Article
Biochemistry & Molecular Biology
Ying Wan, Tianhao Zhou, Elise Slevin, Sachiko Koyama, Xuedong Li, Kelly Harrison, Tian Li, Bingru Zhou, Sugeily Ramos Lorenzo, Yudian Zhang, Wenjuan Xu, James E. Klaunig, Chaodong Wu, Ashok K. Shetty, Chiung-Kuei Huang, Fanyin Meng
Summary: Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by cholestasis, inflammation, and fibrotic scar formation. This study investigated the role of liver-specific microRNA-34a in ductular reaction and liver fibrosis. They found that miR-34a expression was increased in PSC livers, and its knockout in a cholestatic liver disease model reduced ductular pathology and fibrotic responses.
Article
Biochemistry & Molecular Biology
Ester Gonzalez-Sanchez, Haquima El Mourabit, Marion Jager, Marie Clavel, Sophie Moog, Javier Vaquero, Tatiana Ledent, Axelle Cadoret, Jeremie Gautheron, Laura Fouassier, Dominique Wendum, Nicolas Chignard, Chantal Housset
Summary: The study showed that VDR signaling has an anti-inflammatory role in cholangiocytes and cholangiopathy, while PDIA3-mediated effects of vitamin D and its analogs also have anti-inflammatory effects in these settings.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Gastroenterology & Hepatology
Vik Meadows, Lindsey Kennedy, Burcin Ekser, Konstantina Kyritsi, Debjyoti Kundu, Tianhao Zhou, Lixian Chen, Linh Pham, Nan Wu, Jennifer Demieville, Laura Hargrove, Shannon Glaser, Gianfranco Alpini, Heather Francis
Summary: Our study found that MC-FXR plays a key role in regulating liver damage, ductular reaction (DR), and hepatic fibrosis by altering intestinal and biliary FXR/FGF15 signaling. Patients with liver injury show increased MC number and biliary FXR expression. MC injection exacerbates liver damage, inflammation, and fibrosis in mice models.
Article
Pathology
Donghai Wang, Ivan A. Gonzalez, Pierre A. Russo, Dhanpat Jain, Xuchen Zhang
Summary: Pseudoacini are usually considered as a morphologic feature of hepatocellular carcinoma, but they can also be seen in focal nodular hyperplasia, which may present diagnostic challenges. This study aims to evaluate the occurrence of pseudoacini in focal nodular hyperplasia and their clinicopathologic correlations.
AMERICAN JOURNAL OF SURGICAL PATHOLOGY
(2022)
Review
Cell Biology
Anca D. Petrescu, Sharon DeMorrow
Summary: Recent studies have shown that cirrhosis ranks as the 11th leading cause of death worldwide, highlighting the urgent need for new therapies to slow the progression of liver damage in the early stages. Cholestasis, caused by accumulation of hydrophobic bile acids in the liver, has led to investigations on detoxification strategies and downregulation of genes involved in bile acid production. Dysregulation of FXR signaling has been linked to changes in autophagy due to reactive oxygen species induced by bile acids and increased antioxidant response through NRF2, opening up new avenues for developing more effective therapies.
Article
Gastroenterology & Hepatology
Quentin M. Anstee, Kathryn J. Lucas, Sven Francque, Manal F. Abdelmalek, Arun J. Sanyal, Vlad Ratziu, Adrian C. Gadano, Mary Rinella, Michael Charlton, Rohit Loomba, Edward Mena, Joern M. Schattenberg, Mazen Noureddin, Donald Lazas, George B. B. Goh, Shiv K. Sarin, Yusuf Yilmaz, Miljen Martic, Rowan Stringer, Jossy Kochuparampil, Li Chen, Gerardo Rodriguez-Araujo, Elaine Chng, Nikolai V. Naoumov, Clifford Brass, Marcos C. Pedrosa
Summary: This study assessed the safety and efficacy of the combined treatment of tropifexor and cenicriviroc for NASH, compared to monotherapy. The combination treatment did not show substantial incremental efficacy compared to monotherapy.
Article
Pharmacology & Pharmacy
Yonghong Hu, Xiaoli He, Xiaoxi Zhou, Yue Liang, Yadong Fu, Linzhang Zhang, Jing Fang, Wei Liu, Gaofeng Chen, Yongping Mu, Hua Zhang, Hong Cai, Chenghai Liu, Ping Liu, Jiamei Chen
Summary: This study found that GPs can attenuate ductular reaction (DR) and liver fibrosis by inhibiting hedgehog signaling, providing new evidence for the anti-fibrotic effect of GPs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biology
Shikai Hu, Jacquelyn O. Russell, Silvia Liu, Catherine Cao, Jackson McGaughey, Ravi Rai, Karis Kosar, Junyan Tao, Edward Hurley, Minakshi Poddar, Sucha Singh, Aaron Bell, Donghun Shin, Reben Raeman, Aatur D. Singhi, Kari Nejak-Bowen, Sungjin Ko, Satdarshan P. Monga
Summary: Loss of beta-catenin in BECs results in sustained DR and fibrosis, potentially contributing to the hepatic pathology of cystic fibrosis.
