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Purpose: There are some challenges to diagnosis in the context of similar diagnostic criteria for late-life depression (LLD) and adult depression due to cognitive impairment and other clinical manifestations. The association between gut microbiota and inflammation remains unclear in LLD. We analyzed gut microbiota characteristics and serum inflammatory cytokines in individuals with LLD to explore the combined role of these two factors in potential biomarkers of LLD. Methods: This was an observational cross-sectional study. Fecal samples and peripheral blood from 29 patients and 33 sex- and age-matched healthy controls (HCs) were collected to detect gut microbiota and 12 inflammatory factors. We analyzed differences in diversity and composition of gut microbiota and evaluated relations among gut microbiota, inflammatory factors, and neuropsychological scales. We extracted potential biomarkers using receiver-operating characteristic curve analysis to predict LLD utilizing the combination of the microbiota and inflammatory cytokines. Results: Elevated systemic inflammatory cytokine levels and gut microbiota dysbiosis were found in LLD patients. Relative abundance of Verrucomicrobia at the phylum level and Megamonas, Citrobacter, and Akkermansia at the genus level among LLD patients was lower than HCs. Abundance of Coprococcus, Lachnobacterium, Oscillospira, and Sutterella was higher in LLD patients. Notably, IL6, IFNγ, Verrucomicrobia, and Akkermansia levels were correlated with depression severity. Our study identified IL6, Akkermansia, and Sutterella as predictors of LLD, and their combination achieved an area under the curve of 0.962 in distinguishing LLD patients from HCs. Conclusion: This research offers evidence of changes within gut microbiota and systemic inflammation in LLD. These findings possibly help elucidate functions of gut microbiota and systemic inflammation in LLD development and offer fresh ideas on biomarkers for clinical practise in the context of LLD. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is a condition of glucose intolerance, which may be accompanied with inflammation. The levels of hematological parameters during pregnancy can reflect inflammatory conditions in pregnant women. This study aims to describe the dynamic change of blood cell parameters from the first trimester (6– 12 weeks of gestation) to the second trimester (24– 28 weeks of gestation) and to investigate the associations of these biomarkers with the risk of GDM. Methods: This study was a prospective double-center study conducted in Beijing, China (clinical trial number: NCT03246295). Hematological parameters were tested four times during the follow-up. Logistic regression analysis and Receiver Operating Characteristic (ROC) curve analysis were used to explore the association and predictive ability of hematological parameters for GDM. Results: There were 258 of 1027 pregnant women in our study developed GDM. Among the 1027 pregnant women, white blood cells (WBC) gradually increased, and red blood cells (RBC), hemoglobin (HGB), and platelet (PLT) tended to decrease from the first trimester to second trimester. After adjusting for confounding factors, higher levels of RBC, HGB, and PLT in both early and middle pregnancy were positively associated with GDM risk, whereas the level of WBC was associated with GDM risk only in early pregnancy. WBC, RBC, HGB, and PLT in early and middle pregnancy were all correlated with fasting insulin (FINS) in early pregnancy. Conclusion: Higher levels of hematological parameters in early and middle pregnancy were associated with glucose metabolism in early pregnancy and the subsequent risk of GDM. [ABSTRACT FROM AUTHOR]

Background: Ischemic injury in stroke is followed by extensive neurovascular inflammation and changes in ischemic penumbra gene expression patterns. However, the key molecules involved in the inflammatory response during the acute phase of ischemic stroke remain unclear. Methods: Gene expression profiles of two rat ischemic stroke-related data sets, GSE61616 and GSE97537, were downloaded from the GEO database for Gene Set Enrichment Analysis (GSEA). Then, GEO2R was used to screen differentially expressed genes (DEGs). Furthermore, 170 differentially expressed intersection genes were screened and analyzed for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Candidate genes and miRNAs were obtained by DAVID, Metascape, Cytoscape, STRING, and TargetScan. Finally, the rat middle cerebral artery occlusion-reperfusion (MCAO/R) model was constructed, and qRT-PCR was used to verify the predicted potential miRNA molecule and its target genes. Results: GO and KEGG analyses showed that 170 genes were highly associated with inflammatory cell activation and cytokine production. After cluster analysis, seven hub genes highly correlated with post-stroke neuroinflammation were obtained: Cxcl1, Kng1, Il6, AnxA1, TIMP1, SPP1, and Ccl6. The results of TargetScan further suggested that miR-340-5p may negatively regulate SPP1, AnxA1, and TIMP1 simultaneously. In the ischemic penumbra of rats 24 h after MCAO/R, the level of miR-340-5p significantly decreased compared with the control group, while the concentration of SPP1, AnxA1, and TIMP1 increased. Time-course studies demonstrated that the mRNA expression levels of SPP1, AnxA1, and TIMP1 fluctuated dramatically throughout the acute phase of cerebral ischemia-reperfusion (I/R). Conclusion: Our study suggests that differentially expressed genes SPP1, TIMP1, and ANXA1 may play a vital role in the inflammatory response during the acute phase of cerebral ischemia-reperfusion injury. These genes may be negatively regulated by miR-340-5p. Our results may provide new insights into the complex pathophysiological mechanisms of secondary inflammation after stroke. [ABSTRACT FROM AUTHOR]

