Review
Neurosciences
Kelley C. C. Atkinson, Marvellous Osunde, Seema K. K. Tiwari-Woodruff
Summary: Multiple sclerosis (MS) is a degenerative disorder of the central nervous system (CNS) with mitochondrial energy production failure. Mitochondrial morphology changes and impaired transport contribute to neurodegeneration and disability in MS. Current methodologies for studying mitochondria in MS only provide a partial understanding, and cell-specific studies in animal models are needed for a comprehensive understanding.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Cell Biology
Ye-J Lee, Bo-Min Kim, Young-Ho Ahn, Ji Ha Choi, Youn-Hee Choi, Jihee Lee Kang
Summary: In a murine model of zymosan-induced peritonitis, enhanced STAT6 signaling leads to PPAR gamma-mediated macrophage programming, contributing to increased efferocytosis and inflammation resolution. STAT6 deficiency exacerbates proinflammatory responses and impairs resolution of inflammation.
Article
Clinical Neurology
Lida Zoupi, Sam A. Booker, Dimitri Eigel, Carsten Werner, Peter C. Kind, Tara L. Spires-Jones, Ben Newland, Anna C. Williams
Summary: Neurodegeneration in multiple sclerosis may affect specific neuronal components early on, and could be a result of demyelination.
ACTA NEUROPATHOLOGICA
(2021)
Review
Biochemistry & Molecular Biology
Ilias Kalafatakis, Domna Karagogeos
Summary: This review summarizes the regulation of myelination by oligodendrocytes under physiological and pathological conditions, as well as the role of microglia in myelin generation, regeneration, and repair. The beneficial and detrimental roles of microglia in remyelination are discussed, along with the cellular and molecular components involved. Recent findings related to preclinical models using human stem cells for studying microglia in human pathologies and the impact of the microbiome on glial cell functions are also presented.
Article
Biochemistry & Molecular Biology
Hiroyuki Watanabe, Rinka Maekawa, Shimpei Iikuni, Masashi Kakae, Nagisa Matsuo, Hisashi Shirakawa, Shuji Kaneko, Masahiro Ono
Summary: This study characterized four diaryl oxadiazole derivatives as potential myelin-imaging probes for single photon emission computed tomography (SPECT) in multiple sclerosis (MS). The results showed that one of the derivatives, [123I]1,3,4-PODP-DM, could potentially be used as a SPECT probe for imaging myelin in MS.
ACS CHEMICAL NEUROSCIENCE
(2022)
Review
Clinical Neurology
Vanja Tepavcevi, Catherine Lubetzki
Summary: The failure of remyelination in multiple sclerosis (MS) is often characterized by low oligodendrocyte progenitor cell density. Stimulating this process may be crucial for achieving myelin regeneration.
Article
Immunology
Petri Elo, Xiang-Guo Li, Heidi Liljenback, Maria Gardberg, Olli Moisio, Maxwell Miner, Jenni Virta, Antti Saraste, Madduri Srinivasarao, Michael Pugh, Philip S. Low, Juhani Knuuti, Sirpa Jalkanen, Laura Airas, Yingjuan June Lu, Anne Roivainen
Summary: The study demonstrated that EC2319 attenuated inflammation and lesion development in a rat model of chronic progressive MS. Human MS patients were found to have FR-beta-positive cells in chronically active plaques, indicating potential translational relevance of the results.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Medicine, Research & Experimental
Jennifer L. Larson-Casey, Shanrun Liu, Jennifer M. Pyles, Suzanne E. Lapi, Komal Saleem, Veena B. Antony, Manuel Lora Gonzalez, David K. Crossman, A. Brent Carter
Summary: It has been found that environmental heavy metal exposure is associated with lung diseases, including lower respiratory tract infections. Through single-cell RNA sequencing, an increase in Pparg gene expression in lung macrophages from mice exposed to cadmium and/or infected with Streptococcus pneumoniae was observed. However, it was discovered that the heavy metal cadmium or infection led to an inhibitory posttranslational modification of the peroxisome proliferator-activated receptor gamma (PPAR gamma), exacerbating lower respiratory tract infections.
