ABSTRACT
Abnormal function of immune cells is one of the key mechanisms leading to severe clinical symptoms in coronavirus disease 2019 patients, and metabolic pathways can destroy the function of the immune system by affecting innate and adaptive immune responses. However, the metabolic characteristics of the immune cells of the SARS-CoV-2 infected organs in situ remaining elusive. We reanalyzed the metabolic-related gene profiles in single-cell RNA sequencing data, drew the metabolic landscape in bronchoalveolar lavage fluid immune cells, and elucidated the metabolic remodeling mechanism that might lead to the progression of COVID-19 and the cytokine storm. Enhanced glycolysis is the most important common metabolic feature of all immune cells in COVID-19 patients. CCL2+ T cells, Group 2 macrophages with high SPP1 expression and myeloid dendritic cells are among the main contributors to the cytokine storm produced by infected lung tissue. Two metabolic analysis methods, including Compass, showed that glycolysis, fatty acid metabolism, bile acid synthesis and purine and pyrimidine metabolism levels of CCL2+ T cells, Group 2 macrophages and myeloid dendritic cells were upregulated and correlated with cytokine storms of COVID-19 patients. This might be the key metabolic regulatory factor for immune cells to produce large quantities of cytokines.
Subject(s)
COVID-19 , Bronchoalveolar Lavage Fluid , Cytokine Release Syndrome , Cytokines , Humans , SARS-CoV-2ABSTRACT
BACKGROUND: Tooth loss is suggested to be associated with an increased risk of dementia in many studies. But the relationship between tooth loss and dementia is not yet fully understood. This systematic review and meta-analysis aimed to determine the relative effect of tooth loss on dementia risk. METHODS: An electronic search of PubMed, Scopus, Embase, and Web of Knowledge was conducted in March 2018 to identify relevant observational studies with the English language restriction. Studies were included if they assessed the relationship between tooth loss and risk of dementia. Study quality was detected by the modified Downs and Black scale. Odds risks (ORs) were pooled using a random-effects model in the crude model. RESULTS: The literature search initially yielded 1574 articles, and 21 observational studies published between 1994 and 2017 were finally included for the analyses. The crude results with random-effects model showed that patients with multiple tooth loss had higher incidence of dementia (OR 2.62, 95% CI 1.90-3.61, P < 0.001, I2 = 90.40%). The association remained noted when only adjusted results were pooled from 18 studies (OR 1.55, 95% CI 1.41-1.70, P = 0.13, I2 = 28.00%). Meta-regression analysis showed that study design explained about 16.52% of heterogeneity in the crude model. The overall quality rating scores of studies ranged from 11 to 16. CONCLUSIONS: Findings from this review evidenced that tooth loss is positively associated with an increased risk of dementia in adults. Future well-designed longitudinal researches examining the direct and indirect relationship between tooth loss and dementia risk are encouraged.
Subject(s)
Dementia/etiology , Tooth Loss/psychology , Adult , Aged , Dementia/epidemiology , Female , Humans , Incidence , Male , Middle Aged , Observational Studies as Topic , Odds Ratio , Regression Analysis , Risk FactorsABSTRACT
AIMS: Oxidative stress is frequently implicated in the pathology of neurodegenerative diseases. This study aimed to investigate the effects and their underlying mechanism(s) of edaravone upon hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in HT22 cells, a murine hippocampal neuronal model. METHODS: HT22 cells were treated with H2O2 in the presence of various concentrations of edaravone or in its absence. A CCK-8 assay, Hoechst 33342 staining, and flow cytometry were used to detect cytotoxicity and apoptosis. In addition, the levels of reactive oxygen species (ROS) and the expression of Bcl-2, Bax, p-ERK 1/2, p-JNK, and p-P38 proteins in HT22 cells were examined. RESULTS: Exogenous H2O2 decreased cell viability in a concentration-dependent manner and was associated with increased apoptosis and ROS production. Moreover, H2O2 significantly activated and upregulated the expression of p-ERK 1/2, p-JNK, and p-P38, while edaravon protected HT22 cells against H2O2-induced injury by inhibiting the production of ROS and activating the MAPK signaling pathway. CONCLUSIONS: Our results provide the first evidence that edaravone can protect H2O2-induced cell injury in HT22 neurons via its antioxidant action. These findings suggest that edaravone may be useful in the treatment of neurodegenerative disorders in which oxidative stress has been principally implicated.
Subject(s)
Antipyrine/analogs & derivatives , Apoptosis/drug effects , Free Radical Scavengers/pharmacology , Hydrogen Peroxide/pharmacology , MAP Kinase Signaling System/drug effects , Neurons/drug effects , Neuroprotective Agents/pharmacology , Animals , Antipyrine/pharmacology , Cell Survival/drug effects , Cells, Cultured , Edaravone , Hippocampus/drug effects , Hippocampus/pathology , Mice , Neurons/pathology , Reactive Oxygen Species/metabolismABSTRACT
The aim of this study was to evaluate in rats, changes in peripheral blood immune cells and mammary tissue after an intramammary infusion of lipopolysaccharide (LPS). The results of the study showed that infusion of LPS induced a rapid migration of neutrophils (PMNs) from the blood to mammary alveoli, increased the activity of myeloperoxidase (MPO) and the concentration of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) in mammary tissues, decreased the activity of myeloperoxidase in serum and reduced the CD4+/CD8+ ratio. This is the first report of changes in peripheral blood immune cells and mammary tissue in rat mastitis.
