Review
Biochemistry & Molecular Biology
Marija Brankovic, Igor Jovanovic, Marija Dukic, Tijana Radonjic, Svetlana Opric, Slobodan Klasnja, Marija Zdravkovic
Summary: The emerging issues of concern are non-alcoholic fatty liver disease (NAFLD) and its advanced stage non-alcoholic steatohepatitis (NASH), which may lead to chronic liver complications. Oxidative stress and metabolic disorders play important roles in the progression of NASH. Currently, NASH treatment is primarily focused on lifestyle changes due to the lack of approved therapeutic options.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Maria Luz Martinez-Chantar, Teresa C. Delgado, Naiara Beraza
Summary: NAFLD is the most common form of chronic liver disease, with NASH representing an advanced stage. NK cells play a key role in supporting hepatic inflammation in NASH, with research showing differential functions in different environments. Therapeutic approaches based on the modulation of NK cells show potential in managing NASH progression.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Cheng Zhu, Qian Huai, Xu Zhang, Hanren Dai, Xiaolei Li, Hua Wang
Summary: This review summarizes the multiple roles of ceramides in the onset of fatty liver disease and the pathogenic mechanisms underlying their effects, and also discusses recent advances and challenges in pharmacological interventions targeting ceramide metabolism for the treatment of NAFLD.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Laia Bertran, Ailende Eigbefoh-Addeh, Marta Portillo-Carrasquer, Andrea Barrientos-Riosalido, Jessica Binetti, Carmen Aguilar, Javier Ugarte Chicote, Helena Bartra, Laura Artigas, Mireia Coma, Cristobal Richart, Teresa Auguet
Summary: This study investigated the relationship between Runt-related transcription factor 1 (RUNX1) and nonalcoholic fatty liver disease (NAFLD) using systems biology. The results suggest that RUNX1 may play a significant role in the pathogenesis of NAFLD and could be a potential therapeutic target for this disease.
Article
Gastroenterology & Hepatology
Fasiha Kanwal, Jay H. Shubrook, Zobair Younossi, Yamini Natarajan, Elisabetta Bugianesi, Mary E. Rinella, Stephen A. Harrison, Christos Mantzoros, Kim Pfotenhauer, Samuel Klein, Robert H. Eckel, Davida Kruger, Hashem El-Serag, Kenneth Cusi
Summary: There are significant management gaps between clinical guidelines and practice in patients with NAFLD and NASH, and there is no single global guiding strategy for their management. An international conference convened experts in gastroenterology, hepatology, endocrinology, and primary care providers to discuss promising approaches for clinical practice and prepare a comprehensive, unified strategy for the care of NAFLD/NASH patients. Participants also identified specific high-yield targets for clinical research and called for a unified, international public health response to NAFLD and NASH.
Article
Endocrinology & Metabolism
Laurianne Bonnet, Ida Alexandersson, Ritesh K. K. Baboota, Tobias Kroon, Jan Oscarsson, Ulf Smith, Jeremie Boucher
Summary: Cellular senescence plays a causal role in the development of non-alcoholic steatohepatitis (NASH) by modulating glucose and lipid metabolism, favoring hepatic steatosis.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Gastroenterology & Hepatology
Natalia da Silva Lima, Marcos F. Fondevila, Eva Novoa, Xabier Buque, Maria Mercado-Gomez, Sarah Gallet, Maria J. Gonzalez-Rellan, Uxia Fernandez, Anne Loyens, Maria Garcia-Vence, Maria Del Pilar Chantada-Vazquez, Susana B. Bravo, Patricia Maranon, Ana Senra, Adriana Escudero, Magdalena Leiva, Diana Guallar, Miguel Fidalgo, Pedro Gomes, Marc Claret, Guadalupe Sabio, Marta Varela-Rey, Teresa C. Delgado, Rocio Montero-Vallejo, Javier Ampuero, Miguel Lopez, Carlos Dieguez, Laura Herrero, Dolors Serra, Markus Schwaninger, Vincent Prevot, Rocio Gallego-Duran, Manuel Romero-Gomez, Paula Iruzubieta, Javier Crespo, Maria L. Martinez-Chantar, Carmelo Garcia-Monzon, Agueda Gonzalez-Rodriguez, Patricia Aspichueta, Ruben Nogueiras
Summary: ATG3, induced in the liver of NAFLD patients, plays a role in lipid metabolism and may contribute to the development of steatosis. Inhibition of hepatic ATG3 can improve fatty acid metabolism by reducing JNK1, leading to increased SIRT1, CPT1a, and mitochondrial function, independent of its autophagic action.