Article
Biochemistry & Molecular Biology
Marije J. D. Huitema, Eva M. M. Strijbis, Antonio Luchicchi, John G. J. M. Bol, Jason R. Plemel, Jeroen J. G. Geurts, Geert J. Schenk
Summary: Multiple sclerosis is a demyelinating and neurodegenerative disease of the central nervous system. This study introduced and validated a novel standardized method for more precise myelin quantification in progressive MS brains. The method showed excellent inter-rater agreement and reliability in quantifying myelin content in human post-mortem samples.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Milena Sales Pitombeira, Michel Koole, Kenia R. Campanholo, Aline M. Souza, Fabio L. S. Duran, Davi J. Fontoura Solla, Maria F. Mendes, Samira L. Apostolos Pereira, Carolina M. Rimkus, Geraldo Filho Busatto, Dagoberto Callegaro, Carlos A. Buchpiguel, Daniele de Paula Faria
Summary: This study used PET imaging to investigate the characteristics of microglia activation and myelin injury in different phenotypes and disability stages of multiple sclerosis. The results showed that innate immune cell characteristics and myelin loss occurred independently in both white matter and gray matter structures, and were associated with disability.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2022)
Article
Pharmacology & Pharmacy
Federica Perego, Rosalia Maria Ticozzi, Adriano Troia, Mauro Prato, Donatella Taramelli, Nicoletta Basilico
Summary: The study found that dextran-shelled Oxygen-Loaded NanoDroplets (OLNDs) can promote the killing of Enterococcus faecalis (E. faecalis) by macrophages and reduce inflammatory responses, potentially providing an innovative approach to healing chronic wounds.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Paco Lopez-Cuevas, Can Xu, Charlotte E. Severn, Tiah C. L. Oates, Stephen J. Cross, Ashley M. Toye, Stephen Mann, Paul Martin
Summary: This study demonstrates that silencing or knocking out a specific immune cell-expressed miRNA, microRNA-223 (miR223), can reduce cancer progression. By using miniature artificial protocells (PCs) to deliver anti-inflammatory miRNAs, the interactions between immune cells and cancer cells are altered, resulting in reduced tumor burden.
Article
Chemistry, Multidisciplinary
Xue Zheng, Ke Sun, Yonghui Liu, Xiaona Yin, Haomiao Zhu, Fan Yu, Wei Zhao
Summary: A synthetic sialic acid analogue was successfully used for exosome labeling, leading to the development of a resveratrol-loaded exosome formulation for multiple sclerosis treatment. The study demonstrated the feasibility and efficacy of engineered exosome administration as a potential therapeutic strategy for CNS diseases.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Biochemistry & Molecular Biology
Vebjorn Martinsen, Petri Kursula
Summary: MBP is an abundant protein in CNS myelin and is studied in relation to the pathogenesis of MS. While its direct role as a primary antigen in human MS is unclear, MBP and its functions in myelin formation and maintenance are linked to the disease. This molecule demonstrates the complex relationship between normal nervous system development and neurodegenerative disease.
Review
Biochemistry & Molecular Biology
Laura Bellingacci, Andrea Mancini, Lorenzo Gaetani, Alessandro Tozzi, Lucilla Parnetti, Massimiliano Di Filippo
Summary: Multiple sclerosis (MS) is not only a chronic inflammatory disease of white matter, but gray matter pathology and synaptic structures also play crucial roles in MS-related disability. During the course of MS, interaction between the immune system and synaptic structures leads to changes in brain network dynamics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Gastroenterology & Hepatology
Sarra Smati, Arnaud Polizzi, Anne Fougerat, Sandrine Ellero-Simatos, Yuna Blum, Yannick Lippi, Marion Regnier, Alexia Laroyenne, Marine Huillet, Muhammad Arif, Cheng Zhang, Frederic Lasserre, Alain Marrot, Talal Al Saati, JingHong Wan, Caroline Sommer, Claire Naylies, Aurelie Batut, Celine Lukowicz, Tiffany Fougeray, Blandine Tramunt, Patricia Dubot, Lorraine Smith, Justine Bertrand-Michel, Nathalie Hennuyer, Jean-Philippe Pradere, Bart Staels, Remy Burcelin, Francoise Lenfant, Jean-Francois Arnal, Thierry Levade, Laurence Gamet-Payrastre, Sandrine Lagarrigue, Nicolas Loiseau, Sophie Lotersztajn, Catherine Postic, Walter Wahli, Christophe Bureau, Maeva Guillaume, Adil Mardinoglu, Alexandra Montagner, Pierre Gourdy, Herve Guillou
Summary: The study found that different diets induced more severe NAFLD in male mice, characterized by lipid accumulation and inflammation/fibrosis. Sex-biased hepatic gene signatures showed different responses to various dietary challenges, with Peroxisome proliferator-activated receptor alpha (PPAR alpha) playing a key role in gender-specific and NAFLD pathophysiology.
