Article
Biochemistry & Molecular Biology
Andrea Caddeo, Marta Anna Kowalik, Marina Serra, Massimiliano Runfola, Andrea Bacci, Simona Rapposelli, Amedeo Columbano, Andrea Perra
Summary: The novel THR beta agonist TG68 demonstrated significant anti-steatogenic effects and improvement of liver injury in mice fed a high-fat diet, without extra-hepatic side effects, suggesting it may be a useful tool for treating NAFLD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Eveline Bruinstroop, Jin Zhou, Madhulika Tripathi, Winifred W. Yau, Anita Boelen, Brijesh Kumar Singh, Paul M. Yen
Summary: The study found that in the early stages of nonalcoholic fatty liver disease, Dio1 gene expression and activity increased, which was associated with an increased T(3)/T-4 ratio. The results suggest that Dio1 regulates hepatic triglyceride content during hepatosteatosis and early nonalcoholic steatohepatitis.
MOLECULAR METABOLISM
(2021)
Article
Public, Environmental & Occupational Health
Alice R. Carter, Eleanor Sanderson, Gemma Hammerton, Rebecca C. Richmond, George Davey Smith, Jon Heron, Amy E. Taylor, Neil M. Davies, Laura D. Howe
Summary: Mediation analysis aims to explain how an exposure affects an outcome, with Mendelian randomisation (MR) offering improved causal inference. This paper outlines two approaches for mediation analysis with MR: multivariable MR (MVMR) and two-step MR, which are not affected by confounding and measurement errors according to simulations.
EUROPEAN JOURNAL OF EPIDEMIOLOGY
(2021)
Article
Endocrinology & Metabolism
Bing Liu, Wei Yi, Xiaoxiang Mao, Ling Yang, Caijun Rao
Summary: The study found that ECH1 expression was significantly increased in human NASH biopsy specimens and in methionine choline-deficient (MCD) diet-fed mice. Overexpression of ECH1 alleviated hepatic steatosis, inflammation, fibrogenesis, apoptosis, and oxidative stress in mice, while also reducing alanine aminotransferase and proinflammatory cytokine levels in serum and triglyceride levels in livers. ECH1 may act as a potential therapeutic target for NASH by inhibiting ferroptosis.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Nikolaos Perakakis, Pavlina Chrysafi, Michael Feigh, Sanne Skovgard Veidal, Christos S. Mantzoros
Summary: Empagliflozin has shown beneficial metabolic and hepatic effects (mainly anti-inflammatory) in non-diabetic DIO-NASH mice, improving glucose homeostasis and inflammation without affecting body weight, composition, or insulin sensitivity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Shuai Yuan, Lili Yu, Wanglong Gou, Lijuan Wang, Jing Sun, Doudou Li, Ying Lu, Xiaxia Cai, Huanling Yu, Changzheng Yuan, Ju-Sheng Zheng, Susanna C. Larsson, Evropi Theodoratou, Xue Li
Summary: This study utilized phenome-wide Mendelian randomisation (MR-PheWAS) analysis and systematic review of MR studies to investigate the health effects of serum calcium. The findings suggest that high serum calcium is associated with increased or decreased risk of various diseases, with some associations being replicated in two-sample MR analysis.
Article
Cell Biology
Songhua Zhang, Aryanna Sousa, Mengqui Lin, Ayako Iwano, Rishubh Jain, Bing Ma, Chang Min Lee, Jin Wook Park, Suchitra Kamle, Rolf Carlson, Ghun Geun Lee, Jack A. Elias, Jack R. Wands
Summary: The recently discovered human glycoprotein Chi3L1 has been found to potentially play a role in inflammation, tissue remodeling, and visceral fat accumulation. Inhibition of the Chi3L1 gene could reduce lipid accumulation and improve insulin signaling in the liver. High-fat diet induced increased Chi3L1 expression in the liver, while anti-Chi3L1 monoclonal antibodies partially restored insulin signaling and decreased hepatic lipid accumulation.
Review
Neurosciences
Bernd Taschler, Stephen M. Smith, Thomas E. Nichols
Summary: This research introduces causal inference methods based on Mendelian randomisation and aims to improve the reliability of population-scale neuroimaging studies. It explains the motivation for using MR techniques, the underlying assumptions, and common methods, with a focus on the importance of sensitivity analysis.
Article
Medicine, Research & Experimental
Mohammad Irshad Reza, Anees A. Syed, Pragati Singh, Athar Husain, Jiaur R. Gayen
Summary: Mitochondrial dysfunction induced by PST is responsible for hepatic steatosis in T2D, and protection from these abnormalities can be achieved by knockdown of Chga gene or administration of PST inhibitor.
Article
Pediatrics
Luis E. Simental-Mendia, Cesar Javier Ortega-Pacheco, Elvira Garcia-Guerrero, Maria Alejandra Sicsik-Aragon, Fernando Guerrero-Romero, Gerardo Martinez-Aguilar
Summary: This study found that the TyG index is highly associated with hepatic steatosis in children with overweight or obesity. Compared to other biochemical markers, the TyG index may be a more effective indicator for detecting fatty liver in this population.
