Bioinformatics-based design of a fusion vaccine with CTLA-4 variable region to combat Brucella.

Brucellosis has become a global zoonotic disease, seriously endangering the health of people all over the world. Vaccination is an effective strategy for protection against Brucella infection in livestock in developed countries. However, current vaccines are pathogenic to humans and pregnant animals, which limits their use. Therefore, it is very important to improve the safety and immune protection of Brucella vaccine. In this study, different bioinformatics approaches were carried out to predict the physicochemical properties, T/B epitope, and tertiary structure of Omp2b and Omp31. Then, these two proteins were sequentially linked, and the Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) variable region was fused to the N-terminal of the epitope sequence. In addition, molecular docking was performed to show that the structure of the fusion protein vaccine had strong affinity with B7 (B7-1, B7-2). This study showed that the designed vaccine containing CTLA-4 had high potency against Brucella, which could provide a reference for the future development of efficient brucellosis vaccines.

Bioinformatics-based design of a fusion vaccine with CTLA-4 variable region to combat Brucella

Brucellosis has become a global zoonotic disease, seriously endangering the health of people all over the world. Vaccination is an effective strategy for protection against Brucella infection in livestock in developed countries. However, current vaccines are pathogenic to humans and pregnant animals, which limits their use. Therefore, it is very important to improve the safety and immune protection of Brucella vaccine. In this study, different bioinformatics approaches were carried out to predict the physicochemical properties, T/B epitope, and tertiary structure of Omp2b and Omp31. Then, these two proteins were sequentially linked, and the Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) variable region was fused to the N-terminal of the epitope sequence. In addition, molecular docking was performed to show that the structure of the fusion protein vaccine had strong affinity with B7 (B7-1, B7-2). This study showed that the designed vaccine containing CTLA-4 had high potency against Brucella, which could provide a reference for the future development of efficient brucellosis vaccines.

Decreased microRNA-146a in CD4+T cells promote ocular inflammation in thyroid-associated ophthalmopathy by targeting NUMB.

OBJECTIVE: The aim of the study was to explore the functional role of miR-146a in CD4+T cells of active thyroid-associated ophthalmopathy (TAO) patients and to identify the possible molecular mechanism for the modulation of miR-146a in TAO. PATIENTS AND METHODS: The experimental group collected six cases of peripheral venous blood of patients with active TAO. The healthy control group collected six cases of normal peripheral venous blood. All specimens excluded other eye diseases and autoimmune diseases, tumors, asthma, chronic inflammation, Human Immunodeficiency Virus (HIV), recent history of trauma, infection, and showed normal thyroid function. All patients with active TAO and age- and sex-matched healthy control subjects in this study. RESULTS: miR-146a is downregulated in active TAO CD4+T cells. NUMB was a target of miR-146a. CONCLUSIONS: We observed that miR-146a expression was downregulated in CD4+T cells during the active stage of patients with TAO. At the same time, it was found that NUMB can be targeted by miR-146a in CD4+T cells in TAO patients. Decreased microRNA-146a in CD4+T cells promotes ocular inflammation in active TAO by targeting NUMB.

[A clinical study on the pathogenesis of lung cancer-related cerebral infarction].

Objective: To explore the risk factors for lung cancer-related cerebral infarction. Methods: The hospitalized active lung cancer patients on anti-cancer therapy with no traditional stroke risk factors, who experienced an acute cerebral infarct in the First Affiliated Hospital of Guangxi Medical University from January 2005 to December 2015, were consecutively collected as the LCRS (lung cancer-related stroke) group. The active lung cancer patients without cerebral infarction hospitalized at the same peroid matched with the LCRS group for age and gender were collected as the LC (lung cancer) group. Clinical data from the two groups were analyzed. Results: A total of 139 LCRS patients and 139 LC patients were enrolled in the study, with 110 male and 29 female in each group, and there were no significant difference for the mean age between the LCRS group (52.1±10.4 years old ) and the LC group (52.1±10.1 years old). Two or more acute ischemic lesions of the brain were showed by MRI in most patients in the LCRS group (117 cases, 84.2%). Compared with the LC group, more patients in the LCRS group were found with adenocarcinoma, metastasis, elevated plasma D-dimer, CA125 and CA199 levels [88 cases (63.3%) vs 47 cases (33.8%); 98 cases (70.5%) vs 56 cases (40.3%); (468.38±291.37) µg/L vs (277.59±191.22) µg/L; (221.42±146.34) U/ml vs (106.84±69.97) U/ml; (254.68±185.84) U/ml vs (97.15±63.64) U/ml; with all P<0.001]. By logistic regression analysis of multiple factors, the elevated plasma D-dimer, CA125 and CA199 levels were showed to be independent risk factors for the cerebral infarction (OR=1.003, 95%CI 1.001-1.004; OR=1.006, 95%CI 1.003-1.010; OR=1.011, 95%CI 1.007-1.015). Conclusions: The elevated plasma D-dimer, CA125 and CA199 levels are the risk factors for the lung cancer related cerebral infarction, which may lead to hypercoagulation and induce cerebral infarction eventually.

Genetic polymorphisms in extracellular superoxide dismutase Leu53Leu, Arg213Gly, and Ala40Thr and susceptibility to type 2 diabetes mellitus.

The most common type of endocrine disease is type 2 diabetes mellitus (T2DM); genetic factors contribute to the development to T2DM. In this study, we investigated the role of the Leu53Leu, Arg213Gly, and Ala40Thr polymorphisms in extracellular superoxide dismutase (EC-SOD) gene in the development of T2DM in a Chinese population. DNA was extracted from peripheral blood samples obtained from 256 T2DM patients and 324 control subjects recruited from our hospital between January 2013 and March 2015. DNA was genotyped by polymerase chain reaction-restriction fragment length polymorphism. The obtained data was then statistically analyzed. The chi-square test revealed a statistically significant difference in the genotype frequencies of EC-SOD Ala40Thr (χ2 = 13.26, P = 0.001) between the patients and controls. Unconditional regression analysis indicated that the GA and AA genotypes of EC-SOD Ala40Thr were associated with an increased risk of T2DM compared to the GG genotype {adjusted odds ratio (OR) [95% confidence interval (CI)] = 1.46 (1.01-2.11) and 2.67 (1.48-4.85), respectively}. In the dominant model, the GA+AA genotype of EC-SOD Ala40Thr was correlated with a higher risk of T2DM, in comparison with the GG genotype (OR = 1.64, 95%CI = 1.16-2.33). In the recessive model, AA of EC-SOD Ala40Thr showed a 2.19-fold higher risk of developing T2DM than the GG+GA genotype. In conclusion, people with the Ala40Thr polymorphism in EC-SOD are at a higher risk of developing T2DM; therefore, this may be utilized as a biomarker for early screening of T2DM in a Chinese population.