Results 71 to 80 of about 25,894 (252)

Deep Contrastive Learning for High‐Throughput Prediction of Drug Resistance Mutations from Sequences

Advanced Science, EarlyView.
This study presents DeepMutDTA, a deep learning framework aimed at predicting mutation‐induced changes in protein‐drug interactions and prioritizing variants potentially linked to drug resistance. Trained on large‐scale data, it incorporates SimSiam‐MuTF, a label‐aware contrastive fine‐tuning strategy that encourages separation between WT and MT ...
Xiaowen Hu, Pan Zhang, Shangqian Wu, Hao Sun, Minwei Li, Sophia Tsoka, Zizhang Sheng, Lei Deng   +7 more
wiley   +1 more source

Structure-based drug repositioning explains ibrutinib as VEGFR2 inhibitor.

PLoS ONE, 2020
Many drugs are promiscuous and bind to multiple targets. On the one hand, these targets may be linked to unwanted side effects, but on the other, they may achieve a combined desired effect (polypharmacology) or represent multiple diseases (drug ...
Melissa F Adasme, Daniele Parisi, Kristien Van Belle, Sebastian Salentin, V Joachim Haupt, Gary S Jennings, Jörg-Christian Heinrich, Jean Herman, Ben Sprangers, Thierry Louat, Yves Moreau, Michael Schroeder   +11 more
doaj   +1 more source

Astrocytic Phenotypic Switching in Posterior Piriform Cortex Orchestrates Bone Cancer Pain–Depression Comorbidity via Purinergic–Noradrenergic Signaling

Advanced Science, EarlyView.
Bone cancer pain and depression share a common origin: astrocytic A2‐to‐A1 transition in the posterior piriform cortex. This phenotypic shift disrupts the ATP–adenosine–A2AR–norepinephrine axis, simultaneously driving nociceptive and affective dysfunction.
Jiang‐Ping Liu, Jun‐Han Zhang, Zhi‐Xuan Tan, Wei‐Bing Yan, Ya‐Ru Yuan, Yao Liu, Bing‐Di Wei, Meng‐Qi Ding, Zhuo‐Min Fu, Ying Liu, An‐Qi Wang, Lin Ma, Yong‐Hong Li, Er‐Qing Chai, Chao‐Jun Wei   +14 more
wiley   +1 more source

Materials‐Guided Gene‐Ionizable Lipid Nanoparticles to Reverse Iron‐Associated Immune Resistance in Renal Cancer

Advanced Science, EarlyView.
ABSTRACT Iron overload is a common metabolic disturbance in cancer and contributes to poor outcomes in renal cell carcinoma (RCC), yet its effects on the tumour immune microenvironment remain unclear. Here we identify a previously unrecognized immunosuppressive axis in which iron overload downregulates the palmitoyltransferase ZDHHC12 in CD8+ T cells ...
Xin Jin, Yulong Hong, Chengliang Yin, Wanyang Guo, Yaxuan Wang, Ruijiang Zeng, Ruilin Liu, Zexian Ding, Xinlin Liu, Shangqing Ren, Qiyang Liang, Yaohui Wang, Xu Zhang, João Conde, Yuan Li, Xin Ma, Liangyou Gu   +16 more
wiley   +1 more source

Mastication‐Induced Electrical Stimulation Activates Prg4+ Chondroprogenitors for Osteoarthritis Therapy

Advanced Science, EarlyView.
This study presents a ″trash‐to‐treasure″ strategy that converts harmful joint overloads into beneficial electrical cues. The biodegradable MagPie, by providing piezoelectrical stimulation and releasing Mg2+ during mastication, exerts synergistic pro‐regenerative and anti‐inflammatory effects on Prg4+ cells via the ECM‐mediated FAK‐PI3K‐Akt axis ...
Shi‐Yang Feng, Jing‐Rong Cheng, Yu Qin, Jie Lei, Chen‐Chen Gao, Hong‐Ying Fu, Li‐Ping Wu, Thanh D. Nguyen, Xu‐Liang Deng, Kai‐Yuan Fu, Yang Liu   +10 more
wiley   +1 more source

