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关键词： Malaria   Immune responses   Uric acid   Cytokines   River nile state  

摘要： Background Malaria, a prevalent disease in Sudan, has a significant impact on socioeconomic conditions. Cytokines play a crucial role in regulating the immune response during infectious diseases. This study investigates the interplay between malaria and immune response modulation in the River Nile State, focusing on tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), transforming growth factor-beta1 (TGF-beta 1), and interleukin-10 (IL-10). Method Ninety participants with microscopy-confirmed malaria were enrolled. Parasite density and COVID-19 co-infection were assessed. Cytokine levels were measured using ELISA. Results TNF-alpha, IFN-gamma, and TGF-beta 1 levels were significantly associated with parasite density (P < 0.05), but not IL-10. TGF-beta 1 was significantly higher in P. vivax infections, while IL-10 was elevated in P. falciparum cases. Uric acid levels were lower in participants co-infected with COVID-19 (P < 0.05). Conclusion The study's findings show how cytokines affect the immune response, impacting both parasite clearance. TNF-alpha, IFN-gamma, and TGF-beta 1 are positively linked to parasite density (r = 0.42, 0.38, 0.51;P < 0.01). IL-10 levels were higher in P. falciparum compared to P. vivax (560.0 vs. 415.6 pg/mL, P = 0.019).

关键词： Alcohol   Acute duodenal injury   Ethnopharmacology   Ampelopsis grossedentata   Apoptosis   TNF-a  

摘要： Ethnopharmacological relevance: Ampelopsis grossedentata (AG) is a popular folk tea that has been used in China for more than 1000 years. It is noteworthy that AG is widely recognized for preventing alcohol hangover in folk, and its protective effects on alcohol-induced hepatic steatosis have been demonstrated. Aim of the study: Alcohol overconsumption can induce acute duodenal injury (ADI) that lacks effective therapeutic strategies. This study investigated the gastrointestinal protective effects of AG on alcoholic ADI in mice. Materials and methods: AG extract was chemically characterized by HPLC analysis. Institute of Cancer Research (ICR) mice were pre-administered AG extract via gavage, and then subjected to an ethanol-induced ADI. After treatment, duodenal tissues were stained with hematoxylin and eosin (H&E), and cell apoptosis was detected by TUNEL staining and immunofluorescence. Untargeted metabolomics was employed to identify the differentially expressed metabolites, and the gene expressions of duodenal tissues were determined using RNA sequencing, immunofluorescence, immunohistochemistry, and western blotting. Results: Acute ethanol administration caused severe duodenal damage, characterized by necrosis and shedding of duodenal villi, hemorrhagic injury, mucosal edema, and disruption of intestinal barrier in mice, which was improved by the pre-treatment with AG extract. Notably, administration of AG aqueous extract suppressed ethanol-induced duodenal villous apoptosis in mice by inhibiting caspase-3/7. In addition, untargeted metabolomics data showed AG extract improved ethanol-induced disruption of amino acid biosynthesis and metabolism, and increased the levels of amino acids, such as L-serine, L-histidine, L-leucine, L-glutamine and Ltryptophan. RNA sequencing analysis revealed that ethanol intake activated TNF, IL-17, MAPK and apoptosis pathways, and these pathways were inhibited by AG extract pre-treatment. Immunofluorescence and immunohistochemistr

关键词： Major histocompatibility complex   Sequence alignment   Multiple alignment calculation   Contaminants   Protein sequencing   B cells   Database searching   Vaccines  

摘要： Background The goal in vaccinology is to identify candidate antigens for clinical trials that will elicit an immune response for a significant portion of the target population. Unfortunately, promising data generated at the preclinical level often cannot be replicated in larger sample sizes. The goal of this project was to develop a methodology for processing MAE-generated data to identify MHC epitopes, minimize non-specific contaminants, find binding motifs, and utilize genetic connections among donors to determine which peptides were presented by specific MHC *** Our approach demonstrated that mild acid elution of peptides from seven consanguineous B-lymphocyte lines accurately reflects the HLA genotypes within family members, highlighting the specificity of MAE. Additionally, the data successfully reproduced known MHC binding motifs and partially deconvoluted the originating HLA alleles of the *** These findings suggest that our approach could be applied to numerous cell lines globally to evaluate a wide array of HLA haplotypes. This may help to reveal candidate vaccine antigens that induce immune protection for a wider population.

