课程文献中心 更多>>

关键词： HLA-DQA1*01:173   HLA-DQA1*03:82   new allele   next-generation sequencing  

摘要： HLA-DQA1*01:173 and -DQA1*03:82, two novel HLA-DQA1 alleles detected by next generation sequencing.

关键词： cloning   HLA-B*40:186:02   long-range PCR   novel allele   Sanger sequencing  

摘要： Full genomic sequence shows HLA-B*40:186:02 differs from HLA-B*40:186:01 by a cytosine substitution in exon 2.

关键词： IgA vasculitis   Proinflammatory cytokine gene polymorphisms   ACE gene polymorphism  

摘要： Objective Immunoglobulin-A vasculitis (IgAV) is an inflammatory disease that affects small blood vessels. This study was performed to identify an association between protein tyrosine phosphatase non-receptor type 22 (PTPN22) + 788G > A (rs33996649), transforming growth factor-beta (TGF-beta) -509C > T (rs18004069), interleukin 1-beta (IL-1 beta) -511C > T (rs16944), interleukin 5 (IL-5) -746C/T (rs2069812), and angiotensin-converting enzyme (ACE) I/D (rs4646994) gene polymorphisms, susceptibility to IgAV, as well as the mRNA levels of IL-1 beta, IL-1 beta, and *** A total of 53 patients with IgAV and 50 healthy controls were enrolled. PTPN22, TGF-beta, IL-1 beta, ACE gene polymorphisms, ACE gene I/D polymorphisms, and mRNA expression levels were analyzed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, allele-specific PCR, and real-time PCR with TaqMan kits, *** PTPN22, TGF-beta, IL-1 beta, IL-5, and ACE variants showed no genotype or allele differences between patients with IgAV and controls. Increased levels of IL-1 beta and TGF-beta mRNA expressions were observed in patients with IgAV (p < 0.001). Patients with the IL-1 beta AG genotype showed significantly increased amounts of arthritis than patients with non-AG (p = 0.004). Age at disease onset was found to be significantly different in patients with IgAV according to the presence of TGF-beta TT genotype (p = 0.047).Conclusion Polymorphisms in PTPN22, TGF-beta, IL-5, IL-1 beta, and ACE genes are unlikely to confer susceptibility to IgAV. However, the presence of the AG genotype of IL-1 beta is associated with susceptibility to IgAV-related arthritis. This is the first study to report a significant increase in serum mRNA levels of IL-1 beta and TGF-beta in IgAV patients, supporting a susceptibility to IgAV in childhood.

关键词： HLA-C*04:535   Japanese population   next generation sequencing   novel allele  

摘要： The novel HLA-C*04:535 allele differs from HLA-C*04:01:01:01 by two substitutions in exon 3 and 3 ' UTR.

关键词： major depression   TNF-alpha   IL-6   blood-brain-barrier   CLDN5   stress   genetic interaction   proinflammatory citoknes   depression symptoms  

关键词： Stem cells  

摘要： The treatment of large bone defects remains challenging due to the lack of spatiotemporal management of the immune microenvironment, inflammation response and bone remodeling. To address these issues, we designed and developed a nanoparticle/hydrogel hybrid system that can achieve the combined and sequential delivery of an anti-inflammatory factor (IL-10) and osteogenic drug (icariin, ICA). A photopolymerizable composite hydrogel was prepared by combining gelatin methacryloyl (GelMA) and heparin-based acrylated hyaluronic acid (HA) hydrogels containing IL-10, and poly(dl-lactide-co-glycolide) (PLGA)-HA nanoparticles loaded with ICA were incorporated into the composite hydrogels. The nanoparticle/hydrogel hybrid system demonstrates an array of features including mechanical strength, injectability and photo-crosslinking. The rapid release of IL-10 from the hydrogel effectively exerts immunomodulatory activity, whereas the long-term sustained release of icariin from the PLGA-HA nanoparticles significantly triggers the osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Notably, the combined delivery of IL-10 and ICA from the hybrid system exhibit a synergistic effect for bone remodeling in a critical cranial defect rat model. Our findings indicate the importance of the immunomodulatory microenvironment and osteogenic differentiation for high-quality skull remodeling, and thus the dual-factor releasing nanoparticle/hydrogel hybrid system could be a promising candidate for repairing bone defects. © 2024

关键词： HLA-DRB1*04:01   Immunotherapy   Machine Learning   Prediction Method   BLAST search   Antigen binders  

摘要： HLA-DRB1*04:01 is associated with numerous diseases, including sclerosis, arthritis, diabetes, and COVID-19, emphasizing the need to scan for binders in the antigens to develop immunotherapies and vaccines. Current prediction methods are often limited by their reliance on the small datasets. This study presents HLA-DR4Pred2, developed on a large dataset containing 12,676 binders and an equal number of non-binders. It's an improved version of HLA-DR4Pred, which was trained on a small dataset, containing 576 binders and an equal number of non-binders. All models were trained, optimized, and tested on 80 % of the data using five-fold cross-validation and evaluated on the remaining 20 %. A range of machine learning techniques was employed, achieving maximum AUROC of 0.90 and 0.87, using composition and binary profile features, respectively. The performance of the composition-based model increased to 0.93, when combined with BLAST search. Additionally, models developed on the realistic dataset containing 12,676 binders and 86,300 non-binders, achieved a maximum AUROC of 0.99. Our proposed method outperformed existing methods when we compared the performance of our best model to that of existing methods on the independent dataset. Finally, we developed a standalone tool and a webserver for HLADR4Pred2, enabling the prediction, design, and virtual scanning of HLADRB1*04:01 binding peptides, and we also released a Python package available on the Python Package Index (htt ps://***/raghava/hladr4pred2/;https://***/raghavagps/hladr4pred2;https://***/p roject/hladr4pred2/).

