Genes & Diseases最新文献_第10页

The 21-base pair deletion mutant Calpain3 does not inhibit wild-type Calpain3 activity 21 碱基对缺失突变体 Calpain3 不会抑制野生型 Calpain3 的活性

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-04-08 DOI: 10.1016/j.gendis.2024.101301

引用次数: 0

TULP4 degrades RYBP to enhance DNA damage repair and chemosensitivity of pancreatic ductal adenocarcinoma TULP4 降解 RYBP，增强胰腺导管腺癌的 DNA 损伤修复能力和化疗敏感性

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-04-05 DOI: 10.1016/j.gendis.2024.101288

Jingyao Dai , Su Liu , Yangyang Xie , Yixuan Wang , Xiyun Bian , Tian Yu , Tiantian Li , Linchuang Jia , Zhigang Zhao , Zhiqiang Liu , Xiaozhi Liu

引用次数: 0

TFR2 gene alterations in idiopathic erythrocytosis reinforce a possible relation between erythrocytosis and iron metabolism 特发性红细胞增多症中的 TFR2 基因改变加强了红细胞增多症与铁代谢之间的可能关系

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-04-05 DOI: 10.1016/j.gendis.2024.101291

引用次数: 0

MicroRNAs in adipose tissue fibrosis: Mechanisms and therapeutic potential 脂肪组织纤维化中的微RNA：机制和治疗潜力

IF 6.8 2区医学

Genes & Diseases Pub Date : 2024-04-05 DOI: 10.1016/j.gendis.2024.101287

Mei Tian, Yang Zhou, Yitong Guo, Qing Xia, Zehua Wang, Xinying Zheng, Jinze Shen, Junping Guo, Shiwei Duan, Lijun Wang

{"title":"MicroRNAs in adipose tissue fibrosis: Mechanisms and therapeutic potential","authors":"Mei Tian, Yang Zhou, Yitong Guo, Qing Xia, Zehua Wang, Xinying Zheng, Jinze Shen, Junping Guo, Shiwei Duan, Lijun Wang","doi":"10.1016/j.gendis.2024.101287","DOIUrl":"https://doi.org/10.1016/j.gendis.2024.101287","url":null,"abstract":"Adipose tissue fibrosis, characterized by abnormal extracellular matrix deposition within adipose tissue, signifies a crucial indicator of adipose tissue malfunction, potentially leading to organ tissue dysfunction. Various factors, including a high-fat diet, non-alcoholic fatty liver disease, and insulin resistance, coincide with adipose tissue fibrosis. MicroRNAs (miRNAs) represent a class of small non-coding RNAs with significant influence on tissue fibrosis through diverse signaling pathways. For instance, in response to a high-fat diet, miRNAs can modulate signaling pathways such as TGF-β/Smad, PI3K/AKT, and PPAR-γ to impact adipose tissue fibrosis. Furthermore, miRNAs play roles in inhibiting fibrosis in different contexts: suppressing corneal fibrosis via the TGF-β/Smad pathway, mitigating cardiac fibrosis through the VEGF signaling pathway, reducing wound fibrosis via regulation of the MAPK signaling pathway, and diminishing fibrosis post-fat transplantation via involvement in the PDGFR-β signaling pathway. Notably, the secretome released by miRNA-transfected adipose-derived stem cells facilitates targeted delivery of miRNAs to evade host immune rejection, enhancing their anti-fibrotic efficacy. Hence, this study endeavors to elucidate the role and mechanism of miRNAs in adipose tissue fibrosis and explore the mechanisms and advantages of the secretome released by miRNA-transfected adipose-derived stem cells in combating fibrotic diseases.","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"2016 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140582606","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

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-04-05 DOI: 10.1016/j.gendis.2024.101289

Xiaohong Wang , Yanli Wang , Tianlin Jiang , Jiwei Jiang , Linlin Wang , Shiyi Yang , Mengfan Sun , Yuan Zhang , Ziyan Jia , Wenyi Li , Qiwei Ren , Cuicui Zhang , Jianjian Liu , Yinwei Zhu , Min Zhao , Shirui Jiang , Huiying Zhang , Jinglong Chen , Jun Xu

引用次数: 0

Inhibiting HMGCR represses stemness and metastasis of hepatocellular carcinoma via Hedgehog signaling 抑制 HMGCR 可通过刺猬信号抑制肝细胞癌的干性和转移

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-04-03 DOI: 10.1016/j.gendis.2024.101285

Zhirong Zhang , Jiayao Yang , Rui Liu , Jing Ma , Kai Wang , Xiaojun Wang , Ni Tang