关键词： atopic dermatitis   caspase-1   CD81   IL-18   pathogenic group 2 innate lymphoid cells   single-cell RNA sequencing  

摘要： Autonomous artificial intelligence (AI) models for deciding treatment strategies are available but rarely applied prospectively in clinical settings. Here we present a prospective study of deploying daGOAT, an algorithm we have developed, as a conditional autonomous AI agent to prescribe a drug to prevent severe (grade 3-4) acute graft-versus-host disease (acute GvHD) following human leukocyte antigen (HLA)-mismatched haematopoietic cell transplantation (***, NCT05600855). During the enrollment period physicians invite 85% of eligible patients to participate and 88% of the invited patients agree. Among the 110 enrolled participants who receive HLA-haploidentical transplants, daGOAT predicts intermediate to high risk of severe acute GvHD in 57 participants between days +17 and +23 posttransplant and prescribes ruxolitinib in addition to the existing regimen to intensify immune suppression. The initial compliance with AI prescription is 98% (56/57), with dose and/or schedule deviating from the AI prescription within one month in a total of eight participants. In conclusion, we show that many physicians and patients are receptive to using conditional autonomous AI to prescribe a drug and that the decision for pharmaceutical intervention could be facilitated by autonomous AI.

关键词： 肺疾病,慢性阻塞性   呼吸道合胞病毒   呼吸功能试验   细胞因子类  

摘要： 目的 探讨呼吸道合胞病毒(RSV)载量对慢性阻塞性肺疾病急性加重期(AECOPD)病人肺功能的影响及与血清细胞因子水平的关系。方法 选取2018年6月-2021年6月我院收治的224例AECOPD病人为研究对象。根据病人RSV载量分为高RSV载量组(132例)和低RSV载量组(92例),采用实时荧光定量PCR(RT-PCR)法检测RSV-RNA载量,采用化学发光法、酶联免疫吸附试验(ELISA)法和凝血酶时间法分别检测血清白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)和纤维蛋白原(FIB)水平,应用肺功能检测仪测定第一秒用力呼气容积(FEV1)及FEV1/用力肺活量(FVC)比值。结果 与低RSV载量组比较,高RSV载量组血清IL-6、TNF-α、FIB水平均升高,FEV1、FEV1/FVC均降低(t=4.443～12.051,P<0.05)。RSV载量与血清细胞因子IL-6、TNF-α、FIB水平呈正相关(r=0.391～0.487,P<0.05),与肺功能指标FEV1、FEV1/FVC呈负相关(r=-0.481、-0.477,P<0.05)。RSV载量和血清IL-6、TNF-α、FIB水平以及Logistic模型评估AECOPD病人肺功能重度不可逆气流受限的曲线下面积(AUC)分别为0.657、0.805、0.734、0.629和0.880。结论 RSV载量与AECOPD病人血清细胞因子水平相关,对AECOPD病人肺功能评估具有一定价值。

关键词： Breast neoplasms   HLA Antigens   Interferon-induced transmembrane protein   Natural killer cell-mediated cytotoxicity   β-catenin  

摘要： Purpose:Interferon-induced transmembrane protein 1 (IFITM1) is associated with a poor prognosis in triple-negative breast cancer (TNBC); however, the mechanisms by which IFITM1 contributes to oncogenesis in TNBC are unclear. Materials and Methods:We established two stable cell lines: IFITM1-overexpressing cell line (MB-231-IFITM1-OE) and IFITM1 knockdown cell line (BT-20-IFITM1-KD). The transcriptional activity of β-catenin and the cytotoxic activity of natural killer (NK) cells were evaluated using the luciferase assay and the lactate dehydrogenase cytotoxicity assay. The expression of IFITM1, β-catenin, and HLA class I was assessed by immunohistochemistry in patients with TNBC. Results:Knockdown of IFITM1 in BT-20 cells reduced cell proliferation and ectopically expressed IFITM1 in MB-231 cells increased cell proliferation. RNA sequencing analysis revealed that IFITM1 expression positively correlated with the Wnt/β-catenin signaling pathway and NK cell-mediated cytotoxicity. MB-231-IFITM1-OE cells showed increased β-catenin transcriptional activity and NK cell cytotoxic activity compared with controls, while transient knockdown of IFITM1 in MB-231-IFITM1-OE cells led to a decrease in β-catenin transcriptional activity and NK cell cytotoxic activity. MB-231-IFITM1-OE cells exhibited decreased HLA class I expression, which may have contributed to their increased susceptibility to NK cell-mediated lysis. β-catenin or JAK inhibitor reduced NK cell-mediated cytotoxicity via upregulation of HLA class I. Patients with IFITM1 overexpression showed a trend toward increased β-catenin positivity and HLA class I negativity. Conclusion:IFITM1 overexpression was associated with Wnt/β-catenin signaling and NK cell-mediated cytotoxicity via downregulation of HLA class I in TNBC cells, suggesting that IFITM1 might have immunoregulatory effects on the tumor microenvironment.