Article
Biochemistry & Molecular Biology
Laura Vila, Nuria Cabedo, Carlos Villarroel-Vicente, Ainhoa Garcia, Alvaro Bernabeu, Nathalie Hennuyer, Bart Staels, Xavier Franck, Bruno Figadere, Maria-Jesus Sanz, Diego Cortes
Summary: The study synthesized three new series of prenylated benzopyrans containing different numbers of isoprenoid units and explored their hPPAR transactivation activity and structure activity relationships. The results demonstrated that 2-prenylated benzopyrans with seven-carbon and nine-carbon side chains are good lead compounds for preventing cardiovascular diseases.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Eline B. A. van den Berg, Jaap C. W. Hendriks, Everdine W. Elsinga, Mark Eggink, Eef H. C. Dirksen
Summary: Antibody-drug conjugates (ADCs) are a promising class of oncology therapeutics that can deliver cytotoxic drugs to specific locations. This study investigated the impact of disulfide bond reduction time on drug load and isomers of ADCs, revealing a dynamic relationship between them.
Review
Endocrinology & Metabolism
Joanne A. Hoogerland, Bart Staels, David Dombrowicz
Summary: The incidence of non-alcoholic fatty liver disease (NAFLD) has significantly increased over the past two decades. NAFLD can progress to fibrosis and hepatocellular carcinoma (HCC) and the role of the immune system in hepatic physiology and NAFLD progression is increasingly recognized.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Nutrition & Dietetics
Justine Gillard, Corinne Picalausa, Christoph Ullmer, Luciano Adorini, Bart Staels, Anne Tailleux, Isabelle A. Leclercq
Summary: Activation of TGR5 has beneficial effects on glucose tolerance and MAFLD, particularly when activated in the enterohepatic system.
Article
Medicine, Research & Experimental
Alexis Boulinguiez, Christian Duhem, Alicia Mayeuf-Louchart, Benoit Pourcet, Yasmine Sebti, Kateryna Kondratska, Valerie Montel, Stephane Delhaye, Quentin Thorel, Justine Beauchamp, Aurore Hebras, Marion Gimenez, Marie Couvelaere, Mathilde Zecchin, Lise Ferri, Natalia Prevarskaya, Anne Forand, Christel Gentil, Jessica Ohana, France Pietri-Rouxel, Bruno Bastide, Bart Staels, Helene Duez, Steve Lancel
Summary: The study shows that NR1D1 plays a crucial role in regulating skeletal muscle SR calcium homeostasis by repressing the expression of the SERCA inhibitor myoregulin. Lower NR1D1 expression is observed in patients with Duchenne muscular dystrophy, while pharmacological activation of NR1D1 improves calcium homeostasis and muscle structure and function.
