Results 121 to 130 of about 778,835 (257)

Integrative Multi‐Omics Approaches Reveal Selectivity Profiles and Molecular Mechanisms of FIIN‐2, a Covalent FGFR Inhibitor

Advanced Science, Volume 12, Issue 14, April 10, 2025.
Using integrative multi‐omics analyses, this study maps FIIN‐2's targets and signaling networks in liver cancer cells, and identifies covalent AMPKα1 binding as a novel autophagy‐activating mechanism. The findings resolve both on‐target FGFR inhibition and off‐target protein engagement, providing a molecular roadmap to refine covalent kinase inhibitors
Ying Fu, Dandan Zhu, Xiaojuan Chen, Lingzhi Qu, Ming Guo, Shuhong Zhang, Guangyu Xu, Zhuchu Chen, Maoyu Li, Yongheng Chen   +9 more
wiley   +1 more source

Adrenal High‐Expressional CYP27A1 Mediates Bile Acid Increase and Functional Impairment in Adult Male Offspring by Prenatal Dexamethasone Exposure

Advanced Science, Volume 12, Issue 14, April 10, 2025.
Prenatal dexamethasone exposure (PDE) can induce dysfunction in adrenal steroid synthesis in adult male offspring. This study demonstrate that the mechanism is associated with the upregulation of fetal adrenal cholesterol 27 hydroxylase (CYP27A1)promoter region histone 3 lysine 27 acetylation (H3K27ac) levels and expression mediated by PDE through the ...
Jiangang Cao, Wen Hu, Yawen Chen, Aihemaitijiang Ailikaiti, Ziyi Zhang, Lingbo Rong, Hong Yu, Hui Wang   +7 more
wiley   +1 more source

Nanomedicine Penetrating Blood‐Pancreas Barrier for Effective Treatment of Acute Pancreatitis

Advanced Science, Volume 12, Issue 13, April 3, 2025.
This study introduces tungsten‐based heteropolyacid nano‐antioxidants (mTWNDs), which are co‐modified with tannic acid (TA) and melanin (A). It is able to cross the damaged blood‐pancreas barrier (BPB) to reach the mitochondria of the pancreatic acinar cells (PACs) and specifically scavenge reactive oxygen species (ROS) to treat acute pancreatitis (AP)
Dan Wang, Shuya Wang, Jinjin Liu, Xiaojing Shi, Tingli Xiong, Ruishi Li, Wei Wei, Liandong Ji, Qiong Huang, Xuejun Gong, Kelong Ai   +10 more
wiley   +1 more source

Disturbing Cholesterol/Sphingolipid Metabolism by Squalene Epoxidase Arises Crizotinib Hepatotoxicity

Advanced Science, Volume 12, Issue 14, April 10, 2025.
Crizotinib induces excessive accumulation of squalene epoxidase (SQLE) by blocking its autophagic degradation. This accumulation disrupts cholesterol and sphingolipid metabolism, leading to hepatic steatosis or hepatocyte apoptosis, respectively. Autophagy activators, such as metformin, or SQLE enzymatic inhibitors, like terbinafine, possesses the ...
Hao Yan, Xiangliang Huang, Yourong Zhou, Yuan Mu, Shaoyin Zhang, Yashi Cao, Wentong Wu, Zhifei Xu, Xueqin Chen, Xiaochen Zhang, Xiaohong Wang, Xiaochun Yang, Bo Yang, Qiaojun He, Peihua Luo   +14 more
wiley   +1 more source

Myocardial inflammation is associated with impaired mitochondrial oxidative capacity in ischaemic cardiomyopathy

ESC Heart Failure, Volume 12, Issue 2, Page 1246-1255, April 2025.
Abstract Aims Myocardial inflammation and impaired mitochondrial oxidative capacity are hallmarks of heart failure (HF) pathophysiology. The extent of myocardial inflammation in patients suffering from ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and its association with mitochondrial energy metabolism are unknown.
Julius Borger, Elric Zweck, Constanze Moos, Patrick Horn, Fabian Voß, Heinz‐Peter Schultheiss, Jacob Eifer Møller, Udo Boeken, Hug Aubin, Artur Lichtenberg, Malte Kelm, Michael Roden, Amin Polzin, Ralf Westenfeld, Julia Szendroedi, Daniel Scheiber   +15 more
wiley   +1 more source

