American journal of clinical and experimental immunology最新文献

Successful implantation and pregnancy rely on complex interactions between the embryo and the maternal reproductive tract. Seminal plasma components, including proteins, cytokines, and growth factors, are pivotal in enhancing endometrial receptivity and inducing maternal immune tolerance to the developing conceptus. Exposure to seminal plasma facilitates pathogen clearance, supports embryo development, and modulates immune responses by altering the endometrial transcriptome and promoting regulatory T cell (Treg) expansion. Proteomic studies have identified seminal plasma factors involved in these processes. Changes in the immunomodulatory components of seminal plasma can diminish its positive effects on the endometrium, potentially resulting in reduced fertility and increased risk of adverse pregnancy outcomes. This review explores how seminal plasma influences maternal immune responses and highlights the clinical implications, particularly its potential to improve outcomes in assisted reproductive technologies (ART) like in vitro fertilization (IVF). Understanding the molecular dialogue between seminal plasma and the endometrium may lead to new strategies for enhancing fertility and promoting healthy pregnancy.

Background: Prostate cancer (PRAD) poses a significant threat to male health. The tumor microenvironment (TME) plays a crucial role in its development process, yet the regulatory significance of specific extracellular matrix proteins such as Dermatopontin (DPT) in PRAD remains poorly understood.

Methods: A total of 534 PRAD transcriptome profiles were retrieved from The Cancer Genome Atlas (TCGA) database. CIBERSORT and ESTIMATE computational methods were used to quantify the presence of immune and stromal components. Differentially expressed genes (DEGs) were identified based on ImmuneScore and StromalScore, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) pathway enrichment analyses. DPT expression was analyzed in relation to overall survival, TNM staging, immune-related pathways using Gene Set Enrichment Analysis (GSEA), and tumor-infiltrating immune cells (TICs).

Results: A total of 454 DEGs overlapping between high ImmuneScore and StromalScore groups were enriched in immune-related processes and pathways. DPT expression was positively correlated with the survival of PRAD patients, especially the N Stage of PRAD. GSEA revealed that high DPT expression correlated with immune-related activities such as allograft rejection, apical junction, complement, and epithelial mesenchymal transition while low DPT expression was correlated with metabolic pathways such as E2f targets, G2m checkpoint, mitotic spindle, and mitorc1 signaling. Analysis of TICs showed that DPT expression was positively correlated with resting mast cells and neutrophils. Conversely, regulatory T cells, M1 macrophages, M2 macrophages, and resting dendritic cells exhibited negative correlations with DPT expression.

Conclusions: DPT may serve as a novel prognostic biomarker in PRAD, potentially affecting the survival of PRAD patients by regulating the immune environment of TME. These findings provide new insights into the immunomodulatory role of DPT and its potential as a therapeutic target for PRAD.

This study aimed to investigate the relationship between immunosenescence and osteoarthritis (OA) and analyze its potential clinical implications. Thus, we conducted transcriptome sequencing by collecting clinical meniscus (Aging_meniscus:Control_meniscus = 3:7) and cartilage tissues (Aging_cartilage:Control_cartilage = 2:6). Meanwhile, immune-related genes (IRGs) and aging-related genes (ARGs) were included in this research. The differentially expressed genes (DEGs) between Aging_meniscus and Control_meniscus as well as Aging_cartilage and Control_cartilage were analyzed by differential analysis, respectively. Then, differentially expressed IRGs (DEIRGs) were generated by crossing DEG with IRGs. Similarly, differentially expressed ARGs (DEARGs) were achieved by intersecting DEG and ARGs. To obtain genes simultaneously associated with immune and aging in both meniscus and cartilage samples, biomarkers were screened out by crossing share.IRGs and share.ARGs overlapped by DEIRGs1 and DEIRGs2 as well as DEARGs1 and DEARGs2, respectively. In addition, the biomarkers' functions were analyzed by gene set enrichment analysis (GSEA). To detect the regulatory mechanism, a miRNA-mRNA-transcription factors (TFs) regulatory network and a X2K network were constructed. Moreover, disease association analysis and potential small molecule drugs for biomarkers were also performed to further reveal the possible role of biomarkers for OA. Then, 3 biomarkers, namely Insulin-like Growth Factor 1 Receptor (IGF1R), Interleukin 7 receptor (IL7R) and Leptin receptor (LEPR), were selected out through the intersection of 14 share.IRGs and 4 share.ARGs. And they were all enriched in 'ribosome' from both meniscus and cartilage samples, and had complex regulatory networks. In all, the expression of IGF1R was markedly up-regulated in OA (P < 0.05). Eventually, mecasermin could stably bind to IGF1R and simvastatin could stably bind to LEPR. It suggested that mecasermin and simvastatin may exhibit significant clinical potential in treating immunosenescence-related OA.

