Article
Multidisciplinary Sciences
Umeharu Ohto, Yukie Kamitsukasa, Hanako Ishida, Zhikuan Zhang, Karin Murakami, Chie Hirama, Sakiko Maekawa, Toshiyuki Shimizu
Summary: This study reveals the cryo-electron microscopy structure of the dodecameric form of NLRP3 and its binding site with the inhibitor MCC950. It provides insights into the role of NLRP3 in membrane association and activation, offering potential targets for drug development.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Xiaoling Peng, Jihong Wang, Zheng Li, Xiaoqian Jia, Anqi Zhang, Jie Ju, Volker Eulenburg, Feng Gao
Summary: This study explores the role of TLR2 in morphine tolerance and its relationship with melatonin and NLRP3 inflammasome. It is found that morphine tolerance is associated with increased TLR2 expression and NLRP3 inflammasome activation in the spinal cord, while melatonin level is down-regulated. Chronic melatonin administration reduces TLR2 expression and NLRP3 inflammasome activation, partially restoring the analgesic effect of morphine. Inhibition of TLR2 and microglia activation attenuates the development of morphine tolerance by restoring spinal melatonin level and suppressing NLRP3 inflammasome signaling.
NEUROCHEMICAL RESEARCH
(2023)
Article
Nutrition & Dietetics
Feng Wang, Jeong-Su Park, Yuanqiang Ma, Hwan Ma, Yeo-Jin Lee, Gyu-Rim Lee, Hwan-Soo Yoo, Jin-Tae Hong, Yoon-Seok Roh
Summary: Saponin extract significantly alleviated hepatic steatosis, fibrosis, and inflammation in NAFLD induced by a fast food diet. The extract contained increased amounts of ginsenosides, which exerted anti-steatotic, antifibrotic, anti-inflammatory, and pro-mitophagy effects in various cell types. Mechanistically, saponin extract inhibited NLRP3 inflammasome activation by promoting mitophagy, thereby preventing inflammation-mediated pathological inflammasome activation and NAFLD development.
Article
Environmental Sciences
Li Jing, Dan Zheng, Xuejing Sun, Zhixiong Shi
Summary: In this study, it was found that DBDPE could cause aortic endothelial injury and cell pyroptosis. Specifically, DBDPE activated the NOD-like receptor signaling pathway, involving NLRP3 and IL-18. RIPK2 knockdown was shown to inhibit the activation of this pathway and decrease cell death. It was also demonstrated that DBDPE could induce ROS generation and activate NLRP3 inflammasome through upregulation of the NOD-like receptor signaling pathway.
ENVIRONMENTAL POLLUTION
(2023)
Article
Medicine, Research & Experimental
Chao Wu, Yanqin Bian, Bingjie Lu, Dan Wang, Nisma Lena Bahaji Azami, Gang Wei, Feng Ma, Mingyu Sun
Summary: In this study, the efficacy and mechanism of rhubarb free anthraquinones (RFAs) in treating nonalcoholic fatty liver disease (NAFLD) by inhibiting nucleotide oligomerization domain-like receptors containing pyrin domain 3 (NLRP3) inflammasome were explored. The results demonstrated that RFAs inhibited the production of IL-1β and improved liver function and inflammation levels in NAFLD. These findings suggest that RFAs may be a potential therapeutic agent for NAFLD.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Review
Immunology
Liyun Xu, Wen Liu, Fuxiang Bai, Yong Xu, Xiaohong Liang, Chunhong Ma, Lifen Gao
Summary: Non-alcoholic fatty liver disease is becoming increasingly common worldwide, with hepatic macrophages, specifically Kupffer cells, playing a key role in its progression. Understanding the diverse roles of hepatic macrophages in the development of fatty liver disease may lead to more promising therapeutic strategies for inflammatory liver diseases.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Pharmacology & Pharmacy
Lili Yu, Wei Hong, Shen Lu, Yanrong Li, Yaya Guan, Xiaogang Weng, Zhiwei Feng
Summary: NAFLD is a common primary liver disease worldwide with no effective treatment currently available. Recent studies suggest that activation of the NLRP3 inflammasome plays a crucial role in the development of NAFLD. Several NLRP3 inflammasome inhibitors have shown promising results in experimental and clinical studies.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mauricio P. Contreras, Hsuan Pai, Yasin Tumtas, Cian Duggan, Enoch Lok Him Yuen, Angel Vergara Cruces, Jiorgos Kourelis, Hee-Kyung Ahn, Kim-Teng Lee, Chih-Hang Wu, Tolga O. Bozkurt, Lida Derevnina, Sophien Kamoun
Summary: Nucleotide-binding domain leucine-rich repeat (NLR) immune receptors are important components of plant and metazoan innate immunity. In asterid plant species, the NLR required for cell death (NRC) immune receptor network is composed of multiple resistance protein sensors and downstream helpers. The study reveals the activation and release model for NLRs in the NRC immune receptor network and provides insights into the activation mechanisms of plant paired NLRs.
