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关键词： Diabetic rats   TNF-alpha antagonist   Colon enlargement   Tissue remodeling  

摘要： Purpose: We investigated the effect of tumor necrosis factor (TNF)-alpha antagonist on the structure and function of the streptozotocin-nicotinamide (STZ-NA)-induced diabetic rat colon. Methods: Thirty rats were divided into normal control (NC), diabetic control (DC), and diabetic etanercept (DE) groups. The DE group was injected with etanercept twice a week. Blood glucose, body weight, fecal pellet, colonic transit time, and plasma TNF-alpha were measured. The colon was dissected out, followed by weight and length measurements. Toluidine blue and Verhoeff's staining, immunohistochemistry for TNF-alpha, RAGE, iNOS, arginase, and western blot for RAGE were performed on the colonic tissue. Results: Administration of TNF-alpha antagonist had no significant effect on the body weight and blood glucose level of the diabetic groups. However, the DE group had a shorter and lighter colon and less coarse and less dense collagen fibers in the submucosal layer than the DC group. Weaker immunoreactivity of TNF-alpha, RAGE, iNOS, and arginase I was observed in colon tissue sections of the DE groups compared with the DC group. Although the etanercept effect on colonic function was not significantly different, the preventive effect size of etanercept on colon remodeling was considerably large, as shown by calculated-Cohen's d>0.8. Conclusions: TNF-alpha signaling in the colonic tissue of diabetic rats has a strong effect on tissue remodeling, leading to colon enlargement. TNF-alpha antagonists may be beneficial in preventing diabetic-related pathology in the colon in combination with anti-diabetic drugs.

关键词： HLA   HLA-A*31:217   polymerase chain reaction with sequence-based typing  

摘要： HLA-A*31:217 differs from HLA-A*31:01:02:01 in codon 37 in exon 2.

关键词： Gastrointestinal malignancies   Cytokine   TNF-alpha  

摘要： Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that plays a role in the hemostasis of the immune system, inflammation, and cell proliferation. However, it can also have a dark side as it is involved in pro-inflammatory cytokines and pathological processes such as cell growth and death, autoimmunity, and inflammation, leading to a wide range of chronic inflammatory diseases, including digestive cancer. TNF-alpha binds to two distinct receptors, TNFRI and TNFRII. Upon binding of the ligand to these receptors, TNF receptorassociated factors (TRAFs) are recruited to the cytoplasmic receptor, triggering the activation of transcription factors such as NF-kB and Activator protein 1 (AP_1). In contrast, binding of cytokines to certain family members, such as TNF RI and Fas Ligand (Fas L), leads to the secretion and initiation of apoptosis. Gastrointestinal malignancies are among the most common types of cancer globally. Despite extensive research, the exact cause of these tumors remains a mystery. Unfortunately, they often have a poor prognosis and are often detected at a late stage. The global incidence of gastrointestinal cancers, including those of the stomach, esophagus, colon, liver, and pancreas, is on the rise, leading to a surge in both incidence and mortality. Growth factors and cytokines, which are signaling molecules found in the tumor microenvironment, are thought to be major contributors to the development and metastasis of these cancers. In this review, we explored the role of TNF-alpha, and its receptors in the development of digestive cancers, including its signaling pathways and functions.

关键词： cloning   HLA-B*46:01:25   long-range PCR   novel allele   Sanger sequencing  

摘要： Full genomic sequence shows HLA-B*46:01:25 differs from HLA-B*46:01:01:01 by a thymine substitution in exon 4.

关键词： COVID-19   HLA polymorphism   neutralizing antibody  

摘要： Studies have suggested an association between polymorphisms in class I genes of the major histocompatibility complex, specifically the human leukocyte antigen (HLA), and susceptibility to SARS-CoV-2. To explore this, 135 individuals with positive serological tests for SARS-CoV-2 were recruited. All the samples were collected before the advent of vaccines, avoiding immunization effects. Participants were divided into high and low neutralizing antibody titer groups, and polymorphisms in HLA-A, HLA-B, and HLA-DRB1 genes were examined using PCR-SSO. Allele prevalence in the study population was compared to the National Bone Marrow Volunteer Donors Register (REDOME) in S & atilde;o Paulo and between the high and low titer groups within the study population. Results indicated that the HLA-B*15 polymorphism was more prevalent in the COVID-19 positive group compared to the control population (COVID-19 = 0.1370;Control = 0.0875;p = 0.0067). The HLA-B*18 polymorphism was less prevalent in the COVID-19 group (COVID-19 = 0.0185;Control = 0.0534;p = 0.0064). Additionally, the HLA-A*30 polymorphism was more prevalent in the high titer group within the (high = 0.10937;low = 0.02816;p = 0.0125). Other polymorphisms showed no significant differences. These findings align with international studies, suggesting these genes plays a role in COVID-19 pathophysiology, however, further research is required to fully understand their impact.

