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关键词： Atopic dermatitis   Genetics   HLA   ERAP1  

摘要： Atopic dermatitis (AD) is one of the most common dermatoses. According to current data 2.6 % of the world's population suffer from AD. Atopic dermatitis is a multifactorial disease. The immune genes polymorphism is also associated with an increased risk of AD. The human leukocyte antigen (HLA) system is a group of genes that plays a crucial role in the immune response. The endoplasmic reticulum aminopeptidases ERAP (1 and 2) are trimming longer peptides to an optimal length for binding to HLA-I molecules. HLA class I (HLA-B) and class II (HLA-DRB1) typing and ERAP1-rs7063 genotyping were performed for 152 patients suffering from AD and 187 control subjects. Frequencies of HLA-B allele group and majority of HLA-DRB1 allele group did not differ between patients and controls. The exception was HLA-DRB1*07 allele group (OR = 0.34;95 % CI = 0.20;0.61, p = 0.0039) whose frequency was lower in patients than in controls. ERAP1 19-exon to 20- exon ratio, governed by rs7063, did not seem to affect the susceptibility to AD.

关键词： Human leukocyte antigen   Allele frequency   Haplotype frequency   Next generation sequencing   India  

摘要： Background: The huge diversity of Human Leukocyte Antigen (HLA) system is well-known to be associated with various diseases, anthropology, population genetics, and transplantation. The frequencies of HLA alleles in different populations are crucial for both research and clinical applications. This study determined the allelic and haplotype frequencies of all HLA class I and class II loci in 595 consecutive samples from patients who underwent solid organ transplantation (SOT) and hematopoietic progenitor cell transplantation (HPCT). Method: High-resolution HLA typing for HLA-A, B, C, DRB1, and DQB1 was conducted using a next generation sequencing (NGS) platform. Results: The most frequent alleles observed among all HLAs were A*11:01:01 (0.1849), A*24:02:01 (0.1202) and A*01:01:01 (0.1143) in A locus, B*40:06:01 (0.1050), B*52:01:01 (0.0950) and B*51:01:01 (0.0723) in B locus, C*07:02:01 (0.1303), C*04:01:01 (0.1227) and C*15:02:01 (0.1185) in C locus, DRB1*07:01:01 (0.1286), DRB1*15:01:01 (0.1134) and DRB1*03:01:01 (0.0966) in DRB1 locus, and DQB1*06:01:01 (0.1849), DQB1*03:01:01 (0.1471) and DQB1*02:02:01 (0.0966) in DQB1 locus. The most frequent (>2 %) five-locus A similar to B similar to C similar to DRB1 similar to DQB1 haplotypes were A*33:03:01 similar to B*44:03:02 similar to C*07:06:01 similar to DQB1*02:02:01 similar to DRB1*07:01:01 (2.97 %), A*26:01:01 similar to B*08:01:01 similar to C*07:02:01 similar to DQB1*02:01:01 similar to DRB1*03:01:01 (2.23 %) and A*02:11:01 similar to B*40:06:01 similar to C*15:02:01 similar to DQB1*06:01:01 similar to DRB1*15:01:01(2.15 %). Among all tested loci, the HLA-B locus had the most polymorphism, whereas the HLA-DQB1 locus had the least polymorphism. Conclusion: The data represent the distribution of HLA-A, B, C, DRB1, DQB1 alleles and their haplotype frequencies among the population in India.

关键词： HLA   HLA-B*56:102   new allele   next generation sequencing  

摘要： HLA-B*56:102 differs from HLA-B*56:01:01:02 by one nucleotide substitution at codon 240 in exon 4.

关键词： anti-PD-1   bioinformatic analysis   colorectal cancer   combinatorial immunotherapy   interferon-alpha   RIG-I  

摘要： BackgroundsImmunotherapy is a promising and effective approach that has achieved significant curative effects in colorectal cancer (CRC). Recently, retinoic acid-inducible gene I (RIG-I) has been shown to play a critical role in tumor immunity. However, the correlation between RIG-I and immunotherapy in CRC remains ***-I expression was measured in CRC and normal samples based on analysis of the public databases, a tissue microarray, and CRC cell lines. The correlation between RIG-I and immune microenvironment was explored using well-established biological algorithms and in vitro and in vivo *** discovered that RIG-I expression was downregulated in CRC compared with normal samples. The bioinformatic algorithms indicated that high RIG-I-expressing samples showed a positive correlation with IFN-alpha response and enrichment of antitumor immune cells, especially CD8+ T cells. Furthermore, knockdown of RIG-I expression efficiently reduced the cell death, STAT1 phosphorylation, and CXCL10/11 expression induced by IFN-alpha in CRC cells. Finally, an in vivo study showed that the infiltration of CD3+ CD8+ T cells was significantly decreased in the RIG-I knockout group. An animal model further confirmed that the inhibition of tumor growth induced by IFN-alpha plus anti-PD-1 therapy was dependent on RIG-I ***-I is a promising biomarker for CRC immunotherapy, which provides a novel concept for combinatorial immunotherapy.

