Zobrazení zdroje stránky Stentofthickman7297

Sepsis is the leading cause of death among patients, especially elderly patients, in intensive care units worldwide. In this study, we established a sepsis model using naturally aged rats and injected 5×106 umbilical cord-derived MSCs via the tail vein. Each group of rats was analyzed for survival, examined for biochemical parameters, stained for organ histology, and analyzed for the Th cell subpopulation ratio and inflammatory cytokine levels by flow cytometry. Western blotting was performed to detect the activity of the JAK-STAT signaling pathway. We designed the vitro experiments to confirm the regulatory role of MSCs, and verified the possible mechanism using JAK/STAT inhibitors. It was revealed from the experiments that the 72 h survival rate of sepsis rats treated with MSCs was significantly increased, organ damage and inflammatory infiltration were reduced, the levels of organ damage indicators were decreased, the ratios of Th1/Th2 and Th17/Treg in peripheral blood and spleen were significantly decreased, the levels of pro-inflammatory cytokines such as IL-6 were decreased, the levels of anti-inflammatory cytokines such as IL-10 were increased, and the levels of STAT1 and STAT3 phosphorylation were reduced. These results were validated in in vitro experiments. Therefore, this study confirms that MSCs can control the inflammatory response induced by sepsis by regulating Th cells and inflammatory factors, and that this leads to the reduction of tissue damage, protection of organ functions and ultimately the improvement of survival in aged sepsis model rats. Inhibition of the JAK-STAT signaling pathway was surmised that it may be an important mechanism for their action.Visceral leishmaniasis, caused by L. donovani infection is fatal if left untreated. The intrinsic complexity of visceral leishmaniasis complicated further by the increasing emergence of drug resistant L. donovani strains warrants fresh investigations into host defense schemes that counter infections. Accordingly, in a mouse model of experimental visceral leishmaniasis we explored the utility of host Wnt5A in restraining L. donovani infection, using both antimony sensitive and antimony resistant L. donovani strains. We found that Wnt5A heterozygous (Wnt5A +/-) mice are more susceptible to L. donovani infection than their wild type (Wnt5A +/+) counterparts as depicted by the respective Leishman Donovan Units (LDU) enumerated from the liver and spleen harvested from infected mice. Higher LDU in Wnt5A +/- mice correlated with increased plasma gammaglobulin level, incidence of liver granuloma, and disorganization of splenic white pulp. Progression of infection in mice by both antimony sensitive and antimony resistant strains of L. donovani could be prevented by activation of Wnt5A signaling through intravenous administration of rWnt5A prior to L. donovani infection. Wnt5A mediated blockade of L. donovani infection correlated with the preservation of splenic macrophages and activated T cells, and a proinflammatory cytokine bias. Taken together our results indicate that while depletion of Wnt5A promotes susceptibility to visceral leishmaniasis, revamping Wnt5A signaling in the host is able to curb L. donovani infection irrespective of antimony sensitivity or resistance and mitigate the progression of disease.<br /><br /> Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to considerable morbidity/mortality worldwide, but most infections, especially among children, have a mild course. However, it remains largely unknown whether infected children develop cellular immune memory.<br /><br /> To determine whether a memory T cell response is being developed, we performed a longitudinal assessment of the SARS-CoV-2-specific T cell response by IFN-γ ELISPOT and activation marker analyses of peripheral blood samples from unvaccinated children and adults with mild-to-moderate COVID-19.<br /><br /> Upon stimulation of PBMCs with heat-inactivated SARS-CoV-2 or overlapping peptides of spike (S-SARS-CoV-2) and nucleocapsid proteins, we found S-SARS-CoV-2-specific IFN-γ T cell responses in infected children (83%) and adults (100%) that were absent in unexposed controls. Frequencies of SARS-CoV-2-specific T cells were higher in infected adults, especially several cases with moderate symptoms, compared to infected children. The S-SARS-CoV-2 IFN-γ T cell response correlated with S1-SARS-CoV-2-specific serum antibody concentrations. Predominantly, effector memory CD4+ T cells of a Th1 phenotype were activated upon exposure to SARS-CoV-2 antigens. Frequencies of SARS-CoV-2-specific T cells were significantly reduced at 10 months after symptom onset, while S1-SARS-CoV-2-specific IgG concentrations were still detectable in 90% of all children and adults.<br /><br /> Our data indicate that an antigen-specific T cell and antibody response is developed after mild SARS-CoV-2 infection in children and adults. It remains to be elucidated to what extent this SARS-CoV-2-specific response can contribute to an effective recall response after reinfection.<br /><br />Our data indicate that an antigen-specific T cell and antibody response is developed after mild SARS-CoV-2 infection in children and adults. [https://www.selleckchem.com/ selleck compound] It remains to be elucidated to what extent this SARS-CoV-2-specific response can contribute to an effective recall response after reinfection.Convalescent plasma is a suggested treatment for Coronavirus disease 2019 (Covid-19), but its efficacy is uncertain. We aimed to evaluate whether the use of convalescent plasma is associated with improved clinical outcomes in patients with Covid-19.In this systematic review and meta-analysis, we searched randomized controlled trials investigating the use of convalescent plasma in patients with Covid-19 in Medline, Embase, Web of Science, Cochrane Library, and medRxiv from inception to October 17th, 2021. Two reviewers independently extracted the data. The primary efficacy outcome was all-cause mortality. