Results 151 to 160 of about 232,343 (304)

Mitochondrial stress in advanced fibrosis and cirrhosis associated with chronic hepatitis B, chronic hepatitis C, or nonalcoholic steatohepatitis

Hepatology, EarlyView., 2022
Adaptive mitochondrial mechanisms allow mitochondrial resilience and prevent the worsening of fibrosis, while deregulation of these mechanisms promotes the progression from no/minimal‐mild (F0‐F2) fibrosis to advanced fibrosis and cirrhosis (F3‐F4). Abstract Background and Aims Hepatitis B virus (HBV) infection causes oxidative stress (OS) and alters ...
Dimitri Loureiro, Issam Tout, Stéphanie Narguet, Cheikh Mohamed Bed, Morgane Roinard, Ahmad Sleiman, Nathalie Boyer, Nathalie Pons‐Kerjean, Corinne Castelnau, Nathalie Giuly, Dorothy Tonui, Vassili Soumelis, Jamel El Benna, Patrick Soussan, Richard Moreau, Valérie Paradis, Abdellah Mansouri, Tarik Asselah   +17 more
wiley   +1 more source

Glutamine Deprivation Triggers Tribbles Homolog 3 Dependent G‐Quadruplex Resolution to Maintain DNA Repair and Tumor Survival

Advanced Science, EarlyView.
Glutamine deprivation triggers transient DNA damage yet activates adaptive repair in hepatocellular carcinoma cells. We identify TRIB3 as a stress‐induced nuclear scaffold that associates with DDX5 and G‐quadruplex DNA atBRCA1 andRAD51AP1 promoters. TRIB3 loss increases G4 accumulation, suppresses HR gene transcription, elevates γ‐H2A.X, and sensitizes
Qiang Ji, Xuedan Sun, Zhangran Sun, Mengfan Li, Xinyu Cheng, Shuai Tian, Rick F. Thorne, Jinming Li, Guangzhi Liu, Mian Wu, Xiaoying Liu   +10 more
wiley   +1 more source

Targeted Degradation of eEF2K by a Structure‐Guided PROTAC Strategy for the Treatment of Triple‐Negative Breast Cancer

Advanced Science, EarlyView.
This study developed an eEF2K‐targeting PROTAC, A6, that efficiently degrades eEF2K in TNBC cells, inhibiting tumor growth in vitro and in vivo. To enhance tumor‐specific delivery, we engineered A6@ZIF‐8, a pH‐sensitive nanocarrier, which improved drug accumulation at tumor sites, offering a promising therapeutic strategy for TNBC through targeted ...
Shijun Cao, Changxin Zhong, Shilong Jiang, Yungui Li, Yang Xi, Mingxuan Xiao, Ting Jiang, Xiaoya Wan, Zonglin Chen, Xiaohui Yu, Yan Cheng   +10 more
wiley   +1 more source

The ITGB2‐COPS3‐SOX2 Axis and SOX2 Liquid‐Liquid Phase Separation: Dual Mechanisms Governing Osteosarcoma Stemness

Advanced Science, EarlyView.
Osteosarcoma stemness is driven by the ITGB2‐COPS3‐SOX2 signaling axis. This study reveals that nuclear COPS3 stabilizes SOX2, which in turn undergoes liquid‐liquid phase separation to promote stemness. Based on this mechanism, a novel COPS3 inhibitor, Z‐5891, was developed, effectively suppressing tumor growth and stemness in vivo, offering a ...
Lei Guo, Zhiqing Zhao, Wei Wang, Jianfang Niu, Bing Wang, Yunfei Lin, Wei Guo, Taiqiang Yan   +7 more
wiley   +1 more source

Dual Aptamers‐Based SETDB1 PROTACs as Effective Anti‐Tumor Strategies for Breast Cancer

Advanced Science, EarlyView.
This study establishes dual‐aptamer PROTACs targeting SETDB1 using a SETDB1‐specific aptamer conjugated to AS1411. The designed PROTACs penetrate cells, recruit MDM2 to degrade SETDB1, and inhibit cancer cell proliferation and migration. Remarkably, they also overcome tamoxifen resistance and enhance CD8+ T cell cytotoxicity, suppressing tumor growth ...
Yanxuan Guo, Yingge Lv, Shuyu Huang, Chang Liu, Yan Ouyang, Bei Lan, Chenghao Xuan   +6 more
wiley   +1 more source

