Results 151 to 160 of about 279,979 (283)

Natural Products Inspired Scaffold Diversification Leads to Unnatural Molecular Warhead and Covalent Strategy to Modulating Protein Function through Electrophilic Bromine Transfer

Advanced Science, EarlyView.
We report a new thiolate‐reactive α,α‐gem‐dibromo lactam warhead that activates transcription factor Nrf2 and demonstrates anti‐inflammatory activities, which have implications in cancer, neurodegeneration, and cardiovascular diseases. RNA‐seq illuminated detailed transcriptional profiles, and chemical reactions with cysteine‐containing compounds ...
Beau R. Brummel, Sofia Kokkaliari, Qiwen Gao, Jinjing Chen, Larissa Costa de Almeida, Srinivasarao Tenneti, Derek A. Leas, Eli Levit, Lewis S. Alexander, Khalil A. Abboud, Pingrong Wei, Michael D. Cameron, James R. Rocca, Ranjala Ratnayake, Donna D. Zhang, Hendrik Luesch, Robert W. Huigens III   +16 more
wiley   +1 more source

Improved Systemic Immunochemotherapy Employing an Oxaliplatin‐TLR7/8 Agonist Prodrug Strategy

Advanced Science, EarlyView.
A platinum(IV) prodrug is developed to systemically deliver the TLR7/8 agonist gardiquimod. Tumor‐targeting is mediated by an albumin‐binding maleimide, which limits premature complex activation. Ox‐Gardi‐Mal accumulates specifically in the tumor, where it activates the immune system.
Michael Gutmann, Martijn Dijkstra, Philipp Salomon, Jamie Cowles, Anja Federa, Dina Baier, Carola Jaunecker, Iemima Semerean, Venla Karvonen, Christine Pirker, Maria Sibilia, Dietmar Herndler‐Brandstetter, Petra Heffeter, Bernhard K. Keppler, Christian R. Kowol, Walter Berger   +15 more
wiley   +1 more source

BGN/MDK Axis in the Melanoma Tumor Microenvironment Strengthens Tumor Malignancy by Modulating Cancer Cells and Cancer‐Associated Fibroblasts Crosstalk

Advanced Science, EarlyView.
This study reveals that m6A regulators cooperatively upregulate BGN in melanoma, promoting malignancy. Within the tumor microenvironment, CAFs show highest BGN expression. The BGN/MDK axis mediates cancer‐stroma crosstalk, driving normal fibroblast (NF) activation and enhancing the pro‐tumor effect of CAFs, highlighting a promising therapeutic target ...
Hao‐ze Shi, Ming‐yang Wu, Jin‐quan Liu, Cuicui Tian, Li Ma, Xue‐mei Zhou, Ze‐Hao Sun, Zhi‐yong Xu, Run‐dong Zhang, Shan‐yuan Ye, Li‐ming Huang, Yan Wang, Jing‐shu Xiong, Wen‐bo Bu, Xian‐feng Cheng, Jian‐fang Sun, Hao Chen   +16 more
wiley   +1 more source

Endogenous “Time Bomb” – Mislocalized Phospholipase A2 as a Critical Mediator of Ultra‐Rapid Mortality in Sepsis and Acute Lung Injury

Advanced Science, EarlyView.
Phospholipase A2 (PLA2), a dormant enzyme, becomes lethal when activated—collapsing lungs in minutes. Our dual therapy (DOPS + varespladib) boosts survival from 0% to >90% in sepsis/ALI. A breakthrough for acute lung injury treatment. ABSTRACT This study reveals that phospholipase A2 (PLA2), normally stable and nontoxic, can be activated specifically ...
Jianyu Wang, Zhongxing Xu, Lin Wang, Xin Sui, Yuan Luo, Xiuli Zhao, Jun Yang, Yongan Wang   +7 more
wiley   +1 more source

Mechanostimulatory Cues Determine Intestinal Fibroblast Fate and Profibrotic Remodeling in a Physiodynamic Human Gut‐on‐a‐Chip

Advanced Science, EarlyView.
A healthy gut barrier shields underlying fibroblasts from luminal shear forces, illustrating that “good fences make good neighbors.” Barrier damage exposes fibroblasts to shear stress, inducing cell death and the emergence of stress‐adapted, profibrotic fibroblasts. Sustained shear exposure promotes the formation of stiff aggregates of mechanoadapative
Soyoun Min, Nam Than, Yong Cheol Shin, Elif G. Ertugral, Chandrasekhar R. Kothapalli, Olumuyiwa Awoniyi, Hyun Jung Kim   +6 more
wiley   +1 more source