EUROPEAN JOURNAL OF PEDIATRICS
(2021)
Article
Nutrition & Dietetics
Paul Carter, Shuai Yuan, Siddhartha Kar, Mathew Vithayathil, Amy M. Mason, Stephen Burgess, Susanna C. Larsson
Summary: This Mendelian randomisation study investigated the causal associations of coffee consumption with various cancers. The results showed that coffee consumption was associated with an increased risk of oesophageal cancer, but not with the majority of other cancer types. However, coffee consumption was associated with an increased risk of multiple myeloma and a reduced risk of ovarian cancer.
CLINICAL NUTRITION
(2022)
Article
Biology
Vasileios Karageorgiou, Dipender Gill, Jack Bowden, Verena Zuber
Summary: Multivariable Mendelian randomisation (MVMR) is an instrumental variable technique that extends the MR framework to multiple exposures. In order to mitigate the pitfall of multicollinearity, we propose the use of sparse PCA algorithms to create principal components of subsets of the exposures. This approach achieves a superior balance of sparsity and biologically insightful grouping of the variables.
Article
Medicine, General & Internal
Claire Prince, Gemma C. Sharp, Laura D. Howe, Abigail Fraser, Rebecca C. Richmond
Summary: This study explores the genetic correlation and causal relationships between various female reproductive factors. The findings suggest that women's reproductive factors are genetically correlated and have causal effects on each other. Future research should take into account a woman's entire reproductive history and the causal interplay between reproductive factors.
Article
Biochemistry & Molecular Biology
Lena Seidemann, Anne Krueger, Victoria Kegel-Huebner, Daniel Seehofer, Georg Damm
Summary: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of end-stage liver disease, with unsatisfactory pharmacological treatment options available. Genistein, a soy isoflavone, shows beneficial effects on lipid metabolism and may be a candidate for NAFLD treatment. In an in vitro model, genistein treatment affects PPAR alpha and SREBP-1c signaling pathways, playing a significant role in hepatic lipid metabolism.
Article
Biochemistry & Molecular Biology
Mariana Silva Thomaz, Marcela Nascimento Sertorio, Marcos Leoni Gazarini, Daniel Araki Ribeiro, Luciana Pellegrini Pisani, Marcia Regina Nagaoka
Summary: Non-alcoholic fatty liver is the leading cause of liver disease worldwide. This study investigated the role of kinins in experimental non-alcoholic steatohepatitis (NASH) and found that kinins affect the antioxidant system and reduce superoxide dismutase activity in NASH.
Article
Multidisciplinary Sciences
Satoshi Okawa, Carmen Salto, Srikanth Ravichandran, Shanzheng Yang, Enrique M. Toledo, Ernest Arenas, Antonio del Sol
NATURE COMMUNICATIONS
(2018)
Article
Cell & Tissue Engineering
Daniel Gyllborg, Maqsood Ahmed, Enrique M. Toledo, Spyridon Theofilopoulos, Shanzheng Yang, Charles Ffrench-Constant, Ernest Arenas
Article
Cell Biology
Enrique M. Toledo, Shanzheng Yang, Daniel Gyllborg, Kim E. van Wijk, Indranil Sinha, Manuel Varas-Godoy, Christopher L. Grigsby, Peter Lonnerberg, Saiful Islam, Knut R. Steffensen, Sten Linnarsson, Ernest Arenas
Article
Multidisciplinary Sciences
Jose Meseguer-Ripolles, Baltasar Lucendo-Villarin, Carl Tucker, Sofia Ferreira-Gonzalez, Natalie Homer, Yu Wang, Philip J. Starkey Lewis, Enrique M. Toledo, Esther Mellado-Gomez, Joanna Simpson, Oliver Flint, Himjyot Jaiswal, Nicola L. Beer, Allan E. Karlsen, Stuart J. Forbes, James W. Dear, Jeremy Hughes, David C. Hay
Summary: Liver disease is a leading cause of premature death, with oxidative stress in the liver being a key driver. The compound dimethyl fumarate (DMF) has been shown to activate antioxidant responses and protect against liver damage. This study demonstrated that DMF could reduce liver damage and cell senescence by inhibiting Nf-κB and TGF-β signaling pathways.
