American journal of clinical and experimental immunology最新文献

In the intensive care unit (ICU), patients often experience restricted mobility due to their critical condition, potentially leading to negative effects on both muscle strength and immune function. Previous research has highlighted the beneficial effects of early mobilization among patients, regardless of mechanical ventilation status. Hence, early bed cycling serves as a potential facilitator for early mobilization and is considered a feasible intervention for critically ill patients within the ICU. To mitigate this concern, we propose a randomized controlled clinical trial aiming to assess the efficacy of early bed cycling for patients undergoing mechanical ventilation and analgosedation. The study will encompass 56 participants randomly assigned to either the treatment or control group, each consisting of 28 patients. Participants in both groups will receive health education. However, the control group will not receive any therapeutic intervention throughout the study. In contrast, the experimental group will undergo passive bed cycling of their lower extremities for 20 minutes at a rate of 30 revolutions per minute. Primary outcomes will focus on changes in the rectus femoris muscle area and thickness, evaluated using ultrasound, interleukin-6 (IL-6), IL-10, and nitric oxide (NO) production function. Secondary endpoints will encompass the modified Barthel index score, Medical Research Council total score at 1, 2, and 4 weeks following the final treatment session, participants' mechanical ventilation duration, rate of extubation in the second week, 28-day survival rate, and occurrence of adverse reactions. Any encountered side effects will be duly documented. Statistical analysis will be employed to compare patient outcomes between the treatment and control groups.

Mistletoe extracts contain the ribosome inactivating protein viscumin, which exhibits effectiveness in alternative therapies but also presents considerable toxicity risks. Hence, specific and sensitive diagnostics for identifying viscumin exposure should be developed. This study aimed to develop monoclonal antibodies (mAbs) to viscumin and to test their protective capacity against its cytotoxic effects. A peptide epitope, representing A-chain of viscumin of 9 amino acids, was synthesized and conjugated to Bovine Serum Albumin (BSA) for the immunization of BALB/c mice. Spleen cells from immunized mice were fused with SP2/0 myeloma cells to obtain hybridomas. The generated mAbs for viscumin were selected through ELISA and further characterized. The cytotoxicity of mistletoe extract against Hep-G2 cells was conducted with the SRB assay, which revealed a reduction in cell viability, respectively: about 80% at 2.5 μg/mL, 64% at 5 μg/mL, and 46% at 10 μg/mL. Interestingly, it was observed that the mAbs significantly mitigated the cytotoxic activity of viscumin, causing the viability of about 86% at all tested concentrations. Hence, they showed potential for mAbs in developing sensitive diagnostic assays and therapeutic strategies to counteract the toxic effects of viscumin. Further mAb variants' characterization, epitope mapping, and determination of the affinity should be conducted to improve both diagnostic and therapeutic avenues of viscumin-induced toxicity.

Background: Systemic lupus erythematosus (SLE) and dilated cardiomyopathy (DCM) are closely linked biologically, especially regarding immune responses. However, key biomarkers mediating the onset and development of both diseases are still lacking. This study uses bioinformatic methods to analyse the immune microenvironment of the ventricles of DCM patients and to search for biomarkers related to DCM and SLE.

Methods: Single-cell and bulk transcriptomic data for DCM were obtained from the GEO database, while GWAS data for SLE were obtained from the FinnGen database. The SMR method was used to identify genetic variants in the ventricles associated with SLE. Differential analysis was used to detect genes specific to monocyte-macrophages. Subsequently, a combination of machine learning algorithms was employed to select hub genes. Finally, small molecule drugs targeting the hub genes were retrieved from the DGIdb database.

Results: Mononuclear macrophages were found to be significantly infiltrated in dilated cardiomyopathy (DCM) samples. Seven key genes (HLA-DQB1, CD52, FCER1A, etc.) were identified by cross-tabulation analysis, of which FCER1A was the best-performing (AUC 0.8-0.9) among ten machine learning models. Validation of multiple datasets showed that FCER1A was highly expressed in the DCM group, was mainly involved in the immune cell activation pathway, and strongly interacted with other cells in the myocardial microenvironment through the MK/PROS pathway. The gene was highly expressed in the middle and late stages of monocyte-macrophage differentiation and was associated with drugs such as benzathine penicillin polylysine and omalizumab.

Conclusion: FCER1A was found to be a key differentially expressed gene in mononuclear macrophages in DCM myocardial tissue, and its significantly high expression was closely associated with immune cell activation in the myocardial microenvironment, which lays a theoretical foundation for immunotherapy of DCM and requires further clinical validation.

Objective: This study aimed to utilize single-cell RNA sequencing (scRNA-seq) to elucidate the autophagic landscape in breast cancer and to develop a prognostic model for breast cancer patients based on traditional high-throughput RNA sequencing (bulk RNA-seq).