Article
Multidisciplinary Sciences
Marie Bobowski-Gerard, Clemence Boulet, Francesco P. Zummo, Julie Dubois-Chevalier, Celine Gheeraert, Mohamed Bou Saleh, Jean-Marc Strub, Amaury Farce, Maheul Ploton, Loic Guille, Jimmy Vandel, Antonino Bongiovanni, Ninon Very, Eloise Woitrain, Audrey Deprince, Fanny Lalloyer, Eric Bauge, Lise Ferri, Line-Carolle Ntandja-Wandji, Alexia K. Cotte, Corinne Grangette, Emmanuelle Vallez, Sarah Cianferani, Violeta Raverdy, Robert Caiazzo, Viviane Gnemmi, Emmanuelle Leteurtre, Benoit Pourcet, Rejane Paumelle, Kim Ravnskjaer, Guillaume Lassailly, Joel T. Haas, Philippe Mathurin, Francois Pattou, Laurent Dubuquoy, Bart Staels, Philippe Lefebvre, Jerome Eeckhoute
Summary: The transcription factor Basonuclin 2 (BNC2) is found to play a key role in driving myofibroblast activation in liver fibrosis. Its expression is induced in fibrotic livers and it integrates pro-fibrotic stimuli to induce matrisome gene expression. BNC2 deficiency leads to reduced collagen deposition in the liver. Furthermore, the study identifies a potential drug target, CC-885, as a BNC2 inhibitor.
NATURE COMMUNICATIONS
(2022)
Article
Endocrinology & Metabolism
Raphael Decoin, Laura Butruille, Thomas Defrancq, Jordan Robert, Nicolas Destrait, Augustin Coisne, Samy Aghezzaf, Eloise Woitrain, Zouriatou Gouda, Sofia Schino, Cedric Klein, Patrice Maboudou, Francois Brigadeau, Didier Klug, Andre Vincentelli, David Dombrowicz, Bart Staels, David Montaigne, Sandro Ninni
Summary: This study suggests that metabolic dysfunction-associated fatty liver disease (MAFLD) and liver fibrosis severity have an impact on left atrial (LA) structure and function. MAFLD patients with a high risk of F3-F4 liver fibrosis showed abnormalities in LA low-voltage areas, peak left atrial longitudinal strain, and volume, as well as a higher rate of atrial fibrillation (AF) recurrence.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Suzanne A. E. van Wouw, Marlene van den Berg, Maroua El Ouraoui, Amber Meurs, Jenina Kingma, Roelof Ottenhoff, Melanie Loix, Marten A. Hoeksema, Koen Prange, Gerard Pasterkamp, Jerome J. A. Hendriks, Jeroen F. J. Bogie, Jan B. van Klinken, Frederic M. Vaz, Aldo Jongejan, Menno P. J. de Winther, Noam Zelcer
Summary: LXR transcription factors play an important role in regulating the composition of lipid species in cellular membranes, particularly lysoplasmalogens. This study identified TMEM86a as a sterol-regulated lysoplasmalogenase in macrophages, which contributes to sterol-dependent membrane remodeling. TMEM86a has been found to have lysoplasmalogenase activity and its overexpression reduces lysoplasmalogen abundance and membrane fluidity in macrophages.
JOURNAL OF LIPID RESEARCH
(2023)
Article
Multidisciplinary Sciences
Niamh B. B. McNamara, David A. D. Munro, Nadine Bestard-Cuche, Akiko Uyeda, Jeroen F. J. Bogie, Alana Hoffmann, Rebecca K. K. Holloway, Irene Molina-Gonzalez, Katharine E. E. Askew, Stephen Mitchell, William Mungall, Michael Dodds, Carsten Dittmayer, Jonathan Moss, Jamie Rose, Stefan Szymkowiak, Lukas Amann, Barry W. W. McColl, Marco Prinz, Tara L. L. Spires-Jones, Werner Stenzel, Karen Horsburgh, Jerome J. A. Hendriks, Clare Pridans, Rieko Muramatsu, Anna Williams, Josef Priller, Veronique E. E. Miron
Summary: This study reveals the crucial role of resident microglia in maintaining myelin health in the central nervous system. Microglia are involved in regulating myelin growth, preserving myelin integrity, and influencing cognitive function. Disruption of the TGF beta 1-TGF beta R1 axis is implicated in the mechanism underlying the loss of myelin health. The findings suggest that targeting microglia could be a potential therapeutic approach for conditions with dysregulated myelin growth and integrity.
