Nitric oxide (NO) is involved in several biological processes, but its role in human melanogenesis and vitiligo need further studies. Previous studies revealed that exposure to UVA and UVB were capable of the inducing nitric oxide production in keratinocytes and melanocytes through the activation of constitutive nitric oxide synthase, whereas inducible nitric oxide synthase overexpression has been reported to play an important role in hyperpigmentary disorders. The aim of this study was to evaluate iNOS inhibitor aminoguanidine (AG) as a therapeutic agent in our mouse model of vitiligo. In this study, male C57BL/6J Ler-vit/vit mice were purchased to evaluate the effect of iNOS inhibitor (aminoguanidine) (50 and 100 mg/kg) and L-arginine (100 mg/kg) in a mouse model of vitiligo induced by monobenzone 40%. Moreover, we used phototherapy device to treat the mice with NBUVB as a gold standard.The findings revealed that monobenzone was capable of inducing depigmentation after 6 weeks. However, aminoguanidine in combination with monobenzone was decrease the effect of monobenzone, while L-arginine play a key role in promoting the effect of monobenzone (P<0.001). Based on the phototherapy, the efficacy of phototherapy significantly increased by adding L-arginine (P<0.05). Taken together, we suggest that iNOS inhibitor can be a novel treatment for the prevention and treatment of vitiligo by combination of NBUVB therapy, furthermore; NO agents like L-arginine could also increase the effectiveness of phototherapy. Taken together, this pilot study showed significant repigmentation of vitiligous lesions treated with iNOS inhibitor plus NBUVB therapy, where other aspect including expression of an inducible iNOS, NO and TNF levels remained to be evaluated in mice model.

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In this meta-analysis, we tried to clear the relationship between breast cancer risk and LSP1 gene rs3817198T>C polymorphism. This meta-analysis was conducted according to PRISMA protocol. We searched PubMed/Medline, Web of sciences and EMBASE. All literature investigating the association of LSP1 gene rs3817198T>C and breast cancer risk were considered to include in the meta-analysis. We pooled ORs using both fixed and random-effect models. Egger’s test and funnel plot were used to evaluate Publication bias and small study effect. After evaluation and screening of citations, 14 publications were eligible for final analysis after applying of inclusion and exclusion criteria. Overall, 30,204 cases and 35,282 controls included in this meta-analysis. There was the significant association between LSP1 gene rs3817198T>C polymorphism and breast cancer only in homozygote genetic model (OR=1.14 [1.05-1.24]) and no association was found in heterozygotes (OR=1.03 [0.98-1.07]). The association was significant for popula ion-based studies and European & American & African population in both homozygote and heterozygote genetic model. There was no evidence of bias of literature and no small study effect. In conclusion, it seems that LSP1 gene rs3817198 polymorphism play its role in breast cancer incidence and other SNPs and environment are such triggers. Nevertheless, we recommend genome-wide association studies to evaluate the effect of SNPs in combination, not as single SNPs.

Objective: The aim of this meta-analysis was to discover the effect of dominant and recessive genetic models of LSP1 gene rs3817198 polymorphism on breast cancer risk. Material and Method: We performed this meta-analysis according to PRISMA protocol. Three databases, including PubMed/Medline, Web of sciences, and EMBASE were searched. In this meta-analysis, we included all studies that evaluated the association between LSP1 gene rs3817198 and breast cancer risk. ORs and their reported 95% confidence interval (CI) for dominant and recessive inheritance models were extracted from final retrieved studies. ORs were pooled using both fixed and the random-effect models. Egger’s test and contour-enhanced funnel plot were used to evaluate publication bias and small study effect. Twelve publications were eligible for final analysis after observing our defined inclusion and exclusion criteria. Results: Totally, this meta-analysis composed of 15,530 cases and 20,258 controls. This study revealed a significant association between LSP1 gene rs3817198 polymorphism and breast cancer in the dominant genetic model (OR=1.07 [1.01-1.14]). Inversely, no association was found in the recessive genetic model (OR=1.10 [0.93-1.32]). Subgroup analysis displayed a significant association in population-based studies and European & American and African population only in the dominant genetic model. Begg’s funnel plot and Egger’s test revealed no publication bias. Conclusion: According to our findings, it seems that LSP1 gene rs3817198 polymorphism is associated with breast cancer risk and this risk is more prominent in Caucasians.