Article
Biochemistry & Molecular Biology
Zhenyang Shen, Weiming Dai, Yuecheng Guo, Junjun Wang, Bo Shen, Binghang Li, Lungen Lu, Xiaobo Cai
Summary: Liver fibrosis is associated with the expansion and differentiation of liver progenitor cells (LPCs). YAP plays a crucial role in regulating LPCs proliferation and differentiation during liver fibrosis, and manipulating YAP expression in LPCs may present a potential treatment for chronic liver diseases.
Article
Pharmacology & Pharmacy
Shengjie Li, Aoxiang Zhuge, Kaicen Wang, Jiafeng Xia, Qiangqiang Wang, Shengyi Han, Jian Shen, Lanjuan Li
Summary: This study investigates the effects of obeticholic acid (OCA), ferrostatin-1 (Fer-1), and their combination on various clinical profiles in non-alcoholic steatohepatitis (NASH). Results show that Fer-1 has better effects on improving body weight, blood glucose levels, transaminase levels, and insulin resistance compared to OCA. OCA has a profound effect on ameliorating lipid accumulation. The combination of OCA and Fer-1 significantly reduces inflammation and protects against liver oxidative stress. Additionally, OCA and Fer-1 differentially reshape the intestinal microbiota and affect the hepatic lipidome.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Nerea Lazcanoiturburu, Juan Garcia-Saez, Carlos Gonzalez-Corralejo, Cesareo Roncero, Julian Sanz, Carlos Martin-Rodriguez, M. Pilar Valdecantos, Adoracion Martinez-Palacian, Laura Almale, Paloma Bragado, Silvia Calero-Perez, Almudena Fernandez, Maria Garcia-Bravo, Carmen Guerra, Lluis Montoliu, Jose Carlos Segovia, Angela M. Valverde, Isabel Fabregat, Blanca Herrera, Aranzazu Sanchez
Summary: Inactivating EGFR signaling in the liver can reduce liver damage and promote efficient regeneration following cholestatic injury. This effect involves enhanced activation of mitogenic/survival signals and changes in cell turnover, which are associated with differences in the profile of intrahepatic immune cells.
JOURNAL OF PATHOLOGY
(2022)
Article
Medicine, Research & Experimental
I. S. Bebiashvili, M. Sh Kakabadze, S. M. Gvidiani, K. B. Tsomaia, S. A. Gusev, D. J. Kordzaia
Summary: Ductular reaction is a phenomenon that occurs during liver regeneration, fibrosis, and carcinogenesis, but the types, stages, and locations of ductular profiles in different pathologies are not well studied. Using a model of common bile duct occlusion, it was found that the number and location of ductular profiles are closely related to the duration of biliary obstruction. Ductular profiles can be found in various locations within the liver and can be formed through different mechanisms such as bile duct expansion, cholangiocyte proliferation, and hepatocyte transdifferentiation and activation of stem cells.
BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Konstantina Kyritsi, Lindsey Kennedy, Vik Meadows, Laura Hargrove, Jennifer Demieville, Linh Pham, Amelia Sybenga, Debjyoti Kundu, Karla Cerritos, Fanyin Meng, Gianfranco Alpini, Heather Francis
Summary: The study demonstrates that reintroduction of MCs through TGF-beta 1 promotes cholestatic liver injury characterized by fibrosis, angiogenesis, and ductular reaction. However, blocking TGF-beta 1 with TGF-beta Ri can reverse these pathological processes.
Review
Gastroenterology & Hepatology
Michal Prokopic, Ulrich Beuers
Summary: PSC is a rare liver disease characterized by bile duct abnormalities leading to liver fibrosis and potential cholangiocarcinoma. The exact pathogenesis is still unclear, with strong association with inflammatory bowel disease. Current medical treatments have not been proven effective, with liver transplantation remaining the most viable option for late-stage disease.
HEPATOLOGY INTERNATIONAL
(2021)
Article
Gastroenterology & Hepatology
Nadir Abbas, Emma L. Culver, Douglas Thorburn, Neil Halliday, Hannah Crothers, Jessica K. Dyson, April Phaw, Richard Aspinall, Salim I. Khakoo, Yiannis Kallis, Belinda Smith, Imran Patanwala, Anne McCune, Chenchu R. Chimakurthi, Vinod Hegade, Michael Orrell, Rebecca Jones, George Mells, Colette Thain, Robert-Mitchell Thain, David Jones, Gideon Hirschfield, Palak J. Trivedi
Summary: This study aimed to evaluate the effectiveness of obeticholic acid (OCA) and fibric acid derivatives as second-line treatments for primary biliary cholangitis. The study found that rates of biochemical response and drug discontinuation were similar between fibric acid derivatives and OCA in patients in the United Kingdom.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Medicine, Research & Experimental
Yuwen Zhu, Yan Guo, Yujia Xue, Anqi Zhou, Ying Chen, Yifei Chen, Xiulian Miao, Fangqiao Lv
Summary: BRG1 plays an important role in HSC-myofibroblast transition and targeting it could be a reasonable strategy for liver fibrosis intervention.
