Results 131 to 140 of about 9,370,992 (242)

Inhibition of MEKK3 Prevents Cerebral Cavernous Malformation Progression Via Restoring Endothelial Integrity and Restricting Microglial Activation

Advanced Science, EarlyView.
In this study, we demonstrate that aberrant MEKK3 signaling in endothelial cells and microglia drives the progression of cerebral cavernous malformations (CCMs). Furthermore, we identify DPDH as a potent small‐molecule MEKK3 inhibitor with substantial therapeutic potential for CCM treatment.
Weiwei Zheng, Suyun Yu, Liwenyu Chen, Jing Ma, Peiliang Shen, Chang Yu, Xiaoqing Xin, Qiuhong Shen, Jing Chen, Song Ke, Hao Liu, Xiaobing Jiang, Ruogu Qi, Juming Yan, Jia Li, Jaesung P. Choi, Yin Lu, Yang Zhao   +17 more
wiley   +1 more source

Targeting Nupr1‐Mediated p53 Mitochondrial Sequestration Alleviates Aortic Dissection by Restoring the Gadd45b‐Dependent Survival Program

Advanced Science, EarlyView.
This study identifies Nupr1 as a crucial stress‐responsive orchestrator driving AD. Under severe stress, Nupr1 massively accumulates within mitochondria to sequester p53, triggering apoptosis and concurrently repressing the Gadd45b‐mediated survival program.
Xi Yang, Ke‐Yuan Chen, Yue Tian, Zong‐Sheng Jiang, Jian Lei, Xing‐Hui Zhuang, Jiang‐Bin Wu, Le‐Le Tang, Hao‐Yu Li, Xiao‐Hui Chen, Yue Wang, Yu‐Mei Li, Zhi‐Huang Qiu, Zi‐Wen Cai, Liang‐Wan Chen   +14 more
wiley   +1 more source

Myeloid p38 activation maintains macrophage–liver crosstalk and BAT thermogenesis through IL‐12–FGF21 axis

Hepatology, EarlyView., 2022
Physiological activation of myeloid p38 controls macrophage IL‐12 production and crosstalk to the liver by modulating hepatic FGF21, and subsequently, brown adipose tissue thermogenesis during obesity Abstract Obesity features excessive fat accumulation in several body tissues and induces a state of chronic low‐grade inflammation that contributes to ...
María Crespo, Ivana Nikolic, Alfonso Mora, Elena Rodríguez, Luis Leiva‐Vega, Aránzazu Pintor‐Chocano, Daniel Horrillo, Lourdes Hernández‐Cosido, Jorge L. Torres, Eva Novoa, Rubén Nogueiras, Gema Medina‐Gómez, Miguel Marcos, Magdalena Leiva, Guadalupe Sabio   +14 more
wiley   +1 more source

β‐Adducin Restrains PLA2G4A‐Dependent Lysosomal Membrane Permeabilization and Neuronal Death in Ischemic Stroke

Advanced Science, EarlyView.
This study identifies β‐adducin as a regulator of lysosomal integrity in ischemic neurons. Ischemia‐associated FTO loss increases m6A modification and destabilizes Add2 mRNA, reducing β‐adducin expression and promoting PLA2G4A accumulation at lysosomes.
Hui‐qin Li, Pin‐yi Liu, Dan Wu, Fei‐yu Ma, Yi Bai, Sheng‐nan Xia, Hai‐yan Yang, Xin‐yu Bao, Yun Xu, Xiang Cao   +9 more
wiley   +1 more source

Loss of hepatic SMLR1 causes hepatosteatosis and protects against atherosclerosis due to decreased hepatic VLDL secretion

Hepatology, EarlyView., 2022
The role of SMLR1 in lipid metabolism (high fat + cholesterol diet in mice) Abstract Background and Aims The assembly and secretion of VLDL from the liver, a pathway that affects hepatic and plasma lipids, remains incompletely understood. We set out to identify players in the VLDL biogenesis pathway by identifying genes that are co‐expressed with the ...
Willemien van Zwol, Antoine Rimbert, Justina C. Wolters, Marieke Smit, Vincent W. Bloks, Niels J. Kloosterhuis, Nicolette C. A. Huijkman, Mirjam H. Koster, Umesh Tharehalli, Simon M. de Neck, Colin Bournez, Marceline M. Fuh, Jeroen Kuipers, Sujith Rajan, Alain de Bruin, Henry N. Ginsberg, Gerard J. P. van Westen, M. Mahmood Hussain, Ludger Scheja, Joerg Heeren, Philip Zimmerman, Bart van de Sluis, Jan Albert Kuivenhoven   +22 more
wiley   +1 more source