JOURNAL OF HEPATOLOGY
(2022)
Letter
Gastroenterology & Hepatology
Amandeep Singh, Rajat Garg, Rocio Lopez, Naim Alkhouri
Summary: This study aims to develop a simple noninvasive fibrosis score to detect advanced fibrosis in patients with diabetes and compare its performance with other fibrosis scores.
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
(2022)
Article
Endocrinology & Metabolism
Fasiha Kanwal, Jay H. Shubrook, Zobair Younossi, Yamini Natarajan, Elisabetta Bugianesi, Mary E. Rinella, Stephen A. Harrison, Christos Mantzoros, Kim Pfotenhauer, Samuel Klein, Robert H. Eckel, Davida Kruger, Hashem El-Serag, Kenneth Cusi
Summary: NAFLD and NASH are common conditions with significant management gaps, lacking a single global guiding strategy. The American Gastroenterological Association, along with professional associations, convened an international conference to develop a comprehensive, unified strategy for primary care providers and specialists, calling for a unified international public health response to NAFLD and NASH.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2021)
Article
Gastroenterology & Hepatology
Emma L. Shepherd, Raquel Saborano, Ellie Northall, Kae Matsuda, Hitomi Ogino, Hiroaki Yashiro, Jason Pickens, Ryan E. Feaver, Banumathi K. Cole, Stephen A. Hoang, Mark J. Lawson, Matthew Olson, Robert A. Figler, John E. Reardon, Nobuhiro Nishigaki, Brian R. Wamhoff, Ulrich L. Guenther, Gideon Hirschfield, Derek M. Erion, Patricia F. Lalor
Summary: Fructose is a major driver of NAFLD pathogenesis, cleared through enzymatic phosphorylation by KHK enzyme. Inhibition of KHK activity has been shown to improve steatosis, fibrosis, and inflammation in NAFLD patients.
Review
Biochemistry & Molecular Biology
Baozhen Qu, Xuemao Liu, Yanjiao Liang, Keke Zheng, Chunling Zhang, Linlin Lu
Summary: This article summarizes the related targets regulated by salidroside (SDS) in treating non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and discusses the potential mechanisms underlying its effects.
CHEMISTRY & BIODIVERSITY
(2022)
Review
Endocrinology & Metabolism
Alexandra S. Aaldijk, Cristy R. C. Verzijl, Johan W. Jonker, Dicky Struik
Summary: Beta klotho (KLB) is a crucial component in fibroblast growth factor receptor (FGFR) signaling, serving as an essential coreceptor for the hormones fibroblast growth factor 19 (FGF19) and fibroblast growth factor 21 (FGF21). It has emerged as a potential drug target for treating metabolic diseases, but clinical trials have raised questions about human KLB biology and the variable responses in patients. Understanding human KLB biology could improve the efficacy and safety of KLB-targeting drugs.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Gastroenterology & Hepatology
Stefania Grimaudo, Paola Dongiovanni, Jussi Pihlajamaki, Mohammed Eslam, Hannele Yki-Jarvinen, Rosaria Maria Pipitone, Guido Baselli, Calogero Camma, Vito Di Marco, Marco Enea, Miriam Longo, Grazia Pennisi, Daniele Prati, Rossella Zito, Anna Ludovica Fracanzani, Antonio Craxi, Jacob George, Stefano Romeo, Luca Valenti, Salvatore Petta
Summary: The NR1H4 gene rs35724 C allele is protective against severity of steatosis, steatohepatitis, and liver fibrosis, but is associated with higher total circulating cholesterol levels. Patients carrying the NR1H4 rs35724 C allele show increased hepatic mRNA levels of FXR and genes involved in bile acid synthesis. This suggests that increased hepatic FXR expression due to the NR1H4 rs35724 C allele may have potential therapeutic implications for NAFLD.
LIVER INTERNATIONAL
(2021)
Review
Biochemistry & Molecular Biology
Elke Roeb
Summary: The liver is linked to metabolic-inflammatory diseases and plays a role in the pathogenesis of metabolic syndrome. IL-13 may have protective effects on the development of metabolic-dysfunction-associated steatohepatitis (MASH), but it can also contribute to the progression of MASH through gut barrier dysfunction and enhanced hepatic fibrosis. However, there is limited research on IL-13's effects on metabolic diseases and potential therapies. This review article summarizes and discusses the contradictory aspects of IL-13's effects on the liver and metabolic liver diseases based on recent literature.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Environmental Sciences
Norma David, Jean-Philippe Antignac, Marine Roux, Philippe Marchand, Sophie Michalak, Frederic Oberti, Isabelle Fouchard, Adrien Lannes, Odile Blanchet, Paul Cales, Etienne B. Blanc, Jerome Boursier, Clemence M. Canivet
Summary: This study found a significant association between PFHpA and liver steatosis in NAFLD, possibly through beta-oxidation and biosynthesis of fatty acids.