Review
Chemistry, Multidisciplinary
Juan Jin, Tao-jie Zhou, Gui-ling Ren, Liang Cai, Xiao-ming Meng
Summary: NLRs, a major subfamily of pattern recognition receptors, have gained considerable attention due to their involvement in mediating the immune response and inflammatory pathways. This review summarises recent progress on the functions and mechanisms of NLRs in different types of renal diseases.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Immunology
Ling-Cui Meng, Jia-Yi Zheng, Yu-Hui Qiu, Li Zheng, Jue-Yan Zheng, Yu-Qing Liu, Xiao-Lu Miao, Xin-Yi Lu
Summary: In this study, the protective effects of Salvianolic acid B (SalB) on non-alcoholic fatty liver disease (NAFLD) were investigated. The results showed that SalB significantly reduced body and liver weights, improved plasma markers of liver damage, and reduced hepatic lipid accumulation in a mouse model of NAFLD. SalB also inhibited inflammation and the activation of NLRP3 inflammasome. These findings suggest that SalB has potential as a hepatoprotective agent against NAFLD.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Yuki Ohta, Masayuki Fujii, Sirirat Takahashi, Ai Takano, Kosaku Nanki, Mami Matano, Hikaru Hanyu, Megumu Saito, Mariko Shimokawa, Shingo Nishikori, Yoshiko Hatano, Ryota Ishii, Kazuaki Sawada, Akihito Machinaga, Wataru Ikeda, Takeshi Imamura, Toshiro Sato
Summary: This study develops an experimental platform for tracking cancer stem cells in colorectal cancer and identifies dormant LGR5(+) cancer stem cells. Transcriptome analysis reveals an upregulation of cell-adhesion molecule COL17A1 in dormant cancer stem cells, and chemotherapy disrupts this dormancy through FAK-YAP activation. Inhibition of YAP signaling prevents chemoresistant cells from exiting dormancy and delays tumor regrowth.
Article
Multidisciplinary Sciences
Jawaher Alharthi, Ali Bayoumi, Khaled Thabet, Ziyan Pan, Brian S. Gloss, Olivier Latchoumanin, Mischa Lundberg, Natalie A. Twine, Duncan McLeod, Shafi Alenizi, Leon A. Adams, Martin Weltman, Thomas Berg, Christopher Liddle, Jacob George, Mohammed Eslam
Summary: This study investigates the negative regulatory role of MBOAT7 in TLR signaling, showing that its deficiency can lead to inflammatory responses and various diseases. Activation of MBOAT7 can reverse these effects, suggesting it as a potential therapeutic target for diseases associated with dysregulation of the TLR signaling cascade.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Xiaolin Xu, Xianli Wu, Gengyu Yue, Qimin An, Jun Lou, Xiaoxu Yang, Zhe Jin, Jianhong Ding, Yanxia Hu, Qian Du, Jingyu Xu, Rui Xie
Summary: This article summarizes the activation mechanisms of inflammasomes and their relationship with diseases, and provides an overview of the effects of intracellular and extracellular ion activities and ion channels on inflammasome activation.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Chuanyue Gao, Huan Zhang, Lulin Nie, Kaiwu He, Peimao Li, Xingxing Wang, Zaijun Zhang, Yongmei Xie, Shupeng Li, Gongping Liu, Xinfeng Huang, Huiping Deng, Jianjun Liu, Xifei Yang
Summary: This study aimed to investigate the therapeutic potential of Chrysin (CN) against high-fat diet induced non-alcoholic fatty liver disease (NAFLD) and elucidate its mechanism. The results showed that CN treatment significantly reduced liver fat accumulation and inflammation, improving obesity and liver injury in NAFLD mice. Proteomic analysis revealed that CN modified the expression of proteins related to energy, metabolism, and inflammation. Mechanistically, CN activated AMP-activated protein and phosphorylated CoA, reducing inflammation and inhibiting NLRP3 expression.
