A main feature of neurodegenerative diseases is the loss of neurons. One of the most prevalent neurodegenerative illnesses is Parkinson disease (PD). Although several medications are already approved to treat neurodegenerative disorders, most of them only address associated symptoms. The main aim of the current study was to examine the neuroprotective efficacy and underlying mechanism of Lobophytum sp. crude extract in a rotenone-induced rat model of neurodegeneration mimicking PD in humans. The influence of the treatment on antioxidant, inflammatory, and apoptotic markers was assessed in addition to the investigation of TH (tyrosine hydroxylase) immunochemistry, histopathological changes, and α-synuclein. Metabolomic profiling of Lobophytum sp. crude extract was done by using High-Resolution Liquid Chromatography coupled with Mass Spectrometry (HR-LC-ESI-MS), which revealed the presence of 20 compounds (1-20) belonging to several classes of secondary metabolites including diterpenoids, sesquiterpenoids, steroids, and steroid glycosides. From our experimental results, we report that Lobophytum sp. extract conferred neuroprotection against rotenone-induced PD by inhibiting ROS formation, apoptosis, and inflammatory mediators including IL-6, IL-1β, and TNF-α, NF-кB, and subsequent neurodegeneration as evidenced by decreased α-synuclein deposition and enhanced tyrosine hydroxylase immunoreactivity. Moreover, a computational network pharmacology study was performed for the dereplicated compounds from Lobophytum sp. using PubChem, SwissTarget Prediction, STRING, DisGeNET, and ShinyGO databases. Among the studied genes, CYP19A1 was the top gene related to Parkinson's disease. Dendrinolide compounds annotated a high number of parkinsonism genes. The vascular endothelial growth factor (VEGF) pathway was the top signaling pathway related to the studied genes. Therefore, we speculate that Lobophytum sp. extract, owing to its pleiotropic mechanisms, could be further developed as a possible therapeutic drug for treating Parkinson's disease.
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http://dx.doi.org/10.1038/s41598-024-66781-9 | DOI Listing |
Nat Genet
January 2025
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Transcription factors are frequent cancer driver genes, exhibiting noted specificity based on the precise cell of origin. We demonstrate that ZIC1 exhibits loss-of-function (LOF) somatic events in group 4 (G4) medulloblastoma through recurrent point mutations, subchromosomal deletions and mono-allelic epigenetic repression (60% of G4 medulloblastoma). In contrast, highly similar SHH medulloblastoma exhibits distinct and diametrically opposed gain-of-function mutations and copy number gains (20% of SHH medulloblastoma).
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January 2025
From the Computational Biology Centre and the Laboratory of Psychiatric-Neuroimaging-Genetic and Comorbidity, Tianjin Anding Hospital, Tianjin Mental Health Centre of Tianjin Medical University, Nankai University Affiliated Tianjin Anding Hospital, Tianjin, China.
Background: Clozapine is superior to all other antipsychotics in treating schizophrenia in terms of its curative efficacy; however, this drug is prescribed only as a last resort in the treatment of schizophrenia, given its potential to induce cardiac arrest. The mechanism of clozapine-induced cardiac arrest remains unclear, so we aimed to elucidate the potential mechanisms of clozapine-induced cardiac arrest using network pharmacology and molecular docking.
Methods: We identified and analyzed the overlap between potential cardiac arrest-related target genes and clozapine target genes.
J Neurosci
January 2025
Institute of Neuroimmunology, Slovak Academy of Science, 84510 Bratislava, Slovakia.
Extracellular matrix (ECM) is a network of macromolecules which has two forms - perineuronal nets (PNNs) and a diffuse ECM (dECM) - both influence brain development, synapse formation, neuroplasticity, CNS injury and progression of neurodegenerative diseases. ECM remodeling can influence extrasynaptic transmission, mediated by diffusion of neuroactive substances in the extracellular space (ECS). In this study we analyzed how disrupted PNNs and dECM influence brain diffusibility.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Collagen nanoparticles (collagen-NPs) possess numerous applications owing to their minimal immunogenicity, non-toxic nature, excellent biodegradability and biocompatibility. This study presents a novel sustainable technique for one-step green synthesis of hydrolyzed fish collagen-NPs (HFC-NPs) using a hot-water extract of Ulva fasciata biomass. HFC-NPs were characterized using TEM, FTIR, XRD, ζ-potential analyses, etc.
View Article and Find Full Text PDFNeuroimage
January 2025
Department of Psychiatry, University of Florida, Gainesville, FL-32610; McKnight Brain Institute, University of Florida, Gainesville, FL-32610. Electronic address:
Sepsis is a state of systemic immune dysregulation and organ failure that is frequently associated with severe brain disability. Epidemiological studies have indicated that younger females have better prognosis and clinical outcomes relative to males, though the sex-dependent response of the brain to sepsis during post-sepsis recovery remains largely uncharacterized. Using a modified polymicrobial intra-abdominal murine model of surgical sepsis, we characterized the acute effects of intra-abdominal sepsis on peripheral inflammation, brain inflammation and brain functional connectivity in young adult mice of both sexes.
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