent scholarly articles. We discovered the prognostic genes linked to IFN-γ and SASP in STAD using Cox regression analysis. Next, we applied non-negative matrix factorization (NMF) to categorize LIHC into distinct molecular subtypes, identifying differentially expressed genes across these subtypes. Following this, we developed a predictive model using Cox and LASSO regression analyses to stratify patients into specific risk categories, validating the model to assess the prognostic significance of the identified signatures. Lastly, we integrated single-cell data to elucidate the immune landscape of STAD and identified potential drugs along with their sensitivity profiles.</p><p><strong>Results: </strong>We identified 17 prognostic genes related to IFN-γ and SASP, successfully classifying patients into two distinct molecular subtypes. These subtypes exhibited notable differences in immune profiles and prognostic outcomes. We pinpointed three differentially expressed genes to establish risk characteristics and created a prognostic model capable of accurately predicting patient outcomes. Our findings revealed a strong association between STAD and the extracellular matrix, low-risk group exhibited favorable prognosis, and may derive greater benefits from immunotherapy.</p><p><strong>Conclusion: </strong>We developed a risk model using IFN-γ and SASP-associated genes to predict the prognosis of STAD patients more accurately. Additionally, we assessed the immune landscape of STAD by integrating bulk RNA and single-cell sequencing analyses. This approach may yield valuable insights for clinical decision-making and immunotherapy strategies in STAD.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007595","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}
Genes & genomicsPub Date : 2025-04-28DOI: 10.1007/s13258-025-01645-8
Jaegoo Yeon, Sung-Suk Suh, Ui-Joung Youn, Badamtsetseg Bazarragchaa, Ganbold Enebish, Jong Bae Seo
{"title":"Iris bungei Maxim. extract promotes brown adipocyte differentiation.","authors":"Jaegoo Yeon, Sung-Suk Suh, Ui-Joung Youn, Badamtsetseg Bazarragchaa, Ganbold Enebish, Jong Bae Seo","doi":"10.1007/s13258-025-01645-8","DOIUrl":"https://doi.org/10.1007/s13258-025-01645-8","url":null,"abstract":"<p><p>BACKGROUND : Iris bungei Maxim., a plant native to the desert grasslands of the Inner Mongolian Plateau and traditionally used in Mongolian medicine, has been shown to influence adipocyte differentiation in white adipose tissue. However, its effects on brown adipocyte differentiation have not been previously explored.</p><p><strong>Objective: </strong>This study aimed to investigate the effects of Iris bungei Maxim. (IB) extract on brown adipocyte differentiation, focusing on lipid accumulation, gene expression, mitochondrial biogenesis, and functionality.</p><p><strong>Methods: </strong>Immortalized murine brown preadipocytes were treated with IB extract during differentiation. Lipid accumulation, expression of brown adipocyte-specific genes, and mitochondrial biogenesis (MitoTracker Red staining, mitochondrial DNA content, oxidative phosphorylation protein levels) were evaluated. Additionally, mitochondrial respiration and isoproterenol-induced UCP-1 expression were analyzed to assess functional effects. Bioactive compounds in the IB extract were identified using feature-based molecular networking (FBMN) with the Global Natural Products Social Molecular Networking (GNPS).</p><p><strong>Results: </strong>The IB extract significantly enhanced brown adipocyte differentiation, as evidenced by increased lipid accumulation and upregulation of brown adipocyte-specific genes, such as UCP-1, PGC-1α, and PRDM16. Moreover, mitochondrial biogenesis was notably elevated, as indicated by enhanced MitoTracker Red staining, increased mitochondrial DNA content, and upregulated oxidative phosphorylation protein expression. The extract also improved mitochondrial respiration, suggesting enhanced mitochondrial functionality. Furthermore, the IB extract amplified isoproterenol-induced UCP-1 expression, indicating its potential role in thermogenesis regulation. Additionally, FBMN-GNPS analysis identified the chemical constituents in the IB extract by mass replication in the spectral matching to those in online databanks.</p><p><strong>Conclusion: </strong>These findings suggest that the methanol extract of IB could be a promising agent for promoting brown adipocyte differentiation and enhancing mitochondrial activity, with potential applications in managing obesity and metabolic disorders.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997894","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}
Genes & genomicsPub Date : 2025-04-22DOI: 10.1007/s13258-025-01644-9
Anh Huynh Luu, Trifan Budi, Worapong Singchat, Chien Phuoc Tran Nguyen, Thitipong Panthum, Nivit Tanglertpaibul, Thanyapat Thong, Kanithaporn Vangnai, Aingorn Chaiyes, Chotika Yokthongwattana, Chomdao Sinthuvanich, Kyudong Han, Narongrit Muangmai, Darren K Griffin, Michael N Romanov, Prateep Duengkae, Ngu Nguyen Trong, Kornsorn Srikulnath
{"title":"Comparison of unique Dong Tao chickens from Vietnam and Thailand: genetic background and differences for resource management.","authors":"Anh Huynh Luu, Trifan Budi, Worapong Singchat, Chien Phuoc Tran Nguyen, Thitipong Panthum, Nivit Tanglertpaibul, Thanyapat Thong, Kanithaporn Vangnai, Aingorn Chaiyes, Chotika Yokthongwattana, Chomdao Sinthuvanich, Kyudong Han, Narongrit Muangmai, Darren K Griffin, Michael N Romanov, Prateep Duengkae, Ngu Nguyen Trong, Kornsorn Srikulnath","doi":"10.1007/s13258-025-01644-9","DOIUrl":"https://doi.org/10.1007/s13258-025-01644-9","url":null,"abstract":"<p><strong>Background: </strong>Rare Dong Tao (DT) chickens are a unique and highly productive poultry breed introduced from Vietnam to Thailand ~ 30 years ago. It has a very peculiar appearance, including enormously enlarged feet with reddish scales, and considered local and culturally significant to both countries. Their adaptability and distinct genetic traits have attracted global interest, underscoring their potential for breeding programs and a need for their thorough genetic makeup assessment.