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used. This study was registered with PROSPERO, CRD42021284861. Of the 8874 studies identified in the initial search, sixteen trials comprising 16 317 patients with Covid-19 were included. In the overall population, the all-cause mortality was 23.8% (2025 of 8524) with convalescent plasma anpero/, identifier PROSPERO (CRD42021284861).<br /><br />https//www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD42021284861).Rheumatoid arthritis (RA) is one of the most common autoimmune diseases that affect synovitis, bone, cartilage, and joint. RA leads to bone and cartilage damage and extra-articular disorders. However, the pathogenesis of RA is still unclear, and the lack of effective early diagnosis and treatment causes severe disability, and ultimately, early death. Accumulating evidence revealed that the regulatory network that includes long non-coding RNAs (lncRNAs)/circular RNAs (circRNAs), micro RNAs (miRNAs), and messenger RNAs (mRNA) plays important roles in regulating the pathological and physiological processes in RA. lncRNAs/circRNAs act as the miRNA sponge and competitively bind to miRNA to regulate the expression mRNA in synovial tissue, FLS, and PBMC, participate in the regulation of proliferation, apoptosis, invasion, and inflammatory response. Thereby providing new strategies for its diagnosis and treatment. In this review, we comprehensively summarized the regulatory mechanisms of lncRNA/circRNA-miRNA-mRNA network and the potential roles of non-coding RNAs as biomarkers and therapeutic targets for the diagnosis and treatment of RA.Translationally controlled tumor protein (TCTP) is a highly conserved protein possessing numerous biological functions and molecular interactions, ranging from cell growth to immune responses. However, the molecular mechanism by which TCTP regulates immune function is largely unknown. Here, we found that knockdown of Bombyx mori translationally controlled tumor protein (BmTCTP) led to the increased susceptibility of silkworm cells to virus infection, whereas overexpression of BmTCTP significantly decreased the virus replication. We further demonstrated that BmTCTP could be modified by SUMOylation molecular BmSMT3 at the lysine 164 via the conjugating enzyme BmUBC9, and the stable SUMOylation of BmTCTP by expressing BmTCTP-BmSMT3 fusion protein exhibited strong antiviral activity, which confirmed that the SUMOylation of BmTCTP would contribute to its immune responses. Further work indicated that BmTCTP is able to physically interact with interleukin enhancer binding factor (ILF), one immune molecular, involved in antivirus, and also induce the expression of BmILF in response to virus infection, which in turn enhanced antiviral activity of BmTCTP. Altogether, our present study has provided a novel insight into defending against virus via BmTCTP SUMOylation signaling pathway and interacting with key immune molecular in silkworm.Although gut dysbiosis had been demonstrated to be an important factor affecting hyperuricemia (HUA) and gout, little is known for its potential mechanistic connections. In this study, Uox-KO mice model that with spontaneously developed pronounced HUA and urate nephropathy was used to explore the pathophysiologic mechanism of microbiota alterations in HUA and gout with integrated multi-omics analysis. 16S rRNA gene sequencing was performed to characterize the characteristic bacteria, and untargeted LC/MS analysis was applied to reveal the featured metabolites. Our results showed there was a significant shift in gut microbiota composition and function in Uox-KO mice compared to WT mice and apparent metabolomics differences between the two groups. Among them, amino acids metabolism appears to play a critical role. Correlation analysis further revealed that the characteristic metabolites were strongly influenced by the discrepant bacterial genera. Furthermore, impairment of intestinal integrity and profound alterations in the profile of solute carrier family resulted in dysregulation of amino acids transportation, which subsequently impacted serum uric acid level and CD4+ Th17 driven inflammation. Together, these data indicate that gut dysbiosis promotes purine metabolism disorder and inflammation in Uox-KO mice. Remodeling the gut microbiota is a promising strategy to combat HUA and gout.Hirame novirhabdovirus (HIRRV) is an ongoing threat to the aquaculture industry. The water temperature for the onset of HIRRV is below 15°C, the peak is about 10°C, but no mortality is observed over 20°C. Previous studies found the positive signal of matrix protein of HIRRV (HIRRV-M) was detected in the peripheral blood leukocytes of viral-infected flounder. Flow cytometry and indirect immunofluorescence assay showed that HIRRV-M was detected in mIgM+ B lymphocytes in viral-infected flounder maintained at 10°C and 20°C, and 22% mIgM+ B lymphocytes are infected at 10°C while 13% are infected at 20°C, indicating that HIRRV could invade into mIgM+ B lymphocytes. Absolute quantitative RT-PCR showed that the viral copies in mIgM+ B lymphocytes were significantly increased at 24 h post infection (hpi) both at 10°C and 20°C, but the viral copies in 10°C infection group were significantly higher than that in 20°C infection group at 72 hpi and 96 hpi. Furthermore, the B lymphocytes were sorted from HIRRV-infected flounder maintained at 10°C and 20°C for RNA-seq.