Phosphatidic Acid‐TRIM59‐Olig2 Signaling Couples Metabolic Dysfunction to Myelination Failure in PWMI

Advanced Science, EarlyView.
PA accumulates after hypoxic‐ischemic injury and stabilizes the E3 ligase TRIM59 in OPCs. Stabilized TRIM59 enhances ubiquitination and degradation of Olig2, blocking differentiation and causing hypomyelination in PWMI. Modulating PA synthesis restores Olig2 levels, improves myelination, and ameliorates behavioral deficits, defining a metabolically ...
Xinyu Li, Yanan Liu, Meng Zhang, Yiwei Liu, Meiting Liu, Kaishen Zhu, Zhian Liu, Chao Ren, Ruiqin Yao   +8 more
wiley   +1 more source

TRIM40 Drives Pathological Cardiac Hypertrophy and Heart Failure via Ubiquitination of PKN2

Advanced Science, EarlyView.
This study identifies the E3 ligase TRIM40 as a key driver of pathological cardiac hypertrophy. TRIM40 binds PKN2 via its B‐box domain and, through its C29‐dependent catalytic activity, mediates K63‐linked ubiquitination of PKN2. This modification enhances PKN2 phosphorylation at Ser815, thereby driving hypertrophy.
Risheng Zhao, Xiaoli Cui, Huizhu Du, Zhuoqun Wang, Chang Liu, Linxin Zhang, Jianing Qi, Di Yang, Hui Yu, Shuang Yan, Wei Liu, Haiming Sun, Mengyang Wang   +12 more
wiley   +1 more source

ZSL Orchestrates Synaptonemal Complex Assembly as a Central Region Scaffold to Ensure Synapsis Fidelity and Crossover Control in Polyploid Meiosis

Advanced Science, EarlyView.
A central molecular adaptor, ZSL, is identified that links transverse filaments ZYP1 to central element SCEP1/2 to drive synaptonemal complex assembly in Brassica napus. Loss of ZSL abolishes synaptonemal complex formation, disrupts meiotic chromosome segregation, and markedly increases crossovers, providing mechanistic insight into meiotic fidelity ...
Miaowei Geng, Shaochen Jia, Fei Cao, Cuiping Liu, Heshuang Zhang, Gang Xu, Jixin Zhuang, Yashi Zhang, Can Liu, Yuhang Zhao, Zilin Guo, Xinjie Yuan, Jiaqing Yang, Lei Chu, Bowei Cai, Hu Zhao, Chao Yang   +16 more
wiley   +1 more source

Loss of VMP1 Impairs Tight Junction Recycling and Aggravates Intestinal Barrier Dysfunction in Inflammatory Bowel Disease

Advanced Science, EarlyView.
This study identifies vacuole membrane protein 1 (VMP1) as a critical regulator of intestinal epithelial barrier homeostasis. VMP1 facilitates the recruitment of CORO1C to late endosomes, supporting Retromer‐mediated recycling of the tight junction protein Occludin.
Jiawei Zhao, Jianjun Zou, Chen Zhou, Yingui Wang, Yiman Liu, Yanqing Zhou, Yuxiang Wang, Xinyu Zhang, Huishu Yang, Hongjie Yin, Dongsheng Bai, Yue Zhao, Na Lu   +12 more
wiley   +1 more source

ZMAT1 Promotes Osteoclastogenesis Through TRIM46 Mediated YAP1 Degradation and Inhibits Osteoblastogenesis

Advanced Science, EarlyView.
Zmat1 deficiency mitigates pathological bone loss by impairing osteoclastogenesis and promoting osteoblastogenesis. Mechanistically, in osteoclasts, Zmat1 loss relieves transcriptional repression of the E3 ligase TRIM46, promoting YAP1 degradation and inhibiting osteoclastogenic genes.
Xinyu Chang, Yijin Hou, Likun Cui, Huiqi Yu, Rong Liu, Junhao Sui, Zhong Zheng, Lu Liu, Jie Chen, Mengchen Chen, Chen Ding, Shuogui Xu, Sheng Xu, Hao Zhang   +13 more
wiley   +1 more source