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Stroke represents a significant public health burden, ranking as a leading cause of death and disability globally. The prevalence of stroke increases with age, with ischemic stroke accounting for nearly 87% of cases globally. The pathophysiology of stroke is characterized by neuronal injury, neuroinflammation, and oxidative stress, which exacerbate brain damage and hinder recovery. Myeloid Differentiation Factor 2 (MD2), an accessory protein of Toll-like receptor 4 (TLR4), has emerged as a key player in mediating inflammatory responses in stroke. This short review discusses the molecular mechanisms by which MD2 contributes to neuroinflammation and neuronal death following stroke and highlights MD2 as a promising therapeutic target for stroke treatment. Subsequently, we investigate the potential of MD2 inhibitors, their underlying mechanisms, and the therapeutic prospects of such inhibitors in reducing stroke-induced brain damage.
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http://dx.doi.org/10.3390/biom15070961 | DOI Listing |
Sci Transl Med
September 2025
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
IFN-β, a type I interferon, has been used as a first-line therapy for patients with multiple sclerosis (MS) for more than 30 years; however, the cellular and molecular basis of its therapeutic efficacy remains unclear. Here, we first used experimental autoimmune encephalomyelitis (EAE), a mouse model for MS, to show that the therapeutic effects of IFN-β were associated with a down-regulation of microRNA-21 (miR-21) and pathogenic T17 (pT17) cells. In vitro experiments demonstrated that genetic knockout of miR-21 directly inhibited pathogenic T17 cell differentiation.
View Article and Find Full Text PDFMed Oncol
September 2025
Division of Hematology and Blood Bank, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
Acute Myeloid Leukemia (AML) patient-derived Mesenchymal Stem Cells (MSCs) behave differently than normal ones, creating a more protective environment for leukemia cells, making relapse harder to prevent. This study aimed to identify prognostic biomarkers and elucidate relevant biological pathways in AML by leveraging microarray data and advanced bioinformatics techniques. We retrieved the GSE122917 dataset from the NCBI Gene Expression Omnibus and performed differential expression analysis (DEA) within R Studio to identify differentially expressed genes (DEGs) among healthy donors, newly diagnosed AML patients, and relapsed AML patients.
View Article and Find Full Text PDFElife
September 2025
Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, United States.
The microglial surface protein Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) plays a critical role in mediating brain homeostasis and inflammatory responses in Alzheimer's disease (AD). The soluble form of TREM2 (sTREM2) exhibits neuroprotective effects in AD, though the underlying mechanisms remain elusive. Moreover, differences in ligand binding between TREM2 and sTREM2, which have major implications for their roles in AD pathology, remain unexplained.
View Article and Find Full Text PDFFront Oncol
August 2025
Department of Pathology, Institute of Clinical Pathology, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Despite the generally favorable prognosis of differentiated thyroid carcinoma (DTC) following surgery and radioactive iodine (RAI) therapy, approximately 10% of cases eventually develop resistance to RAI. This condition, known as radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC), is associated with a poor prognosis, with a 10-year survival rate of only 10% from the time of metastasis detection. The limited availability of safe and effective alternative treatments poses a significant challenge to clinical management.
View Article and Find Full Text PDFChem Biodivers
September 2025
School of Pharmaceutical Science, Yunnan Key Laboratory of Pharmacology for Natural Products/College of Modern Biomedical Industry, NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, P. R. China.
20(R)-ginsenoside Rg3 can reduce the effects of oxidative stress and cell death in cerebral ischemia‒reperfusion injury (CIRI). Neuroinflammation is crucial post-CIRI, but how 20(R)-Rg3 affects ischemia‒reperfusion-induced neuroinflammation is unclear. To study 20(R)-Rg3's effects on neuroinflammation and neuronal preservation in stroke models and explore toll-like receptor 4/myeloid differentiation factor-88/nuclear factor kappa B (TLR4/MyD88/NF-κB) pathway mechanisms.
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