Results 101 to 110 of about 2,935,830 (275)

The inhibitors of cyclin-dependent kinases and GSK-3β enhance osteoclastogenesis

Biochemistry and Biophysics Reports, 2016
Osteoclasts are multinucleated cells with bone resorption activity that is crucial for bone remodeling. RANK‐RANKL (receptor activator of nuclear factor κB ligand) signaling has been shown as a main signal pathway for osteoclast differentiation. However,
Yosuke Akiba, Akiko Mizuta, Yoshito Kakihara, Juri Nakata, Jun Nihara, Isao Saito, Hiroshi Egusa, Makio Saeki   +7 more
doaj   +1 more source

Concerted Action of Targeted Nucleic Acid Therapeutics as Flexible, Precision and Personalized Cancer Treatment

Advanced Science, EarlyView.
Combinations of small activating RNAs and small interfering RNAs were developed as personalized precision therapies that simultaneously activate tumor suppressors and silence oncogenes according to the molecular signatures of patient tumors. This combination strategy demonstrated superior anticancer efficacy, highlighting the promise of precision ...
Jing Wu, Jiaxuan Chen, Abdechakour Elkihel, Wenjun Lan, Nicolas Fraunhoffer, Dandan Zhu, Baoping Lian, Christina Galanakou, Zhancun Bian, Xi Liu, Odile Gayet, Loic Moubri, Julie Aglietti Roques, Vikash Reebye, Nagy Habib, Xiaoxuan Liu, Nelson Dusetti, Juan Lucio Iovanna, Ling Peng   +18 more
wiley   +1 more source

Combinatorial targeting of G‐protein‐coupled bile acid receptor 1 and cysteinyl leukotriene receptor 1 reveals a mechanistic role for bile acids and leukotrienes in drug‐induced liver injury

Hepatology, EarlyView., 2022
CHIN117 is a dual cysteinyl leukotriene receptor 1 (CYSLTR1) antagonist and G‐protein‐coupled bile acid receptor 1 (GPBAR1) agonist. In the liver, GPBAR1 and CYSLTR1 are coexpressed by liver sinusoidal endothelial cells (LSECs), HSCs, circulating monocytes/macrophages, and liver resident macrophages (Kupffer cells).
Michele Biagioli, Silvia Marchianò, Cristina di Giorgio, Rosalinda Roselli, Martina Bordoni, Rachele Bellini, Bianca Fiorillo, Valentina Sepe, Bruno Catalanotti, Chiara Cassiano, Maria Chiara Monti, Eleonora Distrutti, Angela Zampella, Stefano Fiorucci   +13 more
wiley   +1 more source

USP5 Stabilizes TGFBR1 to Drive Vascular Smooth Muscle Cell Senescence and Atherosclerosis

Advanced Science, EarlyView.
This study reveals that USP5 drives vascular smooth muscle cell senescence and atherosclerosis by stabilizing TGFBR1, suppressing IDH2, and promoting glycolytic reprogramming, identifying the USP5‐TGFBR1‐IDH2 axis as a potential therapeutic target. ABSTRACT Vascular smooth muscle cell (VSMC) senescence contributes importantly to atherosclerotic plaque ...
Xinhai Cui, Yuanlong Hu, Lin Lin, Lei Zhang, Chao Li, Yunlun Li   +5 more
wiley   +1 more source

TP53 R249S mutation in hepatic organoids captures the predisposing cancer risk

Hepatology, EarlyView., 2022
The systematic approach in elucidating the gain‐of‐function (GOF) roles of TP53 mutations in early liver carcinogenesis. Unique downstream targets of TP53 L3 mutations were identified from chormatin immunoprecipitation sequencing in HCC cell lines, followed by a series of validation assays to substantiate the exclusive transcriptional regulations ...
Yin Kau Lam, Jianqing Yu, Hao Huang, Xiaofan Ding, Alissa M. Wong, Howard H. Leung, Anthony W. Chan, Kelvin K. Ng, Mingjing Xu, Xin Wang, Nathalie Wong   +10 more
wiley   +1 more source

