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关键词： Legionella pneumophila   enteritis   inflammatory cytokines   caspase 3   IL-6  

摘要： Background: Since Legionella pneumophila (Lp) is widely present in natural and artificial water environments, it has a high potential risk of outbreak. Diarrhea caused by Lp pulmonary infection is an important symptom of Legionnaires' disease (LD);however, the underlying mechanism of the diarrhea has not yet been revealed. This not only has a negative impact on clinical diagnosis and treatment, but may also cause misdiagnosis. Methods: In the present study, a mouse model of enteritis caused by pulmonary infection of Lp was established. By using this mouse model, we explored the underlying mechanisms of the enteritis caused by Lp pulmonary infection. Results: The results indicated that the systemic inflammatory response played a very important role in the enteritis phenotype caused by a strong-virulence strain of Lp. Furthermore, we found that the expression of Bcl-2 was downregulated by IL-6 through the p53 signaling pathway, thereby activating the caspase 3 of intestinal epithelial cells (IECs), causing the apoptosis of IECs, and ultimately leading to the enteritis phenotype. Conclusions: The IL-6-caspase 3 axis plays an important role in enteritis caused by Lp pulmonary infection.

关键词： HLA-DRB4*01:03:01:22   new allele   third-generation sequencing  

摘要： HLA-DRB4*01:03:01:22 differs from HLA-DRB4*01:03:01:06 by one nucleotide change in intron 2.

摘要： Doxorubicin (DOX) is a first-line chemotherapy agent known for its cardiac toxicity. DOX-induced cardiotoxicity (DIC) severely limits the use for treating malignant tumors and is associated with a poor prognosis. The sensitivity to DIC varies among patients, but the precise mechanisms remain elusive. Here we constructed a mouse model of DIC using DOX to investigate potential mechanisms contributing to the differential susceptibility to DIC. Through surface-enhanced Raman spectroscopy and single-cell RNA sequencing, we explored the mechanisms underlying DIC phenotypic variations. In vitro and in vivo studies with small-molecule drugs were conducted. DIC-insensitive mice displayed preserved ejection fractions, lower DOX levels in cardiac tissues and higher levels in the serum. Single-cell RNA sequencing revealed differences of gene expression in cardiac endothelial cells between DIC-insensitive and DIC-sensitive groups. The expression of IFN-gamma pathway-related genes was high in DIC-insensitive mice. IFN-gamma administration decreased the DOX distribution in cardiac tissues, whereas PPAR-gamma activation increased DIC susceptibility. IFN-gamma stimulation upregulated P-glycoprotein expression, leading to increased DOX efflux and DIC insensitivity. Our model provides insights into the mechanisms of DIC sensitivity and potential preventive strategies.

关键词： Anterior chamber   Immunology   Inflammation   Retina  

摘要： Background/aims To explore and characterise the clinical phenotype of acute anterior uveitis flares with delayed severity in patients with human leucocyte antigen B27 (HLA-B27)-associated anterior *** Retrospective chart review of patients with HLA-B27-associated anterior uveitis. Demographic and clinical data were recorded, as well as the clinical characteristics of acute anterior uveitis flares. A flare was considered to have delayed severity if any of the following criteria were met within 3-21 days of symptomatic onset: a two-step increase in anterior chamber inflammation on consecutive exams;a new development of hypopyon or fibrinoid aqueous reaction on consecutive examinations or a significant worsening of *** A total of 371 patient charts were identified, of which 137 were included. 321 acute anterior uveitis flares were documented, with 36 (11.2%) meeting the criteria for a delayed severity flare. The average time from symptomatic onset was 10.2 days, and patients presented with an average anterior chamber cell grade of 3.5 in delayed severity flares compared with 1.6 in non-delayed severity flares. No significant difference in frequency of delayed severity presentation was noted based on the presence or absence of systemically associated rheumatological disease, papillitis on initial presentation and retinal vasculitis on initial presentation. The frequency of topical steroid therapy after symptomatic onset was not significantly different between the two flare *** Our study presents the novel characterisation of a delayed severity phenotype of HLA-B27-associated acute anterior uveitis flares.

关键词： HBV   Discontinuation   Peg-IFN   Relapse  

关键词： Acute severe ulcerative colitis   Anti-TNF   Infliximab   Predictors   Biomarkers  

摘要： Background Acute severe ulcerative colitis (ASUC) affects up to 25% of patients with UC and is associated with an increased risk of colectomy. Despite improvements in medical management, individual patient prognostication and risk stratification in ASUC remains challenging. We explored clinical, biochemical, and endoscopic factors as potential predictors for colectomy in patients hospitalized with ASUC. Methods A retrospective analysis of patients with ASUC as defined by Truelove and Witts criteria admitted to the Mount Sinai Hospital between 2011 and 2020 was conducted. Data on disease history, medication use, clinical symptoms, and laboratory results during admission for ASUC were included. Colectomy risk during hospitalization and within one year was assessed. Results We included 158 patients;34 (21.5%) underwent colectomy during hospital admission and 41 (25.9%) within a year. On multivariable analysis, prior anti-TNF exposure (odds ratio [OR] 4.59, 95% confidence interval [CI] 1.57-13.4, P = 0.005), and biologic use at admission (OR 3.31, 95%CI 1.14-9.63, P = 0.028) were associated with an increased risk of 1-year colectomy. Conversely, mesalamine use at admission decreased this risk (OR 0.31, 95%CI 0.13-0.72, P = 0.006). Other risk factors included recent UC-related hospitalization (< 1 year of admission), higher bowel movement frequency after 3 days of treatment, low hemoglobin and albumin levels, and elevated CRP. Infliximab treatment was associated with decreased risk of urgent (OR 0.30, 95%CI 0.13-0.73, P = 0.007) and 1-year colectomy (OR 0.31, 95%CI 0.14-0.73, P = 0.007). Conclusion In patients with ASUC, prior anti-TNF exposure is linked to a higher risk of both short- and long-term colectomy, while recycling infliximab may reduce colectomy risk.