关键词： Praevia vasa   Screening   Ultrasound   Umbilical cord insertion   Low-lying placenta   IVF  

摘要： Tumor invasion is the hallmark of tumor malignancy. The invasive infiltration pattern of tumor cells located at the leading edge is highly correlated with metastasis and unfavorable patient outcomes. However, the regulatory mechanisms governing tumor malignancy at the invasive margin remain unclear. The IL-17B/IL-17RB pathway is known to promote pancreatic cancer invasion and metastasis, yet the specific mechanisms underlying IL-17RB upregulation during invasion are poorly understood. In this study, we unveiled a multistep process for IL-17RB upregulation at the invasive margin, which occurs through direct communication between tumor cells and fibroblasts. Tumor ATP1A1 facilitates plasma membrane expression of SEMA7A, which binds to and induces IGFBP-3 secretion from fibroblasts. The resulting gradient of IGFBP-3 influences the direction and enhances IL-17RB expression to regulate SNAI2 in invasion. These findings highlight the importance of local tumor-fibroblast interactions in promoting cancer cell invasiveness, potentially leading to the development of new therapeutic strategies targeting this communication.

关键词： COVID-19   IL-6   ICU   Mortality   AKI  

摘要： In summary, among COVID-19 patients admitted to the ICU, IL-6 normalization had a strong negative association with mortality and outcomes reflecting respiratory and renal organ dysfunction. [...]the associations remained significant after adjusting for baseline APACHE-III score. [...]our study suggests that serial IL-6 measurement in clinical practice can support prognostication and off-label application of treatments. All Patients IL-6 < 7 pg/mL IL-6 ≥ 7 pg/mL p-value N 184 25 159 Age 54.8 ± 15.5 50.9 ± 17.1 55.4 ± 15.2 0.224 Male 123 (66.3%) 13 (52.0%) 110 (69.2%) 0.142 Comorbidities DM 62 (33.7%) 10 (40.0%) 52 (32.7%) 0.624 CAD 21 (11.4%) 3 (12.0%) 18 (11.9%) 1.000 COPD 16 (8.7%) 2 (8.0%) 14 (8.8%) 1.000 CKD 39 (21.2%) 3 (12.0%) 36 (22.6%) 0.3436 Cirrhosis 10 (5.4%) 1 (4.0%) 9 (5.7%) 1.00 CHF 21 (11.4%) 1 (4.0%) 20 (12.6%) 0.317 Obesity 83 (45.1%) 11 (44.0%) 72 (45.2%) 1.000 APACHE-III Scores 81.7 ± 36.0 63.0 ± 28.6 84.6 ± 36.3 0.002 ARDS 89 (48.4%) 7 (28.0%) 82 (51.6%) 0.002 Baseline IL-6 (pg/mL) 417.0 ± 1022.7 96.7 ± 233.8 467.37 ± 1088.3 <0.001 Days Since First Presentation 1.9 (IQR 1.0–8.6) 1.6 (IQR 1.1–9.5) 2.0 (IQR 1.0–8.5) 0.581 Race 0.783 White 113 (61.4%) 14 (56.0%) 99 (62.3%) Asian 20 (10.9%) 3 (12.0%) 17 (10.7%) Black 27 (14.7%) 5 (20.0%) 22 (13.8%) Native American 7 (3.8%) 2 (8.0%) 5 (3.1%) Pacific Islander 4 (2.2%) 0 (0%) 4 (2.5%) Other 2 (1.1%) 0 (0%) 2 (1.3%) Unknown 11 (6.0%) 1 (4.0%) 10 (6.3%) Hispanic 0.395 Yes 61 (33.2%) 11 (44.0%) 50 (31.4%) No 115 (62.5%) 13 (52.0%) 102 (64.2%) Unknown 8 (4.3%) 1 (4.0%) 7 (4.4%) COVID-19 targeted therapy Steroids 127 (69.0%) 19 (76.0%) 108 (67.9%) 0.563 Tocilizumab 5 (2.7%) 0 (0%) 5 (3.1%) 1.000 Remdesivir 72 (39.1%) 10 (40.0%) 62 (40.0%) 1.000 Outcomes In-hospital Mortality 71 (38.5%) 1 (4.0%) 71 (44.7%) <0.001 NIH Ordinal Scale ≥6 at 2 weeks 111 (60.3%) 8 (32.0%) 103 (64.8%) <0.001 Incident AKI 86 (46.7%) 5 (20.0%) 81 (50.9%) 0.004 Time to IL-6 normalization (Days) – 7(IQR 3–7) – Table 1 Baseline charact