Article
Biochemistry & Molecular Biology
Zhenhua Feng, Siyue Tao, Zhaobo Huang, Bingjie Zheng, Xiangxi Kong, Yufeng Xiang, Qibin Zhang, Haixin Song, Zhikun Xu, Xiaoan Wei, Fengdong Zhao, Jian Chen
Summary: It has been found that the deubiquitinase UCHL1 serves as a negative regulator in bone resorption. UCHL1 deubiquitinates and stabilizes TAZ protein, inhibiting osteoclastogenesis. Additionally, UCHL1 competes with CNA for binding to NFATC1, inhibiting NFATC1 dephosphorylation and nuclear transport and impeding osteoclastogenesis. Therefore, activating UCHL1 may be a potential therapeutic strategy for various bone diseases.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Joseph S. Bednash, Finny Johns, Daniela Farkas, Ajit Elhance, Jessica Adair, Kirstin Cress, Jacob S. Yount, Adam D. Kenney, James D. Londino, Rama K. Mallampalli
Summary: SARS-CoV-2 enters host cells through the interaction of its spike protein with ACE2. The research discovered that UCHL1 enzyme can regulate ACE2 protein levels, making it a potential therapeutic target for developing small molecule drugs to treat COVID-19.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Zhe Li, Francesco Baccianti, Susanne Delecluse, Ming-Han Tsai, Anatoliy Shumilov, Xianliang Cheng, Sicong Ma, Ingrid Hoffmann, Remy Poirey, Henri-Jacques Delecluse
Summary: The viral noncoding RNA EBER2 accelerates B cell growth by potentiating expression of the UCHL1 deubiquitinase, even in Burkitt's lymphoma cells that do not express the virus's known oncogenes. This study identifies a direct cellular target of a viral noncoding RNA that is likely crucial for EBV's oncogenic properties.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Zheng Gong, Qing Ye, Jia-Wei Wu, Jun-Ling Zhou, Xiang-Yong Kong, Li-Kun Ma
Summary: The study found that UCHL1 promotes angiotensin II-induced cardiac fibrotic responses by activating the NF-KB signaling pathway, and inhibition of the NF-KB pathway can interfere with the fibrotic responses caused by UCHL1 overexpression. This suggests that UCHL1 positively regulates cardiac fibrosis by modulating the NF-KB signaling pathway.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Batudeligen, Zhiqiang Han, Hongmei Chen, Yanhua Xu, Gegentaoli Han
Summary: TCM with single or compound materials is effective for liver fibrosis. Components from Deduhonghua-7 powder showed inhibitory effects on hepatic stellate cells. Luteolin was found to attenuate liver fibrosis by regulating metabolic pathways and DNA repair.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2023)
Article
Plant Sciences
Huizi Zhao, Lin Wu, Yuan Zhang, Shiqi Feng, Yuhao Ding, Xin Ding, Rui Feng, Jun Li, Taotao Ma
Summary: BA can promote the expression of SOCS1 by inhibiting the interaction between Lck and SOCS1, followed by the inhibition of JAK/STAT phosphorylation to prevent the progression of liver fibrosis.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jiahuan Li, Xiaoling Deng, Shuhan Wang, Qianqian Jiang, Keshu Xu
Summary: The study demonstrated that RvD1 effectively reduced liver injury and fibrosis induced by CCl4 in mice by inhibiting pro-fibrotic gene expression and restoring damaged histological architecture. In vitro, RvD1 suppressed LX-2 cell activation and proliferation. Additionally, RvD1 exerted its protective effects by inhibiting autophagy in hepatic stellate cell activation, partly through the AKT/mTOR pathway.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Apoorva Tangri, Kinzie Lighty, Jagadish Loganathan, Fahmi Mesmar, Ram Podicheti, Chi Zhang, Marcin Iwanicki, Ronny Drapkin, Harikrishna Nakshatri, Sumegha Mitra
Summary: The study found that the overexpression of neuronal deubiquitinating enzyme UCHL1 in HGSOC promotes tumor growth by maintaining protein homeostasis. Inhibition of UCHL1 can reduce tumor cell proliferation and invasion, as well as decrease the metastatic growth of ovarian cancer xenografts. This indicates that UCHL1 plays a crucial role in HGSOC progression through the regulation of protein homeostasis.
