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关键词： neuroinflammation   circadian rhythms   depression-like behavior   mitochondria   RNA-seq  

摘要： Neuroinflammation is involved in the development of depression and may induce depression-like behaviors by affecting metabolism through interactions with circadian rhythms. As the hub of metabolism, mitochondria are regulated by various types of metabolism and release signals that regulate cellular functions. In this study, we performed transcriptomic analysis of the hippocampus of IL-33-overexpressing mice to provide new ideas to explore the pathogenesis of inflammation-mediated depression at the transcriptional level. Male C57BL/6J mice and IL-33-overexpressing mice were subjected to behavioral tests. The hippocampus was extracted during the light or dark period, and differential gene expression analysis was conducted using RNA sequencing. Differential gene enrichment analysis was performed, as well as multilayered analysis of mitochondrial transcriptional rhythms by integrating the regulatory networks and Mito 3.0 database. The results were further verified using RT-qPCR. IL-33-overexpressing mice exhibited depressive behaviors associated with rhythmic disorders and shortened circadian cycles. Differential KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis showed that the top 20 pathways with the lowest p-values included mood-related, immune-related, and circadian rhythm-related pathways. Differential gene GO (Gene Ontology) enrichment analysis showed that 20 of the top 30 pathways with the lowest p-values were related to metabolism. Transcriptome data from IL-33-overexpressing mice showed that the mitochondrial-encoded subunit of the oxidative respiratory complex showed predominantly increased expression during the light period. Metabolic disorders and disrupted mitochondrial transcriptional rhythm were also observed. Weighted gene correlation network analysis showed that the circadian cycle is associated with depression-like behavior disorders. Network analysis showed that circadian-related genes were enriched in mitochondrial pathways related t

关键词： Rs1800896 (-1082 A > G)   Rs1800871 (-819 C > T)   Rs1800872 (-592 C > A)   Severe acute respiratory syndrome-related   coronavirus   Polymorphism   Single nucleotide   Interleukin-10   Polymorphism   Single nucleotide   Interleukin-10  

摘要： Background: Elevated concentrations of IL-10 have been detected in coronavirus disease (COVID-19) patients and are a possible disease severity marker. Single nucleotide variants (SNVs) and their haplotypes can be associated with differences in IL-10 levels and with viral disease susceptibility. Aim: Evaluate the associations of SNVs and their haplotypes in Brazilian patients with COVID-19 severity and outcome. Methods: In this cross-sectional and case-control study, the patients were selected from the University Hospital of State University of Londrina (HU-UEL) (n = 367) and were subdivided into mild (n = 165), moderate (n = 72) and severe (n = 130) groups. The DNA samples of the participants were subjected to real-time PCR for the detection of rs1800896 (A>G), rs1800871 (C>T) and rs1800872 (C>A) genotypes. The haplotypes were inferred with PHASE v2.1.1. Results: The severe cases of COVID-19 were independently associated with the GG genotype (rs1800896) (P = 0.038, OR 2.522, 95 % CI 1.053-6.038) as well as with the GCC haplotype in homozygosity (P = 0.037, OR 2.767, 95 % CI 1.065-7.191). Conclusion: These results showed that the GG genotype of rs1800896 or the GCC haplotype are associated with COVID-19 severity in Brazilian patients.

关键词： hypertension, pulmonary   inflammation   interleukin   macrophage   mice  

摘要： BACKGROUND:The infiltration of macrophages into the lungs is a common characteristic of perivascular inflammation, contributing to vascular remodeling in pulmonary hypertension (PH). Peli1 (pellino E3 ubiquitin-protein ligase 1) plays a critical role in regulating the production of proinflammatory cytokines and the polarization of macrophages in various diseases. However, the role of Peli1 in PH remains to be ***:The expression and biological function of Peli1 were investigated in both human and experimental models of PH. Peli1-deficient mice and bone marrow transplant mice were utilized to explore the roles of Peli1 in macrophages in vivo. Proteomic analysis and molecular biology techniques were used to uncover the underlying ***:The upregulation of Peli1 in the lungs and alveolar macrophages was observed in hypoxia-treated mice. Peli1 knockout mice and myeloid Peli1-deficient mice significantly ameliorated hypoxia-induced right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary vascular remodeling. Mechanistically, Peli1 facilitated the ubiquitination and subsequent proteasomal degradation of Foxp1 (forkhead box p1), thereby alleviating its suppression of IL (interleukin)-6 transcription and contributing to macrophage activation. Furthermore, myeloid Foxp1 deficiency partially eliminates the protective effect of myeloid Peli1 deficiency in hypoxia-induced PH ***:Our findings demonstrate that the Peli1-Foxp1-IL-6 pathway plays a crucial role in macrophage activation and recruitment during the development of PH, underscoring the potential of Peli1 as a therapeutic target for PH.