In vivo applications and toxicities of AAV-based gene therapies in rare diseases

Orphanet Journal of Rare Diseases
Adeno-associated virus (AAV), renowned for its exceptionally low pathogenicity and significant efficacy in clinical gene therapy, has emerged as a leading delivery vector in the field of gene therapy.
Qian Zhao, Huifang Peng, Yujin Ma, Huijun Yuan, Hongwei Jiang   +4 more
doaj   +1 more source

A Dual‐Functional Nanoplatform Targeting the dsDNA–cGAS Axis to Mitigate Disc Degeneration and Aberrant Innervation

Advanced Science, EarlyView.
RU@PEI‐ZIF integrates dsDNA scavenging with local cGAS inhibition to suppress the dsDNA–cGAS–STING/Netrin‐1 axis in intervertebral disc degeneration. By attenuating nucleus pulposus cell senescence, inflammatory and matrix‐catabolic responses, and pathological sensory innervation, this dual‐functional nanoplatform preserves disc integrity and reduces ...
Zhaojun He, Tianyu Chen, Zezheng Liu, Xinlin Huang, Ruitangbin Jiang, Yihao Liu, Baojing Xu, Yuxiang Li, Kangning Zhao, Huibo Yan, Lei Zhou, Can Liu, Qingchu Li   +12 more
wiley   +1 more source

Adeno‐associated virus serotype 2 capsid variants for improved liver‐directed gene therapy

Hepatology, EarlyView., 2022
Abstract Background and Aims Current liver‐directed gene therapies look for adeno‐associated virus (AAV) vectors with improved efficacy. With this background, capsid engineering is explored. Whereas shuffled capsid library screenings have resulted in potent liver targeting variants with one first vector in human clinical trials, modifying natural ...
Nadja Meumann, Marti Cabanes‐Creus, Moritz Ertelt, Renina Gale Navarro, Julie Lucifora, Qinggong Yuan, Karin Nien‐Huber, Ahmed Abdelrahman, Xuan‐Khang Vu, Liang Zhang, Ann‐Christin Franke, Christian Schmithals, Albrecht Piiper, Annabelle Vogt, Maria Gonzalez‐Carmona, Jochen T. Frueh, Evelyn Ullrich, Philip Meuleman, Steven R. Talbot, Margarete Odenthal, Michael Ott, Erhard Seifried, Clara T. Schoeder, Joachim Schwäble, Leszek Lisowski, Hildegard Büning   +25 more
wiley   +1 more source

RBMS1 Contributes to Early Arteriovenous Fistula Neointimal Remodeling Through Modulation of VSMC Phenotypic Responses

Advanced Science, EarlyView.
Postoperative arteriovenous fistulas exhibit increased RBMS1 in vascular smooth muscle cells (VSMCs). In experimental AVFs, RBMS1 overexpression aggravates, whereas deletion attenuates, neointimal hyperplasia. RBMS1 binds MPZL1 mRNA and promotes exon 5 skipping to generate MPZL1‐Δ5, which interacts with G3BP1 to activate AKT, driving VSMC proliferation,
Zongda Li, Chengwei Zhang, Xinying Yu, Shuang Yao, Yiting Lai, Xiaozhu Sun, Yao Zhao, Xiaoyu Lan, Tingting Hu, Wenjin Li, Zhenzhen Ma, Huimin Ma, Zihan Wang, Haihai Liang, Jundong Jiao   +14 more
wiley   +1 more source

c‐Rel–dependent Chk2 signaling regulates the DNA damage response limiting hepatocarcinogenesis

Hepatology, EarlyView., 2022
In response to genotoxic injury, c‐Rel upregulates ATM‐Chk2‐p53 pathway DNA damage proteins to limiting hepatocarcinogenesis. Abstract Background and Aims Hepatocellular carcinoma (HCC) is a leading cause of cancer‐related death. The NF‐κB transcription factor family subunit c‐Rel is typically protumorigenic; however, it has recently been reported as a
Jack Leslie, Jill E. Hunter, Amy Collins, Amelia Rushton, Lauren G. Russell, Erik Ramon‐Gil, Maja Laszczewska, Misti McCain, Marco Y. W. Zaki, Amber Knox, Yixin Seow, Laura Sabater, Daniel Geh, Neil D. Perkins, Helen L. Reeves, Dina Tiniakos, Derek A. Mann, Fiona Oakley   +17 more
wiley   +1 more source