Drug Repurposing in the Treatment of COVID-19

Bezmiâlem Science, 2020
The use of drugs that have been previously defined for certain indications in new indications is defined as the repurposing/repositioning of the drug. The requirement of all clinical research steps that starts from healthy volunteers, due to the slowness
Mehmet SOYLU, Emine Nur ÖZBEK, Günay YETİK ANACAK   +2 more
doaj   +1 more source

Mechanical Activation of Piezo1 Drives Osteoarthritis Through Kdm5c‐Mediated Epigenetic Silencing

Advanced Science, EarlyView.
Excessive mechanical stress activates Piezo1, triggering Ca2+‐dependent cytoskeletal forces that deform the nucleus and reduce H3K4me3. Kdm5c demethylates H3K4me3 at Col2a1 and Runx3 promoters. Kdm5c knockout rescues degradation. Repurposed telmisartan directly inhibits Kdm5c, blocking this axis and showing disease‐modifying efficacy in mouse OA models
Tianyou Kan, Xuran Li, Han Wang, Lin Sun, Yao Wang, Jiangdong Wu, Junqi Cui, Yiqi Yang, Kai Yuan, Linyang Chu, Liao Wang, Hanjun Li, Mengning Yan, Zhifeng Yu   +13 more
wiley   +1 more source

Lactate‐Driven Restriction of Mitochondrial Permeability Transition Promotes Resistance to Chemo‐Immunotherapy by Suppressing Tumor PANoptosis

Advanced Science, EarlyView.
Tumor‐derived lactate establishes a metabolic lock that drives chemo‐immunotherapy resistance by suppressing PANoptosis. Mechanistically, KAT8 lactylates the mitochondrial translocator ANT2, which recruits PGAM5 to dephosphorylate CypD. This cascade restricts mitochondrial permeability transition pore opening, preventing pro‐inflammatory mtDNA leakage.
Sen Zhong, Wenlong Chen, Fanglong Liu, Shengyi Zhou, Bolin Yu, Yuying Wang, Xiqian Zhou, Xuehui Wang, Diya Liu, Zhuoyu Zhang, Xinran Wang, Mounia Lalouly, Yiwen Li, Zhefei Du, Tao Yan, Zhihui Xiao, Zhou Zhou, Huanhuan Zhu, Fengyuan Qian, Bowen Zheng, Lin Fang   +20 more
wiley   +1 more source

Drug repositioning based on individual bi-random walks on a heterogeneous network

BMC Bioinformatics, 2019
Background Traditional drug research and development is high cost, time-consuming and risky. Computationally identifying new indications for existing drugs, referred as drug repositioning, greatly reduces the cost and attracts ever-increasing research ...
Yuehui Wang, Maozu Guo, Yazhou Ren, Lianyin Jia, Guoxian Yu   +4 more
doaj   +1 more source

PRMT5‐Dependent Stabilization of VPS34 Orchestrates Copper Trafficking to Shield Cancer Cells from Cuproptosis and Radiotherapy

Advanced Science, EarlyView.
Radioresistance arises partly from tumor cells evading cuproptosis via unknown defenses. This study reveals that the PRMT5‐VPS34 axis acts as a radiation‐activated anticuproptotic mechanism: PRMT5 methylates VPS34 at Arg174, recruiting USP10 to remove K48‐linked ubiquitination and prevent degradation.
Wei Chen, Ming‐Ying Xiao, Lan‐Lan Guo, Hao‐Yue Hu, Sui‐Xian Zhang, Bai‐Qiang Dong, Chen‐Fei Wu, Xia‐Hang Huang, Li Li, Run‐Zhe Chen, Yuan‐Yang Huang, Ying Jin, Hai Song, Ying Wang, Qi‐Wen Li, Ming Chen, Xuan Li, Yuan‐Yuan Chen   +17 more
wiley   +1 more source