Biochemical Genetics最新文献

{"title":"The Sonic Hedgehog Pathway is Activated in Cushing's Disease with USP8 Mutations.","authors":"Shan Huang, Yihua Xu, Xiang Zhou, Jiahuan Lu, Xiaoyun Cao","doi":"10.1007/s10528-026-11383-5","DOIUrl":"https://doi.org/10.1007/s10528-026-11383-5","url":null,"abstract":"<p><p>Cushing's disease (CD) is a neuroendocrine disorder characterized by excessive adrenocorticotropic hormone (ACTH) secretion from pituitary adenomas, closely associated with ubiquitin-specific protease 8 (USP8) mutations. This study aimed to investigate whether USP8 mutations activate the Sonic Hedgehog (SHH) pathway by deubiquitinating its key component Smoothened (SMO), thereby promoting ACTH production in CD. mRNA expression profiles of USP8-mutated and wild-type CD patients (GEO dataset GSE132982) were analyzed for differentially expressed genes, followed by GO and KEGG pathway enrichment. USP8 mutant/wild-type plasmids were transfected into HeLa cells. Co-immunoprecipitation and Western blot evaluated USP8-SMO interaction and SMO ubiquitination. RT-qPCR, luciferase reporter assays, and nuclear translocation analysis assessed SHH pathway gene expression and GLI2 transcriptional activity. Immunohistochemistry detected SMO/SHH proteins in 9 USP8-mutated and 9 wild-type pituitary adenomas. Primary tumor cells were treated with the SMO inhibitor cyclopamine, and POMC mRNA/ACTH secretion were measured by RT-qPCR/ELISA. Chromatin immunoprecipitation (ChIP) verified GLI2 binding to the POMC promoter. SHH pathway genes were significantly dysregulated in USP8-mutated CD. Mutant USP8 enhanced SMO interaction, reduced SMO ubiquitination, and upregulated SHH target genes, promoting GLI2 nuclear translocation/activity. SMO-positive cells were more frequent in mutated tumors, with unchanged SHH expression. Cyclopamine suppressed POMC/ACTH specifically in mutated cells, and ChIP confirmed GLI2-POMC promoter binding. USP8 mutations activate the SHH pathway via SMO deubiquitination, driving GLI2-mediated POMC transcription and excessive ACTH secretion in CD. Targeting the SHH pathway may offer a novel therapeutic strategy for USP8-mutated Cushing's disease.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831896","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":"Saikosaponin D Attenuates Postherpetic Neuralgia and Reduces Inflammation by Regulating Gut Microbiota in a Rodent Model.","authors":"Shaokang Cai, Chunhua Sun, Qun Wu, Xianbao Yao","doi":"10.1007/s10528-026-11387-1","DOIUrl":"https://doi.org/10.1007/s10528-026-11387-1","url":null,"abstract":"<p><p>Saikosaponin D (SSD) is a triterpenoid saponin derived from Bupleuri Radix and has therapeutic potential for the treatment of neuropathic pain. This study investigates the roles and underlying mechanisms of SSD in cellular and mouse models of resiniferatoxin (RTX)-induced postherpetic neuralgia (PHN). C57BL/6 mice were randomly assigned into four groups: control, RTX, RTX + vehicle, and RTX + SSD. Mechanical and thermal sensitivity were assessed to evaluate pain behaviors. Gut microbiota was depleted using antibiotic treatment, and fecal microbiota transplantation was used to restore gut flora in RTX-treated mice that received either vehicle or SSD. In vitro, RTX-stimulated human neuroblastoma SH-SY5Y cells were used as a cellular model of PHN. TRPA1 expression levels in mouse dorsal root ganglion and SH-SY5Y cells were measured by RT-qPCR and immunofluorescence staining. The levels of proinflammatory cytokines were evaluated in serum samples and SH-SY5Y cells via RT-qPCR or ELISA. Western blot was performed to assess protein levels of genes involved in TLR4/NF-κB and JAK/STAT3 pathways. Results showed that SSD attenuated RTX-induced neuralgia in mice. In both in vitro and in vivo models, SSD significantly reduced TRPA1 expression and proinflammatory cytokine levels. The protective effects of SSD against neuralgia were abolished following antibiotic-mediated gut microbiota depletion in mice. Fecal microbiota transplantation from SSD-treated mice alleviated RTX-induced neuralgia and inflammation in PHN model mice. Moreover, SSD reduced TLR4 protein level and reduced phosphorylation ratios of NF-κB p65, STAT3, and JAK in the lumbar spinal cord of RTX-treated mice and in SH-SY5Y cells. In conclusion, SSD alleviates RTX-induced PHN and inflammation in mice by modulating gut microbiota via the TLR4/NF-κB and JAK/STAT3 pathways.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831929","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":"Identification of Key Genes Related to SUMOylation and Potassium Channels and Their Mechanism of Influence on Pulmonary Arterial Hypertension.","authors":"Lingyun Gao, Wei Huang, Qianqian Wang, Sen Lei","doi":"10.1007/s10528-026-11388-0","DOIUrl":"https://doi.org/10.1007/s10528-026-11388-0","url":null,"abstract":"","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759005","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":"Evolutionary and Structural Insights into Proline Metabolism Genes Associated with Salt Resilience in Mango.","authors":"Laxmi Rastogi, Anju Bajpai, Sumit K Soni, M Muthukumar","doi":"10.1007/s10528-026-11375-5","DOIUrl":"https://doi.org/10.1007/s10528-026-11375-5","url":null,"abstract":"","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758933","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":"The Complete Mitochondrial Genome of a Newly Recorded Chinese Species of Diglyphus sabulosus (Hymenoptera: Eulophidae) and Insights into Its Phylogenetic Position.","authors":"Lu-Chao Fang, Zhi-Qiang Ge, Ou-Yan Xi, Ze-Lu Mu, Hong-Ying Hu","doi":"10.1007/s10528-026-11382-6","DOIUrl":"https://doi.org/10.1007/s10528-026-11382-6","url":null,"abstract":"<p><p>Diglyphus Walker, 1844 is an economically important