MOLECULAR CANCER RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Qiannan Ye, Yang Zhou, Changqing Zhao, Lieming Xu, Jian Ping
Summary: Sal can effectively alleviate liver injury, hepatocyte apoptosis, and liver fibrosis in vivo by suppressing JNK activation and modulating the SphK/S1P/S1PRs axis. In vitro, it was observed that Sal might alleviate LX-2 migration and activation induced by exosomal SphK1 by inhibiting the AKT activation.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Food Science & Technology
Guliang Yang, Jianfeng Zhan, Yiwen Yang, Li Yuan, Peilei Wang, Chi-Tang Ho, Shiming Li
Summary: The study found that oxyresveratrol has a protective effect against liver fibrosis in rats by reducing oxidative damage and regulating gene expression, showing better efficacy than resveratrol. This may be attributed to the extra hydroxyl group at the 2-position on oxyresveratrol, making it more susceptible to oxidation.
FOOD SCIENCE AND HUMAN WELLNESS
(2021)
Article
Pharmacology & Pharmacy
Jie Huang, Yan Li, Dingwei Xu, Xiao Zhang, Xiaoyang Zhou
Summary: In this study, it was found that the expression of RUNX1 was upregulated in LF mice, and RUNX1 knockdown alleviated CCl4-induced LF. RUNX1 silencing reduced the viability and migration of HSCs. Besides, as a transcription factor, RUNX1 bound to the promoter of USP9X and regulated the expression of USP9X. USP9X, a deubiquitination enzyme, was found to be upregulated in LF mice. Silencing of USP9X reduced the viability and migration of HSCs, thereby inhibiting LF.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Cell Biology
Qi Liu, Chengqian Lv, Qianqian Huang, Lei Zhao, Xiaoli Sun, Dandan Ning, Jingyang Liu, Yanan Jiang, Shizhu Jin
Summary: Genetically modified HF-MSCs, such as ECM1-HF-MSCs, have shown therapeutic potential for liver cirrhosis by improving liver function, inhibiting HSC activation, and expressing hepatocyte-specific markers in the injured liver.
CELL DEATH DISCOVERY
(2022)
Review
Biochemistry & Molecular Biology
Yuanqiang Ma, Gyurim Lee, Su-Young Heo, Yoon-Seok Roh
Summary: This review summarizes the relationship between oxidative stress and the development of nonalcoholic fatty liver disease (NAFLD), and discusses the potential role of antioxidants as therapeutic agents for NAFLD.
Article
Genetics & Heredity
Feizuo Wang, Xiaojian Yin, Yuan-Ming Fan, Xinyao Zhang, Chao Ma, Keke Jia, Wei Zhou, Zongxiang Tang, Lian-Wen Qi, Jia Li
Summary: Metabolic dysregulations play a significant role in cardiovascular disorders and fibrotic diseases. This study shows that glycolytic reprogramming mediated by PFKFB3 is a potential therapeutic target for alleviating cardiac fibrosis post-myocardial infarction.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2023)
Article
Nutrition & Dietetics
Daniela Gabbia, Sara Carpi, Samantha Sarcognato, Luana Cannella, Martina Colognesi, Michela Scaffidi, Beatrice Polini, Maria Digiacomo, Jasmine Esposito Salsano, Clementina Manera, Marco Macchia, Paola Nieri, Maria Carrara, Francesco Paolo Russo, Maria Guido, Sara De Martin
Summary: This study evaluated the anti-fibrotic and anti-inflammatory effects of oleocanthal extracted from extra virgin olive oil. Results showed that OC can significantly downregulate fibrotic and inflammatory gene expression, offering a promising therapeutic approach for liver fibrosis.
FRONTIERS IN NUTRITION
(2021)
Letter
Gastroenterology & Hepatology
Zoe Hall, Fiona Oakley, Michele Vacca, Julian L. Griffin
Article
Gastroenterology & Hepatology
Jack Leslie, Daniel Geh, Ahmed M. Elsharkawy, Derek A. Mann, Michele Vacca
Summary: HCV hijacks host metabolic processes to aid in viral replication, resulting in hepatic and extrahepatic metabolic dysfunction. Obesity, insulin resistance, and hepatic steatosis play key roles in the progression of chronic hepatitis C (CHC) to hepatocellular carcinoma (HCC). While direct-acting antivirals (DAAs) effectively eliminate the virus, long-lasting metabolic diseases can persist, particularly in the presence of obesity, increasing the risk of liver disease progression.
