Article
Cell Biology
Ruiyuan Xu, Jianlu Song, Rexiati Ruze, Yuan Chen, Xinpeng Yin, Chengcheng Wang, Yupei Zhao
Summary: This study reveals squalene epoxidase (SQLE) as a novel oncogene that promotes pancreatic cancer (PC) growth by mitigating endoplasmic reticulum stress and activating lipid raft-regulated Src/PI3K/Akt signaling pathway. SQLE facilitates cell proliferation, induces cell cycle progression, and inhibits apoptosis in vitro, while promoting tumor growth in vivo. SQLE inhibitors effectively suppress PC cell proliferation and xenograft tumor growth, highlighting the potential of SQLE as a therapeutic target for PC.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Marta Correia de Sousa, Nicolas Calo, Cyril Sobolewski, Monika Gjorgjieva, Sophie Clement, Christine Maeder, Dobrochna Dolicka, Margot Fournier, Laurent Vinet, Xavier Montet, Jean-Francois Dufour, Bostjan Humar, Francesco Negro, Christine Sempoux, Michelangelo Foti
Summary: Despite being considered a potent oncomiR in human cancers, genetic deletion of miR-21 in mouse models surprisingly promotes hepatocellular carcinoma (HCC) development by affecting various signaling pathways and immune responses. These results challenge the current belief in miR-21 as an oncogene and raise caution regarding using miR-21 inhibition as a therapeutic approach for HCC.
Article
Gastroenterology & Hepatology
Pedro M. Rodrigues, Marta B. Afonso, Andre L. Simao, Tawhidul Islam, Maria M. Gaspar, Colm J. O'Rourke, Monika Lewinska, Jesper B. Andersen, Enara Arretxe, Cristina Alonso, Alvaro Santos-Laso, Laura Izquierdo-Sanchez, Raul Jimenez-Aguero, Emma Eizaguirre, Luis Bujanda, Maria J. Pareja, Carina Prip-Buus, Jesus M. Banales, Cecilia M. P. Rodrigues, Rui E. Castro
Summary: This study evaluated the role of hsa-miRNA-21-5p in the development of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) patients. The expression of hsa-miRNA-21-5p was found to increase with NAFLD severity and was associated with hepatic lipotoxicity. Inhibition of hsa-miRNA-21-5p was shown to prevent the progression of NAFLD to NASH and HCC.
LIVER INTERNATIONAL
(2023)
Article
Agriculture, Dairy & Animal Science
Yan Huang, Chenxu Zhao, Yaoquan Liu, Yezi Kong, Panpan Tan, Siqi Liu, Fangyuan Zeng, Yang Yuan, Xinwei Li, Guowen Liu, Baoyu Zhao, Jianguo Wang
Summary: The study shows that NEFA can activate hepatocyte autophagy through the PERK pathway, contributing to lipid metabolism. These findings enhance our understanding of energy redistribution and utilization during the perinatal period of dairy cows.
Article
Biochemistry & Molecular Biology
Yaobin Liu, Rukmini Mukherjee, Florian Bonn, Thomas Colby, Ivan Matic, Marius Glogger, Mike Heilemann, Ivan Dikic
Summary: The SidE family of Legionella effectors, particularly SdeA, catalyzes non-canonical phosphoribosyl-linked ubiquitination of host proteins to disrupt Golgi integrity. This disruption prevents Golgi linking proteins GRASP55 and GRASP65 from clustering and forming oligomeric structures on multiple serine residues, impacting the host secretory pathway. The Golgi manipulation strategy by Legionella highlights how the bacterium hijacks the secretory pathway to promote bacterial infection.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Pharmacology & Pharmacy
Weimin Yu, Gang Xu, Hui Chen, Li Xiao, Gang Liu, Pingping Hu, Siqi Li, Vivi Kasim, Chunyu Zeng, Xiaoyong Tong
Summary: Pulmonary hypertension (PH) is a life-threatening disease characterized by pulmonary vascular remodeling and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). This study identifies the impact of C674 oxidative inactivation on pulmonary vascular remodeling and PH development, highlighting the importance of C674 in maintaining pulmonary vascular homeostasis by restricting PASMC proliferation. The IRE1 alpha/XBP1s pathway and SERCA2 may serve as potential targets for PH therapy.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Medicine, Research & Experimental
Yaqi Zhang, Yinu Wang, Guangyuan Zhao, Edward J. Tanner, Mazhar Adli, Daniela Matei
Summary: This study identified FOXK2 as a highly expressed stemness-specific transcription factor in ovarian cancer, which regulates the expression of IRE1? and activates stemness pathways. The findings shed light on potentially targetable pathways in cancer stem cells (CSCs) and provide valuable insights for developing new treatments.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Environmental Sciences
Yue Zhang, Dongxu Wang, Kai Yin, Hongjing Zhao, Hongmin Lu, Xin Meng, Lulu Hou, Junbo Li, Mingwei Xing
Summary: In complex ecosystems, birds serve as good bioindicators for monitoring environmental contaminants due to their long lifespan and high trophic positions. However, the effects of microplastics (MPs) on myocardial development in birds remain unknown. This study established an in vivo model of chicks exposed to polystyrene microplastics (PS-MPs) and an in vitro model using chicken embryos to explore the molecular mechanisms underlying the impact of PS-MPs on bird myocardial development. The results showed that PS-MPs induced myocardial dysplasia in birds through the ER stress-mediated autophagic pathway. This research provides valuable data for protecting birds from the health risks of MPs pollution and offers insights into addressing the issue of MPs pollution in complex ecosystems.
