In vitro assessment of the efficiency of the PIM-1 kinase pharmacological inhibitor as a potential treatment for Burkitt's lymphoma.

Burkitt's lymphoma is an aggressive form of lymphoma affecting B lymphocytes. It occurs endemically in Africa and sporadically in the rest of the world. Due to the high proliferation rate of this tumor, intensive multi-drug treatment is required; however, the risk of tumor syndrome lysis is high. Overexpression of the proto-oncogene proviral integration of the Moloney murine leukemia virus (PIM-1) kinase is associated with the development of hematological abnormalities, including Burkitt's lymphoma (BL). PIM-1 primarily exerts anti-apoptotic activities through BAD phosphorylation. The aim of the present study was to investigate the in vitro efficiency of a PIM-1 kinase pharmacological inhibitor (PIM1-1) in BL. The impact of PIM1-1 was evaluated in terms of the viability and apoptosis status of the BL B cell lines, Raji and Daudi, compared with K562 leukemia cells, which highly express PIM-1. Cell viability and apoptotic status were assessed with western blotting, and PIM-1 gene expression was assessed with reverse transcription-quantitative PCR. After 48 h of treatment, PIM1-1 inhibited the Daudi, Raji and K562 cell viability with a half-maximal inhibitory concentration corresponding to 10, 20 and 30 µM PIM1-1, respectively. A significant decrease of ERK phosphorylation was detected in PIM1-1-treated Daudi cells, confirming the antiproliferative effect. The addition of 10 µM PIM1-1 significantly decreased the PIM-1 protein and gene expression in Daudi cells. An inhibition of the pro-apoptotic BAD phosphorylation was observed in the Daudi cells treated with 0.1-1 µM PIM1-1 and 10 µM PIM1-1 decreased BAD phosphorylation in the Raji cells. The apoptotic status of both PIM1-1-treated cells lines were confirmed with the detection of cleaved capase-3. However, no change in cell viability and PIM-1 protein expression was observed in the 10 µM PIM1-1-treated K562 cells. In conclusion, the findings indicated that the PIM1-1 pharmacological inhibitor may have therapeutic potential in BL, but with lower efficiency in leukemia.

Erythropoietin-Induced Hypertension: A Review of Pathogenesis, Treatment, and Role of Blood Viscosity.

Anemia is a common complication of certain chronic diseases and can be treated by stimulating hematopoietic cells to increase red blood cell count, and this action is achieved by recombinant human erythropoietin. In this review article, we have discussed about hypertension, which develops as a result of erythropoietin therapy. We have explored the pathogenesis of erythropoietin-induced hypertension and discussed some ways to prevent and treat this condition. Also, an attempt has been made to find out the role of blood viscosity in erythropoietin-induced hypertension. We conducted a comprehensive review of literature by collecting data from online databases like PubMed and Google Scholar. We mainly studied clinical trials that unraveled the mechanism of hypertension caused by erythropoietin. Hypertension is mainly caused due to enhanced vascular responsiveness to constrictors and impaired action of vasodilators. Role of blood viscosity in the pathogenesis of hypertension is doubtful due to the lack of consistency in the studies. Incidence of hypertension can be reduced by achieving slow correction of anemia and by switching to subcutaneous route of administration. Conventional anti-hypertensives have been found to be beneficial in the treatment. In some severe and persistent cases, temporary discontinuation of erythropoietin may be needed.

How Clinically Efficient Is Lumacaftor/Ivacaftor for Cystic Fibrosis Patients? An Updated Literature Review.

Cystic fibrosis (CF) is an autosomal recessive illness caused by the defective cystic fibrosis transmembrane conductance regulator (CFTR) gene. These patients suffer from repeated chronic sinuses and lung infections, resulting in frequent hospital admissions and antibiotic (Abx) courses. These are the major contributing factors responsible for a low health-related quality of life (HRQoL) and increasing the disease burden. The introduction and approval of CFTR modulators-lumacaftor (LUM) and ivacaftor (IVA) in 2015 by the US Food and Drug Administration (FDA) reduced the mortality and morbidity rates associated with the disease. In 2018, the FDA approved these drugs from age two and five years with two copies of F5806 del. This literature review aims to present the studies centered on the clinical effects of LUM/IVA. We searched for the relevant articles, from 2016 to 2020, in PubMed Central (PMC), Google Scholars, and Journal of Cystic Fibrosis. LUM/IVA has a broader range of effects. They showed marked improvement in the reduction of pulmonary exacerbations (PEx), Hospitalization rates, Abx use, and modification in forced expiratory volume in one second (FEV1) status of pre-existing severe lung disease. Now, there is a need for an initiative to conduct more clinical trials and studies in the future to assess and evaluate the long-term clinical benefits and safety of LUM/IVA therapy in all age groups.