Results 91 to 100 of about 241,661 (217)

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

Decoding Biomolecular Phase Separation: From Physiological Roles to Pathological Mechanisms and Therapeutic Biomaterials Design

Advanced Science, EarlyView.
This review systematically elaborates on the mechanisms underlying physiological regulation and pathological dysregulation of biomolecular phase separation. It also summarizes advances in phase‑separation‑targeted therapeutic strategies and the design of functional biomaterials inspired by this process.
Jiawei Zhu, Jingbo Dong, Qiufang Gong, Xuejiao Song, Zhifa Shen, Chao Liang   +5 more
wiley   +1 more source

Emergence of highly profibrotic and proinflammatory Lrat+Fbln2+ HSC subpopulation in alcoholic hepatitis

Hepatology, EarlyView., 2022
Lrat+ quiescent hepatic stellate cells (qHSC) give rise to Lrat+Fbln2+ activated HSC (aHSC) in alcohol‐associated hepatitis and this subpopulation is highly profibrotic, inflammatory, and immunoregulatory based on their single cell transcriptomic profile. Abstract Background and Aims Relative roles of HSCs and portal fibroblasts in alcoholic hepatitis (
Steven Balog, Reika Fujiwara, Stephanie Q. Pan, Khairat B. El‐Baradie, Hye Yeon Choi, Sonal Sinha, Qihong Yang, Kinji Asahina, Yibu Chen, Meng Li, Matthew Salomon, Stanley W.‐K. Ng, Hidekazu Tsukamoto   +12 more
wiley   +1 more source

Mechanically Regulated Secretion: How Physical Forces Instruct the Secretory Pathway and Remodel the Secretome

Advanced Science, EarlyView.
Mechanical cues, including ECM stiffness, stretch, compression, shear stress, and traction forces, remodel trafficking across the secretory pathway, from the ER and Golgi to endolysosomal compartments and the plasma membrane. The resulting secretome reshapes ECM composition and tissue mechanics, establishing feedback loops that support homeostasis or ...
Domenico Russo, Seetharaman Parashuraman, Maria Luigia Maresca, Angela Francesca Dinoi, Alessia Calcagnì, Riccardo Rizzo   +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

SEC Mediates m6A Deposition and Transcription Pause Release to Drive Cell Identity Transition

Advanced Science, EarlyView.
The SEC promotes cell identity transitions by facilitating transcription pause release at key identity‐associated genes, including Klf4 and Myc during iPSC reprogramming and Nes and Tubb3 during ESC‐to‐neuroectodermal differentiation. During early iPSC reprogramming, this function additionally involves cooperation with METTL3‐associated m6A regulation.
Zhijing Zhang, Jingyi Xu, Yonghong Wu, Yitong Qu, Xinglin Hu, Yuchen Sun, Yanshuang Wu, Zhonghua Liu, Jiaqiang Wang, Lei Lei   +9 more
wiley   +1 more source

Low‐Density Lipoprotein Receptor‐Targeted Biomimetic Nanoplatform Suppresses Glioblastoma Stemness and Remodels Antitumor Immunity via Dual Metabolic Disruption

Advanced Science, EarlyView.
A low‐density lipoprotein receptor‐oriented biomimetic nanoplatform couples brain‐tumor delivery with a mechanistically matched regorafenib‐erythrodiol combination. Concurrent disruption of autophagic nutrient salvage and cholesterol homeostasis collapses bioenergetic and signaling support, suppresses glioblastoma stemness, and promotes immunogenic ...
Yining Jiang, Wenzhuo Yang, Wenting Cheng, Jing Zuo, Lin Pan, Sheng Zhong, Ren Geng, Yao Zhao, Zijian Chen, Canhua Huang, Yang Bai, Liyan Zhao, Yunqian Li   +12 more
wiley   +1 more source

Fc‐Dependent Targeting of the GAS6–MERTK Axis With Monoclonal and Bispecific Antibodies Overcomes Drug Resistance Across EGFR Mutations in Exons 19, 20, and 21

Advanced Science, EarlyView.
EGFR mutations drive a substantial fraction of non‐small cell lung cancers (NSCLC) and are effectively targeted by tyrosine kinase inhibitors (TKIs), including osimertinib. However, resistance inevitably develops through secondary mutations and compensatory receptor activation, including the GAS6 receptor MERTK.
Suvendu Giri, Boobash Raj Selvadurai, Nitin Gupta, Arturo Simoni‐Nieves, Alessandro Genna, Moshit Lindzen, Rishita Chatterjee, Marieke Van Daele, Deepthi Ramesh Kumar, Mirie Zerbib, Roni Oren, Isabelle Sophie Meijer, Elisabeth Franziska Wippich, Yahel Avraham, Rony Dahan, Yuya Haga, Laura E. Kilpatrick, Simon Platt, Stephen J. Hill, Lipika R. Pal, Eytan Ruppin, Yasuo Tsutsumi, Eliane Hadas Yardeni, Muhammad Abu Ahmad, Olga Radinsky, Donatella Romaniello, Mattia Lauriola, Angel Porgador, Yosef Yarden   +28 more
wiley   +1 more source

A DNA G‐Quadruplex‐Targeting Ligand Suppresses c‐MYC Expression: Implications for Gemcitabine‑Resistant Pancreatic Cancer

Angewandte Chemie, EarlyView.
PQB‐4, a fluorescent small‐molecule ligand that targets c‐MYC DNA G‐quadruplexes (G4s), showed marked synergy with gemcitabine in resistant PANC‐1 cells (CI = 0.027). In vivo, the ligand reduced tumor weight by 44% in a PANC‐1 xenograft model. These results highlight the therapeutic potential of c‐MYC DNA G4‐targeting ligands for treating gemcitabine ...
Bo‐Xin Zheng, Ya‐Kun Wang, Ze‐Xin Chen, Yi‐Wen Meng, Meng‐Ting She, Jia‐Peng Dong, Yingying Zheng, Yao‐Xun Zeng, Wen‐De Zheng, Wei Long, Wing‐Leung Wong   +10 more
wiley   +2 more sources

Tubocapsenolide A Overcomes Oxaliplatin Resistance in Colorectal Cancer by Targeting PLK1 to Impair CEP55–ESCRT‐Associated Vesicular Damage Clearance

Advanced Science, EarlyView.
Oxaliplatin‐resistant colorectal cancer cells utilize a previously unappreciated PLK1‐CEP55‐ESCRT‐driven vesicular extrusion mechanism to clear L‐OHP‐induced cellular damage. The natural withanolide Tubocapsenolide A directly targets and inhibits PLK1 to disrupt this specific damage‐clearance machinery. This blockade induces severe nucleolar stress and
Yueying Yang, Jing Liang, Lu Wang, Hongyan Zhang, Zhiruo Zhang, Yang Liu, Rui Zhu, Wen Xu, Shaohua Xu, Dejuan Sun, Ke Xiang, Yali Wang, Zhimin Fan, Zheng Wang, Hua Li, Lixia Chen   +15 more
wiley   +1 more source