Genes & Diseases最新文献_第9页

Novel oral compound Z526 mitigates cancer-associated cachexia via intervening NF-κB signaling and oxidative stress 新型口服化合物 Z526 通过干预 NF-κB 信号传导和氧化应激减轻癌症相关恶病质

IF 6.8 2区医学

Genes & Diseases Pub Date : 2024-04-08 DOI: 10.1016/j.gendis.2024.101292

Xiaofan Gu, Shanshan Lu, Shuang Xu, Yiwei Li, Meng Fan, Guangyu Lin, Yiyuan Liu, Yun Zhao, Weili Zhao, Xuan Liu, Xiaochun Dong, Xiongwen Zhang

{"title":"Novel oral compound Z526 mitigates cancer-associated cachexia via intervening NF-κB signaling and oxidative stress","authors":"Xiaofan Gu, Shanshan Lu, Shuang Xu, Yiwei Li, Meng Fan, Guangyu Lin, Yiyuan Liu, Yun Zhao, Weili Zhao, Xuan Liu, Xiaochun Dong, Xiongwen Zhang","doi":"10.1016/j.gendis.2024.101292","DOIUrl":"https://doi.org/10.1016/j.gendis.2024.101292","url":null,"abstract":"Cancer-associated cachexia (CAC) is a severe metabolic disorder syndrome mainly characterized by muscle and fat loss, which accounts for one-third of cancer-related deaths. No effective therapeutic approach that could fully reverse CAC is available. NF-κB signaling and oxidative stress play vital roles in both muscle atrophy and fat loss in CAC. Here, we showed that our developed oral compound Z526 exhibited potent anti-CAC efficacy by inhibiting NF-κB signaling and ameliorating oxidative stress. , Z526 alleviated C2C12 myotube atrophy and 3T3-L1 adipocyte lipolysis induced by conditioned mediums of multiple cachectic tumor cells or pro-cachectic inflammatory cytokines. , Z526 attenuated the cachectic symptoms of C26 or LLC tumor-bearing mice. Z526 treatment reduced weight loss without impacting tumor growth and improved muscle atrophy, fat loss, and impaired grip force. Besides, serum TNF-α and IL-6 levels were reduced after Z526 treatment in C26 tumor-bearing mice. Of note, Z526 significantly prolonged the survival of LLC tumor-bearing mice. Activated NF-κB signaling and oxidative stress in cachectic muscle and fat tissues were reversed by Z526. Furthermore, Z526 exhibited a promising preclinical safety profile. Thus, oral Z526, which exhibited potent anti-CAC activities and , multiple interventions in diverse pathogenic mechanisms (NF-κB signaling and oxidative stress), and a favorable preclinical safety profile, holds the promise to be developed into a novel and beneficial therapeutic option for CAC.","PeriodicalId":12689,"journal":{"name":"Genes & Diseases","volume":"7 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140582610","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

Glucose metabolism perturbations influence tumor microenvironments via LINC01139 pathway and facilitate immunotherapy in hepatocellular carcinoma 葡萄糖代谢紊乱通过 LINC01139 通路影响肿瘤微环境，促进肝细胞癌的免疫疗法

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-04-08 DOI: 10.1016/j.gendis.2024.101302

Yueying Gao , Jinyang Yu , Zhi Li , Kefan Liu , Jiwei Pan , Ya Zhang , Yanlin Ma , Jiwei Zhang , Zhigang Liu , Yongsheng Li

引用次数: 0

Novel heterozygous missense variants in the TOE1 gene linked to pontocerebellar hypoplasia type 7 与浮小脑发育不全 7 型有关的 TOE1 基因新杂合错义变体

IF 6.9 2区医学

Genes & Diseases Pub Date : 2024-04-08 DOI: 10.1016/j.gendis.2024.101290

引用次数: 0

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 6.8 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, 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