Genes & Diseases最新文献_第9页

circFKBP8(5S,6)-encoded protein promotes stress susceptibility in mice by down-regulating dopamine D3 receptor expression and its downstream AMPK/mTOR/ULK1 autophagy signaling circFKBP8（5S,6）编码蛋白通过下调多巴胺D3受体表达及其下游AMPK/mTOR/ULK1自噬信号通路，促进小鼠的应激易感性

IF 9.4 2区医学

Genes & Diseases Pub Date : 2026-03-01 Epub Date: 2025-06-18 DOI: 10.1016/j.gendis.2025.101718

Dandan Xu , Zihan Huang , Gaojia Zhang , Jiao Jiao , Yujia Cao , Mengyu Liu , Yan Kong , Zhijun Zhang

{"title":"circFKBP8(5S,6)-encoded protein promotes stress susceptibility in mice by down-regulating dopamine D3 receptor expression and its downstream AMPK/mTOR/ULK1 autophagy signaling","authors":"Dandan Xu , Zihan Huang , Gaojia Zhang , Jiao Jiao , Yujia Cao , Mengyu Liu , Yan Kong , Zhijun Zhang","doi":"10.1016/j.gendis.2025.101718","DOIUrl":"10.1016/j.gendis.2025.101718","url":null,"abstract":"<div><div>Major depressive disorder (MDD) is a serious mental disorder, yet the mechanism by which circular RNAs (circRNAs) are involved in the pathogenesis of MDD by encoding proteins is unknown. Our previous study has shown that circFKBP8(5S,6) relies on its encoded protein, namely cFKBP8, to promote susceptibility to chronic unpredictable mild stress (CUMS) in mice, but the precise molecular mechanisms are unknown. Here we found that overexpression of circFKBP8(5S,6) or cFKBP8 in neurons of the prelimbic cortex (PrL) of CUMS mice down-regulated the expression levels of DRD3 and its downstream AMPK/ULK1 (Ser555) and AMPK/mTOR/ULK1 (Ser757) pathways, which resulted in down-regulation of neuronal autophagy levels. Interestingly, both the activation and overexpression of DRD3 ameliorated the exacerbation of depressive-like behaviors induced by circFKBP8(5S,6) or cFKBP8, activated both the AMPK/ULK1 (Ser555) pathway and the AMPK/mTOR/ULK1 (Ser757) pathway, and up-regulated neuronal autophagy levels. In conclusion, circFKBP8(5S,6) or cFKBP8 promotes susceptibility to CUMS in mice, at least in part, by down-regulating DRD3 expression and its downstream AMPK/mTOR/ULK1 signaling pathway-mediated neuronal autophagy.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101718"},"PeriodicalIF":9.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

cGAS knockout inhibited endotoxin-induced uveitis in mice cGAS敲除抑制内毒素诱导的小鼠葡萄膜炎

IF 9.4 2区医学

Genes & Diseases Pub Date : 2026-03-01 Epub Date: 2025-07-29 DOI: 10.1016/j.gendis.2025.101786

Yue Guo , Ruiping Gu , Jiaojiao Wei , Chunhui Jiang

{"title":"cGAS knockout inhibited endotoxin-induced uveitis in mice","authors":"Yue Guo , Ruiping Gu , Jiaojiao Wei , Chunhui Jiang","doi":"10.1016/j.gendis.2025.101786","DOIUrl":"10.1016/j.gendis.2025.101786","url":null,"abstract":"<div><div>Our research focused on the impact of the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) pathway on retinal inflammation and employed an endotoxin-induced uveitis (EIU) model. EIU was provoked in mice through the intravitreal administration of lipopolysaccharide. Transcriptome analysis was performed via bulk RNA sequencing. Cytosolic mitochondrial DNA levels in the retina were quantified via PCR. Western blotting was used to assess the activation of cGAS‒STING signaling at specified times after intravitreal lipopolysaccharide injection. To understand the influence of the cGAS‒STING pathway on inflammatory retinal disorders, Cgas knockout mice were developed. Fundus imaging and fluorescein angiography were conducted to observe vitreous inflammation. Microstructural analysis of the eyes was performed, and histopathological scoring was performed. Retinal leukocytosis assays were used to evaluate retinal inflammation. Analysis of these differentially expressed mRNAs revealed activation of the cGAS‒STING signaling pathway, which was confirmed by western blotting analysis of these proteins. Using Cgas knockout mice, we observed significant inhibition of endotoxin-induced intraocular inflammation, including reduced vitreous inflammation, reduced retinal vascular leakage, decreased leukocyte adhesion, inhibited infiltration and activation of macrophages in the retina, and inhibited microglial activation. These findings suggest that cGAS might be a potential novel therapeutic target for uveitis.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101786"},"PeriodicalIF":9.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chondrogenic potential of mesenchymal progenitors from somatic and cartilage-derived iPSCs is predicted by their transcriptomic signatures 体细胞和软骨源性多能干细胞间充质祖细胞的成软骨潜能是通过其转录组特征来预测的