Cell-free DNA (cfDNA) fragmentomics has emerged as a powerful and noninvasive approach for cancer detection, characterization, and monitoring. By analyzing genome-wide fragmentation patterns - including fragment length distributions, end motifs, nucleosome footprints, and copy number variations - cfDNA fragmentomics provides high-resolution insights into tumor-specific biological signals even at low tumor burden. This technology offers advantages over conventional mutation-based assays by capturing aggregate structural and epigenomic alterations without requiring prior knowledge of driver mutations. In non-small cell lung cancer (NSCLC), cfDNA fragmentomics enables early detection, discrimination of malignant pulmonary nodules, and post-surgical monitoring of minimal residual disease. Recent studies have demonstrated that fragmentomic risk scores can accurately stratify recurrence risk and improve prognostic sensitivity beyond traditional genomic assays. In hepatocellular carcinoma (HCC), integration of fragment size selection, CNV profiling, and end-motif analysis has led to high-performing models for early diagnosis, particularly in high-risk populations. Moreover, cfDNA fragmentomics has proven effective in detecting malignant transformation in patients with neurofibromatosis-associated peripheral nerve sheath tumors, distinguishing benign from premalignant or malignant lesions with high precision. Expanding beyond these major cancers, fragmentomic approaches have demonstrated diagnostic potential in gastric, urological, hematologic, and pediatric malignancies. Notably, the DELFI-TF (DNA Evaluation of Fragments for early Interception-Tumor Fraction) framework has shown prognostic relevance by correlating pre-treatment cfDNA features with survival outcomes in colorectal and lung cancer patients, outperforming conventional imaging. All of these results highlight the translational importance of cfDNA fragmentomics as a cutting-edge precision oncology tool. Its continued integration into clinical workflows may redefine early cancer detection, facilitate subtype-specific interventions, and enable real-time, individualized treatment monitoring.

Lymph nodes are essential for immune function as they contain immune cells that activate responses and filter pathogens from lymph. This study investigates how diabetes-related metabolic challenges affect immune function, focusing on the impact of Lactobacillus probiotics on lymph node responses to meningococcal vaccines in thirty male Albino rats with Streptozotocin-induced diabetes, established two weeks before vaccination. The diabetic rats were divided equally and randomly into three groups: one untreated (UD group), one receiving two shots of the meningococcal vaccine (DM group), and one receiving the same vaccination regimen alongside oral doses of Lactobacillus rhamnosus probiotics (DML group). We monitored the rats' weights and measured the expression levels of inflammatory cytokines (IL-1β, TNF-α, and IL-2) in their lymph nodes as markers of immune activation after vaccination. Diabetic rats vaccinated against meningococcal disease showed increased levels of IL-1β and TNF-α, which showed a significant reduction by Lactobacillus supplementation after three weeks. However, following the second vaccination, Lactobacillus significantly increased IL-1β and TNF-α levels. Also, Lactobacillus appeared to modulate the initial spike in IL-2, with a notable increase observed five weeks after the second vaccine dose. Notably, the vaccination protocol did not affect the body weight of the diabetic rats. These findings suggest that while the vaccine elevates inflammatory cytokine levels in the lymph nodes of diabetic rats, Lactobacillus may help mitigate these responses and regulate IL-2 levels, indicating its potential value in enhancing diabetes management, optimizing vaccine effectiveness, and addressing autoimmune issues in diabetic individuals.

Background: The tumor microenvironment (TME) of breast cancer (BRCA) influences disease progression through dynamic interactions between immunity and stroma, but its key regulatory molecules and prognostic value remain to be elucidated. The aim of this study was to explore the prognostic potential of immunoglobulin λ-like polypeptide 5 (IGLL5) in BRCA and its association with immune infiltration in TME.

Methods: 1178 BRCA cases were obtained from The Cancer Genome Atlas (TCGA) database. CIBERSORT and ESTIMATE computational methods were used to quantify the composition of tumor-infiltrating immune cells (TICs) and the presence of immune and stromal components. Prognostic indicator closely associated with BRCA was identified by Cox regression analysis and protein-protein interaction (PPI) network construction. Through Gene Set Enrichment Analysis (GSEA) and other means, the correlations between IGLL5 expression and patient survival, immune activities, metabolic pathways, and immune cell types were studied.

Results: Overall survival was significantly prolonged in patients with high IGLL5 expression (HR=0.62, 95% CI 0.45-0.86, P=0.013) and positively correlated with immune-activating pathways (complement signaling, interferon response) and anti-tumor TICs (CD8⁺ T cells, M1 macrophages) (r>0.3, P<0.001) and negatively correlated with tumor-promoting TICs (M2 macrophages, resting NK cells). The low IGLL5 group was enriched in metabolic pathways (estrogen response, oxidative phosphorylation), suggesting that it may promote immune escape through metabolic reprogramming.

Conclusion: IGLL5 is a novel prognostic marker for BRCA, and its expression level affects patient survival by modulating TME immune infiltration and metabolic reprogramming. This study provides a theoretical basis for IGLL5-directed immunotherapeutic strategies (e.g., combining PD-1 inhibitors), and its mechanism needs to be verified by multicenter clinical cohorts and functional experiments in the future.

