Peripheral bacterial infections without impaired blood-brain barrier integrity have been attributed to the pathogenesis of Parkinson's disease (PD). Peripheral infection promotes innate immune training in microglia and exacerbates neuroinflammation. However, how changes in the peripheral environment mediate microglial training and exacerbation of infection-related PD is unknown. In this study, we demonstrate that GSDMD activation was enhanced in the spleen but not in the CNS of mice primed with low-dose LPS. GSDMD in peripheral myeloid cells promoted microglial immune training, thus exacerbating neuroinflammation and neurodegeneration during PD in an IL-1R-dependent manner. Furthermore, pharmacological inhibition of GSDMD alleviated the symptoms of PD in experimental PD models. Collectively, these findings demonstrate that GSDMD-induced pyroptosis in myeloid cells initiates neuroinflammation by regulating microglial training during infection-related PD. Based on these findings, GSDMD may serve as a therapeutic target for patients with PD.
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http://dx.doi.org/10.1016/j.apsb.2023.04.008 | DOI Listing |
F1000Res
January 2025
Immunology, University of Toronto, Toronto, Ontario, Canada.
Fibroblasts, non-hematopoietic cells of mesenchymal origin, are tissue architects which regulate the topography of tissues, dictate tissue resident cell types, and drive fibrotic disease. Fibroblasts regulate the composition of the extracellular matrix (ECM), a 3-dimensional network of macromolecules that comprise the acellular milieu of tissues. Fibroblasts can directly and indirectly regulate immune responses by secreting ECM and ECM-bound molecules to shape tissue structure and influence organ function.
View Article and Find Full Text PDFMediators Inflamm
January 2025
Faculty of Medical Sciences, Department of Genetics, University of Kragujevac, Kragujevac, Serbia.
L. fruits and leaf extracts have a broad range of immunomodulatory, anti-inflammatory, and antioxidant effects; however, their effects on cardiac protection have not been investigated. The study aims to test the biological activity of L.
View Article and Find Full Text PDFBMJ Oncol
September 2024
Department of Biochemistry, Southern University of Science and Technology, Shenzhen, Guangdong, China.
Circulating tumour cells (CTCs) and CTC clusters are considered metastatic precursors due to their ability to seed distant metastasis. However, navigating the bloodstream presents a significant challenge for CTCs, as they must endure fluid shear forces and resist detachment-induced anoikis. Consequently, while a large number of cells from the primary tumour may enter the circulation, only a tiny fraction will result in metastasis.
View Article and Find Full Text PDFBMJ Oncol
July 2024
Department of Investigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Objective: To evaluate signal transducer and activator of transcription 3 (STAT3) inhibition we conducted a co-clinical trial testing danvatirsen, a STAT3 antisense oligonucleotide (ASO) and checkpoint inhibition in conjunction with preclinical experiments.
Methods And Analysis: Orthotopically implanted pancreatic cancer (pancreatic adenocarcinoma (PDAC)) was treated with STAT3 ASO with immune checkpoint inhibition. Tumour infiltrating immune cell populations were characterised via flow cytometry.
Front Endocrinol (Lausanne)
January 2025
Department of Orthopedics, The First Hospital of China Medical University, Shenyang, China.
Bone remodeling is a continuous cyclic process that maintains and regulates bone structure and strength. The disturbance of bone remodeling leads to a series of bone metabolic diseases. Recent studies have shown that citrate, an intermediate metabolite of the tricarboxylic acid (TCA) cycle, plays an important role in bone remodeling.
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