关键词： HIV   Mycobacterium tuberculosis   LTBI   CD4 T cell   HLA-DR   Immune activation  

摘要： Infection with HIV is associated with dysregulated CD4 T cell responses to Mycobacterium tuberculosis (Mtb) and increased risk of developing tuberculosis. Mtb-specific CD4 T cells in people with HIV have diminished Th1 cytokine production capacity, thus we utilized a flow cytometry-based assay to measure CD40L expression by Mtb-specific CD4 T cells in a cytokine-independent manner. We evaluated the frequency and phenotype of Mtbspecific CD4 responses in Kenyan adults with latent Mtb infection and found that the majority of Mtb-specific CD4 T cells expressed CD40L in the absence of IFN-gamma, regardless of HIV infection status. Expression of HLADR was increased on Mtb-specific CD4 T cells in people with HIV, compared to people without HIV. These data suggest expression of HLA-DR by Mtb-specific CD4 T cells may represent an early biomarker of increased mycobacterial antigen stimulation in people with HIV prior to the development of symptomatic tuberculosis disease.

关键词： HLA-A*11:485   novel allele   sequence-based typing  

摘要： The HLA-A*11:485 allele differs from HLA-A*11:01:01:01 by one nucleotide substitution in codon 39 in exon 2.

关键词： Optic nerve crush   small extracellular vesicles   interferon gamma   interferon-responsive microglia   microRNAs   ribosome activity  

摘要： Aim: Microglial activation plays a pivotal role in the pathogenesis of retinal ganglion cell (RGC) degeneration resulting from optic nerve crush (ONC). Small extracellular vesicles (sEVs) secreted by mesenchymal stem cells (MSCs) have the potential to prevent retinal degeneration by modulating microglial activation. In this study, we elucidated the specific effects of sEVs derived from IFN-gamma-primed MSCs on the phenotypic transition of microglia and the associated pathways in ONC mice. Methods: The ONC mice model was established and administered intravitreal injection with the sEVs derived from native MSCs (native sEVs) and the sEVs derived from MSCs primed with IFN-gamma (IFN gamma-sEVs). Their respective effects on the survival of the retinal ganglion cells (RGCs) and the transition of microglia phenotypes were determined through visual function testing and immunohistochemical staining. Combined with mRNA seq and microRNA seq techniques, we elucidated the mechanism of modulation of microglia phenotypic transformation by sEVs derived from MSCs primed by IFN gamma. Results: It demonstrated that IFN gamma-sEVs exhibited superior protective effects against RGC loss and reduced inflammatory responses in the ONC retina compared to native sEVs. Both types of sEVs promoted microglia activation to disease-associated microglia (DAM) phenotype, while IFN gamma-sEVs especially suppressed interferon- responsive microglia (IRM) activation during RGCs degeneration. Subsequent miRNA sequencing suggested that miR-423-5p, which exhibited the most significant differential expression between the two sEVs types and elevated expression in IFN gamma-sEVs, inhibited the expression of IRM and ribosomal genes. Conclusion: These findings suggest that IFN-gamma-preconditioned MSCs may enhance sEVs of neuroprotection on RGCs by suppressing IRM activation through the secretion of sEVs containing specific microRNAs in ONC mice.

