Association of gene polymorphisms and environmental factors in tuberculosis patients and their household contacts.

BACKGROUND: Tuberculosis (TB) is an important public health problem in China and environmental and genetic factors have an impact on its occurrence and development. We explored the relationship between environmental factors, genetic susceptibility genes and gene-environment interactions and the incidence of TB, as well as their high-risk combination, which can provide a scientific basis for prevention of the disease. METHODS: The 242 individuals, which included 82 TB patients, 67 family genetically related patients and 93 healthy controls, all of whom were of the Han population in Guangdong Province. The basic information of subjects was collected, including general conditions, behaviour habits, family environmental factors and blood samples. Two single nucleotides with potential functions (interleukin-10 [IL-10] rs1800896, interferon-γ [IFN-γ] rs2430561) were screened by bioinformatics tools and identified by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We found that gender, education, TB exposure history, fitness activities, residential areas and indoor hygiene conditions were all associated with the occurrence of TB. In the dominant model, AG+GG of IL-10 and AA of IFN-γ are high-risk genotypes. Multifactor dimensionality reduction (MDR) analysis of TB-prone families shows that a combination of male sex, IL-10 AA and AG genotypes and smoking history are elements of high risk for TB infection (prediction accuracy 62.45%, cross-validation consistency 10/10). The MDR analysis of the TB patients group and the healthy control group showed that the combination of low education level, history of TB exposure, and IFN-γ AA genotype represented a higher risk of TB infection (prediction accuracy 80.34%, cross-validation consistency 10/10). CONCLUSIONS: The occurrence of TB in TB-prone families in the Han population of Guangdong Province is related to environmental factors as well as cytokines IL-10 and IFN-γ. We also found high-risk combinations of genes and environmental factors, providing clues for the timely detection of high-risk groups.

Newly synthesized phenanthroimidazole derivatives L082 as a safe anti-tumor and anti-injury inflammation bifunctional compound.

Chemotherapy drugs exerts beneficial antitumor activity before and after cancer surgery. Post-injury complications are a potential hazard after surgical tumor resection. Inflammation caused by surgical stress is known to promote the progression of post-injury complications. Recent studies have found that chemotherapy drugs can promote post-injury inflammatory response, leading to increased post-injury complications. Imidazole derivatives have effective anticancer activity. However, the impact of post-operative inflammation caused by imidazole derivatives is unclear. In this study, two novel phenanthroimidazole derivatives (L082 and L142) were synthesized and characterized. These compounds showed significant inhibitory effects on different tumor cells. The compound L082 also inhibited liver cancer in vivo. In addition, L082 played a significant role in inhibiting the accumulation of inflammatory cells and promoting the elimination of inflammatory cells at the incision, which may be related to inhibiting the production of ROS and NO in oxidative and nitric stress. These results suggest that L082 can be used as a bifunctional drug to suppress tumors and reduce post-injury inflammation complications.