Our results suggest that the peripheral mechanism of inflammatory injury after stroke may be mediated by TLR4 through a COX-2-dependent pathway.

The genetics of melanoma is complex and, in addition to environmental influences, numerous genes are involved or contribute toward melanoma predisposition. In this study, we evaluated the possible interaction between miR-146a and one of its putative targets ribonuclease L (RNASEL) in the risk of sporadic melanoma. Polymorphisms rs2910164 in miR-146a and rs486907 in the RNASEL gene have both independently been associated with the risk of different cancers, and an interaction between them has been observed in nonmelanoma skin cancer. Polymorphisms rs2910164 G/C and rs486907 A/G were genotyped by restriction fragment length polymorphism analysis in 304 sporadic melanoma patients and 314 control individuals. Genotype distribution between cases and controls for each of the two polymorphisms was compared using Fisher's exact test. Epistasis between the two polymorphisms was tested by a logistic regression model. In the present study, we observed a sex-specific effect of the miR-146a rs2910164 C allele restricted to individuals carrying the RNASEL rs486907 A allele as well. Men carrying this allelic combination have the highest risk of melanoma, whereas it seems to have no effect or even an opposite relationship to melanoma risk in the female population. The results reported in the present study suggest a sex-specific interaction between miR-146a and RNASEL genes in melanoma skin cancer susceptibility, and could account for possible discordant results in association studies when stratification according to sex is not performed.

Our results support the hypothesis that T2D pathology contributes in vivo to increase the inflammatory process associated with the atherosclerotic plaque formation, as shown by an increment of COX-2 and IL1-β mRNA expression.

TWIST1 gene expression resulted higher in stable plaques (P < 0.02). HDAC9 gene expression followed a similar trend (P = 0.11). These results highlighting the significant correlation between TWIST and HDAC9 gene expression suggest that both genes may contribute to plaque stability in a coordinated way.

Inflammation has a key role and translates the effects of many known risk factors for the disease in atherosclerotic vulnerable plaques. Aiming to look into the elements that induce the development of either a vulnerable or stable atherosclerotic plaque, and considering that inflammation has a central role in the progression of lesions, we analyzed the expression of genes involved in the ACE/TLR4/PTGS2 signaling in carotid plaques of symptomatic and asymptomatic patients. Patients with internal carotid artery stenosis undergoing carotid endarterectomy at Verona University Hospital were included in this study. A total of 71 patients was considered for gene expression analysis (29 atherothrombotic stroke patients and 42 asymptomatic patients). Total RNA was extracted from the excised plaques and expression of PTGS2, ACE, TLR4, PTGER4, PTGER3, EPRAP and ACSL4 genes was analyzed by real-time PCR. The correlation between the pair of genes was studied by Spearman coefficient. From the analyzed genes, we did not observe any individual difference in gene expression but the network of co-expressed genes suggests a different activation of pathways in the two groups of plaques.