Synergistic p53 Pathway Activation Through Sono‐Gene Therapy Induced by Ultrasound‐Triggered Theranostic Mesoporous Nanoparticles

Advanced Science, EarlyView.
Schematic representation of ultrasound‐mediated ICG/siCD24@MSN‐LCD from nanostructure to synergistic sono‐gene therapy. This nanoplatform targets ASGPR via the LCD shell, which dissociates to release loaded ICG and siCD24. The core mechanism involves ultrasound‐guided sonodynamic therapy by ICG and CD24 knockdown by siCD24, both activating the p53 axis
Yading Zhao, Lu Guo, Dandan Shi, Xiao Sun, Mengmeng Shang, Song Ning, Shuting Huang, Xiaoxuan Wang, Rui Liu, Yuye Fu, Suyun Li, Jie Li   +11 more
wiley   +1 more source

CDK4/MERCs/PINK1 Axis Drives PFOA/HFPO‐TA‐Induced Cardiac Senescence via Mitophagy Defect and cGAS‐STING Activation: In Vitro Amelioration by Cycloastragenol

Advanced Science, EarlyView.
The present study demonstrated that PFOA and HFPO‐TA exposure suppressed CDK4, disrupted MERCs and impaired PINK1/Parkin‐mediated mitophagy, thereby accelerating cardiac senescence, whereas CAG effectively reversed these pathological changes in vitro. Our findings identify CDK4 as a critical regulator bridging mitophagy defects and cardiac senescence ...
Nuo‐Wa Li, Jun‐Ze Jiang, Ying‐Ying Liu, Tian‐Tian Zhang, Kanwar Kumar Malhi, Xin Yao, Jin‐Long Li   +6 more
wiley   +1 more source

Supramolecular Degraders: An Emerging Paradigm in Targeted Protein Degradation

Advanced Science, EarlyView.
Dynamic supramolecular assembly reshapes targeted protein degradation by coordinating modular degrader construction, delivery, functional integration, and intracellular assembly or activation across proteasomal, endosomal–lysosomal, and autophagy–lysosomal pathways.
Kongjun Liu, Xue Yuan, Yan Zhou, Rui Yuan, Shaocheng Xie, Yong Chen, Peiyi Wang, Jianmei Gao, Qihai Gong   +8 more
wiley   +1 more source

The Mitogen‐Activated Protein Kinase GhNTF3 Modulates the Arbuscular Mycorrhizal Symbiosis‐Immunity Trade‐Off in Cotton by Regulating Salicylic Acid Biosynthesis

Advanced Science, EarlyView.
AM symbiosis induces GhWAK13 to promote fungal colonization. GhNTF3 negatively regulates symbiosis by promoting SA biosynthesis. GhWAK13 sequesters GhNTF3 at the membrane, limiting its nuclear translocation and relieving SA‐mediated suppression. Under Verticillium stress, GhNTF3 enters the nucleus and interacts with GhJAZ6 to activate SA signaling ...
Shuangjie Jia, Jingshang Wen, Jihang Li, Meina Feng, Yiming He, Ruojun Liu, Qian Liu, Junli Zhang, Kai Cheng, Xiangyu Zhang, Xiao Zhang   +10 more
wiley   +1 more source

AS‐TLC‐Based High‐Throughput Screening Integrated with CuAAC Optimization Strategy Facilitates the Rapid Discovery of YTHDC1 Inhibitor

Advanced Science, EarlyView.
We developed Affinity Selection Thin‐Layer Chromatography (AS‐TLC) as a method for high‐throughput screening (HTS) of compound mixtures. Furthermore, we integrated activity assays with AS‐TLC and identified a YTH domain‐containing protein 1 (YTHDC1) inhibitor. Building on this hit, we applied copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) click
Mingchen Wang, Shuiping Fu, Ye Xu, Jia Gao, Jiwei Ren, Xu Yang, Hesong Xu, Ge Sun, Yanjie Li, Yanlin Wang, Lu Jin, Peijuan Chen, Ying Xu, Jianhao Li, Hua Lin, Chujiao Hu, Kaixian Chen, Huan Xiong, Cheng Luo, Shijie Chen   +19 more
wiley   +1 more source