Methods: We analyzed scRNA-seq data from the GSE75688 dataset to explore the expression patterns of autophagy-related genes (ARGs) across distinct cellular clusters. ARGs were retrieved from the GeneCards database, and bulk RNA-seq data were obtained from The Cancer Genome Atlas (TCGA). Cox proportional hazards regression was employed to construct a prognostic risk model based on ARGs. Patients were subsequently stratified into high-risk and low-risk groups according to their risk scores. For external validation, we used gene expression data from the GSE20685 and GSE48390 datasets. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the performance of the 3-gene signature.

Results: Using the FindClusters function in Seurat, all cells were grouped into four distinct clusters, highlighting the intratumoral heterogeneity within the samples. Significant differences in autophagy scores were observed among the clusters. Fifteen differentially expressed autophagy-related genes were identified, and a prognostic signature consisting of three autophagy-related genes - FEZ1, STX11, and ADAMTSL1 - was developed. Based on this model, patients were classified into high- and low-risk groups, with a statistically significant difference in survival between the two groups (log-rank test, P = 0.0011). The model demonstrated robust predictive performance with an AUC of 0.761 in the external validation dataset. A nomogram incorporating the 3-gene signature and clinical factors showed strong prognostic discrimination.

Conclusion: This study uncovered significant variation in autophagy levels among different breast cancer cell clusters. Furthermore, we established a novel 3-gene autophagy-related prognostic model that effectively stratifies patient risk and provides a potential tool for personalized prognosis in breast cancer.

Objective: The PYGO2 gene plays a significant role in various cancers. However, its prognostic significance and involvement in immune infiltration in liver cancer remain unclear. This study aimed to comprehensively evaluate PYGO2 expression and its associations with prognosis and clinicopathological features in liver cancer.

Methods: Data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases were analyzed. Functional enrichment analysis and immune cell infiltration assessments were performed to explore potential pathogenic mechanisms.

Results: PYGO2 was highly expressed in multiple cancer types, including bladder urothelial carcinoma, breast invasive carcinoma, cholangiocarcinoma, diffuse large B-cell lymphoma, and liver cancer. Analysis of 50 paired liver cancer tissues from TCGA revealed significant upregulation of PYGO2 expression. Moreover, high PYGO2 expression was significantly associated with pathological T stage, overall pathological stage, tumor status, and race. Kaplan-Meier survival analysis showed that low PYGO2 expression correlated with improved overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in liver cancer patients. Functional enrichment analysis identified several enriched pathways, including the reactive oxygen species signaling pathway, MYC targets, interferon-alpha response, immune response regulation signaling pathway, and leukocyte migration. Additionally, PYGO2 overexpression was associated with lower proportions of cytotoxic cells, dendritic cells, immature dendritic cells, mast cells, neutrophils, plasmacytoid dendritic cell-like cells, Th17 cells, and regulatory T cells, but a higher proportion of Th2 cells. Furthermore, the high PYGO2 expression group exhibited increased immune checkpoint gene expression, particularly PDCD1.

Conclusion: PYGO2 is a promising prognostic biomarker for liver cancer, given its strong associations with clinicopathological features, survival outcomes, and immune-related characteristics.

IL-10 plays a crucial role in regulating B cell function and differentiation, but its effects on B cells depend on its activation state. The frequency of IL-10R⁺ B cells and how it changes during breast cancer progression have not been studied. This study aimed to evaluate the expression of IL-10R on B cells in the peripheral blood of 50 patients with breast cancer compared to 29 healthy controls. After isolating mononuclear cells, we stained them using anti-CD19 and anti-IL-10R antibodies. We used Flow cytometry to analyze the expression of IL-10R on B cells. We found that over 50% of B cells in both patients with breast cancer and healthy controls expressed IL-10R. However, patients had a significantly lower frequency of IL-10R⁺ B cells compared to healthy individuals (64±16.0% of patients compared to 78.5±6.6% for healthy individuals, P<0.0001). This decrease was not associated with lymph node involvement or tumor size. Phenotypic analysis revealed that IL-10R-expressing B cells consist of both naive and memory B cells, with the majority of peripheral memory B cells expressing IL-10R. The decrease in IL-10R-expressing B cells in breast cancer patients may be due to apoptosis induced by IL-10 in naive or recently activated B cells, or their migration to lymph nodes to combat tumor cells. Our study suggests that IL-10R could be a potential biomarker for detecting breast cancer in its early stages.

Background: Breast cancer is one of the most common cancers in women with high morbidity and mortality. ZNF480, a member of the KRAB-ZNFs family, correlates with cancer progression. However, its role in the development and progression of breast cancer remains unclear.