JOURNAL OF PHARMACY AND PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Tingting Liu, Guang Xu, Longxin Liang, Xiaohe Xiao, Yanling Zhao, Zhaofang Bai
Summary: Inflammation plays a key role in fatty liver diseases, and the aberrant activation of the NLRP3 inflammasome is considered a main factor in driving liver injury, inflammation, steatosis, and fibrosis. Traditional Chinese medicines have been shown to inhibit the activation of the NLRP3 inflammasome and have potential as therapeutic agents for fatty liver diseases.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Yoon Mee Yang, Ye Eun Cho, Seonghwan Hwang
Summary: Alcoholic liver disease (ALD), caused by excessive alcohol consumption, results in liver damage. Studies have shown that there is a relationship between hepatic oxidative stress and inflammatory responses, which may be useful for developing therapeutic approaches for ALD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Lucia Barbier-Torres, Ben Murray, Jin Won Yang, Jiaohong Wang, Michitaka Matsuda, Aaron Robinson, Aleksandra Binek, Wei Fan, David Fernandez-Ramos, Fernando Lopitz-Otsoa, Maria Luque-Urbano, Oscar Millet, Nirmala Mavila, Hui Peng, Komal Ramani, Roberta Gottlieb, Zhaoli Sun, Suthat Liangpunsakul, Ekihiro Seki, Jennifer E. Van Eyk, Jose M. Mato, Shelly C. Lu
Summary: MAT alpha 1 plays a role in reducing activity and causing mitochondrial dysfunction in alcohol-associated liver disease (ALD). This study found that the peptidyl-prolyl cis/trans isomerase PIN1 and kinase CK2 mediate the selective depletion of mitochondrial MAT alpha 1 in ALD. Blocking the interaction between PIN1 and MAT alpha 1 increased mitochondrial levels of MAT alpha 1 and protected against alcohol-induced mitochondrial dysfunction and fat accumulation.
NATURE COMMUNICATIONS
(2022)
Article
Gastroenterology & Hepatology
Guangyue Yang, Liping Zhuang, Tiantian Sun, Yee Hui Yeo, Le Tao, Wei Zhang, Wenting Ma, Liu Wu, Zongguo Yang, Yanqin Yang, Dongying Xue, Jie Zhang, Rilu Feng, Ebert P. Matthias, Steven Dooley, Ekihiro Seki, Ping Liu, Cheng Liu
Summary: By analyzing serum, tissue mRNA, and biopsy data, we found the potential of sGDNF as a novel noninvasive biomarker for predicting cirrhosis in chronic hepatitis B patients.
CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Le Tao, Guangyue Yang, Tiantian Sun, Jie Tao, Chan Zhu, Huimin Yu, Yalan Cheng, Zongguo Yang, Mingyi Xu, Yuefeng Jiang, Wei Zhang, Zhiyi Wang, Wenting Ma, Liu Wu, Dongying Xue, Dongxue Wang, Wentao Yang, Yongjuan Zhao, Shane Horsefield, Bostjan Kobe, Zhe Zhang, Zongxiang Tang, Qigen Li, Qiwei Zhai, Steven Dooley, Ekihiro Seki, Ping Liu, Jianrong Xu, Hongzhuan Chen, Cheng Liu
Summary: This study discovered the presence of TRPV1 in hepatic stellate cells (HSCs) and investigated its function in this cell type and liver fibrosis. TRPV1's expression is associated with liver fibrosis and its antifibrotic properties are attributed to the prevention of HSC activation. This finding could be a potential therapeutic strategy against liver fibrosis.
JOURNAL OF HEPATOLOGY
(2023)
Editorial Material
Gastroenterology & Hepatology
Jieun Kim, Ekihiro Seki
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Cell Biology
Zhijun Wang, So Yeon Kim, Wei Tu, Jieun Kim, Alexander Xu, Yoon Mee Yang, Michitaka Matsuda, Lien Reolizo, Takashi Tsuchiya, Sandrine Billet, Alexandra Gangi, Mazen Noureddin, Ben A. Falk, Sungjin Kim, Wei Fan, Mourad Tighiouart, Sungyong You, Michael S. Lewis, Stephen J. Pandol, Dolores Di Vizio, Akil Merchant, Edwin M. Posadas, Neil A. Bhowmick, Shelly C. Lu, Ekihiro Seki
Summary: Liver metastasis is a major cause of death in colorectal cancer patients with fatty liver, but the underlying mechanism is unclear. Our study found that extracellular vesicles (EVs) derived from hepatocytes in fatty liver enhance the progression of CRC liver metastasis by promoting oncogenic Yes-associated protein (YAP) signaling and an immunosuppressive microenvironment. Fatty liver upregulates Rab27a expression, promoting EV production from hepatocytes. These EVs transfer YAP signaling-regulating microRNAs to cancer cells, augmenting YAP activity by suppressing LATS2.