ENVIRONMENTAL POLLUTION
(2022)
Review
Biophysics
Judy L. M. Kotler, Timothy O. Street
Summary: The Hsp40, Hsp70, and Hsp90 chaperone families play important roles in cellular protein homeostasis. Recent studies have explored the possibility of understanding how these chaperones work together as a unified system. This review focuses on the mechanics of ERdj3 (an Hsp40), BiP (an Hsp70), and Grp94 (an Hsp90) chaperones within the endoplasmic reticulum, examining their interactions and the gaps in our understanding. Calculations are also used to investigate the impacts of client transfer on protein solubilization, protein folding, and triage decisions for protein degradation. Experimental tests of the proposed roles of client transfer among Hsp40-Hsp70-Hsp90 chaperones are discussed.
ANNUAL REVIEW OF BIOPHYSICS
(2023)
Review
Physiology
Vitalii Kryvenko, Istvan Vadasz
Summary: Protein transcription, translation, and folding are essential processes in living cells, with the endoplasmic reticulum (ER) playing a crucial role in these functions. Elevated CO2 levels can impair ER function, leading to both adaptive and maladaptive regulation of protein folding and maturation.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Pharmacology & Pharmacy
David Hernan Martinez-Puente, Rodolfo Garza-Morales, Jose Juan Perez-Trujillo, Aracely Garcia-Garcia, Arnulfo Villanueva-Olivo, Humberto Rodriguez-Rocha, Laura Mireya Zavala-Flores, Odila Saucedo-Cardenas, Roberto Montes de Oca-Luna, Maria de Jesus Loera-Arias
Summary: Targeting the E7 antigen to the ERAD pathway can induce an ER stress response and has a potent therapeutic antitumor effect. DNA constructs COX2-E7 and COX2-E7 Delta ERAD were shown to effectively target the E7 antigen in mice, demonstrating potential utility for designing other antigen-specific therapies.
JOURNAL OF DRUG TARGETING
(2021)
Article
Multidisciplinary Sciences
Brendan K. Sheehan, Nicola S. Orefice, Yajing Peng, Samantha L. Shapiro, Luigi Puglielli
Summary: The acetylation of ATG9A within the ER lumen is regulated by AT-1/SLC33A1, and dysregulation of AT-1 activity can lead to severe disease phenotypes. The induction of reticulophagy requires interactions between ATG9A, FAM134B, and SEC62 on the cytosolic side of the ER. Furthermore, ATG9A associates with various proteins that help maintain ER proteostasis.
Article
Cell Biology
Hongxia Jiang, Yang Niu, Yuanzhou He, Xiaochen Li, Yongjian Xu, Xiansheng Liu
Summary: The Xbp1s-p-JNK pathway plays a critical role in hypoxic vascular remodeling, and targeting this pathway could be an effective strategy to prevent and alleviate the development of HPH.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Karol Fiedorczuk, Jue Chen
Summary: Small molecule chaperones have been widely used as therapeutics for diseases caused by protein misfolding. CFTR correctors are the most successful examples, as they can revert folding defects and are used to treat cystic fibrosis. Cryo-electron microscopy structures reveal that these correctors stabilize TMD1 of CFTR, preventing premature degradation and rescuing disease-causing mutations.
Article
Pharmacology & Pharmacy
Feng Shi, Zhiwei Wang, Qi Wu, Xiaohan Zhong, Min Zhang, Bowen Li, Wei Ren, Shun Yuan, Yuanyang Chen
Summary: This study investigated the underlying mechanism of how iron deficiency (ID) promotes the formation of aortic media degeneration (AMD). The results showed that ID activates endoplasmic reticulum (ER) stress through mitochondrial oxidative stress, leading to increased apoptosis of aortic smooth muscle cells and the formation of AMD.
PHARMACOLOGICAL RESEARCH
(2022)