关键词： compatibility platelets   HLA antibody positivity   intravenous immunoglobulin   nursing   platelet transfusion refractoriness  

摘要： Hepatic arterial infusion chemotherapy in conjunction with the combination therapy of atezolizumab (T) and bevacizumab (A) is widely used in hepatocellular carcinoma. Some adverse events such as hypertension, weakness and elevated transaminase levels occurred during treatment, while there is currently no reported case about thrombocytopenia with concomitant HLA antibody-positive PTR. We summarize the critical care nursing experience of a patient with PTR because of HLA antibody positivity during hepatic arterial infusion chemotherapy in conjunction with atezolizumab plus bevacizumab (T + A) regimen. This paper explains the nursing measures for patients with severe thrombocytopenia and proposes nursing measures for situations where conventional treatments are ineffective. Key nursing points include the administration of intravenous immunoglobulin (IVIG) and HLA-compatible platelets, prevention of complications, psychological care, oral care, and skin management. Through systematic treatment and targeted nursing care, the patient's platelet count rebounded after 9 days, leading to a successful recovery and discharge. Subsequent follow-up assessments revealed the patient's sustained well-being. Thrombocytopenia is a potential adverse reaction during the treatment of liver cancer. When platelet transfusion is ineffective, vigilance is necessary for the possibility of HLA positivity, and prompt symptomatic management is warranted.

关键词： transfer   emergency   elderly   nursing homes   Paris 16  

摘要： Context: In January2023, 14.5 millions people were over 65 (21.3%) and 600,000 people live in nursing homes. A 2018 study showed that 30 % of visits to the emergency room were "avoidable".Measure 5 of the 2019-2022 emergency overhaul pact is to generalize routes dedicated to the elderly to avoid recourse to emergencies. The EMGE (Mobile Extra-Hospital Geriatrics Team) is a key mechanism in coordination between nursing homes and emergency reception services. Objective: Study the reasons why elderly people residing in nursing home go to emergency. Method: We prospectively identified and described emergency transfers of residents of 4 nursing homes, from January 1 to March 31, 2022. Then, retrospectively, we requested a panel of 9 expert in order to judge if the transfer to the emergency was appropriate, based on a questionnaire. Results: 50 (75,6%) transfer were assessed as suitable by at least 5 of the 9 experts. The average age of transferred residents was 91.7 +/- 6.4 years. In 35 % of cases, the symptoms motivating the transfer had been present for more than 48 hours. The main reason for 2 transfers was a fall (35%). A nurse was at the origin of 40 transfers (61%). Conclusion: This study shows that 76% of visits to the emergency room were considered suitable. The management of emergency situations in nursing homes is a real public health issue, and the pivotal role of a GMT is to secure, optimize and streamline the care of elderly people in nursing homes, and to limit as much as possible the transfer to emergencies.

关键词： HLA-A   next generation sequencing   novel allele  

摘要： HLA-B*27:284 differs from HLA-B*27:07:01 by one nucleotide substitution in exon 4, at gDNA position 1614 (G>A).

关键词： Adolescent   Strength training   Oxidative stress   Hormones   IL-6  

摘要： Purpose The aim of the study was to investigate how 8-week strength training affects adolescent athletes' basal hormone concentrations, sex hormone binding globulin (SHBG), insulin-like growth factor binding protein-3 (IGFBP-3), cytokine, and oxidative stress markers. Methods Twenty adolescent handball players participated in this study. The participants were randomly divided into the strength training group (ST, n = 10) and the control group (C, n = 10). ST participates in strength training 3 sessions a week for 8 weeks and C participates only in handball training. We quantified serum basal hormone concentration, SHBG, IGFBP3, oxidative stress markers, and IL-6 in each subject's blood samples before and after 8 weeks of strength training. Results Interestingly, while insulin-like growth factor-1 (IGF-1) concentration declined in group C (p < 0.05), it did not in ST (p > 0.05). Furthermore, the basal concentration of growth hormone (GH), total testosterone (T), cortisol (Cor), total antioxidant status (TAS), and serum-free androgen index (FAI) basal concentration did not change in ST and C. Basal IGFBP-3 and SHBG concentrations decreased only in ST (p < 0.05), but not in C (p > 0.05). Serum-free testosterone (FT) levels increased in ST and C (p > 0.05). Total oxidant status (TOS) and oxidative stress index (OSI) reduced ST and C (p < 0.05). Serum interleukin-6 (IL-6) levels did not alter groups ST and C. Conclusion Strength training did not affect basal serum concentrations of T, GH, IGF-1, COR, IL-6, and TAS, but it caused a decrease in SHBG and IGFBP3 concentrations in ST. Increased basal FT concentration and improved serum TOS may not depend on strength training.