Article
Multidisciplinary Sciences
Tess Dierckx, Sam Vanherle, Mansour Haidar, Elien Grajchen, Fleur Mingneau, Pascal Gervois, Esther Wolfs, Dany Bylemans, Arnout Voet, Tien Nguyen, Ibrahim Hamad, Markus Kleinewietfeld, Jeroen F. J. Bogie, Jerome J. A. Hendriks
Summary: This study reveals the reasons for the failure of remyelination, including the overly inflammatory microenvironment and the intrinsic inability of oligodendrocyte precursor cells to differentiate. The study also shows that phloretin can significantly promote remyelination by acting on the nuclear receptor peroxisome proliferator-activated receptor gamma to promote the maturation of oligodendrocyte precursor cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Elien Grajchen, Melanie Loix, Paulien Baeten, Beatriz F. Corte-Real, Ibrahim Hamad, Sam Vanherle, Mansour Haidar, Jonas Dehairs, Jelle Y. Broos, James M. Ntambi, Robert Zimmermann, Rolf Breinbauer, Piet Stinissen, Niels Hellings, Sanne G. S. Verberk, Gijs Kooij, Martin Giera, Johannes V. Swinnen, Bieke Broux, Markus Kleinewietfeld, Jerome J. A. Hendriks, Jeroen F. J. Bogie
Summary: The imbalance between pathogenic and protective T cell subsets is a key feature of autoimmune disorders such as multiple sclerosis (MS). The molecular mechanisms underlying the impact of fatty acid metabolism on T cell physiology and autoimmunity are poorly understood. The study reveals that fatty acid desaturation by SCD1 acts as an endogenous brake on regulatory T-cell differentiation and enhances autoimmunity, suggesting potential therapeutic strategies for autoimmune disorders such as MS.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Endocrinology & Metabolism
Stefano Rizza, Alessio Luzi, Maria Mavilio, Marta Ballanti, Arianna Massimi, Ottavia Porzio, Andrea Magrini, Juliane Hannemann, Rossella Menghini, Jonathan Cridland, Bart Staels, Peter J. Grant, Rainer H. Boger, Nikolaus Marx, Massimo Federici
Summary: This study aimed to investigate the effects of timed light therapy on rotating night shift workers. The results showed that while light therapy had no impact on inflammatory parameters or glucose tolerance, significant changes in the expression of circadian clock genes were detected in the participants' blood cells.
ACTA DIABETOLOGICA
(2022)
Article
Endocrinology & Metabolism
Carmelo Quarta, Kerstin Stemmer, Aaron Novikoff, Bin Yang, Felix Klingelhuber, Alex Harger, Mostafa Bakhti, Aimee Bastidas-Ponce, Eric Bauge, Jonathan E. Campbell, Megan Capozzi, Christoffer Clemmensen, Gustav Collden, Perla Cota, Jon Douros, Daniel J. Drucker, Barent DuBois, Annette Feuchtinger, Cristina Garcia-Caceres, Gerald Grandl, Nathalie Hennuyer, Stephan Herzig, Susanna M. Hofmann, Patrick J. Knerr, Konxhe Kulaj, Fanny Lalloyer, Heiko Lickert, Arek Liskiewicz, Daniela Liskiewicz, Gandhari Maity, Diego Perez-Tilve, Sneha Prakash, Miguel A. Sanchez-Garrido, Qian Zhang, Bart Staels, Natalie Krahmer, Richard D. DiMarchi, Matthias H. Tschoep, Brian Finan, Timo D. Mueller
Summary: A conjugate drug consisting of a GLP-1 receptor agonist and a PPAR alpha/gamma dual-agonist called tesaglitazar has been found to be more effective in treating diabetes compared to monotherapy. The drug utilizes GLP-1 receptor-dependent cellular delivery of tesaglitazar, leading to improved body weight, food intake, and glucose metabolism. It may be a promising treatment option for hyperglycemia and insulin resistance.
Article
Gastroenterology & Hepatology
Justine Gillard, Laure-Alix Clerbaux, Maxime Nachit, Christine Sempoux, Bart Staels, Laure B. Bindels, Anne Tailleux, Isabelle A. Leclercq
Summary: This study demonstrates that alterations in enterohepatic bile acids significantly contribute to the development of non-alcoholic steatohepatitis in relevant preclinical models. Experimental modulation of bile acid composition restored perturbed FXR and TGR5 signaling and prevented non-alcoholic steatohepatitis and associated metabolic disorders.