Review
Immunology
Yu-Lin Zhang, Zhen-Jiao Li, Hong-Zhong Gou, Xiao-Jing Song, Lei Zhang
Summary: Liver fibrosis is a liver disease caused by various factors, which can progress to cirrhosis and liver cancer if left untreated. Disruption of the gut microbiota and bile acid metabolism is observed in liver fibrosis cases, suggesting the potential role of the gut microbiota-bile acid axis in its progression. Therefore, studying this axis could lead to the discovery of new targets for prevention, diagnosis, and therapy of chronic liver diseases, including liver fibrosis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Huan Lan, Ying Zhang, Minqi Fan, Bingxin Wu, Caiyan Wang
Summary: This review summarizes the role and progress of PXR in the treatment of CLI, which improves CLI by ameliorating cholestasis, inhibiting inflammation, and reducing fibrosis.
DRUG METABOLISM REVIEWS
(2023)
Review
Pharmacology & Pharmacy
Huan Lan, Ying Zhang, Minqi Fan, Bingxin Wu, Caiyan Wang
Summary: Cholestatic liver injury (CLI) is a disease caused by the accumulation of toxic bile acids (BAs) in the liver, resulting in inflammation and liver fibrosis. The regulation of BA synthesis and homeostasis, particularly through the activation of the Pregnane X receptor (PXR), has shown promise in treating CLI. PXR plays a crucial role in the metabolism of endobiotics and xenobiotics, ultimately modulating BA homeostasis and exerting anti-cholestatic effects. Recent studies have also demonstrated the antifibrotic and anti-inflammatory properties of PXR, providing new insights into CLI treatment.
DRUG METABOLISM REVIEWS
(2023)
Review
Pharmacology & Pharmacy
Fangling Zhang, Xiaolin Xiao, Yong Li, Hefei Wu, Xinyu Deng, Yinxiao Jiang, Wenwen Zhang, Jian Wang, Xiao Ma, Yanling Zhao
Summary: This review summarizes the function and mechanisms of GPBAR1 in cholestatic liver disease. GPBAR1 regulates cholestasis through various pathways and plays an important role in protecting against diseases and injuries. However, its proliferative properties also increase the risk of cholangiocarcinoma.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Xiaoyin Ye, Tong Zhang, Han Han
Summary: The activation of FXR receptor can reduce bile acid synthesis and alleviate cholestasis, but the unresponsiveness of some patients and side effects of UDCA or OCA treatment limit their effectiveness. Therefore, researchers have begun to investigate the role of PPARα receptor in regulating bile acid metabolism and transport, and have found its anti-inflammatory effects that can improve the physiological status of patients with cholestatic liver disorders.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Nutrition & Dietetics
Halima Sultana, Michio Komai, Hitoshi Shirakawa
Summary: Vitamin K plays a critical role in liver diseases, particularly in conditions related to cholestasis. By modulating PXR, vitamin K may have a positive impact on cholestasis and liver fibrosis.
Review
Immunology
Anna Bertolini, Romina Fiorotto, Mario Strazzabosco
Summary: Bile acids not only play a role in digestion and absorption, but also have potential therapeutic value in regulating metabolism and immune function for the treatment of liver diseases.
SEMINARS IN IMMUNOPATHOLOGY
(2022)
Article
Gastroenterology & Hepatology
Xinzhu Liu, Jiaxuan Wang, Maogang Li, Jiannan Qiu, Xingying Li, Li Qi, Jia Liu, Ping Liu, Guoxiang Xie, Xiaoning Wang
Summary: FXR plays a key role in both BA and FA metabolism in NAFLD combined with cholestasis, suggesting it may be a potential target for the treatment of disorders in BA and FA metabolism in this condition.
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Plant Sciences
Chunlei Wei, Jing Qiu, Yuyi Wu, Ziqiang Chen, Ziwei Yu, Zecheng Huang, Ke Yang, Huiling Hu, Fang Liu
Summary: This review summarizes the effective single and compound traditional Chinese medicines (TCMs) for the treatment of cholestatic liver disease (CLD). Based on the different clinical stages of CLD, the pharmacological effects and mechanisms of five promising TCM examples, including Yin Chen, Chi Shao, Fu Ling, Huang Qi Decoction (HQD), and Yin Chen Hao Decoction (YCHD), are discussed. The findings suggest that TCMs can effectively control the development of CLD and personalized treatment measures can slow down the progression of the disease.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Jing Zeng, Jiangao Fan, Huiping Zhou
Summary: Chronic cholestatic liver diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), gradually progress to liver fibrosis, cirrhosis, and failure. Disruption of bile acid metabolism and intrahepatic circulation plays a crucial role in accelerating the progression of cholestatic liver diseases. Bile acids not only act as detergents for nutrition absorption but also function as key signaling molecules that regulate hepatic metabolism and immune responses. This review focuses on the role of bile acid-mediated signaling in cholestatic liver disease.