</p><p><strong>Objective: </strong>To assess the genetic diversity and differentiation within the Dong Tao chicken breed, comparing two populations introduced in Thailand with a native population in Vietnam.</p><p><strong>Methods: </strong>Three Dong Tao chicken populations from Thailand and Vietnam-along with 54 other indigenous, local chicken, and red junglefowl populations from Thailand, were analyzed using 28 microsatellite markers.</p><p><strong>Result: </strong>High genetic variability and low inbreeding levels were observed in these populations, indicating their effective management despite historical bottlenecks. Genetic similarities between DT-U and DT-HY and indigenous breeds, as well as the closer alignment of DT-L with red junglefowl, highlighted existing introgression and adaptation processes. Two markers, MCW0098 and MCW0216, showed a variation pattern due to potential impact of directional selection, possibly driven by environmental adaptation pressures. These findings emphasize the importance of DT chickens as genetic resources for breeding programs that focus on climate resilience and productivity enhancement.</p><p><strong>Conclusion: </strong>Dong Tao chickenshared genetic similarities with indigenous and local chicken breeds, and red junglefowl, with potential influence of directional selection driven by environmental adaptation pressures.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981475","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}
Genes & genomicsPub Date : 2025-04-21DOI: 10.1007/s13258-025-01643-w
Ah Jin Lee, Sumaira Kanwal, Manisha Awasthi, Byung-Ok Choi, Ki Wha Chung
{"title":"De novo somatic mosaicisms of INF2 and TRPV4 in patients with Charcot-Marie-Tooth disease.","authors":"Ah Jin Lee, Sumaira Kanwal, Manisha Awasthi, Byung-Ok Choi, Ki Wha Chung","doi":"10.1007/s13258-025-01643-w","DOIUrl":"https://doi.org/10.1007/s13258-025-01643-w","url":null,"abstract":"<p><strong>Background: </strong>Somatic mosaicism is caused by a postzygotic de novo mutation. It is a very rare genetic event, and mosaic cases have been reported only very limitedly among Korean patients with peripheral neuropathies, including Charcot-Marie-Tooth disease (CMT) so far.</p><p><strong>Objective: </strong>This study was performed to identify and characterize somatic mosaicism in Korean families with CMT.</p><p><strong>Methods: </strong>Genetic causes were identified by whole exome sequencing (WES) and a subsequent filtering process of the variants. The level of mosaicism for the de novo somatic mutations was determined by counting altered sequences from approximately 100 colonies/mutation and the ratio of altered sequences per total reads at the mutation site using the WES data.</p><p><strong>Results: </strong>We observed two cases of somatic mosaicism in different families with CMT: p.Cys104Tyr in INF2 (male with CMT1) and p.Ser729Arg in TRPV4 (female with CMT2). The approximate levels of mosaicism were determined to be 24% and 30% in the blood, respectively. A man with the INF2 mutation showed very mild symptoms, while a woman with the TRPV4 mutation showed severe clinical phenotypes. The INF2 mutation is specifically considered a case of gonadal mosaicism. In addition, we confirmed that the p.Cys104Tyr in INF2 is associated with the CMT1 phenotype without focal segmental glomerulosclerosis (FSGS).</p><p><strong>Conclusion: </strong>This study may be the first or second report for the INF2 and TRPV4 mosaicism. The degrees of the phenotypic severity for the mosaic mutations probably depend on the mutation sites and the levels of mosaicism in the affected tissues. This study suggests that somatic mosaicism may contribute to inter- or intra-familial phenotypic heterogeneity.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997365","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}
Genes & genomicsPub Date : 2025-04-17DOI: 10.1007/s13258-025-01642-x
Min Yeong Lee, Nicole Bon Campomayor, Hee Jin Kim, Mikyung Kim
{"title":"Hippocampal MCT4 as a key regulator in excessive exercise-induced cognitive impairment: involvement of neuroinflammation.","authors":"Min Yeong Lee, Nicole Bon Campomayor, Hee Jin Kim, Mikyung Kim","doi":"10.1007/s13258-025-01642-x","DOIUrl":"https://doi.org/10.1007/s13258-025-01642-x","url":null,"abstract":"<p><strong>Background: </strong>As human life expectancy increases, maintaining a healthy lifestyle has become crucial. However, excessive exercise (EE) can lead to negative consequences such as muscle damage and exercise addiction. Recently, numerous reports have indicated that EE negatively impacts cognitive performance, although the exact mechanism remains unclear.</p><p><strong>Objective: </strong>This study aimed to investigate the specific mechanisms underlying cognitive alterations induced by EE.</p><p><strong>Methods: </strong>We conducted the Y-maze, Barnes maze, and Novel Object Recognition Test to assess both short-term and long-term memory, as well as object recognition ability. We then validated our findings using qRT-PCR to elucidate the underlying mechanisms. Additionally, Diclofenac (Dic), an anti-inflammatory drug, was administered to evaluate its effects on cognitive function and the results of the molecular experiments.</p><p><strong>Results: </strong>EE-induced mice exhibited cognitive impairments, along with elevated expression of inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL) -6, and IL-1β, and downregulated monocarboxylate transporters (MCTs) like MCT4. However, animals pre-treated with Dic regained cognitive function, alongside restored levels of IL-6, IL-1β, and MCT4.</p><p><strong>Conclusion: </strong>MCT4 plays may play a crucial role in EE-induced cognitive impairments.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981528","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}