CRP Deficiency Rescues Periodontitis‐Induced Hippocampal Neurogenesis Impairment by Suppressing OPC‐Derived BMP4 Signaling in Rats

Advanced Science, EarlyView.
Chronic periodontitis elevates circulating CRP, which enters the hippocampus to upregulate BMP4 in oligodendrocyte precursor cells (OPCs), thereby impairing neurogenesis and inducing anxiety/depression‐like behaviors in rats. Counteracting this pathway, CRP deficiency helps confer functional resilience to OPCs.
Lingjie Li, Ping Deng, Siyu Hou, Xianbo Xia, Wei Zhao, Xingyu Zhu, Yang Zhang, Chao Wang, Ling Xu, Jinlin Song   +9 more
wiley   +1 more source

PET Imaging of Cardiac Inflammation in Viral Myocarditis Using a DPP4‐Targeted Probe

Advanced Science, EarlyView.
This study describes a DPP4‐targeted PET probe for imaging myocardial inflammation by selectively targeting activated immune cells. Derived from the clinically approved small‐molecule inhibitor linagliptin, the probe demonstrates favorable biodistribution with specific cardiac uptake in myocarditis.
Wanhao Gao, Wenzhu Hu, Du Tang, Xinxin Liu, Kun Yu, Lixia Feng, Minyu Liao, Wang Lin, Wenqiang Zhu, Sanjay Rajagopalan, Xiaoli Lan, Jixin Zhong, Dao Wen Wang, Dawei Jiang, Xiaoquan Rao   +14 more
wiley   +1 more source

Hierarchical Targeting of TREM2+ Myeloid Cells via Acid‐Triggered OMVs Reprogram Immunosuppression and Suppress Osteolysis in Bone‐Metastatic TNBC

Advanced Science, EarlyView.
This study developed a hierarchical targeting nanoplatform, siTREM2@ETP‐PEOz‐OMVs, against triple‐negative breast cancer (TNBC) bone metastasis. It precisely delivers therapeutic siTREM2 to monocytes/macrophages within the metastatic niche. This intervention dually regulates cell fate: reprogramming immunosuppressive macrophages and inhibiting ...
Fanglu Chen, Yucheng Xue, Xiao Ma, Liang Chen, Zhenxuan Shao, Hangxiang Sun, Haochen Mou, Fangqian Wang, Zilong Li, Yechao Shen, Zhaoming Ye, Xiaohua Yu, Shengdong Wang   +12 more
wiley   +1 more source

KCNJ2 is Required for NLRP3 Inflammasome Activation That Drives Allergic Airway Inflammation and Remodeling

Advanced Science, EarlyView.
This study aims to evaluate the impact of the potassium channel KCNJ2 on asthma development. KCNJ2 promotes NLRP3 inflammasome activation through both Ca2+ influx and K+ efflux in airway epithelial cells, which drives allergic airway inflammation and remodeling, suggesting a promising therapeutic target for asthma.
Yachao Cui, Shumei Wu, Yang Peng, Yiqi Liu, Li Che, Shiying Chen, Feng Zhang, Dajiang Qin, Shiyue Li, Pixin Ran, Wenguang Yin   +10 more
wiley   +1 more source

Discovery of an Adaptive Neuroimmune Response Driving Itch and Fast Tick Removal with Implications for Preventing Pathogen Transmission

Advanced Science, EarlyView.
Itch‐induced tick removal (IITR): An acquired neuroimmune mechanism, itch‐induced tick removal, develops after repeated tick exposure, mobilizing T cells and macrophages at the tick bite site to trigger a rapid scratching response that facilitates timely tick removal within a critical window that precedes the transmission of many tick‐borne pathogens ...
Johannes S. P. Doehl, Tiago D. Serafim, Serena Doh, Charles S. Grugan, Eva Iniguez, Luana Rogerio, Ronja Frigard, Ranadhir Dey, Pedro Cecilio, Xinglong Gu, Pang‐Yen Tseng, Aline da Silva Moreira, Mahnaz Minai, James Oristian, Hans Ackerman, Steven Brooks, Caroline Percopo, Siu‐Ping Ng, Derron A. Alves, Lucas Tirloni, Jennifer M. Anderson, Adriana Marques, Fabiano Oliveira, Shaden Kamhawi, Daniel E. Sonenshine, José M. C. Ribeiro, Mark Hoon, Jesus G. Valenzuela   +27 more
wiley   +1 more source