{"title":"Inhibiting HMGCR represses stemness and metastasis of hepatocellular carcinoma via Hedgehog signaling","authors":"Zhirong Zhang , Jiayao Yang , Rui Liu , Jing Ma , Kai Wang , Xiaojun Wang , Ni Tang","doi":"10.1016/j.gendis.2024.101285","DOIUrl":"10.1016/j.gendis.2024.101285","url":null,"abstract":"<div><p>Cancer stem cells (CSCs) play a crucial role in tumor initiation, recurrence, metastasis, and drug resistance. However, the current understanding of CSCs in hepatocellular carcinoma (HCC) remains incomplete. Through a comprehensive analysis of the database, it has been observed that 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), a critical enzyme involved in cholesterol synthesis, is up-regulated in HCC tissues and liver CSCs. Moreover, high expression of HMGCR is associated with a poor prognosis in patients with HCC. Functionally, HMGCR promotes the stemness and metastasis of HCC both <em>in vitro</em> and <em>in vivo</em>. By screening various signaling pathway inhibitors, we have determined that HMGCR regulates stemness and metastasis by activating the Hedgehog signaling in HCC. Mechanistically, HMGCR positively correlates with the expression of the Smoothened receptor and facilitates the nuclear translocation of the transcriptional activator GLI family zinc finger 1. Inhibition of the Hedgehog pathway can reverse the stimulatory effects of HMGCR on stemness and metastasis in HCC. Notably, simvastatin, an FDA-approved cholesterol-lowering drug, has been shown to inhibit stemness and metastasis of HCC by targeting HMGCR. Taken together, our findings suggest that HMGCR promotes the regeneration and metastasis of HCC through the activation of Hedgehog signaling, and simvastatin holds the potential for clinical suppression of HCC metastasis.</p></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"11 5","pages":"Article 101285"},"PeriodicalIF":6.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352304224000825/pdfft?md5=bab357bf267f1c3dc4a061c2d5eaa6ca&pid=1-s2.0-S2352304224000825-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140582511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effect of long-term administration of green tea catechins on aging-related cardiac diastolic dysfunction and decline of troponin I 长期服用绿茶儿茶素对衰老相关心脏舒张功能障碍和肌钙蛋白 I 下降的影响

IF 6.8 2区医学

Genes & Diseases Pub Date : 2024-04-03 DOI: 10.1016/j.gendis.2024.101284

Junjun Quan, Zhongli Jia, Lingjuan Liu, Jie Tian

{"title":"The effect of long-term administration of green tea catechins on aging-related cardiac diastolic dysfunction and decline of troponin I","authors":"Junjun Quan, Zhongli Jia, Lingjuan Liu, Jie Tian","doi":"10.1016/j.gendis.2024.101284","DOIUrl":"https://doi.org/10.1016/j.gendis.2024.101284","url":null,"abstract":"Aging is an independent risk factor for cardiovascular diseases. Cardiac diastolic dysfunction (CDD), ultimately leading to heart failure with preserved ejection fraction, is prevalent among older individuals. Although therapeutics have made great progress, preventive strategies remain unmet medical needs. Green tea catechins have been shown to be effective in improving aging-related cardiovascular and cerebral disorders in animal models and patients. However, little attention has been paid to whether long-term administration of epigallocatechin gallate (EGCG), the major bioactive ingredient of green tea catechins, could prevent the onset and progression of CDD. In this study, 12-month-old female mice were orally administered 50, 100, and 200 mg EGCG mixed with drinking water for 6 months. Aged mice (18 months old) exhibited the major features of heart failure with preserved ejection fraction, including CDD with preserved ejection fraction, cardiac fibrosis, increased cardiomyocyte apoptosis, and mitochondrial damages, as well as elevated A/B-type natriuretic peptide. Cardiac troponin I (cTnI) expression was also reduced. Long-term administration of 100 or 200 mg EGCG prevented aging-related CDD and exercise capacity decline, along with alleviating myocardial apoptosis and mitochondria damage. The transcription and protein expression of cTnI were increased, which might be achieved by inhibiting the expression and activity of histone deacetylase 1 and reducing its binding level near cTnI's promoter, thereby elevating acetylated histone 3 and acetylated lysine 9 on histone H3 in the aged mice. We provide a novel insight that long-term administration of EGCG is a potentially effective strategy in preventing aging-related CDD and cTnI expression decline.","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"46 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140582392","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

MDM2 inhibitors in cancer immunotherapy: Current status and perspective 癌症免疫疗法中的 MDM2 抑制剂：现状与展望

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-03-28 DOI: 10.1016/j.gendis.2024.101279