genus which many species acting as biocontrol agents against agromyzid leafminer pests, but there is a lack of mitogenomic data on the evolutionary relationships within this genus, hindering a comprehensive understanding of its evolutionary history. We used traditional morphological methods to identify species, and present the first complete mitochondrial genome sequence and characterization of features of Diglyphus sabulosus and further infer its phylogenetic position based on the amino acid sequences of 13 protein-coding genes (PCGs). The complete mitochondrial genome of D. sabulosus is 15,690 bp in length, including 13 PCGs, 22 transfer RNA genes, 2 ribosomal RNA genes and a control region. The AT content of the whole genome sequence was 81.0%, indicating a significant AT bias. All protein-coding genes have the typical ATN as the start codon and TAA as the stop codon. Phylogenetic analysis inferred from the amino acid sequences of 13 PCGs revealed that all species within the family Eulophidae constituted a monophyletic clade, supporting the monophyly of this family. D. sabulosus and D. poppoea form a well-supported sister group, representing the species with the closest phylogenetic relationship within the analyzed taxa. In this study, the mitogenome structure was analyzed and the taxonomic status of D. sabulosus was clarified, thus providing a theoretical basis for understanding the phylogenetic relationships of Diglyphus.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759036","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":"CD27 Neutralization Attenuates Rheumatoid Arthritis by Suppressing.","authors":"Anghan Lu, Luqiao Pu, Yadan Tian, Jiaxin Song, Dingxia Luo, Jingjin Wu","doi":"10.1007/s10528-026-11385-3","DOIUrl":"https://doi.org/10.1007/s10528-026-11385-3","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and destruction. Identifying novel therapeutic targets is crucial for improving RA treatment. This study aimed to identify immune-related biomarkers in RA and investigate the potential of CD27 as a therapeutic target. We employed bioinformatics analysis of gene expression data from RA patients and healthy controls (GSE55457), followed by machine learning approaches (LASSO regression and Boruta algorithm) to identify potential biomarkers. Findings were validated in an independent dataset (GSE55235). The therapeutic potential of CD27 neutralization was evaluated in a collagen-induced arthritis (CIA) mouse model. Mechanisms were explored through quantitative real-time PCR, Western blot analysis, ELISA, and flow cytometry to assess T cell subsets, cytokine profiles, and signaling pathways. Bioinformatics analysis identified 714 differentially expressed genes, and machine learning analyses identified CD27, CD24, TNFRSF4, and PDCD1LG2 as potential RA biomarkers, all demonstrating strong diagnostic performance. CD27 showed significant positive correlations with T lymphocyte infiltration. In the CIA model, CD27 neutralization significantly reduced arthritis severity scores. This therapeutic effect was associated with suppression of Th1 responses, evidenced by significantly decreased serum levels of Th1 cytokines (IFN-γ, IL-2, TNF-α) and reduced CD4 + IFN-γ + cell populations, while Th2-related cytokines (IL-4, IL-5) remained largely unaffected. Mechanistically, CD27 neutralization attenuated phosphorylation of AKT and NF-κB p65 in vivo, while p38 MAPK remained unchanged. In vitro, recombinant CD27 protein stimulation of naive CD4 + T cells promoted Th1-biased differentiation, increasing CD4 + IFN-γ + cells and enhancing the phosphorylation of NF-κB p65 and AKT. Our study identifies CD27 as a potential therapeutic target in RA. CD27 neutralization attenuates arthritis severity by suppressing Th1 responses, possibly through modulation of AKT and NF-κB signaling pathways. These findings provide new insights into RA pathogenesis and suggest CD27 as a promising target for RA treatment.</p>","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758917","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":"Network Pharmacology and Molecular Docking Reveal Myricanone's Role in Alleviating Ischemic Cerebral Infarction via Targeting MAPK14.","authors":"Bingbing Zhao, Jie Zhang","doi":"10.1007/s10528-026-11379-1","DOIUrl":"https://doi.org/10.1007/s10528-026-11379-1","url":null,"abstract":"","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758970","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":"Identification of Autophagy-related Genes of the Osteoarthritis Using Machine Learning Algorithm.","authors":"Zongye Zhang, Hongbo Wang, Xingbo Cheng, Zhichang Zhang, Zhenxing Hou, Zhendong Liu, Yanzheng Gao","doi":"10.1007/s10528-026-11358-6","DOIUrl":"https://doi.org/10.1007/s10528-026-11358-6","url":null,"abstract":"","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758865","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":"Cancer-Associated Fibroblasts-Derived Exosomal HOXC8 Promotes Glycolysis and Malignant Metastasis of Lung Cancer Cells via CDKN3.","authors":"Fan Wu, Meng Qiao","doi":"10.1007/s10528-026-11372-8","DOIUrl":"https://doi.org/10.1007/s10528-026-11372-8","url":null,"abstract":"","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715441","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 Method for Imputing scRNA-seq Data Based on Mobile Graph Convolutional Generative Adversarial Networks.","authors":"Qiaosheng Zhang, Mengjie Hu, Zhaoman Zhong, Jie Liu, Wanqin Li, Junjie Xu, Zhengyu Sun","doi":"10.1007/s10528-026-11380-8","DOIUrl":"https://doi.org/10.1007/s10528-026-11380-8","url":null,"abstract":"","PeriodicalId":482,"journal":{"name":"Biochemical Genetics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715493","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}