Results 71 to 80 of about 239,737 (256)

Semi‐Mechanistic PK/PD Modeling of Platelets and Spleen Volume With Navitoclax in Combination With Ruxolitinib in Patients With Myelofibrosis

CPT: Pharmacometrics & Systems Pharmacology
Navitoclax, an oral small molecule BCL‐XL/BCL‐2 inhibitor evaluated in myelofibrosis, was assessed through integrated PK/PD modeling to guide starting dose and dose‐reduction decisions when combined with ruxolitinib.
Akshanth R. Polepally, Aline Goebel, Maulik Patel, Carla Biesdorf, Jalaja Potluri, Rajeev M. Menon, Sven Mensing, Benjamin Engelhardt   +7 more
doaj   +1 more source

Targeting Dnmt3a/m5C/RelA Axis Attenuates Microglia Inflammatory Response and Improves Postoperative Recovery in Chronic Compressive Cervical Spinal Cord Injury

Advanced Science, EarlyView.
A pro‐inflammatory microglial subset persists after decompression in chronic compressive cervical spinal cord injury and shows enhanced Dnmt3a‐driven m5C signaling. By stabilizing RelA mRNA, this axis sustains NF‐κB activation and postoperative neuroinflammation.
Tianyu Qin, Yuan Jiang, Yongheng Xie, Huanwei Qu, Wenbin Yan, Jingle Chen, Yining Chen, Huayi Li, Naibo Feng, Jiajun Wu, Chao Zhang, Zhengqi Huang, Ming Shi, Zhihuai Deng, Guozhi Xiao, Houqing Long   +15 more
wiley   +1 more source

PRMT9 Aggravated Dopaminergic Neurodegeneration in Parkinson's Disease Model by Facilitating the Degradation of DUSP26 and Inducing Mitochondrial Dysfunction

Advanced Science, EarlyView.
In the pathological state of PD induced by MPP+, the upregulated PRMT9 in dopaminergic neurons translocates into mitochondrion and interacts with DUSP26 and catalyzes its arginine methylation, leading to the ubiquitin‐proteasomal degradation of DUSP26 mediated by Trim32.
Tengfei Liu, Xiaomeng Song, Xin Guo, Rui Xiao, Ru Sun, Qiuran Ji, Lu Yu, Yiquan Li, Qingyi Fu, Qidi Xue, Lingjun Kong, Lin Chen, Chengjiang Gao, Huiqing Liu   +13 more
wiley   +1 more source

Exploring the Conformational Space of Bcl-2 Protein Variants: Dynamic Contributions of the Flexible Loop Domain and Transmembrane Region

Molecules, 2019
Members of the Bcl-2 protein family regulate apoptosis through interactions with several proteins. A critical intrinsically disordered region (IDR) present in some members of the Bcl-2 family is essential for their function.
Luis A. Caro-Gómez, Jorge L. Rosas-Trigueros, Edgar Mixcoha, José L. Vique-Sánchez, Humberto Gasperin-Sánchez, Claudia G. Benítez-Cardoza, Absalom Zamorano-Carillo   +6 more
doaj   +1 more source

Intrinsically Mitochondria‐Targeting Nanozyme via Coordination‐Assembly of Natural Quercetin for Cascade Antioxidant Therapy of Cerebral Ischemia‐Reperfusion Injury

Advanced Science, EarlyView.
This study uncovers that quercetin naturally targets mitochondria. By coordinating quercetin with Fe3+, we engineer an ultrasmall cascade nanozyme (MCN) with superoxide dismutase‐catalase activities. MCN crosses the damaged blood–brain barrier, scavenges mitochondrial ROS, prevents mitochondrial DNA leakage, and blocks the cGAS‐STING pathway, thereby ...
Wenxuan Zheng, Zhicheng Wang, Xin Zhou, Shuya Wang, Xiaojing Shi, Tingli Xiong, Ruishi Li, Yuting Lin, Zhen Chen, Jiawen Wei, Fei Li, Jinwen Ge, Kelong Ai, Chong Liu, Guiming Deng   +14 more
wiley   +1 more source