CELL AND BIOSCIENCE
(2023)
Article
Cell Biology
Katia Sayaf, Ilaria Zanotto, Francesco Paolo Russo, Daniela Gabbia, Sara De Martin
Summary: PXR, a nuclear receptor involved in chronic liver diseases, plays a crucial role in liver damage progression, repair, and the neoplastic transition to hepatocellular carcinoma. By modulating the transcription of drug metabolizing enzymes and transporters, PXR is an important factor in chronic liver diseases. PXR and its modulation could be a promising pharmacological target for novel therapeutical approaches to these diseases.
Article
Oncology
Zhenjie Yang, Shanshan Gao, Chi Chun Wong, Weixin Liu, Huarong Chen, Haiyun Shang, Zoe Yuet Wu, Lixia Xu, Xiang Zhang, Nathalie Wong, Ming Kuang, Jun Yu
Summary: Non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC) is a growing malignancy with no available targeted therapy. This study identified TUBB4B as an essential gene for NAFLD-HCC cell growth and demonstrated that its inhibition with mebendazole (MBZ) in combination with navitoclax synergistically inhibited NAFLD-HCC growth by inducing apoptosis and cellular senescence. These findings suggest TUBB4B as a novel therapeutic target for NAFLD-HCC.
JOURNAL OF PATHOLOGY
(2023)
Review
Immunology
Yushu Yang, XiaoSong He, Manuel Rojas, Patrick S. C. Leung, Lixia Gao
Summary: Primary biliary cholangitis (PBC) is an immune-mediated liver disease characterized by cholestasis, biliary injuries, liver fibrosis, and chronic non-suppurative cholangitis. The pathogenesis of PBC involves immune dysregulation, abnormal bile metabolism, and progressive fibrosis, leading to cirrhosis and liver failure. Current treatments have limitations, and there is a need for further research to investigate underlying mechanisms and develop more effective therapies.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Gastroenterology & Hepatology
Beng San Yeoh, Piu Saha, Rachel M. Golonka, Jun Zou, Jessica L. Petrick, Ahmed A. Abokor, Xia Xiao, Venugopal R. Bovilla, Alexis C. A. Bretin, Jesus Rivera-Esteban, Dominick Parisi, Andrea A. Florio, Stephanie J. Weinstein, Demetrius Albanes, Gordon J. Freeman, Amira F. Gohara, Andreea Ciudin, Juan M. Pericas, Bina Joe, Robert F. Schwabe, Katherine A. McGlynn, Andrew T. Gewirtz, Matam Vijay-Kumar
Summary: This study reveals the association between portosystemic shunt (PSS) and the development of hepatocellular carcinoma (HCC). In mice, PSS combined with a fermentable fiber-enriched diet leads to increased serum bile acids (BA), causing liver injury and progression to cholestatic HCC. Human serum analysis also shows that elevated BA is associated with future development of HCC.
