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关键词： Crohn's disease   IBD   cytokines   mucosal immunology   ulcerative colitis  

摘要： IntroductionUlcerative colitis (UC) is a chronic inflammatory bowel disease characterized by a relapsing-remitting colonic inflammation. Despite advances in understanding UC pathogenesis, a definitive cure remains elusive. Current therapies aim to promote symptom resolution, mucosal healing, and ideally histologic remission. Moderate-to-severe UC patients may require advanced therapies, including biologics and small molecules, targeting pathways that have been implicated in the UC *** coveredThis review provides an in-depth analysis of current and emerging therapies targeting the interleukin (IL)-23 pathway in moderate-to-severe UC. It discusses both ustekinumab, a nonselective IL-12/23p40 blocker, and selective IL-23p19 inhibitors (i.e. mirikizumab, guselkumab, and risankizumab), covering their mechanisms of action, clinical efficacy, and safety profiles from registrative and post-marketing studies. The review also explores promising oral therapies under investigation, including IL-23 receptor (IL-23 R) antagonists and TYK2 inhibitors, highlighting their early-phase *** opinionIL-23p19 inhibitors have shown significant efficacy in inducing and maintaining remission in UC, with favorable safety profiles. Oral agents represent an exciting frontier, potentially improving patient adherence and accessibility. Direct comparative trials are needed to refine therapeutic positioning in personalized treatment algorithms.

关键词： activating transcription factor 6   inositol-requiring enzyme 1   Interleukin 18   phosphorylated extracellular signal-regulated kinase   post-traumatic stress disorder  

摘要： Post-traumatic stress disorder (PTSD) is a chronic mental health condition resulting from exposure to traumatic events. It is associated with long-term neurobiological changes and disturbances in emotional regulation. Understanding the sociodemographic profiles, biomarkers, and emotional control in patients with PTSD helps to better comprehend the impact of the disorder on the body and its clinical course. An analysis of biomarkers such as Interleukin-18 (IL-18), Inositol-Requiring Enzyme 1 (IRE1), Phosphorylated Extracellular Signal-Regulated Kinase (pERK), and Activating Transcription Factor-6 (ATF-6) in PTSD patients with varying durations of illness (<= 5 years and >5 years) and a control group without PTSD revealed significant differences. Patients with recently diagnosed PTSD (<= 5 years) showed markedly elevated levels of inflammatory and cellular stress markers, indicating an intense neuroinflammatory response during the acute phase of the disorder. In the chronic PTSD group (>5 years), the levels of these biomarkers were lower than in the recently diagnosed group, but still significantly higher than in the control group. An opposite trend was observed regarding the suppression of negative emotions, as measured by the Courtauld Emotional Control Scale (CECS): individuals with chronic PTSD exhibited a significantly greater suppression of anger, depression, and anxiety than those with recent PTSD or healthy controls. Correlations between biomarkers were strongest in individuals with chronic PTSD, suggesting a persistent neuroinflammatory dysfunction. However, the relationships between biomarkers and emotional suppression varied depending on the stage of PTSD. These findings highlight the critical role of PTSD duration in shaping the neurobiological and emotional mechanisms of the disorder, which may have important implications for therapeutic strategies and patient monitoring.

关键词： HLA   italic>HLA-DQA1*01:142   next-generation sequencing   novel allele  

摘要： HLA-DQA1*01:142 differs from HLA-DQA1*01:02:01:04 by one nucleotide substitution in codon 185 in exon 4.

关键词： Haploidentical hematopoietic stem cell transplant   primary graft failure   donor-specific anti-HLA antibodies   HLA-DQA1   HLA-DQB1  

摘要： BackgroundPrimary graft failure (PGF) is a life-threatening complication of allogeneic hematopoietic stem cell transplants (HSCT) and is associated with poor outcomes. Most clinical studies have focused on donor-specific anti-HLA antibodies (DSAs) against HLA-A, -B, and -DR *** design and methodsWe present the first reported case of PGF associated with a preformed high-level DSA against HLA-DQ alone. The 39-year-old patient was diagnosed with acute myeloid leukemia. She received a haploidentical graft from her son and suffered PGF. She had persistently high levels of DSAs against her son's HLA-DQA1 and HLA-DQB1 molecules after desensitization. No alternative donor was *** circumvent the second graft failure, we adopted an approach of combining two units of unrelated cord blood (CB) and G-CSF-primed bone marrow (BM) and peripheral blood stem cells (PBSCs) from her son's transplants. The BM short tandem repeats (STRs) assay showed that one unit of the CB was fully engrafted, and the grafts from her son still failed to *** conclude that high levels of anti-HLA DQA1/DQB1 DSA could be associated with PGF in our case. Besides DSAs against HLA-A, -B, and -DR, attention should also be paid to DSAs against the HLA-DQ molecule.

