Article
Cell Biology
Magdalena Kopytek, Michal Zabczyk, Piotr Mazur, Anetta Undas, Joanna Natorska
Summary: This study aimed to investigate the effect of LDL cholesterol on plasminogen activator inhibitor 1 (PAI-1) expression in aortic stenosis (AS). Results showed that PAI-1 expression in stenotic valves was correlated with lipid accumulation and AS severity, and co-expressed with nuclear factor-κB (NF-κB). In vitro experiments demonstrated that LDL stimulation increased PAI-1 levels and prolonged clot lysis time (CLT). Inhibition of PAI-1 activity or NF-κB pathway shortened CLT. These findings suggest that valvular PAI-1 overexpression driven by lipid accumulation contributes to hypofibrinolysis and AS severity in severe AS patients.
Article
Immunology
Feng He, Yanrui Huang, Zhi Song, Huanjiao Jenny Zhou, Haifeng Zhang, Rachel J. Perry, Gerald Shulman, Wang Min
Summary: By analyzing the transcriptome landscape in human adipocytes, this study revealed elevated mitochondrial ROS pathway and NF-KB signaling, as well as altered fatty acid metabolism in T2DM adipocytes. Mouse experiments showed that adipose-specific deletion of mitochondrial Trx2 led to excessive mitophagy, increased inflammation, and lipolysis in white adipose tissues. Treatment with ROS scavenger or NF-KB inhibitor improved metabolic disorders and T2DM progression in mice.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Immunology
Cristina C. Clement, Jaspreet Osan, Aitziber Buque, Padma P. Nanaware, Yoke-Chen Chang, Giorgio Perino, Madhur Shetty, Takahiro Yamazaki, Wanxia Li Tsai, Aleksandra M. Urbanska, J. Mauricio Calvo-Calle, Shakti Ramsamooj, Diego Vergani, Giorgina Mieli-Vergani, Benedetta Terziroli Beretta-Piccoli, Massimo Gadina, Cristina Montagna, Marcus DaSilva Goncalves, Federica Sallusto, Lorenzo Galluzzi, Rajesh K. Soni, Lawrence J. Stern, Laura Santambrogio
Summary: A diet rich in saturated fat and carbohydrates can cause chronic inflammation in the liver and other organs, leading to nonalcoholic steatohepatitis. This study found that lipotoxicity and glucotoxicity induced by a high-fat and high-fructose diet can promote abnormal immune reactions to PDIA3 in the liver, resulting in liver damage.
SCIENCE IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anna Maria Giudetti, Daniele Vergara, Serena Longo, Marzia Friuli, Barbara Eramo, Stefano Tacconi, Marco Fidaleo, Luciana Dini, Adele Romano, Silvana Gaetani
Summary: The study found that OEA has antioxidant effects on diet-induced obese rats, improving issues such as obesity, steatosis, and hepatic oxidative stress.
Article
Biochemistry & Molecular Biology
Ji-Hyun Kim, Arukumar Nagappan, Dae Young Jung, Nanjoo Suh, Myeong Ho Jung
Summary: The study shows that histone demethylase KDM7A promotes hepatic steatosis by upregulating DGAT2 expression, leading to nonalcoholic fatty liver disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Lu Cheng, Chong Chen, Wenke Guo, Kun Liu, Qianqian Zhao, Ping Lu, Fudong Yu, Xun Xu
Summary: This study identified EFEMP1 as a potential novel biomarker for choroidal neovascularization in age-related macular degeneration (AMD), particularly in wet AMD patients. The overexpression of EFEMP1 was associated with increased angiogenesis, while knockdown of EFEMP1 led to decreased tube formation and proliferation in endothelial cells. These findings suggest that EFEMP1 could be a promising target for the development of pharmaceuticals and diagnostics for wet AMD.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell & Tissue Engineering
Francesco Bellanti, Giorgia di Bello, Giuseppina Iannelli, Giuseppe Pannone, Maria Carmela Pedicillo, Luke Boulter, Wei-Yu Lu, Rosanna Tamborra, Rosanna Villani, Gianluigi Vendemiale, Stuart J. Forbes, Gaetano Serviddio
Summary: NRF2 plays a key role in the fate of HPCs, with its downregulation leading to the activation and differentiation of liver progenitors, thereby suppressing the ductular reaction in injured liver.
NPJ REGENERATIVE MEDICINE
(2021)
Article
Gastroenterology & Hepatology
Shuang Zhao, Tianyu Song, Yue Gu, Yihua Zhang, Siyi Cao, Qing Miao, Xiyue Zhang, Hongshan Chen, Yuanqing Gao, Lei Zhang, Yi Han, Hong Wang, Jun Pu, Liping Xie, Yong Ji
Summary: The study suggests that H2S alleviates liver damage by activating Keap1 S-sulfhydration and promoting the activation of Nrf2, leading to increased expression of antioxidant proteins, which may have potential therapeutic benefits for liver diseases.