ENVIRONMENT INTERNATIONAL
(2023)
Article
Clinical Neurology
Naomi Niznick, Ronda Lun, Ryan Gotfrit, Marc-Olivier Deguise, Tim Ramsay, Dylan Blacquiere, Daniel Lelli
Summary: This study aimed to evaluate the effectiveness of interventions implemented by Canadian neurology residency programs during the 2020-2021 match cycle. The survey results showed that the majority of medical students perceived the interventions as adequate, with pre-interview virtual information sessions being the most effective. Discordance was found between residency program stakeholders and medical students regarding the most helpful interview period modality.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Leire M. Ledahawsky, Maria Eirini Terzenidou, Ruairidh Edwards, Rachel A. Kline, Laura C. Graham, Samantha L. Eaton, Dinja Hoorn, Helena Chaytow, Yu-Ting Huang, Ewout J. N. Groen, Anna A. L. Motyl, Douglas J. Lamont, Kostas Tokatlidis, Thomas M. Wishart, Thomas H. Gillingwater
Summary: Synapses are a primary pathological target in neurodegenerative diseases, and SFXN3 has been found to have an impact on neurodegeneration and cell death, potentially playing a significant role in regulating neurodegeneration pathways.
Article
Neurosciences
Cylia Rochat, Nathalie Bernard-Marissal, Emma Kaellstig, Sylvain Pradervand, Florence E. Perrin, Patrick Aebischer, Cedric Raoul, Bernard L. Schneider
Summary: This study evaluated the therapeutic potential of gene therapy targeting mutated SOD1 in mature astrocytes. The results showed that this treatment gradually restored neuromuscular connections and significantly improved neuromuscular function. Gene therapy in the spinal cord protected the most vulnerable fast-fatigable motor neurons, and specific muscle fiber types were also preserved.
Article
Biochemistry & Molecular Biology
Viktoriia Bazylianska, Akhil Sharma, Heli Chauhan, Bernard Schneider, Anna Moszczynska
Summary: Methamphetamine is a highly abused stimulant that is neurotoxic and increases the risk of Parkinson's disease. The study found that Methamphetamine itself contributes to mitochondrial dysfunction in the striatum, while dopamine only decreases the levels of certain subunits. The study also suggests that parkin does not regulate the turnover of NDUFS3.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Anna E. Karagianni, Dominic Kurian, Eugenio Cillan-Garcia, Samantha L. Eaton, Thomas M. Wishart, R. Scott Pirie
Summary: This study aims to characterize the effect of training on the local pulmonary immune system in racehorses by analyzing the gene and protein expression of tracheal wash samples. The results showed differentially expressed genes and proteins related to acute phase response, oxidative stress, haemopoietic processes, immune response, and inflammation. The study highlighted the potential mechanisms underlying training-associated airway inflammation.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Aoife Reilly, Marc-Olivier Deguise, Ariane Beauvais, Rebecca Yaworski, Simon Thebault, Daniel R. Tessier, Vincent Tabard-Cossa, Niko Hensel, Bernard L. Schneider, Rashmi Kothary
Summary: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by loss of the SMN1 gene and low SMN protein levels. Current gene therapy and clinical trials for SMA have shown significant improvement in the clinical phenotype but not a complete cure. This study demonstrates the independent contribution of peripheral organs to SMA pathology and suggests that treatments should not be restricted to motor neurons.
Article
Neurosciences
Guzal Khayrullina, Zaida A. Alipio-Gloria, Marc-Olivier Deguise, Sabrina Gagnon, Lucia Chehade, Matthew Stinson, Natalya Belous, Elizabeth M. Bergman, Fritz W. Lischka, Jeremy Rotty, Clifton L. Dalgard, Rashmi Kothary, Kristen A. Johnson, Barrington G. Burnett
Summary: SMN deficiency leads to reactive microglia with exaggerated inflammatory response, potentially impacting SMA neuropathology.