关键词： Interleukin-10   Polymorphism, single nucleotide   Uterine cervical neoplasms  

摘要： Cervical cancer, a leading cancer among women, is strongly associated with Human Papillomavirus infection, but host genetic factors also contribute to the progression from high-grade squamous intraepithelial lesions (HSIL) to invasive cancer. Interleukin-10 (IL-10), an immunosuppressive cytokine, may influence susceptibility to HSIL and cervical cancer through genetic variations. This study aimed to compare IL-10 gene promoter polymorphisms, -1082 A > G and - 819T > C, in women diagnosed with HSIL or cervical cancer and those with negative for intraepithelial lesion or malignancy (NILM). In this case-control study, 309 women were analyzed, including 142 with HSIL or cervical cancer and 167 controls with NILM. Blood samples were collected for DNA extraction and genotyping of polymorphisms through PCR amplification. Statistical analyses included comparisons of genotype and allele frequencies, haplotype frequency, and assessments of Hardy-Weinberg equilibrium and linkage disequilibrium. The mean age was 33.4 years for cases and 41.7 years for controls (p < 0.05). For the - 1082 A > G polymorphism, the GG genotype was significantly associated with a decreased risk of HSIL and cervical cancer (p = 0.0266, OR = 0.35). Recessive model (GG vs. AA + AG) confirmed this association (p = 0.0045, OR = 0.29). AC/GC diplotype was associated with a 2-fold increased risk of cervical lesions. Further studies are needed to confirm our results.

关键词： Rheumatoid arthritis   IL17A   rs2275913   single nucleotide polymorphism   ELISA  

摘要： Objectives: IL17A, part of the IL17 cytokine family, is a pivotal player in synovitis present in RA patients. This research focused on assessing how the IL17A rs2275913 genetic variation influences IL17A serum concentration, disease progression, and prognosis in Egyptian RA patients. Methods: It encompassed a group of 100 healthy individuals and 100 RA patients. The rs2275913 genetic polymorphism was analyzed in both groups using the Taqman genotyping assay. Additionally, IL17A serum concentration was examined through the ELISA technique. Results: RA patients demonstrated significantly elevated IL17A serum levels compared to control subjects (122 +/- 32.5 Pg/mL vs 20.5 +/- 2.8 Pg/mL, p < 0.001). Moreover, the prevalence of the rs2275913 G allele was higher in RA patients than in normal individuals (p < 0.001). Those with the GG genotype exhibited increased levels of all parameters related to disease severity and activity. Individuals with the GG genotype exhibited elevated IL17A serum levels in comparison to those with GA and AA genotypes (127.9 +/- 29.9 Pg/mL vs 111.1 +/- 34.6 Pg/mL, p = 0.013). Conclusion: In summary, the IL17A rs2275913 gene polymorphism has an impact on IL17A serum production, therefore it has role in diseases pathogenesis, and it is linked to increased disease severity in Egyptian RA patients.

关键词： Cytokine   Immune Checkpoint Inhibitor   Immunotherapy   T cell   T regulatory cell - Treg  