Article
Biochemistry & Molecular Biology
Mohammad Nazmul Hasan, Jianglei Chen, David Matye, Huaiwen Wang, Wenyi Luo, Lijie Gu, Yung Dai Clayton, Yanhong Du, Tiangang Li
Summary: This study investigates the enhanced therapeutic efficacy of combining the apical sodium-dependent bile acid transporter inhibitor GSK2330672 and fibroblast growth factor-15 (FGF15) over-expression in Cyp2c70 KO mice. The combined treatment was more effective in alleviating hepatobiliary injury in female Cyp2c70 KO mice, but ineffective in male mice. It reduced bile acid pool and improved gut barrier function.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Toxicology
Ismael R. Barosso, Andres E. Zucchetti, Gisel S. Miszczuk, Andrea C. Boaglio, Diego R. Taborda, Marcelo G. Roma, Fernando A. Crocenzi, Enrique J. Sanchez Pozzi
ARCHIVES OF TOXICOLOGY
(2016)
Article
Toxicology
Flavia D. Toledo, Cecilia L. Basiglio, Ismael R. Barosso, Andrea C. Boaglio, Andres E. Zucchetti, Enrique J. Sanchez Pozzi, Marcelo G. Roma
ARCHIVES OF TOXICOLOGY
(2017)
Article
Infectious Diseases
Julia A. Loos, Valeria A. Davila, Christian R. Rodrigues, Romina Petrigh, Jorge A. Zoppi, Fernando A. Crocenzi, Andrea C. Cumino
PLOS NEGLECTED TROPICAL DISEASES
(2017)
Article
Biochemistry & Molecular Biology
Gisel S. Miszczuk, Ismael R. Barosso, Maria Cecilia Larocca, Julieta Marrone, Raul A. Marinelli, Andrea C. Boaglio, Enrique J. Sanchez Pozzi, Marcelo G. Roma, Fernando A. Crocenzi
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2018)
Article
Toxicology
Cecilia L. Basiglio, Flavia D. Toledo, Andrea C. Boaglio, Sandra M. Arriaga, Justina E. Ochoa, Enrique J. Sanchez Pozzi, Aldo D. Mottino, Marcelo G. Roma
ARCHIVES OF TOXICOLOGY
(2014)
Article
Toxicology
Gisel S. Miszczuk, Ismael R. Barosso, Andres E. Zucchetti, Andrea C. Boaglio, Jose M. Pellegrino, Enrique J. Sanchez Pozzi, Marcelo G. Roma, Fernando A. Crocenzi
ARCHIVES OF TOXICOLOGY
(2015)
Article
Gastroenterology & Hepatology
Andres E. Zucchetti, Ismael R. Barosso, Andrea C. Boaglio, Cecilia L. Basiglio, Gisel Miszczuk, M. Cecilia Larocca, M. Laura Ruiz, Carlos A. Davio, Marcelo G. Roma, Fernando A. Crocenzi, Enrique J. Sanchez Pozzi
Article
Multidisciplinary Sciences
Gisel S. Miszczuk, Jesus M. Banales, Andres E. Zucchetti, Gerardo B. Pisani, Andrea C. Boaglio, Elena Saez, Juan F. Medina, Marcelo G. Roma, Fernando A. Crocenzi
Review
Biochemistry & Molecular Biology
Marcelo G. Roma, Ismael R. Barosso, Gisel S. Miszczuk, Fernando A. Crocenzi, Enrique J. Sanchez Pozzi
CURRENT MEDICINAL CHEMISTRY
(2019)
Article
Toxicology
Romina Belen Andermatten, Nadia Ciriaci, Virginia Soledad Schuck, Nicolas Di Siervi, Maria Valeria Razori, Gisel Sabrina Miszczuk, Anabela Carolina Medeot, Carlos Alberto Davio, Fernando Ariel Crocenzi, Marcelo Gabriel Roma, Ismael Ricardo Barosso, Enrique Juan Sanchez Pozzi
ARCHIVES OF TOXICOLOGY
(2019)
Article
Pharmacology & Pharmacy
Nadia Ciriaci, Romina Belen Andermatten, Maria Valeria Razori, Virginia Soledad Schuck, Gisel Sabrina Miszczuk, Anabela Carolina Medeot, Fernando Ariel Crocenzi, Marcelo Gabriel Roma, Ismael Ricardo Barosso, Maria Laura Ruiz, Enrique Juan Sanchez Pozzi
BIOCHEMICAL PHARMACOLOGY
(2019)
Review
Biochemistry & Molecular Biology
Cecilia L. Basiglio, Fernando A. Crocenzi, Enrique J. Sanchez Pozzi, Marcelo G. Roma
Summary: Most hepatopathies involve cholestatic characteristics and oxidative stress, which impairs bile generation machinery. Despite recent advances in understanding oxidative stress-induced hepatocellular transporter internalization, the cholestatic implications have been overlooked. Future research should focus on understanding the pro-oxidant triggering factors and signaling pathways to develop personalized therapeutic strategies.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Toxicology
Ismael R. Barosso, Gisel S. Miszczuk, Nadia Ciriaci, Romina B. Andermatten, Paula M. Maidagan, Valeria Razori, Diego R. Taborda, Marcelo G. Roma, Fernando A. Crocenzi, Enrique J. Sanchez Pozzi
ARCHIVES OF TOXICOLOGY
(2018)