Molecular understanding of osteoarthritis (OA) has greatly increased through careful analysis of tissue samples, preclinical models, and large-scale agnostic "-omic" studies. There is broad acceptance that systemic and biomechanical signals affect multiple tissues of the joint, each of which could potentially be targeted to improve patient outcomes. In this review six experts in different aspects of OA pathogenesis provide their independent view on what they believe to be good tractable approaches to OA target discovery. We conclude that molecular discovery has been high but future transformative studies require a multidisciplinary holistic approach to develop therapeutic strategies with high clinical efficacy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9107912 | PMC |
http://dx.doi.org/10.1016/j.cger.2021.11.015 | DOI Listing |
Nat Commun
January 2025
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark Kgs., Lyngby, Denmark.
The gut microbiome significantly impacts human health, yet cultivation challenges hinder its exploration. Here, we combine deep whole-metagenome sequencing with culturomics to selectively enrich for taxa and functional capabilities of interest. Using a modified commercial base medium, 50 growth modifications were evaluated, spanning antibiotics, physico-chemical conditions, and bioactive compounds.
View Article and Find Full Text PDFCell Death Dis
January 2025
School of Pharmacy, Faculty of Medicine & State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China.
Small extracellular vesicles (sEVs), carrying PD-L1, have been implicated in immune evasion and tumor progression. However, understanding how PD-L1 sEVs are secreted still needs to be improved. We found that the secretion dynamics of PD-L1 sEVs is similar to that of other sEVs.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 West Culture Road, Jinan 250012, Shandong, China.
-Methyl-d-aspartate (NMDA) receptors, a subtype of ionotropic glutamate receptors in the central nervous system (CNS), have garnered attention for their role in brain disorders. Specifically, GluN2A-containing NMDA receptors have emerged as a potential therapeutic target for the treatment of depressive disorders and epilepsy. However, the development of GluN2A-containing NMDA receptor-selective antagonists, represented by -(4-(2-benzoylhydrazine-1-carbonyl)benzyl)-3-chloro-4-fluorobenzenesulfonamide (TCN-201) and its derivatives, faces a significant challenge due to their limited ability to penetrate the blood-brain barrier (BBB), hampering their characterization and further advancement.
View Article and Find Full Text PDFJ R Soc Interface
January 2025
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Influenza forecasts could aid public health response as shown for temperate regions, but such efforts are more challenging in the tropics and subtropics due to more irregular influenza activities. Here, we built six forecast approaches for influenza in the (sub)tropics, with six model forms designed to model seasonal infection risk (i.e.
View Article and Find Full Text PDFNeuron
January 2025
Molecular Neuroregeneration, Division of Neuroscience, Department of Brain Sciences, Imperial College London, London, UK. Electronic address:
Spinal cord injury (SCI) increasingly affects aged individuals, where functional impairment and mortality are highest. However, the aging-dependent mechanisms underpinning tissue damage remain elusive. Here, we find that natural killer-like T (NKLT) cells seed the intact aged human and murine spinal cord and multiply further after injury.
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