摘要： Background The pathogenesis of dengue is attributed to a complex interaction between the dengue virus (DENV) and the host immune system. The aim of this study is to investigate the clinical, virological, and Interleukin-10 (IL-10) profiles of dengue patients in Vietnam from two consecutive outbreaks in 2021 and 2022. Methods A total of n=306 dengue patients were examined, who were clinically stratified according to dengue without warning signs (DF;n=178), dengue with warning signs (DWS;n=115) and severe dengue (SD;n=13). Patients were screened for dengue, Zika and chikungunya viruses. DENV were subjected to serotype specific real-time RT-PCR. Interleukin-10 (IL-10) levels were measured by ELISA, and IL-10 promoter variants (-1082G/A;-819C/T;-592C/A) were genotyped by direct Sanger sequencing to determine a possible association with susceptibility to dengue and disease severity. Results No chikungunya or Zika viruses were detected. Patients were infected by one of the three different DENV serotypes (DENV-1, -2, -4). Plasma IL-10 levels were significantly elevated in patients (DF vs. DWS, p=0.004;DF vs. SD, p=0.001;DWS vs. SD, p=0.015). While the IL-10 allele -819C contributed to an increased risk of dengue (OR = 1.5, 95% CI = 1.1-2.0, p=0.04), genotype -1082GA showed a protective role against the disease (OR = 0.45, 95% CI = 0.27-0.72, p=0.009), and allele -1082G showed a protective role against DWS (OR = 0.44, 95% CI = 0.22-0.81, p=0.049). Also, the IL-10 GTA (-1082G/-819T/-592A) haplotype was observed to confer protection (OR = 0.31, 95% CI = 0.14-0.67, p< 0.003). Conclusion While DENV-1 and DENV-2 were the predominant serotypes in circulation, plasma IL-10 levels and IL-10 promoter variants were also significantly associated with dengue and its severity.

关键词： APC   antigen-presenting cell   BCLC   Barcelona Clinic Liver Cancer   EBRT   external-beam radiation therapy   HCC   hepatocellular carcinoma   ICI   immune checkpoint inhibitor   IFN   interferon   OS   overall survival   PD   programmed death protein   PD-L   programmed death ligand   RE   radioembolization   RT   radiation therapy   STING   immunogenic stimulator of interferon genes   TAA   tumor-associated antigen   TME   tumor immune microenvironment   90Y   yttrium-90  

摘要： Hepatocellular carcinoma is a leading and increasing contributor to cancer-related death worldwide. Recent advancements in both liver-directed therapies in the form of yttrium-90 (90Y) radioembolization (RE) and systemic therapy in the form of immune checkpoint inhibitors (ICI) have expanded treatment options for patients with an otherwise poor prognosis. Despite these gains, ICIs and 90Y-RE each have key limitations with low objective response rates and persistent hazard of out-offield recurrence, respectively, and overall survival remains low. However, each therapy's strength may mitigate the other's weakness, making them potentially ideal partners for combination treatment strategies. This review discusses the scientific and clinical rationale for combining 90Y-RE with ICIs, highlights early clinical trial data on its safety and effectiveness, and proposes key issues to be addressed in this emerging field. With optimal strategies, combination therapies can potentially result in increasing likelihood of durable and curative outcomes in later stage patients.