摘要： Periodontal disease (PD) is a common chronic inflammatory condition that progresses severely in people living with HIV (PLWH). Although human leukocyte antigen (HLA) class I molecules, including HLA-A alleles, are key to immune function, their role in PD susceptibility among PLWH is poorly understood. To identify the most frequent HLA-A alleles associated with PD in PLWH and determine those independently linked to PD status. A case-control genetic association study was conducted using buffy coat samples from 156 HIV-positive individuals enrolled at the MJAP-ISS Clinic. DNA was extracted, amplified via PCR, and sequenced using the Oxford Nanopore MinION platform. Due to sequencing throughput limitations, only 64 samples yielded usable sequence data. Allele frequencies were compared between PD cases and periodontally healthy controls. Statistical analyses included logistic regression, and ROC curve analysis. Thirteen HLA-A alleles were identified. HLA-A11 was the most common allele among PD cases (48.4%) compared to controls (7.8%). A11 showed a significant association with PD (adjusted odds ratio [AOR] = 12.8; 95% CI: 3.36-61.6; p < 0.001). A sex-stratified analysis showed that the association was significant among females (AOR = 14.3), but not in males. Other alleles, such as A02 and A03 were not significantly associated. The model combining A11 and sex achieved the best performance (AUC = 0.867). HLA-A11 is significantly associated with PD in PLWH, especially among females, suggesting a gene-sex interaction. Further studies are needed to explore the immunological basis and validate findings across diverse populations. Clinical trial Number: Not applicable.

摘要： Clinical studies have demonstrated that recipients of allogeneic hematopoietic cell transplantation (alloHCT), particularly those undergoing HLA-haploidentical alloHCT (haploHCT), exhibit significant immune deficiencies. However, the extent to which major histocompatibility complex (MHC) disparity independently contributes to the observed lymphocyte deficiency post-alloHCT remains unclear. While MHC matching is crucial for thymic selection of T lymphocytes, it has yet to be reported whether haploHCT alters recipient thymus homeostasis compared to MHC-matched HCT and which signaling pathways are implicated in this alteration. In this study, we established mouse models of MHC- matched and haploidentical HCT without any transplant-associated complications. Our findings indicated that MHC disparity significantly disrupted thymic architecture, suppressed thymus-specific gene expression, and resulted in impaired T-cell recovery and functionality following transplantation. Single-cell transcriptomic analysis revealed abnormally enhanced interactions involving TGFB1-TGFBR3 and LRP6-CKLF between thymic lymphocytes and epithelial cells in haploHCT recipients. Furthermore, agonists targeting the TGF-β1 and LRP6 pathways were found to compromise the functional characteristics of normal thymic T cells; conversely, appropriate inhibition of these pathways restored the differentiation and maturation phenotypes of thymic T cells derived from haploHCT recipients. Our study elucidates the independent role of MHC disparity in regulating thymus homeostasis and T-cell recovery while identifying the functional involvement of the TGF-β1 and LRP6 pathways in this context. These findings provide novel insights into the mechanisms underlying immune recovery as well as potential therapeutic strategies for modulating thymic functions following haploHCT.

关键词： Biologic therapy   Crohn's disease   Ulcerative colitis   Vaccination  

摘要： BACKGROUND:Patients with inflammatory bowel disease (IBD) are at increased risk of herpes zoster (HZ) and should receive the recombinant herpes zoster vaccine (RZV). We sought to assess the immunogenicity and safety of RZV series in patients receiving anti-tumor necrosis factor (TNF) therapy compared to those receiving vedolizumab. METHODS:This single-center prospective study enrolled patients with IBD on vedolizumab or anti-TNF monotherapy receiving RZV. Primary outcome assessed cell-mediated immunity (CMI) differences between groups post-vaccination. Secondary outcomes included humoral response, sustained immunity, and safety monitoring for adverse events and IBD flares. Assessments occurred at baseline, 30, 240, and 425 days post-vaccination. Statistical analyses included non-parametric Mann-Whitney U tests for between-group comparisons and Wilcoxon signed-rank tests for within-group changes, with significance set at p<0.05. RESULTS:Thirty-three patients enrolled (16 vedolizumab, 17 anti-TNF). CMI responses increased post-vaccination in both groups (median 56 cells/million [IQR 21-102] vs 33 cells/million [IQR 11-73]; p=0.13), with no significant difference between treatment groups. Both groups showed strong antibody responses to vaccination (pre-immunization median: 349.9 mIU/ml [IQR 276.8-402.5] vs. 90-day median: 605.0 mIU/ml [IQR 525.6-641.0]; p<0.001). CMI responses remained elevated at both day 240 and 425 assessments. Antibody levels remained elevated through day 425 (549.1 mIU/ml, IQR 516.1-585.6), substantially higher than pre-vaccination levels. No IBD flares occurred; most adverse events were mild and transient. CONCLUSIONS:RZV demonstrated robust immunogenicity and favorable safety profile in IBD patients receiving either vedolizumab or anti-TNF therapy. Both cellular and humoral immune responses persisted through 425 days post-vaccination.