JOURNAL OF HEPATOLOGY
(2022)
Correction
Biochemistry & Molecular Biology
Mohsen Malehmir, Dominik Pfister, Suchira Gallage, Marta Szydlowska, Donato Inverso, Elena Kotsiliti, Valentina Leone, Moritz Peiseler, Bas G. J. Surewaard, Dominik Rath, Adnan Ali, Monika Julia Wolf, Hannah Drescher, Marc E. Healy, Daniel Dauch, Daniela Kroy, Oliver Krenkel, Marlene Kohlhepp, Thomas Engleitner, Alexander Olkus, Tjeerd Sijmonsma, Julia Volz, Carsten Deppermann, David Stegner, Patrick Helbling, Cesar Nombela-Arrieta, Anahita Rafiei, Martina Hinterleitner, Marcel Rall, Florian Baku, Oliver Borst, Caroline L. Wilson, Jack Leslie, Tracy O'Connor, Christopher J. Weston, Abhishek Chauhan, David H. Adams, Lozan Sheriff, Ana Teijeiro, Marco Prinz, Ruzhica Bogeska, Natasha Anstee, Malte N. Bongers, Mike Notohamiprodjo, Tobias Geisler, Dominic J. Withers, Jerry Ware, Derek A. Mann, Hellmut G. Augustin, Alexandros Vegiopoulos, Michael D. Milsom, Adam J. Rose, Patricia F. Lalor, Josep M. Llovet, Roser Pinyol, Frank Tacke, Roland Rad, Matthias Matter, Nabil Djouder, Paul Kubes, Percy A. Knolle, Kristian Unger, Lars Zender, Bernhard Nieswandt, Meinrad Gawaz, Achim Weber, Mathias Heikenwalder
Review
Gastroenterology & Hepatology
Daniel Geh, Jack Leslie, Rob Rumney, Helen L. Reeves, Thomas G. Birds, Derek A. Mann
Summary: The success of atezolizumab plus bevacizumab treatment has led to a shift towards combination therapies in the treatment of hepatocellular carcinoma (HCC) that include cancer immunotherapies. The focus of cancer immunotherapy has primarily been on immune checkpoints, but emerging evidence supports the role of neutrophils as important contributors to the development and progression of HCC. Neutrophil-targeted therapies are now being explored in clinical trials and may have therapeutic benefits, including enhancing the effectiveness of conventional immunotherapy.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2022)
Editorial Material
Gastroenterology & Hepatology
Fiona Oakley
Summary: Important studies in 2021 demonstrated sophisticated developments in the study of liver fibrosis through omics, revealing complex intra-hepatic mechanisms and new computational platforms facilitating drug discovery. Key advances included cell-specific mapping of fibrosis-activated transcriptional networks and the integration of single-cell RNA sequencing and flow cytometry studies to identify potential therapies for chronic diseases like NASH.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2022)
Article
Gastroenterology & Hepatology
Jack Leslie, John B. G. Mackey, Thomas Jamieson, Erik Ramon-Gil, Thomas M. Drake, Frederic Fercoq, William Clark, Kathryn Gilroy, Ann Hedley, Colin Nixon, Saimir Luli, Maja Laszczewska, Roser Pinyol, Roger Esteban-Fabro, Catherine E. Willoughby, Philipp K. Haber, Carmen Andreu-Oller, Mohammad Rahbari, Chaofan Fan, Dominik Pfister, Shreya Raman, Niall Wilson, Miryam Muller, Amy Collins, Daniel Geh, Andrew Fuller, David McDonald, Gillian Hulme, Andrew Filby, Xabier Cortes-Lavaud, Noha-Ehssan Mohamed, Catriona A. Ford, Ximena L. Raffo Iraolagoitia, Amanda J. McFarlane, Misti McCain, Rachel A. Ridgway, Edward W. Roberts, Simon T. Barry, Gerard J. Graham, Mathias Heikenwalder, Helen L. Reeves, Josep M. Llovet, Leo M. Carlin, Thomas G. Bird, Owen J. Sansom, Derek A. Mann
Summary: This study found that targeting neutrophils using a CXCR2 small molecule inhibitor can enhance the sensitivity of non-alcoholic steatohepatitis-associated hepatocellular carcinoma (NASH-HCC) to immune checkpoint inhibition therapy (ICI). The combination therapy can reprogram the tumor immune microenvironment, increase the number of anti-tumor immune cells, and improve treatment outcomes.
Article
Oncology
Marco Y. W. Zaki, Sari F. Alhasan, Ruchi Shukla, Misti McCain, Maja Laszczewska, Daniel Geh, Gillian L. Patman, Despina Televantou, Anna Whitehead, Joao P. Mauricio, Ben Barksby, Lucy M. Gee, Hannah L. Paish, Jack Leslie, Ramy Younes, Alastair D. Burt, Lee A. Borthwick, Huw Thomas, Gary S. Beale, Olivier Govaere, Daniela Sia, Quentin M. Anstee, Dina Tiniakos, Fiona Oakley, Helen L. Reeves
Summary: The overexpression of SULF2 in the liver tumour microenvironment (TME) of hepatocellular carcinoma (HCC) is associated with tumour progression and therapy resistance. SULF2 in cancer-associated fibroblasts (CAFs) is independently associated with poor prognosis and immune exhaustion. Additionally, SULF2 affects tumour cell proliferation, invasion, and sorafenib resistance.
