Brucellosis remains a major zoonosis worldwide. Brucella antigens induce the production of T-helper 1 (Th1) cytokines such as interleukin-12 (IL-12) in humans. We aimed to investigate the association of two single nucleotide polymorphisms (SNPs) in the gene encoding the IL-12p40 cytokine (IL-12B) with brucellosis and to examine the functionality of these SNPs through measuring serum levels of IL-12p40. We genotyped IL-12B gene rs3212227, A>C; rs6887695 G>C polymorphisms in a case-control study on a total of 281 subjects including 153 patients with active brucellosis and 128 healthy controls, using RFLP and serum IL-12p40 levels, were assessed by ELISA. The rs3212227 minor allele (C) and homozygote genotype (CC) were more frequent in controls compared with patients with brucellosis (P = 0.006, OR = 0.608, 95%CI = 0.429-0.861 for the C allele; P = 0.024, OR = 0.443, 95% CI: 0.218-0.900 for the CC genotype). Comparison of IL-12B genotypes and serum levels of the IL-12p40 revealed that rs3212227 AA genotype, with higher frequency in patients than in controls, was associated with increased levels of the cytokine (P = 0.0001). Furthermore, the distribution of haplotype and genotype combinations in our study suggested that rs3212227C/rs6887695C haplotype or CC/GC or CC/CC genotype combinations may protect controls against Brucella infection by contributing to a functional downregulation of the serum IL-12p40 production in vivo, as shown by ELISA (P < 0.05). Overall, our study demonstrated that rs3212227 A variant was associated with higher levels of serum IL-12p40 and could possibly contribute to an inherited predisposition to brucellosis.
Our findings indicate that in the DU group, the serum concentrations of IL-12 but not of IL-13 were influenced by bacterial CagA, independent of the VacA status, suggesting that high IL-12 levels may contribute to susceptibility to DU in CagA-positive individuals. These findings could possibly be considered to improve the predictive or prognostic values of inflammatory cytokines for DU, and also to design possible novel therapeutic approaches.
The IL-18 - 607C variant was associated with higher levels of serum IL-18 and an increased risk of DU. Moreover, our findings indicated that serum concentrations of IL-18 were influenced by CagA factor, irrespective of the VacA status, suggesting that high levels of IL-18 in CagA-positive subjects predisposes to susceptibility to DU.
Context: Cancer is a major cause of death worldwide. It was estimated that 7.6 million people died during 2008 due to cancer and this figure is expected to double by 2030. To conquer this disease, discovery of validated targets and new drugs is a necessity. Evidence Acquisition: Telomeres are terminal structures of linear chromosomes in eukaryotes and consist of multiple repetitive sequences. Their main function is to protect and confer stability to chromosome ends and prevent their breakage, end-to-end fusion, and degeneration. Polymerases responsible for replication of DNA in eukaryotes are not able to replicate chromosome ends and, during cell division, chromosomes continuously become shorter from the telomere ends. This shortening will eventually stop cell division. In cancer cells, there is a ribonucleoprotein enzyme called telomerase that allows compensation of telomere shortening and continuation of the cell multiplication process. Results: About 90% of cancers need a high level of this enzyme to continue cell multiplication. Since this enzyme set is absent in normal cells, or present at a very low level, use of telomerase inhibitors cannot have significant effects on normal cells. Conclusions: Since telomerase is expressed in 90% of cancer cells, its inhibition can be considered as a goal of cancer treatment.
Introduction: Opioid addiction (OA) is a neurologically life-threatening challenge associated with socioeconomic and health concerns for individuals and society. The addictive drugs trigger neuromodulators and neurotransmitters through the opioid receptors and corresponding endogenous peptide ligands. In addition, drug addiction is reportedly related to the mu-opioid receptor (OPRM1) encoding gene and its variants. According to the role of the rs648893 polymorphism of the OPRM1 gene in numerous disorders, it has been suggested as a candidate associated with drug addiction. The present case-control study was conducted to evaluate the role of OPRM1 rs648893 polymorphism in the OA risk. Methods: To this end, the rs648893 polymorphism was genotyped by tetra amplification refractory mutation system-polymerase chain reaction among 160 Iranian subjects consisting of 105 OA cases and 155 controls. Results: According to our findings, there was no significant association between OA and the OPRM1 rs648893 gene polymorphism. Moreover, a marginally insignificant difference was found between OA cases and controls in accordance with the allelic frequencies (P=0.05) Conclusion: In general, our results reported no association between OPRM1 rs648893 gene polymorphism and OA although further research among various ethnicities with larger sample sizes is needed to draw a definite conclusion on the association of rs648893 polymorphism and other OPRM1 intronic variants with opioid and other addictions.
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