Article
Multidisciplinary Sciences
Joshua T. Dearborn, Hemanth R. Nelvagal, Nicholas R. Rensing, Keigo Takahashi, Stephanie M. Hughes, Thomas M. Wishart, Jonathan D. Cooper, Michael Wong, Mark S. Sands
Summary: In a mouse model of CLN1 disease, chronic CBD administration reduced neuroinflammation but had no apparent effect on seizures and neuron survival. Higher doses of CBD may be needed to reduce neurodegeneration and seizure frequency.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Zsofia Laszlo, Nicole Hindley, Anna Sanchez Avila, Rachel A. Kline, Samantha L. Eaton, Douglas J. Lamont, Colin Smith, Tara L. Spires-Jones, Thomas M. Wishart, Christopher M. Henstridge
Summary: Increasing evidence suggests that synaptic dysfunction is a central and possibly triggering factor in Amyotrophic Lateral Sclerosis (ALS). This study aimed to assess the molecular profile of ALS synapses using an unbiased synaptic proteomics experiment. The researchers identified ALS-associated proteins and alterations in synaptic protein expression levels, as well as the influence of cognitive decline and a specific genetic mutation on synaptic composition. This study provides novel insights into the role of synaptic dysfunction in ALS pathophysiology.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Review
Cell Biology
Rachel A. Kline, Lena Loesslein, Dominic Kurian, Judit Aguilar Marti, Samantha L. Eaton, Felipe A. Court, Thomas H. Gillingwater, Thomas M. Wishart
Summary: Recent advances in proteomic technologies have enabled unprecedented assessment of molecular composition in various sample types. However, careful consideration is required when applying these technologies, including methodological selection and analysis workflow. The effectiveness of most proteomics screens is hindered by inadequate analyses, rather than technical limitations. Furthermore, studying progressive neurodegenerative conditions presents inherent difficulties that should be addressed.
Article
Cell Biology
Sharon J. Brown, Rachel A. Kline, Silvia A. Synowsky, Sally L. Shirran, Ian Holt, Kelly A. Sillence, Peter Claus, Brunhilde Wirth, Thomas M. Wishart, Heidi R. Fuller
Summary: This study conducted proteomic profiling of skin fibroblasts from different severities of spinal muscular atrophy (SMA) patients. The results showed limited overlap in differentially expressed proteomic profiles among different types of SMA, and the greatest variability was observed within SMA II fibroblasts. Despite limited proteomic overlap, common enriched canonical pathways were identified in two of the three SMA severities. The study also identified protein profiles that may be associated with SMA severity.
Review
Cell Biology
Samantha L. Eaton, Fraser Murdoch, Nina M. Rzechorzek, Gerard Thompson, Claudia Hartley, Benjamin Thomas Blacklock, Chris Proudfoot, Simon G. Lillico, Peter Tennant, Adrian Ritchie, James Nixon, Paul M. Brennan, Stefano Guido, Nadia L. Mitchell, David N. Palmer, C. Bruce A. Whitelaw, Jonathan D. Cooper, Thomas M. Wishart
Summary: The impact of neurological disorders is globally recognized, and the translation from rodent-derived therapeutics to human neurological interventions is challenging. In order to improve translation, higher order mammals with complex neuroanatomy, such as livestock, are being used. We provide comprehensive neurological assessment protocols for large animal species to standardize the characterization of these models and recommend their use in neurological clinical scoring.
Article
Clinical Neurology
Regina R. Reimann, Martina Puzio, Antonella Rosati, Marc Emmenegger, Bernard L. Schneider, Pamela Valdes, Danzhi Huang, Amedeo Caflisch, Adriano Aguzzi
Summary: The cellular prion protein PrPC mediates neurotoxicity of prions and protein aggregates, but the mechanisms are not well understood. Antibody-derived ligands against PrPC induce neurotoxicity through hydrogen bonding and suppressing this bond prolongs the lives of prion-infected mice, suggesting convergent pathways. A study found that the toxic effects of these ligands require a specific amino acid residue within PrPC, which could be a potential target for preventing prion-related neurodegeneration.