{"title":"MDM2 inhibitors in cancer immunotherapy: Current status and perspective","authors":"","doi":"10.1016/j.gendis.2024.101279","DOIUrl":"10.1016/j.gendis.2024.101279","url":null,"abstract":"<div><p>Murine double minute 2 (MDM2) plays an essential role in the cell cycle, apoptosis, DNA repair, and oncogene activation through p53-dependent and p53-independent signaling pathways. Several preclinical studies have shown that MDM2 is involved in tumor immune evasion. Therefore, MDM2-based regulation of tumor cell-intrinsic immunoregulation and the immune microenvironment has attracted increasing research attention. In recent years, immune checkpoint inhibitors targeting PD-1/PD-L1 have been widely used in the clinic. However, the effectiveness of a single agent is only approximately 20%–40%, which may be related to primary and secondary drug resistance caused by the dysregulation of oncoproteins. Here, we reviewed the role of MDM2 in regulating the immune microenvironment, tumor immune evasion, and hyperprogression during immunotherapy. In addition, we summarized preclinical and clinical findings on the use of MDM2 inhibitors in combination with immunotherapy in tumors with MDM2 overexpression or amplification. The results reveal that the inhibition of MDM2 could be a promising strategy for enhancing immunotherapy.</p></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"11 6","pages":"Article 101279"},"PeriodicalIF":6.9,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S235230422400076X/pdfft?md5=e8193d8f3cf4de801a721c4c34ffe215&pid=1-s2.0-S235230422400076X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140402376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

STIM1 promotes acquired resistance to sorafenib by attenuating ferroptosis in hepatocellular carcinoma STIM1 通过减弱肝细胞癌中的铁变态反应，促进对索拉非尼的获得性耐药性

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-03-28 DOI: 10.1016/j.gendis.2024.101281

{"title":"STIM1 promotes acquired resistance to sorafenib by attenuating ferroptosis in hepatocellular carcinoma","authors":"","doi":"10.1016/j.gendis.2024.101281","DOIUrl":"10.1016/j.gendis.2024.101281","url":null,"abstract":"<div><p>Dysregulated calcium (Ca<sup>2+</sup>) signaling pathways are associated with tumor cell death and drug resistance. In non-excitable cells, such as hepatocellular carcinoma (HCC) cells, the primary pathway for Ca<sup>2+</sup> influx is through stromal interaction molecule 1 (STIM1)-mediated store-operated calcium entry (SOCE). Previous studies have demonstrated the involvement of STIM1-mediated SOCE in processes such as genesis, metastasis, and stem cell self-renewal of HCC. However, it remains unclear whether STIM1-mediated SOCE plays a role in developing acquired resistance to sorafenib in HCC patients. In this study, we established acquired sorafenib-resistant (SR) HCC cell lines by intermittently exposing them to increasing concentrations of sorafenib. Our results showed higher levels of STIM1 and stronger SOCE in SR cells compared with parental cells. Deleting STIM1 significantly enhanced sensitivity to sorafenib in SR cells, while overexpressing STIM1 promoted SR by activating SOCE. Mechanistically, STIM1 increased the transcription of SLC7A11 through the SOCE-CaN-NFAT pathway. Subsequently, up-regulated SLC7A11 increased glutathione synthesis, resulting in ferroptosis insensitivity and SR. Furthermore, combining the SOCE inhibitor SKF96365 with sorafenib significantly improved the sensitivity of SR cells to sorafenib both <em>in vitro</em> and <em>in vivo</em>. These findings suggest a potential strategy to overcome acquired resistance to sorafenib in HCC cells.</p></div>","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"11 6","pages":"Article 101281"},"PeriodicalIF":6.9,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2352304224000783/pdfft?md5=24271de70c9addc8ffbf4b8c9b7a8bd7&pid=1-s2.0-S2352304224000783-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140398428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Expanding the spectrum of novel candidate genes using trio exome sequencing and identification of monogenic cause in 27.5% of 320 families with steroid-resistant nephrotic syndrome 利用三组外显子测序扩展新型候选基因谱，在 320 个类固醇耐受性肾病综合征家族中确定 27.5% 的单基因病因

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-03-28 DOI: 10.1016/j.gendis.2024.101280

Ronen Schneider , Shirlee Shril , Florian Buerger , Konstantin Deutsch , Kirollos Yousef , Camille N. Frank , Ana C. Onuchic-Whitford , Thomas M. Kitzler , Youying Mao , Verena Klämbt , Muhammad Y. Zahoor , Katharina Lemberg , Amar J. Majmundar , Bshara Mansour , Ken Saida , Steve Seltzsam , Caroline M. Kolvenbach , Lea Maria Merz , Nils D. Mertens , Tobias Hermle , Friedhelm Hildebrandt

引用次数: 0