Evaluation of miR-15a, miR-16-1, ZAP-70, Ang-2, and Bcl-2 as potential prognostic biomarkers in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a blood cancer characterized by the accumulation of clonal B-lymphocytes. This study evaluated the mRNA gene expression of miR-15a, miR-16- 1, ZAP-70, and Ang-2 by qPCR, as well as the plasma levels of Bcl-2 by Elisa immunoassay, in CLL patients and healthy controls. Significant differences were observed when comparing patients and controls regarding miR-15a (p < 0.001), miR-16-1 (p < 0.001) mRNA, Ang-2 gene expression, and Bcl-2 plasma levels (p < 0.001). When stratified by risk, differences were maintained with a significantly reduced expression in high-risk patients. A positive correlation was observed between miR-15a and platelets (R2 = 0.340; p = 0.009) as well as between Bcl-2 and leukocytes (R2 = 0.310; p = 0.019). Conversely, negative correlations were observed between ZAP-70 and platelets (R2 = - 0.334; p = 0.011), between miR-15a and lymphocytes (R2 = - 0.376; p = 0.004), as well as between miR-16-and lymphocytes (R2 = - 0.515; p = 0.00004). The data suggest that a reduction in miR-15a and miR-16-1 expressions, in addition to an overexpression of Bcl-2, are associated with the reduction in apoptosis and, consequently, to a longer survival of lymphocytes, thus contributing to lymphocyte accumulation and aggravation of the disease. By contrast, Ang-2 expression was significantly higher in A than in B + C Binet groups. This context leads to the speculation that this biomarker should be investigated in more robust studies within populations with a still relevantly indolent form of the disease in an attempt to identify those patients with a greater potential for an aggravation of the disease

Evaluation of MiR-15a and MiR-16-1 as prognostic biomarkers in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a B lineage neoplasm, characterized by the accumulation of B lymphocytes of great longevity, and usually develops as a result of the inhibition of apoptosis. Clinical evolution is extremely variable amongst affected individuals with survival ranging from a few months in aggressive cases, to a few decades in cases of indolent CLL. The identification of new prognostic factors, apart from clinical staging, has been an important research topic aiming at a better understanding of CLL. There are approximately one thousand miRNAs in the human genome. They are expressed in specific tissues and changes in this expression are associated with different pathologies. In recent years, several studies have focused on the role of regulatory miRNAs in the pathogenesis of various diseases, including CLL. It has become evident that the profiles of miRNAs have great potential for application in the evaluation of CLL prognosis, since changes in miRNA expression profiles contribute to cell survival, proliferation and development of the disease. The deletion 13q14, the most prevalent alteration in CLL, leads to the deletion of the human tumor suppressor genes miR-15a and miR-16-1, which act on cell proliferation and in the process of apoptosis. Therefore, in patients with 13q deletion, loss of miR-15a and miR-16-1 displaces the expression balance for higher levels of Bcl-2 anti-apoptotic and pro-apoptotic p53 proteins. Regarding these microRNAs, the correlation of miR-15a and miR-16-1 with low-risk CLL is of particular interest. In this context, this mini review summarizes the current evidences on the role of regulatory miRNAs in the pathogenesis of CLL, particularly miR-15a and miR-16-1, involved on cell proliferation and apoptosis. In addition, it is our intention to highlight the potential role of micro RNAs as a marker of prognosis in this disease and to arouse interest in future studies addressing this interesting issue. Several current and future studies may shed light on the role of microRNAs in the pathogenesis of CLL, possibly leading to the development of new laboratory biomarkers.

Atividade antifúngica das folhas de Cissus verticillata (L.) Nicolson & C. E. Jarvis subsp. verticillata frente a Candida albicans, Candida krusei, Candida parapsilosis e Candida tropicalis / Antifungal activity of the leaves of Cissus verticillata (L.) Nicolson & C. E. Jarvis subsp. verticillata against Candida albicans, Candida krusei, Candida parapsilosis and Candida tropicalis

A espécie vegetal Cissus verticillata (L.) Nicolson & C. E. Jarvis subsp. verticillata é conhecida como "Insulina vegetal" eutilizada na medicina popular no tratamento da diabetes mellitus. O paciente diabético tem maior risco de infecções urinárias e Candida spp. é o principal gênero envolvido. Avaliou-se a atividade antifúngica do extrato hidroalcoólico e de suas frações frente aCandida albicans ATCC 18804, Candida krusei ATCC 6258, Candida parapsilosis ATCC 22019 e Candida tropicalis ATCC 750. Os resultados obtidos indicaram que folhas de C. verticillata verticillata têm potencial antifúngico promissor nas frações diclorometano e clorofórmio, com concentração inibitória mínima de 125 μg/mL em C. krusei e em C. tropicalis respectivamente. São necessários novos testes com constituintes químicos isolados dessas frações, buscando atividade superior na inibição do crescimento de Candida spp.

The specie Cissus verticillata (L.) Nicolson & C. E. Jarvis subsp. verticillata is known as "Vegetable insulin" and is used in popular medicine for the treatment of diabetes mellitus. The diabetic patient has a greater risk of urinary infections, and Candida spp. is the main gender involved. Was evaluated, the antifungal activity of the hydroalcoholic extract and its fractions against Candida albicans ATCC 18804, Candida krusei ATCC 6258, Candida parapsilosis ATCC 22019 and Candida tropicalis ATCC 750. The results indicated that leaves of C. verticillata verticillata has promising potential antifungal in fractions diclormetano andchloroform, with minimum inhibitory concentration of 125 μg/mL in C. krusei and C. tropicalis respectively. We need new tests with chemical constituents of these fractions isolated, seeking higher activity in inhibiting the growth of Candida spp.