Purpose: Sepsis is the main cause of death in intensive care unit. Maladaptive cytokine storm and T-cell lymphopenia are critical prognosis predictors of sepsis. Electroacupuncture (EA) is expected to be an effective intervention to prevent sepsis. This study aims to determine the potential of EA at ST36 (Zusanli) to prevent experimental septic mice. Methods: Mice were randomly assigned into PBS, LPS, or EA+LPS group. EA (0.1 mA, continuous wave, 10 Hz) was performed stimulating the ST36 for 30 min, once a day for 3 days. After the third day, all mice were challenged with PBS or LPS (4 mg/kg) simultaneously. Mice were evaluated for survival, ear temperature, and other clinical symptoms. Lung and small intestine tissue injuries were analyzed by hematoxylin and eosin staining. Bio-Plex cytokine assay was used to analyze the concentration of cytokines. T lymphocytes were analyzed by flow cytometry and Western blot assays. The role of T cells in preventing sepsis by EA was analyzed by using nude mice lacking T lymphocytes. Results: EA at ST36 improved survival, symptom scores, and ear temperature of endotoxemic mice. EA also improved dramatically pulmonary and intestinal injury by over 50% as compared to untreated mice. EA blunted the inflammatory cytokine storm by inducing a lasting inhibition of the production of major inflammatory factors (TNF-α, IL-1β, IL-5, IL-6, IL-10, IL-17A, eotaxin, IFN-γ, MIP-1β and KC). Flow cytometry and Western blot analyses showed EA significantly reduced T-lymphocyte apoptosis and pyroptosis. Furthermore, T lymphocytes were critical for the effects of EA at ST36 stimulation blunted serum TNF-α levels in wild-type but not in nude mice. Conclusion: EA halted systemic inflammation and improved survival in endotoxemic mice. These effects are associated with the protective effect of EA on T lymphocytes, and T cells are required in the anti-inflammatory effects of EA in sepsis. [ABSTRACT FROM AUTHOR]

Background: Extracellular vesicles (EVs) are considered to new types of intercellular communication media, and microRNA is one of the most common transferring components of EVs. This study aimed to explore the potential role of endothelial microparticles (EMPs) derived from primary pulmonary microvascular endothelial cells in regulating lung inflammation of chronic obstructive pulmonary disease (COPD) through transferring microRNA-126 (miR-126). Methods: EMPs generated from primary pulmonary microvascular endothelial cells were isolated by gradient centrifugation and characterized by transmission electron microscopy, flow cytometry and Western blotting. EMPs were treated to in vitro and in vivo COPD models induced by cigarette smoke extract (CSE). miR-126 mimics or inhibitors were transfected into EMPs by calcium chloride. Pathological changes of lung tissue, mRNA and protein levels of inflammation-related factors were measured to explore the effect of EMPs transferring miR-126 on CSE-induced inflammation. Results: Both in vitro and in vivo studies demonstrated that mRNA and protein levels of inflammation-related factors were significantly increased in COPD group, while EMPs could dramatically reverse these increases. In vitro, overexpression of miR-126 in EMPs decreased HMGB1 expression and magnified the decreasing effect of EMPs on inflammation-related factors. Conclusion: The present study reveals that EMPs are capable of alleviating lung inflammation and transferring miR-126 can magnify the anti-inflammatory effect of EMPs, which may provide a novel therapeutic alternative for COPD. [ABSTRACT FROM AUTHOR]