Editorial Material
Oncology
Manish Thiruvalluvan, Neil A. Bhowmick
Article
Oncology
Hayato Muranaka, Andrew Hendifar, Arsen Osipov, Natalie Moshayedi, Veronica Placencio-Hickok, Nicholas Tatonetti, Aleksandr Stotland, Sarah Parker, Jennifer Van Eyk, Stephen J. Pandol, Neil A. Bhowmick, Jun Gong
Summary: Pancreatic cancer is a deadly disease, and finding biomarkers for predicting chemotherapy response is crucial for improving the prognosis of advanced patients. By analyzing plasma metabolites, this study found that the levels of intermediate metabolites in multiple metabolic pathways were statistically different in patients with different responses to chemotherapy. The study demonstrates the feasibility of plasma metabolomics in assessing the effect of enteral feeding as the primary source of nutrition, and suggests that metabolic signatures specific to different chemotherapy regimens could be predictive of patient response.
Review
Gastroenterology & Hepatology
Young-Sun Lee, Ekihiro Seki
Summary: It is crucial to choose an appropriate liver fibrosis model based on the purpose of study and type of disease due to the varied development and progression of liver fibrosis according to its etiology. This review provides a summary and analysis of various in vivo and in vitro liver fibrosis models and their implications and limitations. Liver fibrosis is a common consequence of various chronic liver diseases, and understanding its pathophysiology and identifying potential therapeutic targets is essential as it can progress to advanced liver diseases. Despite numerous studies, the underlying mechanisms of liver fibrosis remain unclear.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Gastroenterology & Hepatology
Jieun Kim, Ekihiro Seki
Summary: Hyaluronan plays a critical role in liver fibrosis by serving as both a key component of the extracellular matrix and a functional signaling molecule. Understanding the regulatory mechanisms of its synthesis and degradation, as well as its pathophysiological effects, is important for therapeutic intervention in liver fibrosis.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Oncology
Le Zhang, Yueyuan Zheng, Wenwen Chien, Benjamin Ziman, Sandrine Billet, H. Phillip Koeffler, De-Chen Lin, Neil A. Bhowmick
Summary: ARID1A deficiency enhances tumor immune response and promotes CD8(+) T cell recruitment and cytolytic activity in esophageal adenocarcinoma (EAC). Additionally, ARID1A regulates fatty acid metabolism genes, influencing CD8(+) T cell recruitment and cytolytic activity.
Meeting Abstract
Gastroenterology & Hepatology
Wei Fan, Jiaohong Wang, Tony Wh Li, Ting Liu, Jose M. Mato, Ekihiro Seki, Heping Yang, Shelly C. Lu
Meeting Abstract
Gastroenterology & Hepatology
Feng Wang, Yoon-Seok Roh, Jin Lee, Jeong-Su Park, So Yeon Kim, Yoon Mee Yang, Ekihiro Seki
Meeting Abstract
Gastroenterology & Hepatology
Hwan Ma, Yoon-Seok Roh, Jin Lee, Jeong-Su Park, Feng Wang, Ekihiro Seki
Article
Biochemistry & Molecular Biology
Sun Myoung Kim, Ga Yeon Song, Aeri Shim, Jee Hyung Lee, Cheol Bin Eom, Cheng Liu, Yoon Mee Yang, Ekihiro Seki
Summary: Liver fibrosis is a disease characterized by excessive extracellular matrix deposition during wound healing after repeated liver injury. Recent research has identified hyaluronan synthase 2 (HAS2) as a driver of liver fibrosis and hepatic stellate cell (HSC) activation. This study reveals that miR-200c negatively regulates HAS2 and contributes to the development of acute liver injury and chronic liver inflammation. Additionally, hyaluronidase-2 (HYAL2) is found to be overexpressed in fibrotic livers, which indicates its potential involvement in liver fibrosis.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)