IF 9.4 2区医学

Genes & Diseases Pub Date : 2026-03-01 Epub Date: 2025-06-22 DOI: 10.1016/j.gendis.2025.101730

Nazir M. Khan , Thanh N. Doan , Jarred M. Kaiser , Hicham Drissi

{"title":"Chondrogenic potential of mesenchymal progenitors from somatic and cartilage-derived iPSCs is predicted by their transcriptomic signatures","authors":"Nazir M. Khan , Thanh N. Doan , Jarred M. Kaiser , Hicham Drissi","doi":"10.1016/j.gendis.2025.101730","DOIUrl":"10.1016/j.gendis.2025.101730","url":null,"abstract":"<div><div>Mesenchymal stem cells (MSCs) are widely used in regenerative therapy but face limitations like low abundance, replicative senescence, donor variability, and restricted plasticity. Induced pluripotent stem cell-derived MSCs (iMSCs) may provide an alternative, but their similarities or intrinsic differences with adult MSCs remain unknown. This study compares the chondrogenic potential of iMSCs derived from chondrocyte-specific induced pluripotent stem cells, with bone marrow-derived MSCs, adipose-derived stem cells, and dedifferentiated chondrocytes. Chondrogenic differentiation was performed in high-density pellet cultures with short-term or long-term TGFβ3 treatment. Chondrogenic gene arrays, gene regulatory networks, and gene ontology analysis revealed divergent signaling pathways. Bulk RNA sequencing was performed to characterize the transcriptomic profiles of each MSC. Results showed that iMSCs produced cartilage with hyaline-like features and minimal hypertrophy, distinguishing them phenotypically from adult MSCs. Gene regulatory network analyses identified EGF, FGFR, FLT1, and HIFA as iMSC hub genes for chondrogenic differentiation. Molecular signaling analysis unveiled that TGFβ3 induced SMAD2/3, not SMAD1/5, suppressing hypertrophy in iMSC chondrogenesis. RNA sequencing highlighted cell-specific differences, functional heterogeneity, and divergent cell signaling profiles between iMSCs and adult MSCs. Using integrated transcriptome and proteome analyses, we identified and validated eight novel non-classical CD markers that may help further characterize MSCs and potentially discriminate iMSCs from other cell types. This study further advanced our understanding of MSC behaviors, emphasizing the importance of origin-specific considerations and refining the molecular description of iMSCs as an unlimited source of chondroprogenitors for cartilage regeneration.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101730"},"PeriodicalIF":9.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hypoxia-mediated CRIP2 activation via NICD1 translocation regulates glycolysis and cell death 通过NICD1易位介导的缺氧介导的CRIP2激活调节糖酵解和细胞死亡

IF 9.4 2区医学

Genes & Diseases Pub Date : 2026-03-01 Epub Date: 2025-06-02 DOI: 10.1016/j.gendis.2025.101704

Sunyoung Park , Sang-Ha Baik , Leon F. Palomera , Eunae Kim , Hark Kyun Kim , Jun-Sik Kim , Jong Ho Kim , Chanhee Kim , Thiruma V. Arumugam , Dong-Gyu Jo

引用次数: 0

Nuclear and cytoplasmic USP30-AS1 coordinately regulate breast cancer progression through HnRNPF/p21 and EZH2/c-Myc/p21 axes 细胞核和细胞质USP30-AS1通过HnRNPF/p21和EZH2/c-Myc/p21轴协调调节乳腺癌的进展

IF 9.4 2区医学

Genes & Diseases Pub Date : 2026-03-01 Epub Date: 2025-05-10 DOI: 10.1016/j.gendis.2025.101684

Yapei Jiang , Weijie Liao , Qilei Xin , Ruonan Wang , Guanglan Lin , Jia Li , Zijian Yang , Shiyue Yang , Haowei Zhang , Xiaolin Li , Qian Peng , Yaou Zhang , Weidong Xie , Naihan Xu