Review
Oncology
Marc-Olivier Deguise, Sarah Blain, Ewurabena Simpson, Mira Liebman, Emanuela Ferretti
Summary: Congenital dyserythropoietic anemia type IV (CDAIV) is a rare genetic blood disorder characterized by severe anemia and hemolysis, requiring recurrent transfusions. We presented a case of a newborn with severe hemolytic anemia who needed intrauterine transfusion and was found to have a pathogenic variant in the KLF1 gene. This case demonstrates the benefits of next-generation sequencing in the diagnosis and management of congenital hemolytic anemia.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Medicine, Research & Experimental
Hemanth R. Nelvagal, Samantha L. Eaton, Sophie H. Wang, Elizabeth M. Eultgen, Keigo Takahashi, Steven Q. Le, Rachel Nesbitt, Joshua T. Dearborn, Nicholas Siano, Ana C. Puhl, Patricia Dickson, Gerard Thompson, Fraser Murdoch, Paul M. Brennan, Mark Gray, Stephen N. Greenhalgh, Peter Tennant, Rachael Gregson, Eddie Clutton, James Nixon, Chris Proudfoot, Stefano Guido, Simon G. Lillico, C. Bruce A. Whitelaw, Jui-Yun Lu, Sandra L. Hofmann, Sean Ekins, Mark S. Sands, Thomas M. Wishart, Jonathan D. Cooper
Summary: CLN1 disease, a fatal neurodegenerative lysosomal storage disorder, has proven challenging to treat. This study tested the efficacy of enzyme replacement therapy (ERT) and found that intracerebrovascular administration of recombinant PPT1 showed therapeutic benefits in mouse and sheep models. The findings highlight the feasibility and therapeutic efficacy of ERT and emphasize the importance of cross-species research in developing successful treatment strategies.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Gastroenterology & Hepatology
Kyle G. Williams, Ramya Kongala, Donna M. Shows, Andrew J. Konecny, Duncan C. Hindmarch, Astrid S. Clarke, James D. Lord
Summary: CD8 T-cell clones are found homogeneously throughout the length of the colon in patients with inflammatory bowel disease (IBD), regardless of inflammation. There is a high degree of repertoire overlap for T-cell receptor (TCR) between the colon and peripheral blood, suggesting T-cell trafficking plays a significant role in the pathogenesis of IBD, particularly in relation to the alpha 4 beta 7+ T-cell subpopulation.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2024)
Article
Gastroenterology & Hepatology
Yueqi Zhang, Yue Luo, Xinhui Liu, Matti Kiupel, Aimin Li, Hongbing Wang, Qing-Sheng Mi, Hua Xiao
Summary: This study reveals a novel mechanism for the onset of NAFLD/NASH and HCC initiated by NCOA5-deficient macrophages, suggesting the NCOA5-PF4 axis in macrophages as a potential target for developing preventive and therapeutic interventions against NAFLD/NASH and HCC.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2024)
Article
Gastroenterology & Hepatology
Daria Krzikalla, Alena Laschtowitz, Lisa Leypoldt, Cornelia Gottwick, Pia Averhoff, Soren Weidemann, Ansgar W. Lohse, Samuel Huber, Christoph Schramm, Dorothee Schwinge, Johannes Herkel, Antonella Carambia
Summary: This study investigated the immune mechanisms that establish liver tolerance. It was found that MBP-specific T cells were activated to produce IFN-gamma in the liver, which induced the up-regulation of recruitment molecules and redirected the T cells into the liver parenchyma. Some of the translocated T cells converted into regulatory T cells producing IL-10 and up-regulated the expression of immune checkpoint molecules. The up-regulation of IFN gamma and immune checkpoint molecules, including CTLA-4, were essential for tolerance induction in the liver.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2024)
Review
Gastroenterology & Hepatology
Hyun Young Kim, Sadatsugu Sakane, Alvaro Eguileor, Raquel Carvalho Gontijo Weber, Wonseok Lee, Xiao Liu, Kevin Lam, Kei Ishizuka, Sara Brin Rosenthal, Karin Diggle, David A. Brenner, Tatiana Kisseleva
Summary: Liver fibrosis is a serious global health problem with no effective therapy currently available. Studies have shown that liver fibrosis is reversible and regression can occur when the underlying cause is removed. This review discusses the research progress in understanding the molecular mechanisms underlying the development and reversibility of liver fibrosis.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2024)
Article
Gastroenterology & Hepatology
Quan Pan, Mingming Gao, Dami Kim, Weiqi Ai, Wanbao Yang, Wen Jiang, Wesley Brashear, Yujiao Dai, Sha Li, Yuxiang Sun, Yajuan Qi, Shaodong Guo
Summary: This study investigates the role of hepatocyte FoxO1 in liver fibrosis and finds that it mediates CCL4-induced liver fibrosis through upregulating hepatocyte TGF-beta 1 expression, stimulating hepatic inflammation, and TGF-beta 1-mediated HSC activation.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2024)