关键词： autism   cytokine imbalance   cytomegalovirus   eating behaviours   sensory processing  

摘要： Background/Objectives: Elevated cytokine levels, including IL-6 and IL-1 beta, can contribute to persistent brain inflammation in children with autism and cytomegalovirus (CMV) infection, exacerbating autism-related behaviours and symptoms. This study evaluates the impact of CMV-induced cytokine increases on the eating behaviours and sensory profiles of children with autism. Methods: A cross-sectional design was employed, involving children aged two to five years (CMV-reactive IgG), with ASD (n= 98) and TD (n = 96). Serological tests using ELISA were conducted to measure IgG CMV, IL-6, and IL-1 beta biomarkers. Eating behaviours were evaluated using the BAMBI (Brief Autism Mealtime Behaviour Inventory), and sensory profiles were assessed using the SSP (Short Sensory Profile). Statistical analyses were performed using Spearman's rank and chi-square tests. Results: The results show that autism significantly affects children's eating behaviours and sensory profiles (p < 0.001), with notable differences found between the groups. Correlation analysis revealed a significant association between IgG CMV and IL-6 (p = 0.026) and IL-1 beta (p = 0.014) in the ASD group. Additionally, eating behaviours (food refusal and limited variety) in ASD correlated with IL-6 and IL-1 beta. Sensory characteristics, such as tactile sensitivity, were found to correlate with IL-6 (p = 0.027) and IL-1 beta (p = 0.002) in the ASD group. Conclusions: These findings suggest that CMV-infected children with autism are at increased risk of IL-6 and IL-1 beta dysregulation, contributing to sensory processing issues and eating behaviours. Further research is needed to enhance CMV testing protocols and better understand the virus's role in the development of sensory and behavioural issues in children with autism.

关键词： Cytokine gene-modified tumor cells   Interleukin-7   Membrane-bound form   Tumor cell vaccine   Tumor therapy  

摘要： Various approaches employing cytokines and cytokine gene-modified tumor cells have been explored to induce antitumor responses, yet their widespread application has been limited due to efficacy concerns and adverse effects. In this study, interleukin-7 was engineered for expression both as a natural secretory form (sIL-7) and as a membrane-bound form fused with the B7.1 type I transmembrane protein (mbIL-7/B7) on CT26 colon cancer cells. Analysis of the resulting cell clones demonstrated that ectopically expressed sIL-7 and mbIL-7/B7 both retained similar capacities to induce the expansion and activation of CD8+ T cells and to enhance antitumor responses in vitro. While the sIL-7 or mbIL-7/B7 clones showed similar growth in culture, the mbIL-7/B7 clone exhibited lower tumorigenicity in mice compared with the sIL-7 clone or wild-type CT26 cells. Specifically, the mbIL-7/B7 clone failed to form tumors in approximately 60% of the mice injected with it. Moreover, 80% of mice that rejected the mbIL-7/B7 clone developed long-term systemic immunity against CT26 cells. Analysis of immune cells within the tumor masses revealed significant increases in CD4+ T cells, CD8+ T cells, and dendritic cells in tumors formed by the mbIL-7/B7 clone compared to those formed by the sIL-7 clone. These findings suggest that the membrane-bound form of IL-7 with B7.1 is more effective than the secretory form in establishing antitumor immunity within the tumor microenvironment. Our strategy of expressing the mbIL-7/B7 chimera holds promise as a novel approach for tumor therapy, particularly in cases requiring IL-7 supplementation. (c) 2024 Published by Elsevier Inc. on behalf of Korean Society for Molecular and Cellular Biology. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： HLA   Alleles   Supertypes   Haplotypes   HSCT  

摘要： This retrospective study analyses the impact HLA heterozygosity, supertypes, and alleles have on incidence of graft versus host disease (GvHD), relapse, overall survival (OS), disease-free survival (DFS) and transplantrelated mortality (TRM) after HSCT. The study included patients who underwent HSCT, typed at allele resolution level for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci. The analysis performed on the entire patient cohort (N = 232) showed that HLA-B07 supertype positive patients demonstrated decreased incidence of relapse, better OS and DFS in comparison to those negative for HLA-B07 supertype. Further, a higher incidence of TRM was observed among patients positive for HLA-B27 supertype. Significant association of the HLA-A*02:01 allele presence with decreased incidence of GvHD was found. The occurrence of HLA-A*11:01 allele was associated with a worse OS, DFS and a higher rate of TRM. The analysis of the subgroup of patients with AML or MDS (N = 148) showed an association of HLA-A24 supertype with a worse OS. The HLA-B07 supertype positive patients demonstrated a lower incidence of relapse and a better DFS. A decline in OS and a higher TRM rate were observed among patients positive for HLAB27 supertype. The presence of HLA-A*11:01 allele was indicative of a worse OS, DFS and a higher rate of TRM. The associations of HLA and HSCT clinical outcome parameters found in this study justify further investigation of this matter.

关键词： Hepatitis B   antisense oligonucleotide   bepirovirsen   pegylated interferon-a-2a   sequential therapy  

摘要： Background & Aims: Bepirovirsen, an antisense oligonucleotide, induces sustained reductions in hepatitis B surface antiger (HBsAg) and HBV DNA to below the lower limit of quantification (