Human Urine Stem Cells Alleviate Pulmonary Fibrosis via Inhibiting Macrophage‐Myofibroblast Transition

Advanced Science, EarlyView.
Therapeutic role and mechanism of human urine stem cells (hUSCs) in pulmonary fibrosis. hUSCs alleviated pulmonary fibrosis by selectively inhibiting macrophage‐myofibroblast transition (MMT) in two ways: on one hand, hUSCs inhibited mitochondrial reactive oxygen species (mtROS) production and apoptosis/senescence of epithelial cells in pulmonary ...
Zhou‐Hang Zhang, Guan‐Lin Guo, Xiao‐Hui Guan, Min Hu, Qi‐Ming Huang, Ding‐Wen Guo, Hao‐Cheng Gu, You‐Qiong Zhuo, Ning Li, Hong‐Bo Xin, Ke‐Yu Deng   +10 more
wiley   +1 more source

Cyclic peptides discriminate BCL-2 and its clinical mutants from BCL-XL by engaging a single-residue discrepancy

Nature Communications
Overexpressed pro-survival B-cell lymphoma-2 (BCL-2) family proteins BCL-2 and BCL-XL can render tumor cells malignant. Leukemia drug venetoclax is currently the only approved selective BCL-2 inhibitor. However, its application has led to an emergence of
Fengwei Li, Junjie Liu, Chao Liu, Ziyan Liu, Xiangda Peng, Yinyue Huang, Xiaoyu Chen, Xiangnan Sun, Sen Wang, Wei Chen, Dan Xiong, Xiaotong Diao, Sheng Wang, Jingjing Zhuang, Chuanliu Wu, Dalei Wu   +15 more
doaj   +1 more source

Alpha-helical destabilization of the Bcl-2-BH4-domain peptide abolishes its ability to inhibit the IP3 receptor.

PLoS ONE, 2013
The anti-apoptotic Bcl-2 protein is the founding member and namesake of the Bcl-2-protein family. It has recently been demonstrated that Bcl-2, apart from its anti-apoptotic role at mitochondrial membranes, can also directly interact with the inositol 1 ...
Giovanni Monaco, Elke Decrock, Koen Nuyts, Larry E Wagner, Tomas Luyten, Sergei V Strelkov, Ludwig Missiaen, Wim M De Borggraeve, Luc Leybaert, David I Yule, Humbert De Smedt, Jan B Parys, Geert Bultynck   +12 more
doaj   +1 more source

A Metal‐Phenolic Nanocluster Orchestrates Mito‐Ca2+ Metabolic Autonomy for Tumor Ca2+ Interference Therapy

Advanced Science, EarlyView.
Tumor Ca2+ interference therapy suffers from self‐protective Ca2+ metabolic autoregulation. In this scenario, a versatile metal‐phenolic nanocluster (TCMH) is engineered to modulate mitochondrial calcium uniporter (MCU) ‐mediated mito‐Ca2+ metabolic autonomy.
Ronglong Chen, Jia Huang, Yuepeng Wang, Shucong Yao, Fei Wu, Juan Liu, Chunxue Song, Li Lin, Xijun Lin, Yingjie Deng, Chao Zhang, Zhiquan Huang, Zixian Huang, Lisi Xie   +13 more
wiley   +1 more source

Identification of a Novel Bcl-2 Inhibitor by Ligand-Based Screening and Investigation of Its Anti-cancer Effect on Human Breast Cancer Cells

Frontiers in Pharmacology, 2019
Bcl-2 family protein is an important factor in regulating apoptosis and is associated with cancer. The anti-apoptotic proteins of Bcl-2 family, such as Bcl-2, are overexpression in numerous tumors, and contribute to cancer formation, development, and ...
Mei Wen, Zhen-ke Deng, Shi-long Jiang, Yi-di Guan, Hai-zhou Wu, Xin-luan Wang, Song-shu Xiao, Yi Zhang, Jin-ming Yang, Dong-sheng Cao, Dong-sheng Cao, Yan Cheng, Yan Cheng   +12 more
doaj   +1 more source