关键词： HLA-DQ   Coeliac disease   Haplotype   Screening   Genetics  

摘要： HLA-DQ2 and -DQ8 carriers are genetically predisposed to develop coeliac disease (CD). Testing negative for HLA-DQ2/DQ8 has a high negative predictive value. Full HLA-DQ genotyping as well as tests only typing for HLA-DQ2/DQ8 are therefore used for screening at-risk populations. However, HLA-DQ7 positive and HLA- DQ2/DQ8 negative CD patients have been described in various populations. In this study we examine the relevance for HLA-DQ7 typing in a large at-risk CD population. The HLA-DQ status of all paediatric and adult patients at-risk of CD that were typed in a tertiary medical centre laboratory between 2012 and 2016 (n = 3983) was obtained. HLA-DQ7 (HLA-DQB1*03:01) positive and HLA-DQ2/DQ8 negative patients were selected. We gathered information on serology, histology and dietary status, and CD diagnosis. In total, 489/3983 patients were HLA-DQ7-positive and HLA-DQ2/DQ8 negative, and after exclusion (missing data on diet or serology/histology), 325 were included. Only one adult patient was diagnosed with CD, based on a duodenal biopsy and a clinical response to a gluten-free diet. Homozygosity was observed in 14.8 %. Based on the current cohort additional typing of HLA-DQ7 does not seem relevant for screening at-risk populations for CD in the Netherlands. It should be considered in patients with a high suspicion of CD.

关键词： Detection performance   Diagnostic performance   Respiratory tract infections   Lateral flow immunoassay  

摘要： Objectives: Respiratory infections are among the most common infectious diseases, resulting in significant morbidity and mortality. C-reactive protein (CRP), serum amyloid A (SAA), procalcitonin (PCT), and interleukin-6 (IL-6) are advantageous for diagnosing respiratory tract infections. This study assessed the analytical performance and accuracy of new kits for Eu3(+)-based CRP/SAA and PCT/IL-6 lateral flow immunoassay and its diagnostic value in respiratory tract infections. Methods: This study evaluated the detection performance of a test kit using guidelines from the Center for Medical Device Evaluation (CMDE) and the Clinical and Laboratory Standards Institute (CLSI). The test results were compared to those of the commercial kits (CRP: Mindray;SAA: Norman;PCT: Shanghai Upper;IL-6: Wantai BioPharm). A total of 156 patients with respiratory tract infections (53 with bacterial infections (Bac group);50 with viral infections (Vir group);and 53 with co-infections (Bac + Vir group)) were enrolled, along with 50 healthy controls (HC group). Venous blood samples were collected to measure levels of SAA, PCT, CRP, and IL-6 using both the test and commercial kits. The diagnostic value of these biomarkers was assessed using receiver operating characteristic (ROC) curves. Results: Correlation analysis demonstrated a strong concordance between the test kits and commercial kits (CRP: r = 0.9396, P < 0.0001;SAA: r = 0.8986, P < 0.0001;PCT: r = 0.9594, P < 0.0001;IL-6: r = 0.9009, P < 0.0001). The diagnostic performance of the test kits in identifying bacterial, viral, and co-infections was highly consistent with that of the commercial kit. Conclusions: The Eu3(+)-based CRP/SAA and PCT/IL-6 lateral flow immunoassay test kits demonstrated high levels of consistency with commercial kits in terms of quantitative outcomes and diagnostic performance for respiratory tract infections.

关键词： Apoptosis   Inflammatory Stress   Rupatadine   Testicular Ischemia/Reperfusion   Vascular Endothelial Growth Factor  

摘要： Backgrounds & aim: Spermatic cord rotation is a common problem in the field of urology, that finally results in necrosis of testicular tissue as well as male infertility. Rupatadine (RUP);a second-generation antihistaminic drug;demonstrated to have a possible protective effect in variable ischemia/reperfusion (I/R) rat models, but its role has not been studied yet in testicular I/R model.
Material & methods: The present study investigated RUP ability to ameliorate testicular I/R injury. The study includes four groups (6 rats/group);sham group, sham group pretreated with RUP (6 mg/kg/day;orally) for 14 days, I/R group, and RUP-I/R pretreated group.
Key findings: The results demonstrated that I/R significantly lowered serum testosterone level and testicular tissue content of reduced glutathione. Besides, a significant elevation in malondialdehyde level, hypoxia-inducible factor-1, signal transducers and activators of transcription-3 (STAT-3), interleukin-6 (IL-6), histamine, and platelet activating factor levels along with an inhibition in testicular tissue level of vascular endothelial growth factor-A (VEGF-A) with an evident increase in caspase-3 immunoexpression in germ cells. Also, I/R significantly lowered p-AKT and mTOR testicular expression. While, RUP-I/R pretreated group showed a reversal in the testicular I/R damaging effects in a significant manner in the all the aforementioned parameters.
Conclusion: Based on these findings;RUP was proved to have a possible protective effect in testicular I/R injury via its antioxidant effect and its ability to modulate IL-6/STAT3, Akt/ mTOR inflammatory signaling pathways with improvement in the testicular VEGF-A level.