{"title":"Nuclear and cytoplasmic USP30-AS1 coordinately regulate breast cancer progression through HnRNPF/p21 and EZH2/c-Myc/p21 axes","authors":"Yapei Jiang , Weijie Liao , Qilei Xin , Ruonan Wang , Guanglan Lin , Jia Li , Zijian Yang , Shiyue Yang , Haowei Zhang , Xiaolin Li , Qian Peng , Yaou Zhang , Weidong Xie , Naihan Xu","doi":"10.1016/j.gendis.2025.101684","DOIUrl":"10.1016/j.gendis.2025.101684","url":null,"abstract":"<div><div>Emerging evidence suggests that aberrant expression of long non-coding RNAs (lncRNAs) is strongly associated with the occurrence and progression of breast cancer. Herein, we identified ubiquitin specific peptidase 30 antisense RNA 1 (USP30-AS1) as a markedly upregulated lncRNA in breast cancer tissues, and the transcription factor SPI1 functions upstream to regulate the expression of USP30-AS1. Gene set enrichment analysis suggests that USP30-AS1 may regulate cell proliferation. Knockdown of USP30-AS1 suppresses breast cancer cell proliferation and tumor growth by up-regulating CDKN1A/p21. Mechanistically, USP30-AS1 exhibits dual localization within breast cancer cells. In the cytoplasm, it interacts with HnRNPF, disrupting its binding to the p21 3′UTR, which destabilizes p21 mRNA and ultimately reduces p21 expression. In the nucleus, USP30-AS1 suppresses p21 transcription by enhancing the activity of c-Myc, a known transcriptional repressor of p21. USP30-AS1 binds to enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, and prevents EZH2 from binding to the c-Myc promoter. This promotes epigenetic up-regulation of c-Myc by reducing H3K27 trimethylation. Together, these findings demonstrate the critical role of USP30-AS1 in breast cancer progression through HnRNPF/p21 and EZH2/c-Myc/p21 axes, highlighting its potential as a therapeutic target for breast cancer treatment.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101684"},"PeriodicalIF":9.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145786894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Electrophysiological and histological study reveals hidden subclinical haploinsufficiency of Otof 电生理和组织学研究发现隐匿的亚临床单倍体功能不全

IF 9.4 2区医学

Genes & Diseases Pub Date : 2026-03-01 Epub Date: 2025-03-13 DOI: 10.1016/j.gendis.2025.101600

Kyu-Hee Han , Yehree Kim , Kwon Woo Kang , Ju Ang Kim , Yonghee Oh , Min Young Kim , Jin Hee Han , Bong Jik Kim , Eunyoung Yi , Byung Yoon Choi

引用次数: 0

Selenoprotein GPX3 regulates NADPH oxidase expression by inhibiting the MAPK signaling pathway and thereby attenuating the inflammatory response in renal ischemia-reperfusion injury 硒蛋白GPX3通过抑制MAPK信号通路调节NADPH氧化酶的表达，从而减轻肾缺血再灌注损伤中的炎症反应

IF 9.4 2区医学

Genes & Diseases Pub Date : 2026-03-01 Epub Date: 2025-04-11 DOI: 10.1016/j.gendis.2025.101640

Jun Pei , Jie Zhang , Chengjun Yu , Jin Luo , Sheng Wen , Yi Hua , Guanghui Wei

{"title":"Selenoprotein GPX3 regulates NADPH oxidase expression by inhibiting the MAPK signaling pathway and thereby attenuating the inflammatory response in renal ischemia-reperfusion injury","authors":"Jun Pei , Jie Zhang , Chengjun Yu , Jin Luo , Sheng Wen , Yi Hua , Guanghui Wei","doi":"10.1016/j.gendis.2025.101640","DOIUrl":"10.1016/j.gendis.2025.101640","url":null,"abstract":"<div><div>Renal ischemia-reperfusion injury (IRI) is one of the major causes of acute kidney injury, and the inflammatory response is considered a key factor. The selenoprotein GPX3, a member of the glutathione peroxidase family, has gradually attracted attention for its anti-inflammatory properties. However, the relationship between GPX3 and the inflammatory response during renal IRI remains unclear. The present study aims to investigate the role of GPX3 on the inflammatory response during renal IRI and related mechanisms. We utilized classic rat models of kidney IRI and cellular hypoxia reoxygenation model. After overexpressing GPX3 via lentiviruses and adeno-associated viruses, we observed a significant reduction in the expression levels of inflammatory factors in renal tissues, along with an increase in the expression of anti-inflammatory factor IL-10, resulting in noticeable alleviation of renal IRI. Meanwhile, we found that GPX3 alleviated the inflammatory response, probably by inhibiting the MAPK signaling pathway and reducing the expression of NAPDH oxidase. To further validate the mechanism by which GPX3 alleviated the inflammatory response, we used the MAPK signaling pathway agonist anisomycin for intervention. The results showed that anisomycin intervention significantly reversed the inhibitory effect of GPX3 on the MAPK signaling pathway, in which the expression level of NADPH oxidase was significantly increased, the secretion of inflammatory factors was increased, and the degree of renal tissue damage was significantly increased. These findings suggest that selenoprotein GPX3 alleviates inflammation during renal IRI by inhibiting the MAPK signaling pathway and reducing NADPH oxidase expression.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101640"},"PeriodicalIF":9.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145733011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hippocampus-targeted BDNF gene therapy to rescue cognitive impairments of Alzheimer's disease in multiple mouse models 海马靶向BDNF基因治疗在多种小鼠模型中拯救阿尔茨海默病的认知障碍