Article
Cell Biology
Pramudi Wijayasiri, Stuart Astbury, Philip Kaye, Fiona Oakley, Graeme J. Alexander, Timothy J. Kendall, Aloysious D. Aravinthan
Summary: This study reveals a direct relationship between hepatocyte senescence and hepatic stellate cell activation in liver fibrosis. The activation of human HSCs by media derived from senescent HepG2 cells indicates the involvement of factors secreted by senescent hepatocytes in driving liver fibrosis.
Article
Pathology
Lucy M. V. Gee, Ben Barron-Millar, Jack Leslie, Claire Richardson, Marco Y. W. Zaki, Saimir Luli, Rachel A. Burgoyne, Rainie I. T. Cameron, Graham R. Smith, John G. Brain, Barbara Innes, Laura Jopson, Jessica K. Dyson, Katherine R. C. McKay, Alexandros Pechlivanis, Elaine Holmes, Rolando Berlinguer-Palmini, Stella Victorelli, George F. Mells, Richard N. Sandford, Jeremy Palmer, John A. Kirby, Christos Kiourtis, Joao Mokochinski, Zoe Hall, Thomas G. Bird, Lee A. Borthwick, Christopher M. Morris, Peter S. Hanson, Diana Jurk, Elizabeth A. Stoll, Fiona E. N. LeBeau, David E. J. Jones, Fiona Oakley
Summary: Patients with cholestatic liver disease can experience cognitive impairments, but the underlying cellular mechanisms are poorly understood. This study used a rodent model and human neuronal cell cultures to explore the neurocognitive symptoms and potential therapies. The results showed that obeticholic acid, a second-line anti-cholestatic agent, could normalize memory function and reverse neuronal senescence.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Suzanne Madgwick, Saimir Luli, Helene Sellier, Jacqueline A. Butterworth, Jack Leslie, Adam J. Moore, Emma K. Corbin, Adrian I. Yemm, Robson T. Chiremba, Dina Tiniakos, Fiona Oakley, Neil D. Perkins, Jill E. Hunter
Summary: Claspin is a crucial protein involved in the regulation of DNA replication stress. Reduced expression of Claspin is associated with cancer development and increased susceptibility to various diseases.
BIOCHEMICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Orsolya Bilkei-Gorzo, Tiaan Heunis, Jose Luis Marin-Rubio, Francesca Romana Cianfanelli, Benjamin Bernard Armando Raymond, Joseph Inns, Daniela Fabrikova, Julien Peltier, Fiona Oakley, Ralf Schmid, Anetta Hartlova, Matthias Trost
Summary: This study reveals the importance of phagosomal ubiquitylation and the E3 ubiquitin ligase RNF115 in regulating innate immune functions during bacterial infections.
Article
Gastroenterology & Hepatology
Jack Leslie, Jill E. Hunter, Amy Collins, Amelia Rushton, Lauren G. Russell, Erik Ramon-Gil, Maja Laszczewska, Misti McCain, Marco Y. W. Zaki, Amber Knox, Yixin Seow, Laura Sabater, Daniel Geh, Neil D. Perkins, Helen L. Reeves, Dina Tiniakos, Derek A. Mann, Fiona Oakley
Summary: c-Rel plays an important role in hepatocellular carcinoma by limiting genotoxic injury and subsequent tumor burden. Inhibiting c-Rel can enhance the effectiveness of DNA damaging agents and reduce HCC growth.
Review
Endocrinology & Metabolism
Samuel T. Orange, Jack Leslie, Mark Ross, Derek A. Mann, Henning Wackerhage
Summary: IL-6 has both anticancer and procancer effects depending on the context, known as the 'exercise IL-6 enigma'. Exercise-induced IL-6 can protect against cancer by improving insulin sensitivity, stimulating the production of anti-inflammatory cytokines, mobilizing immune cells, and reducing DNA damage. However, IL-6 continuously produced in inflammatory sites drives tumorigenesis by promoting chronic inflammation. This review explores the roles of IL-6 in chronic inflammation, tumorigenesis, and exercise-associated cancer prevention and identifies the factors underlying the exercise IL-6 enigma.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2023)