Letter
Allergy
Hananeh Aliee, Florian Massip, Cancan Qi, Maria Stella de Biase, Jos van Nijnatten, Elin T. G. Kersten, Nazanin Z. Kermani, Basil Khuder, Judith M. Vonk, Roel C. H. Vermeulen, Margaret Neighbors, Gaik W. Tew, Michele A. Grimbaldeston, Nick H. T. ten Hacken, Sile Hu, Yike Guo, Xiaoyu Zhang, Kai Sun, Pieter S. Hiemstra, Bruce A. Ponder, Mika J. Makela, Kristiina Malmstrom, Robert C. Rintoul, Paul A. Reyfman, Fabian J. Theis, Corry-Anke Brandsma, Ian M. Adcock, Wim Timens, Cheng-Jian Xu, Maarten van den Berge, Roland F. Schwarz, Gerard H. Koppelman, M. C. Nawijn, Alen Faiz
Article
Respiratory System
Stacey N. Reinke, Shama Naz, Romanas Chaleckis, Hector Gallart-Ayala, Johan Kolmert, Nazanin Z. Kermani, Angelica Tiotiu, David Broadhurst, Anders Lundqvist, Henric Olsson, Marika Strom, Asa M. Wheelock, Cristina Gomez, Magnus Ericsson, Ana R. Sousa, John H. Riley, Stewart Bates, James Scholfield, Matthew Loza, Frederic Baribaud, Per S. Bakke, Massimo Caruso, Pascal Chanez, Stephen J. Fowler, Thomas Geiser, Peter Howarth, Ildiko Horvath, Norbert Krug, Paolo Montuschi, Annelie Behndig, Florian Singer, Jacek Musial, Dominick E. Shaw, Barbro Dahlen, Sile Hu, Jessica Lasky-Su, Peter J. Sterk, Kian Fan Chung, Ratko Djukanovic, Sven-Erik Dahlen, Ian M. Adcock, Craig E. Wheelock
Summary: This study investigates the impact of asthma severity and medication on metabolic processes using metabolomics analysis. The results reveal dysregulated metabolism in severe asthma, with differences observed between OCS-treated and non-treated patients. Altered carnitine metabolism is associated with mitochondrial dysfunction in severe asthma and is independent of OCS treatment.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Cell Biology
Maqsood Ahmed, Matthew J. S. Owens, Enrique M. Toledo, Ernest Arenas, Mark Bradley, Charles ffrench-Constant
Summary: The study identified several matricellular proteins that enhance dopaminergic neuron differentiation, providing a new cell culture strategy for the treatment of Parkinson's disease.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Malgorzata Cyranka, Thomas Monfeuga, Natascia Vedovato, Chelsea M. Larabee, Anandhakumar Chandran, Enrique M. Toledo, Heidi de Wet
Summary: This study demonstrates for the first time that NMDA receptor antagonists increase the release of GLP-1 and highlights the need for comprehensive investigations into their effects on gut hormones, particularly incretin hormones.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Uruj Hoda, Stelios Pavlidis, Aruna T. Bansal, Kentaro Takahashi, Sile Hu, Francois Ng Kee Kwong, Christos Rossios, Kai Sun, Pankaj Bhavsar, Matthew Loza, Frederic Baribaud, Pascal Chanez, Stephen J. Fowler, Ildiko Horvath, Paolo Montuschi, Florian Singer, Jacek Musial, Barbro Dahlen, Norbert Krug, Thomas Sandstrom, Dominic E. Shaw, Rene Lutter, Louise J. Fleming, Peter H. Howarth, Massimo Caruso, Ana R. Sousa, Julie Corfield, Charles Auffray, Bertrand De Meulder, Diane Lefaudeux, Sven-Erik Dahlen, Ratko Djukanovic, Peter J. Sterk, Yike Guo, Ian M. Adcock, Kian Fan Chung
Summary: This study examines the clinical and transcriptomic features of exacerbation-prone asthma and its persistence. The frequent exacerbators (FEs) and persistent FEs (PFEs) are associated with poor asthma control and exhibit higher expression scores of type 1 and type 2 activation pathways.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Florian Klimm, Enrique M. Toledo, Thomas Monfeuga, Fang Zhang, Charlotte M. Deane, Gesine Reinert
Meeting Abstract
Endocrinology & Metabolism
A. D. van Dam, E. M. Toledo, N. Y. Loh, M. J. Neville, K. E. Pinnick, M. Todorcevic, R. Dumbill, L. B. L. Wittemans, C. Langenberg, F. Karpe, C. Christodoulides
Article
Biology
Shanzheng Yang, Enrique M. Toledo, Pedro Rosmaninho, Changgeng Peng, Per Uhlen, Diogo S. Castro, Ernest Arenas
COMMUNICATIONS BIOLOGY
(2018)
Review
Pharmacology & Pharmacy
Enrique M. Toledo, Daniel Gyllborg, Ernest Arenas
BRITISH JOURNAL OF PHARMACOLOGY
(2017)
Article
Gastroenterology & Hepatology
Anna Kan, Shuang Liu, Minke He, Dongsheng Wen, Haijing Deng, Lichang Huang, Zhicheng Lai, Yexing Huang, Ming Shi
Summary: This study reveals the correlation between the transcription factor MZF1 and the immune checkpoint molecule PD-L1 in hepatocellular carcinoma (HCC). The overexpression of MZF1 is associated with an immunosuppressive environment and decreased T-cell infiltration in HCC. Mechanistically, MZF1 accelerates PD-L1 ubiquitination via the CDK4 pathway. Inhibition of CDK4 may restore PD-L1 expression and enhance the efficacy of anti-PD-L1 antibodies.
Article
Gastroenterology & Hepatology
Neehar D. Parikh, Manaav Mehta, Elliot B. Tapper
Summary: The commonly used liver fibrosis screening markers APRI and FIB-4 were found to be suboptimal for identifying advanced fibrosis at the time of and prior to clinical diagnosis, missing over half of patients with cirrhosis. Further research is needed to develop laboratory-based algorithms to aid in population-based screening for liver fibrosis.