摘要： Background Interleukin-2 (IL-2) immunotherapy can induce durable tumor remissions, but its clinical performance has been limited by significant drawbacks such as short serum half-life and high toxicity. Administration of IL-2 in complex with certain anti-IL-2 antibodies (IL-2cx) enhances circulation half-life while also selectivity directing the cytokine to particular immune cell subsets. In particular, IL-2cx has been developed that targets either cells expressing the CD25-containing high-affinity IL-2 receptor (ie, CD25-biased IL-2cx) or cells expressing the CD25-lacking intermediate-affinity IL-2 receptor (ie, CD25-blocking IL-2cx). Since regulatory T (Treg) cells primarily express the high-affinity IL-2 receptor whereas na & iuml;ve effector T and natural killer cells mainly express the low-affinity IL-2 receptor, CD25-blocking IL-2cx have traditionally been considered as potential cancer therapeutics, particularly in combination with immune checkpoint inhibitors (ICIs).Methods Stimulation of antigen-primed T cells by IL-2cx in the absence or presence of ICIs was evaluated through adoptive transfer of primed ovalbumin-specific T cells and analysis of expansion. Effects of IL-2cx on Treg cell-mediated inhibition of CD8+ T cells were assessed by flow cytometry and thymidine incorporation. Tumor-bearing mice received combination treatments comprizing IL-2cx and ICIs, where complexes were delivered either before or after ICIs. Tumor growth and mouse survival were monitored, and immune cell phenotyping was performed. Toxicity was determined by tracking body weight, temperature, and lung edema. Substitution of IL-2cx with single-agent cytokine/antibody fusion proteins (immunocytokines, ICs) was also *** We showed that CD25-biased IL-2cx and ICs synergize with ICIs to completely eradicate large, established tumors despite robust Treg cell expansion. Importantly, we found that timing is crucial, as administration of IL-2cx after (but not before) ICIs led to

关键词： HLA-C   italic>HLA-C*06:402   NGS   novel HLA allele  

摘要： HLA-C*06:402 differs from HLA-C*06:02:01:01 by a nine-nucleotide (TCCTGGCTG) insertion in exon 5.

关键词： Uric acid   Hyperuricemia   Interleukin-6   Interleukin-1beta   Aged   Cross-sectional studies  

摘要： Previous studies have shown the role of uric acid in triggering inflammatory reactions through its influence on a large group of cytokines. Therefore, searching for possible relationships between treating hyperuricemia and the course of inflammatory processes may provide valuable knowledge for clinical practice. The study was designed to determine the relationship between uric acid levels and interleukin-6 (IL-6) and interleukin-1-beta (IL-1 beta) levels determined in older adults during hospitalization. Patients were assigned to different study groups based on the uric acid levels and effectiveness, lack of treatment, or recognition of hyperuricemia. Classical variance analysis methods or nonparametric Kruskal-Wallis tests were used for statistical analysis. The analysis showed different correlations between the concentration of uric acid and the mentioned interleukins and designated study groups. In the case of properly treated hyperuricemia, a weak negative correlation is observed between the level of uric acid and interleukin IL-1 beta. There is a statistically significant positive correlation between the value of uric acid and interleukins IL-6 and IL-1 beta in people with untreated hyperuricemia and, to a lesser extent, in people with normal uric acid levels. The study's results suggest that effective treatment may be associated with appropriate control of uric acid concentration and modulation of the inflammatory response. However, due to several measurement limitations, further research is warranted to better elucidate these associations.

关键词： 戊型肝炎病毒   献血者   抗原   血液筛查  

摘要： 目的了解大连地区无偿献血者戊型肝炎病毒(hepatitis E virus,HEV)的感染情况,为本地区血液安全筛查策略的制定提供依据。方法对2023年12月—2024年2月大连市血液中心的献血者血液标本完成常规血液筛查(ALT、HBsAg、抗-HCV、HIV Ag/Ab、抗-TP、HBV/HCV/HIV NAT)后,采用化学发光免疫分析法(CLIA)检测HEV Ag,对反应性标本进一步做HEV RNA、抗-HEV IgM、抗-HEV IgG检测并对HEV Ag反应性献血者进行追踪随访。结果总共3277份献血者标本中检出6份HEV Ag重复反应性标本,反应性率为0.18%(6/3277)。HEV RNA、抗-HEV IgM、抗-HEV IgG检测均为非反应性;追踪随访6例献血者成功随访到1例,在首次检出HEV Ag反应性后d218,HEV Ag、HEV RNA、抗-HEV IgM、抗-HEV IgG均为非反应性。结论大连地区无偿献血者中HEV抗原筛查反应性率较低,HEV Ag CLIA法操作简便、成本低廉,但存在一定的假反应性,若能提高检测的特异度,并联合NAT技术,对献血者采取选择性筛查HEV策略具有重要意义。