Article
Oncology
Yanqiong Liu, Qiulian Wu, Fuyong Zhang, Xue Qin
Summary: This study provides evidence for the first time that the NRF2 gene rs6721961 variation is a potential genetic marker for susceptibility to hepatocellular carcinoma (HCC).
CANCER CELL INTERNATIONAL
(2023)
Article
Endocrinology & Metabolism
Ye Young Kim, Hagoon Jang, Gung Lee, Yong Geun Jeon, Jee Hyung Sohn, Ji Seul Han, Won Taek Lee, Jeu Park, Jin Young Huh, Hahn Nahmgoong, Sang Mun Han, Jeesoo Kim, Minwoo Pak, Sun Kim, Jong-Seo Kim, Jae Bum Kim
Summary: This study demonstrated that the reduction of hepatic CRY1 protein in diabetic mice is stimulated by FBXL3-dependent proteasomal degradation and GSK3 beta-induced CRY1 phosphorylation. Tight regulation of hepatic CRY1 protein stability is crucial for maintaining systemic glucose homeostasis.
Article
Immunology
Wenting Jian, Huigai Ma, Dingming Wang, Peng Yang, Mengbi Jiang, Yu Zhong, Xiang Long, Jingjing Jiang, Yuan Gong
Summary: This study demonstrates that omaveloxolone exerts significant cardioprotective effects in treating sepsis-induced cardiomyopathy by activating the Nrf2 signaling pathway.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Gastroenterology & Hepatology
Xiaobo Wang, Sharon Zeldin, Hongxue Shi, Changyu Zhu, Yoshinobu Saito, Kathleen E. Corey, Stephanie A. Osganian, Helen E. Remotti, Elizabeth C. Verna, Utpal B. Pajvani, Robert F. Schwabe, Ira Tabas
Summary: This study demonstrates that TAZ protein in pre-tumor NASH-hepatocytes promotes damage to the DNA of hepatocytes, contributing to eventual HCC. Targeting TAZ in NASH therapies may prevent NASH-HCC.
JOURNAL OF HEPATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Andrew M. Jobbins, Nejc Haberman, Natalia Artigas, Christopher Amourda, Helen A. B. Paterson, Sijia Yu, Samuel J. Blackford, Alex Montoya, Marian Dore, Yi-Fang Wang, Alessandro Sardini, Ines Cebola, Johannes Zuber, Sheikh Tamir Rashid, Boris Lenhard, Santiago Vernia
Summary: Pre-mRNA processing is altered in non-alcoholic fatty liver disease (NAFLD), with dysregulated alternative splicing and alternative polyadenylation. Decreased expression of SRSF10, a splicing factor, is associated with dysregulation of pre-mRNA processing in NAFLD.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Caizhi Liu, Bing Zhou, Meiyao Meng, Wenjun Zhao, Dongmei Wang, Youwen Yuan, Ying Zheng, Jin Qiu, Yu Li, Guoqiang Li, Xuelian Xiong, Hua Bian, Huijie Zhang, Hua Wang, Xinran Ma, Cheng Hu, Lingyan Xu, Yan Lu
Summary: The study identified FOXA3 as a key bridging molecule connecting ER stress and NAFLD progression, with its deficiency alleviating fatty liver. Increased levels of FOXA3 were found in the livers of obese mice and patients with NAFLD, suggesting FOXA3 as a potential therapeutic target for fatty liver disease.
JOURNAL OF HEPATOLOGY
(2021)
Article
Medicine, Research & Experimental
Wenjing Wang, Yoichi Miyamoto, Biaobang Chen, Juanzi Shi, Feiyang Diao, Wei Zheng, Qun Li, Lan Yu, Lin Li, Yao Xu, Ling Wu, Xiaoyan Mao, Jing Fu, Bin Li, Zheng Yan, Rong Shi, Xia Xue, Jian Mu, Zhihua Zhang, Tianyu Wu, Lin Zhao, Weijie Wang, Zhou Zhou, Jie Dong, Qiaoli Li, Li Jin, Lin He, Xiaoxi Sun, Ge Lin, Yanping Kuang, Lei Wang, Qing Sang
Summary: By analyzing whole-exome sequencing data of 606 women with PREMBA, researchers have identified a candidate gene KPNA7, which may contribute to the development of PREMBA. The study further revealed that KPNA7 mutations reduce protein levels, impair its binding capacity to substrate RSL1D1, and affect nuclear transport activity. Furthermore, the study found that mouse KPNA2 plays a critical role in embryonic development and its deficiency leads to embryo arrest, similar to human PREMBA cases. These findings provide a mechanistic understanding of PREMBA and a diagnostic marker for PREMBA patients.
JOURNAL OF CLINICAL INVESTIGATION
(2023)