关键词： Head and neck squamous cell carcinoma   AIM2   STAT1   IL17   MAPK pathway  

摘要： Chronic inflammation has been recognized as one of the hallmarks of head and neck squamous cell carcinoma (HNSCC), Absent In Melanoma 2(AIM2) has emerged as important regulators of chronic inflammatory, and participated in initiation, progression of kinds of human cancers. Nonetheless, the biological functions and underlying mechanisms of AIM2 in HNSCC remain inadequately understood. Based on the bioinformatics analysis of public databases, we identified elevated AIM2 expression in HNSCC, which positively correlates with disease stage and HPV infection, thereby possessing both diagnostic and prognostic significance. Immunohistochemistry on clinical samples revealed that AIM2 expression was frequently upregulated in cancerous tissues compared to paracancerous tissues, exhibiting a significant association with Ki-67 expression. Modulating AIM2 expression in HNSCC cell lines through transfection with inhibitors or mimics demonstrated that ectopic AIM2 expression enhances cell growth, migration, tumorigenesis, and metastasis both in vitro and in vivo. A dual luciferase reporter assay indicated that the transcription factor STAT1 can bind directly to the AIM2 promoter region and activate its transcription. The STAT1 inhibitor, fludarabine, reduces AIM2 expression and subsequently diminishes cell proliferation. Mechanistically, AIM2 exerts its tumor-promoting effects through the IL17-MAPK signaling pathway. Collectively, our data demonstrate that AIM2, transcriptionally activated by STAT1, exhibits oncogenic functions by promoting the IL-17-MAPK signaling pathway, suggesting that AIM2 may be a new intervention targets for the diagnostic and treatment of HNSCC.

关键词： Age-related patterns   Gender differences   HLA-B27   Prevalence   Slovak population   Spondyloarthritis  

摘要： Background and objectives: HLA-B27 is a genetic marker associated with spondyloarthropathies, particularly ankylosing spondylitis and axial spondyloarthritis. While its prevalence varies across populations, no data exist for Slovak patients. This study aimed to determine HLA-B27 prevalence in Slovak patients with suspected spondyloarthropathies and assess differences by sex and age. Methods: A retrospective cohort of 1,614 patients (888 females and 726 males) was analyzed for HLA-B27 status (positive/negative) using reverse hybridisation (HLA-B27 StripAssay). Statistical analyses included Pearson's Chi-square test and non-parametric Mann- Whitney U and Kruskal-Wallis tests for sex- and age-related differences. Results: HLA-B27 positivity was 20.57%, with a higher proportion in males (23.28%) than females (18.36%, p = 0.0177). The <20 age group had the highest absolute number of positive cases (126 cases;17.80%), while the 21-40 group had the highest relative positivity (119 cases;29.38%). The lowest positivity was in the >61 age group (17 cases;13.08%), though age distribution differences were not statistically significant (p = 0.7765). Positivity varies across diagnoses, peaking in musculoskeletal (M) and eye disorders (H), where it exceeds 29%. Conclusion: HLA-B27 positivity is strongly associated with rheumatologic and ophthalmologic conditions and exhibits age- and sex-related variability. These findings emphasize the diagnostic significance of HLA-B27 testing in Slovak patients, especially for early detection and management of spondyloarthropathies. Further research on HLA-B27 variability and its clinical implications is needed to optimize diagnostic strategies and patient care.

关键词： A*11:01:79   HLA   novel allele   sequence-based typing   Taiwanese  

摘要： One nucleotide substitution in codon 335 of HLA-A*11:01:01:01 results in the novel allele HLA-A*11:01:79.

关键词： circular dichroism   fibroblasts   IL-4 peptide   iPSCs   molecular docking   myoblasts   SDF-1 peptide  

摘要： Skeletal muscle regeneration depends on satellite cells, which, in response to injury, activate, proliferate, and reconstruct damaged tissue. However, under certain conditions, such as large injuries or myopathies, this process may not be properly executed, and muscle function may be affected. Thus, pro-regenerative actions, such as the use of various factors or cells, are widely tested as a tool to improve muscle regeneration. In the current study, we designed peptides derived from the IL-4 and SDF-1 proteins, namely IL-4-X, IL-4-Y, SDF-1-X, and SDF-1-Y. We showed that these peptides can bind to appropriate receptors and can adopt proper structure in solution. Importantly, we documented, using in vitro culture, that they do not negatively affect the cells that are present and active in skeletal muscles, such as myoblasts and fibroblasts, bone marrow stromal cells, as well as induced pluripotent stem cells, which can serve as a source of myoblasts. The presence of peptides did not affect cell proliferation compared to untreated cells. In vitro culture and differentiation protocols documented that selected IL-4 and SDF-1 peptides increased cell migration and inhibited undesirable adipogenic differentiation. Thus, we proved that these peptides are safe to use in in vivo studies aimed at improving skeletal muscle regeneration.