Article
Medicine, Research & Experimental
Liu Ye, Beibei Liu, Jingling Huang, Xiaolin Zhao, Yuan Wang, Yungen Xu, Shuping Wang
Summary: Doublecortin-like kinase 1 (DCLK1) is a significant prooncogenic factor that is strongly associated with the malignant progression and clinical prognosis of various cancers. DCLK1 plays important roles in stem cell marker regulation, tumor cell reprogramming, and immune evasion. However, the exact biological functions of DCLK1, especially the disparities between its alpha- and beta-form transcripts in cancer progression, remain ambiguous.
Article
Medicine, Research & Experimental
Jiahui Yang, Xiaoyu Chen, Tianjing Liu, Yongyan Shi
Summary: This article reviews the role of bile acids in necrotizing enterocolitis (NEC) and their potential therapeutic value. The dysregulation of bile acids is associated with intestinal injury, and inflammatory factors in the liver also play a crucial role in regulating bile acid transport. The bile acid metabolic pathway is important for regulating intestinal microbiota, cell proliferation, and barrier protection.
Review
Medicine, Research & Experimental
Zhenzheng Zhu, Yuemiao Xu, Yuwei Xia, Xinru Jia, Yixin Chen, Yuyue Liu, Leyin Zhang, Hui Chai, Leitao Sun
Summary: Bile acid, as the final product of cholesterol breakdown, plays a complex regulatory and signaling role in human metabolism. Research suggests that it has the potential to enhance metabolism and regulate chronic metabolic diseases through various pathways. The interaction between bile acid and gut microbiota is also of great significance.
Article
Medicine, Research & Experimental
Xin He, Hong-Xu Zhou, Xian Fu, Kai-Di Ni, Ai-Zhi Lin, Ling-Tong Zhang, Hou-Hua Yin, Qing Jiang, Xue Zhou, Yi-Wen Meng, Jun-Yan Liu
Summary: DON exposure causes an increase in deoxycholic acid (DCA), which contributes to intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity.
Article
Medicine, Research & Experimental
Zhitao Wang, Heng Ma, Abdul Nasir, Sufang Liu, Zhisong Li, Feng Tao, Qian Bai
Summary: This study reveals the involvement of TET1-mediated epigenetic regulation in chronic TMJ pain through trigeminal TNF alpha signaling.
Article
Medicine, Research & Experimental
Lu Yu, Hao Ran, Yaru Lu, Qian Ma, Huan Huang, Weibin Liu
Summary: This study found that the HIF-1 alpha inhibitor BAY 87-2243 can alleviate the symptoms of the Experimental Autoimmune Myasthenia Gravis (EAMG) inflammation model. BAY 87-2243 can restore the balance of CD4(+)T cell subsets, reduce the production of pro-inflammatory cytokines, and act as both an immune imbalance regulator and anti-inflammatory.
Article
Medicine, Research & Experimental
Alex Peralvarez-Marin, Montse Sole, Judith Serrano, Alice Taddeucci, Belen Perez, Clara Penas, Gemma Manich, Marcel Jimenez, Pilar D'Ocon, Francesc Jimenez-Altayo
Summary: This study provides the first evidence that TRPV2 channels may modulate vascular tone by balancing opposing inputs from the endothelium and smooth muscle, leading to net vasodilation. The amplification of TRPV2 channel-induced activity by NO emphasizes the pathophysiological relevance of these findings.
Article
Medicine, Research & Experimental
Amin Ullah, Jing Zhao, Jiakun Li, Rajeev K. Singla, Bairong Shen
Summary: Gastric cancer is the fifth-most prevalent and second-most deadly cancer worldwide. Late onset of symptoms makes early detection important. CXC chemokines play an important role in the pathological process of gastric cancer, but their exact role in diagnosis and prognosis is not fully understood. Inhibiting CXC chemokines shows promise as a targeted therapy.
Article
Medicine, Research & Experimental
Menna S. Zeyada, Salma M. Eraky, Mamdouh M. El-Shishtawy
Summary: The current study demonstrates the prophylactic and antifibrotic effects of Trig against BLM-induced PF by targeting multiple signaling pathways. The combination of Trig and Pirf may be a promising approach to enhance Pirf's anti-fibrotic effect.