IF 9.4 2区医学

Genes & Diseases Pub Date : 2026-03-01 Epub Date: 2025-04-22 DOI: 10.1016/j.gendis.2025.101649

Siqi Tang , Wenshu Luo , Shihao Wu , Meng Yuan , Jiashuo Wen , Guoshen Zhong , Leshan Shen , Wei Jiang , Cheng Cheng , Xia Wu , Xiao Xiao

{"title":"Hippocampus-targeted BDNF gene therapy to rescue cognitive impairments of Alzheimer's disease in multiple mouse models","authors":"Siqi Tang , Wenshu Luo , Shihao Wu , Meng Yuan , Jiashuo Wen , Guoshen Zhong , Leshan Shen , Wei Jiang , Cheng Cheng , Xia Wu , Xiao Xiao","doi":"10.1016/j.gendis.2025.101649","DOIUrl":"10.1016/j.gendis.2025.101649","url":null,"abstract":"<div><div>Brain-derived neurotrophic factor (BDNF) can protect neurons from apoptosis and maintain normal synaptic structures, indicating a significant potential for Alzheimer's disease (AD) treatment. However, the method of <em>in vivo</em> BDNF delivery requires further optimization, and the therapeutic efficacy of BDNF in AD animal models needs to be further evaluated. Here, we demonstrated that a newly engineered adeno-associated virus (AAV) serotype termed AAVT42 showed better tropism for neurons than AAV9 in the central nervous system (CNS). We analyzed the therapeutic potentials of AAVT42-delivered BDNF in three AD mouse models: amyloid precursor protein/presenilin-1 (APP/PS1), rTg4510, and 3 × Tg. Long-term BDNF expression in the hippocampus mitigated neuronal degeneration or loss in these AD mice, and alleviated their cognitive impairment, with no discernible effect on amyloid-β deposition or tau phosphorylation. Furthermore, transcriptomic analysis in 3 × Tg mice revealed that BDNF orchestrated the up-regulation of genes associated with neuronal structural organization and synaptic transmissions, such as Neuropeptide Y (<em>Npy</em>), Corticotropin-releasing hormone (<em>Crh</em>), Tachykinin precursor 1 (<em>Tac1</em>), and the down-regulation of Bone morphogenetic proteins (<em>Bmps</em>). Our study highlighted the efficacy of AAVT42 in gene delivery to CNS and validated the therapeutic benefits of BDNF in treating AD, which will be useful for future translational research on AD treatment using an AAV delivery system.</div></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"13 2","pages":"Article 101649"},"PeriodicalIF":9.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A cohort study on the A8G6 neutralizing antibody intranasal spray for preventing SARS-CoV-2 infection in healthcare workers A8G6中和抗体鼻喷预防医护人员SARS-CoV-2感染的队列研究

IF 9.4 2区医学

Genes & Diseases Pub Date : 2026-03-01 Epub Date: 2025-04-01 DOI: 10.1016/j.gendis.2025.101617

Shu Zhang , Zhigang Chu , Siyuan Yang , Qiuling Shi , Qinghua Zhao , Dawei He , Hongmei Xu , Dan Zhang , Zhu Yang , Ailong Huang

引用次数: 0

CTHRC1 promotes the progression of clear cell renal cell carcinoma via the PI3K/AKT/GSK3β signaling pathway CTHRC1通过PI3K/AKT/GSK3β信号通路促进透明细胞肾细胞癌的进展

IF 9.4 2区医学

Genes & Diseases Pub Date : 2026-03-01 Epub Date: 2025-05-13 DOI: 10.1016/j.gendis.2025.101688

Wei Xie , Zhouyong Fu , Thomas Skutella , Qing Jiang , Ronggui Zhang , Yuanfeng Zhang

引用次数: 0