Methods: We utilized transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Genotype Tissue Expression (GTEx) databases of breast cancer patients to investigate the potential pro-cancer role of ZNF480, including differential expression of ZNF480 in breast cancer, prognostic value, clinicopathological features, immune cell infiltration relevance and function enrichment analysis.

Results: Our results indicate that ZNF480 is upregulated in breast cancer and is correlations with survival, clinical stage, race and tumor subtype in breast cancer patients. Additionally, immune infiltration analysis revealed significant negative correlations between ZNF480 expression and multiple tumor infiltrating immune cells, including aDC, B cells, CD8 T cells, Cytotoxic cells, DC, iDC, Macrophages, Neutrophils, NK CD56bright cells, NK CD56dim cells, NK cells, pDC, T cells, Tem, TFH and Th1 cells, whereas a significant positive correlation was observed with the infiltration of T helper cells, Tcm, Tgd and Th2 cells. Furthermore, functional enrichment analysis indicated that ZNF480 may be involved in Angiogenesis, Allograft rejection, TNFα signaling via NFκB, Coagulation, IL6 Jak STAT3 signaling, Inflammatory response, Interferon gamma response and other processes.

Conclusion: ZNF480 is highly expressed in breast cancer and correlates with immune cell infiltration, and may be a candidate prognostic biomarker, which may assist in breast cancer treatment.

Background: Esophageal carcinoma (ESCA) is deemed a highly lethal malignancy with a grim prognosis and stands as the fourth leading cause of cancer-related mortality. Recent research has revealed the potential crucial role of fragile X mental retardation 1 (FMR1) protein in tumor development and progression. However, the correlation between FMR1 and immune regulation in ESCA remains unclear. In this study, we aimed to assess the clinicopathological and prognostic significance of FMR1 expression, and its relationship with immune cell infiltration, immune biomarkers and the pathway involved in ESCA.

Methods: The Cancer Genome Atlas (TCGA) pan-cancer data and the Gene Expression Omnibus (GEO) database were used to analyze the expression of FMR1. The correlation between FMR1 and cancer stage, time-dependent survival curve and receiver operating characteristic (ROC) curve were performed using R package. Immune cell infiltration was assessed using the samples found in TCGA. Functional enrichment analyses were performed to investigate the potential signaling pathway and biological functions.

Results: FMR1 was upregulated in 7 tumors and downregulated in 4 tumors. Overexpression of FMR1 considerably associated with cancer stage and poor prognosis in ESCA. The ROC area was 0.745 and 0.830 for 3-year and 5-year respectively. FMR1 exhibited a positive correlation with common lymphoid progenitor and T cell CD4+ Th2, and a negative correlation with B cell memory, B cell plasma, endothelial cell, monocyte, neutrophil, T cell CD4+ Th1, and T cell CD4+ effector memory in ESCA. The enrichment analysis revealed FMR1 was primarily associated with cell development and predominantly enriched in immune-related pathways.

Conclusion: FMR1 may act as a prognostic biomarker for ESCA and participate in immune regulation in ESCA.

Endocannabinoids (eCBs) play a crucial role in regulating the pathophysiological progression of chronic liver disease through hepatic cannabinoid receptor 2 (CB2). According to the literature, various treatment options are available for liver disease patients, including transplantation and physical activity both before and after the procedure. The aim of this study is to assess the response of endocannabinoids to pre- and post-therapeutic exercises in liver transplant patients (LTx). This analytical case-control longitudinal study was conducted on patients aged 18-70 at King Fahad Specialist Hospital in Dammam, Saudi Arabia. Participants were divided into two groups: an intervention group of LTx patients (n = 26) and a control group of end-stage liver disease patients (n = 23) who were not candidates for liver transplantation (LT). Blood samples were collected before the initiation of preoperative exercises, one month before LT, and three months after LT following postoperative exercises. The median arachidonoyl ethanolamide (AEA) levels in the control group were comparatively higher after therapeutic exercises compared to before; however, the Wilcoxon signed-rank test showed no significant differences (P = 0.212). In the LTx group, the median difference in AEA between pre- and post-therapeutic exercises was marginally significant (P = 0.091). Additionally, the Wilcoxon signed-rank test revealed a highly significant increase in median 2-arachidonoylglycerol (2-AG) levels after therapeutic exercises compared to before in the LTx group (P = 0.049), while the control group showed no significant change in post- vs. pre-therapeutic exercise median 2-AG levels (P = 0.346). The study's findings revealed an increased concentration of 2-AG after therapeutic exercises in LTx patients but not in the control group, while AEA levels were elevated after therapeutic exercises in both groups. The effect of post-therapeutic exercises on hematological and biochemical markers was significant between the control and LTx groups, particularly concerning platelet count, total bilirubin, total protein, albumin/globulin ratio, international normalized ratio, and calcium levels.