Polymorphisms and gene expression of metalloproteinases and their inhibitors associated with cerebral ischemic stroke in young patients with sickle cell anemia.

BACKGROUND: Sickle cell anemia (SCA) is a genetic disease with great clinical heterogeneity and few viable strategies for treatment; hydroxyurea (HU) is the only widely used drug. Thus, the study of single nucleotide polymorphisms (SNPs) and the gene expression of MMPs 1, 2, 9, 7 and TIMPs 1 and 2, which are involved in the regulation of extracellular matrix, inflammation, and neuropathies, may provide further insights into the pathophysiology of the disease and elucidate biomarkers and molecules as potential therapeutic targets for patients with SCA. METHODS AND RESULTS: We evaluated 251 young individuals with SCA from northeastern Brazil. The groups were divided according to vaso-occlusive crisis (VOC) and cerebrovascular disease (CVD), compared to control individuals. SNP detection and gene expression assays were performed by real-time PCR, TaqMan system®. Both the expression levels of MMP1 gene, and the SNP MMP1-1607 1G/2G were associated with the risk of cerebral ischemic stroke (IS), and the expression of MMP1 was also associated with a higher frequency of VOC/year. Expression levels of MMP7, TIMP1, and TIMP2 were increased in patients conditioned to IS. The SNP 372T>C (rs4898) TIMP1 T alleles were more frequent in patients with > 5 VOC events/year. The SNP rs17576 of MMP9 showed differences in gene expression levels; it was increased in the genotypes AG, and AG+GG. CONCLUSION: The findings of this study, the SNPs, and expression provide initial support for understanding the role of MMPs-TIMPs in the pathophysiology of SCA in young patients.

Potential role of circulating miR-21 in the diagnosis of hepatocellular carcinoma: a systematic review and meta-analysis.

OBJECTIVE: Identify original articles that analyzed the diagnostic value of miR-21 in hepatocellular carcinoma without language restriction or publication date. METHODOLOGY: We performed structured searches on PubMed, Web of Science, VHL, and EMBASE. The Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields was used to assess the quality of each study. Random effect models were used to study heterogeneity, evaluated based on the Higgins I2 statistic. RESULTS: 12 articles were evaluated and contained raw data from 1,329 individuals, of which 617 had HCC, 473 were healthy, and 239 had Chronic liver disease. The combined sensitivity and combined specificity of miR-21 for diagnosing HCC were, respectively, 0.83(95% CI:0.78-0.89) and 0.85(95% CI:0.80-0.90). The sensitivity and specificity, in that order, by type of control were 0.81 (95% CI: 0.71-0.91) and 0.88 (95% CI: 0.82-0.93) for CLDs and 0.86(95% CI: 0.81-0.91) and 0.83(95% CI:0.74-0.91) for Healthy controls. CONCLUSION: miR-21 has a moderate overall performance in diagnosing HCC and may serve as a potential non-invasive marker for this early-stage disease. Thus, it may contribute to complementing the results of alpha-fetoprotein in the diagnosis and help to detect HCC at an earlier stage, increasing the survival chances of these patients.