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  • Calderon Mahmood posted an update 12 days ago

    Rheum palmatum L. (RPL) is a known traditional herbal medicine with the functions of “heat-clearing and damp-drying” in traditional Chinese medicine. Its anti-cancer effect against lung cancer has been confirmed previously, but the related mechanisms and active substances for its action has been little studied. This study adopted the network pharmacology, built the network map of drug ingredients and disease targets (DDN), and discussed the effective components of RPL and its possible mechanisms. All constituents of RPL were collected through database search and literature mining, and the potential active constituents were screened. The inverse pharmacophore matching model was used to predict the targets of active ingredients, and the method was supplemented by database retrieval and literature mining. Compounds-target data were inputted into Cytoscape software to build the DDN of RPL, and functional annotation analysis and pathway enrichment analysis were carried out. Finally, 20 active compounds were screened, which acted on 817 targets. selleckchem A total of 22,418 lung cancer-related targets were collected, and 761 overlapped with drug targets. By bioinformatics annotation of these overlapping genes, a total of 235 gene ontology (GO) functional annotation analyses and 46 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were obtained. It was found that the enrichment of GO and KEGG was associated with apoptosis, suggesting RPL plays an anti-lung cancer role via inducing cell apoptosis. Subsequent cell experiment results showed RPL and its active constituents inhibited the proliferation of A549 cells and reduced clone formation rate of A549 cells via induction of apoptosis. In this study, the pharmacodynamic basis and mechanism of RPL against lung cancer were studied from the perspective of systematic pharmacology, which would be beneficial for further elucidating the anticancer effect of RPL on lung cancer.Objective The association between hippocampal volume and memory is continuing to be characterized in healthy older adults. Prior research suggests smaller hippocampal volume in healthy older adults is associated with poorer episodic memory and processing speed, as well as working memory, verbal learning, and executive functioning as measured by the NIH Toolbox Fluid (Fluid Cognition Composite, FCC) and Crystalized Cognition Composites (CCC). This study aimed to replicate these findings and to evaluate the association between (1) hippocampal asymmetry index and cognition; and (2) independent contributions of the left and right hippocampal volume and cognition in a large sample of healthy older adults. Participants and Methods One-hundred and eighty-three healthy older adults (M age = 71.72, SD = 5.3) received a T1-weighted sequence on a 3T scanner. Hippocampal subfields were extracted using FreeSurfer 6.0 and combined to provide left, right, and total hippocampal volumes. FCC subtests include Dimensional Changwith FCC, namely episodic memory. The present study also suggests the left hippocampal volume may be more broadly associated with both episodic and working memory. Studies should continue to investigate lateralized hippocampal contributions to aging processes to better identify predictors of cognitive decline.Postoperative delirium (POD) is the most common postoperative complication affecting elderly patients, yet the underlying mechanism is elusive, and effective therapies are lacking. The neuroinflammation hypothesis for the pathogenesis of POD has recently emerged. Accumulating evidence is supporting the role of specialized proresolving lipid mediators (SPMs) in regulating inflammation. Neuroprotectin D1 (NPD1), a novel docosahexaenoic acid (DHA)-derived lipid mediator, has shown potent immunoresolvent and neuroprotective effects in several disease models associated with inflammation. Here, using a mouse model of POD, we investigated the role of NPD1 in postoperative cognitive impairment by assessing systemic inflammatory changes, the permeability of the blood-brain barrier (BBB), neuroinflammation, and behavior in aged mice at different time points. We report that a single dose of NPD1 prophylaxis decreased the expression of tumor necrosis factor alpha TNF-α and interleukin (IL)-6 and upregulated the expression of IL-10 in peripheral blood, the hippocampus, and the prefrontal cortex. Additionally, NPD1 limited the leakage of the BBB by increasing the expression of tight junction (TJ)-associated proteins such as ZO-1, claudin-5, and occludin. NPD1 also abolished the activation of microglia and astrocytes in the hippocampus and prefrontal cortex, which is associated with improved general and memory function after surgery. In addition, NPD1 treatment modulated the inflammatory cytokine expression profile and improved the expression of the M2 marker CD206 in lipopolysaccharide (LPS)-stimulated macrophages, which may partly explain the beneficial effects of NPD1 on inflammation. Collectively, these findings shed light on the proresolving activities of NPD1 in the pro-inflammatory milieu both in vivo and in vitro and may bring a novel therapeutic approach for POD.

    Excessive aggregation of α-synuclein is the key pathophysiological feature of Parkinson’s disease (PD). Rapid eye movement sleep behavior disorder (RBD) is also associated with synucleinopathies and considered as a powerful predictor of PD. Growing evidence suggests the diminished clearance of α-synuclein may be partly attributable to poor interstitial fluid drainage, which can be reflected by magnetic resonance imaging (MRI)-visible enlarged perivascular space (EPVS). However, the effect of MRI-visible EPVS on iRBD and PD, and their correlation with clinical characteristics remain unclear.

    To evaluate the clinical and neuroimaging significance of MRI-visible EPVS in iRBD and PD patients.

    We enrolled 33 iRBD patients, 82 PD (with and without RBD) patients, and 35 healthy controls (HCs), who underwent clinical evaluation and 3.0 Tesla MRI. Two neurologists assessed MRI-visible EPVS in centrum semiovale (CSO), basal ganglia (BG), substantia nigra (SN), and brainstem (BS). Independent risk factors for iRBD and PD were investigated using multivariable logistic regression analysis.

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