In Vitro Evaluation of CYP‐Mediated Metabolism of Fezolinetant and Pharmacokinetic Interaction Between Fezolinetant and Fluvoxamine in Healthy Postmenopausal Smokers and Nonsmokers

The Journal of Clinical Pharmacology, Volume 65, Issue 4, Page 508-519, April 2025.
Abstract Fezolinetant is an oral, nonhormonal, neurokinin 3 receptor antagonist treatment option for moderate to severe vasomotor symptoms associated with menopause. An in vitro study using human recombinant cytochrome P450 (CYP) enzymes and human liver microsomes showed that fezolinetant is metabolized to its major but inactive metabolite, ES259564 ...
Megumi Iwai, Jace Nielsen, Mayuko Miyagawa, Melanie Patton, Peter L. Bonate, Xuegong Wang, Tomasz Wojtkowski, Angela Sinn, Jiayin Huang   +8 more
wiley   +1 more source

Deterministic and Stochastic Models in Enzyme Kinetics [PDF]

arXiv
Enzyme kinetics has historically been described by deterministic models, with the Michaelis-Menten (MM) equation serving as a paradigm. However, recent experimental and theoretical advances have made it clear that stochastic fluctuations, particularly at low copy numbers or single-enzyme levels, can profoundly impact reaction outcomes.
arxiv  

Deubiquitinating Enzymes Regulate Skeletal Muscle Mitochondrial Quality Control and Insulin Sensitivity in Patients With Type 2 Diabetes

Journal of Cachexia, Sarcopenia and Muscle, Volume 16, Issue 2, April 2025.
ABSTRACT Background Activation of mitochondrial fission and quality control occur early in the onset of insulin resistance in human skeletal muscle. We hypothesized that differences in mitochondrial dynamics, structure and bioenergetics in humans would explain the onset and progression of type 2 diabetes (T2D). Methods Fifty‐eight sedentary adults (37 ±
Wagner S. Dantas, Elizabeth C. Heintz, Elizabeth R. M. Zunica, Jacob T. Mey, Melissa L. Erickson, Kathryn P. Belmont, Analisa L. Taylor, Gangarao Davuluri, Hisashi Fujioka, Ciarán E. Fealy, Charles L. Hoppel, Christopher L. Axelrod, John P. Kirwan   +12 more
wiley   +1 more source

Sulfonamide‐Bearing Pyrazolone Derivatives as Multitarget Therapeutic Agents: Design, Synthesis, Characterization, Biological Evaluation, In Silico ADME/T Profiling and Molecular Docking Study

Pharmacology Research &Perspectives, Volume 13, Issue 2, April 2025.
ABSTRACT The research and design of new inhibitors for the treatment of diseases such as Alzheimer's disease and glaucoma through inhibition of cholinesterases (ChEs; acetylcholinesterase, AChE and butyrylcholinesterase, BChE) and carbonic anhydrase enzymes are among the important targets.
Nebih Lolak, Suleyman Akocak, Meryem Topal, Ümit Muhammet Koçyiğit, Mesut Işık, Cüneyt Türkeş, Fevzi Topal, Mustafa Durgun, Şükrü Beydemir   +8 more
wiley   +1 more source

Animal Models of Traumatic Brain Injury and Their Relevance in Clinical Settings

CNS Neuroscience &Therapeutics, Volume 31, Issue 4, April 2025.
Traumatic brain injury (TBI) is a significant global health concern. Animal models are crucial for understanding the complex pathophysiology of TBI and developing effective treatments. This review explores common animal models of TBI, assessing their strengths and limitations in mimicking human injury.
Payal Chauhan, Nikita Yadav, Karan Wadhwa, Subbulakshmi Ganesan, Chakshu Walia, Gulshan Rathore, Govind Singh, Mosleh Mohammad Abomughaid, Abhilasha Ahlawat, Athanasios Alexiou, Marios Papadakis, Niraj Kumar Jha   +11 more
wiley   +1 more source