Background: Hybridoma technology is an essential method used to produce monoclonal antibodies, providing equal specificity and scalability for biomedical applications. This methodology utilizes a hybridoma formation process through fusing short-lived, antibody-producing B lymphocytes with immortalized myeloma cells, thus providing hybridoma clones that produce monoclonal antibodies that are highly specific. Monoclonal antibodies produced through hybridoma technology have a consistent and reproducibility benefits over polyclonal forms of antibodies, making monoclonal antibodies an essential product in diagnostics and therapeutics. In this study, we attempted to produce monoclonal antibodies in order to target a synthetic peptide from venom of Buthotus Saulcyi, a medically important scorpion in the family Buthidae, native to Iran, known for having potent toxicity that is most dangerous in children and the elderly.

Methods: Balb/c mice were immunized with the synthetic peptide P4 before fusion to Sp2/0-Ag14 myeloma cells using polyethylene glycol at a 5:1 ratio. Hybridoma cells were cultured in HAT selective media with a single clone isolated using limiting dilution.

Result: Cell production was confirmed with an enzyme-linked immunosorbent assay (ELISA) and determined specificity to recognize B. Saulcyi venom. Neutralization was determined using MTT and SRB cell lines HepG2 and determined the monoclonal antibody treatment for B. Saulcyi venom had efficacy.

Conclusion: These findings highlight the potential of this mAb as a diagnostic tool for rapid detection of B. Saulcyi venom in clinical settings, paving the way for improved management of scorpion envenomation.

Background: DCUN1D3, a member of the DCNL (defective in cullin neddylation-like) protein family, has been implicated in ultraviolet (UV) radiation-induced cell cycle checkpoints, cell growth, survival, and neddylation. However, its specific function in male germ cells and potential involvement in spermatogenesis remain poorly understood.

Methods: To investigate the role of Dcun1d3 in male reproduction, we generated Dcun1d3 knockout (KO) mice. Sperm parameters were evaluated using computer-assisted sperm analysis (CASA), while histological and immunohistochemical analyses were performed to assess spermatogenesis.

Results: Dcun1d3-KO mice exhibited no significant differences in testicular histology, sperm quality, levels of germ cell apoptosis, or fertility outcomes compared to wild-type controls.

Conclusions: These findings indicate that Dcun1d3 is not essential for spermatogenesis or male fertility in mice. This study provides evidence to streamline future investigations by excluding Dcun1d3 as a critical regulator of male germ cell development and offers useful insights for human fertility gene research.

Background: This study aims to evaluate the diagnostic value of CD138 and CD20 immunohistochemical staining in chronic endometritis (CE).

Methods: A total of 131 patients with reproductive needs, treated at the Second Affiliated Hospital of Fujian Medical University between August 2020 and July 2021, were enrolled. Patients were divided into a CD138-positive group (n=91) and a CD138-negative group (n=40). All participants provided informed consent and underwent hysteroscopic examination using an Olympus 30° scope, following standard operating procedures. Lesion shape and size were recorded in detail. CE diagnosis was based on hysteroscopic findings of patchy bleeding and confirmed by endometrial biopsy of suspicious areas. Biopsy tissues were subjected to immunohistochemical staining for CD138 and CD20. Expression levels were assessed under low-power and high-power magnification (Original magnification: ×400. Scale bar: 20 μm).

Results: CD20 expression differed significantly between the CD138-positive and CD138-negative groups (χ²=45.440.160, P<0.05). The kappa coefficient for agreement between CD20 and CD138 was 0.530 (95% CI 2.072-4.684, P<0.05). A significant difference in CD20 expression at ×400 magnification was also observed between the two groups (χ²=12.520, P<0.05), with a kappa coefficient of 0.300(95% CI 0.594-1.164, P<0.05). The area under the ROC curve (AUC) for CD20 in predicting CE was 0.732, and 0.665 for CD20 at ×400 magnification, indicating reliable diagnostic performance for both.

Conclusions: In patients with chronic endometritis, both the positive expression of CD20 and its high-level expression at ×400 magnification provide valuable diagnostic indicators, demonstrating better diagnostic utility.

BMAL1 is a core gene involved in the regulation of circadian rhythm; however, its role in sepsis remains incompletely understood. In this study, we investigated the molecular mechanisms by which BMAL1 influences sepsis. Sepsis models were established both in vivo using C57BL/6J mice and in vitro using THP-1-derived macrophages. We observed a significant downregulation of BMAL1 expression in peritoneal macrophages and hepatic Kupffer cells during sepsis. Overexpression of BMAL1 in macrophages via plasmid transfection suppressed LPS-induced inflammatory responses and promoted M2 macrophage polarization. Conversely, administration of STL1267, a BMAL1 inhibitor, reduced BMAL1 expression in mice and further exacerbated systemic inflammation and multi-organ injury. Moreover, we identified PGC-1α as a key downstream effector of BMAL1. Knockdown of PGC-1α using short hairpin RNA (shRNA) abrogated BMAL1-mediated anti-inflammatory effects. Collectively, these findings uncover a novel mechanism by which BMAL1 regulates acute inflammatory responses and organ damage in sepsis, highlighting its potential as a therapeutic target.