E2F1­mediated RAB34 upregulation accelerates the proliferation and inhibits the cell cycle arrest and apoptosis of acute myeloid leukemia cells.

Acute myeloid leukemia (AML) is a malignant disease that is mainly arisen from myeloid stem/progenitor cells. The pathogenesis of AML is complex. Ras-related protein member RAS oncogene GTPases (RAB) 34 protein has been reported to serve an important role in the development of cancer. However, to the best of our knowledge, the role of RAB34 in AML has not been previously reported. The GEPIA database was used to predict the expression levels of RAB34 in patients with AML. Reverse transcription-quantitative PCR and western blotting were used to detect the expression of RAB34 in AML cell lines. Cell transfection with short hairpin (sh)RNAs targeting RAB34 was used to interfere with RAB34 expression. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine staining were used to measure cell proliferation. Flow cytometry was used to investigate cell cycle distribution and apoptosis. Western blotting was used to assess the protein expression levels of RAB34 and E2F transcription factor 1 (E2F1), and cell cycle- and apoptosis-associated proteins, including Bcl-2, Bax, CDK4, CDK8 and cyclin D1. The potential binding between E2F1 and RAB34 was then verified by luciferase reporter and chromatin immunoprecipitation assays. Subsequently, cells were co-transfected with RAB34 shRNA and the E2F1 overexpression plasmid before cell proliferation, cell cycle and apoptosis were analyzed further. The expression of RAB34 was found to be significantly increased in AML cell lines. Knocking down RAB34 expression in AML cells was found to significantly inhibit cell proliferation, induce cell cycle arrest and promote apoptosis. E2F1 activated the transcription of RAB34 and E2F1 elevation reversed the impacts of RAB34 silencing on cell proliferation, cell cycle and apoptosis in AML. Therefore, these findings suggest that E2F1-mediated RAB34 upregulation may accelerate the malignant progression of AML.

Loss of runx1 function results in B cell immunodeficiency but not T cell in adult zebrafish.

Transcription factor RUNX1 holds an integral role in multiple-lineage haematopoiesis and is implicated as a cofactor in V(D)J rearrangements during lymphocyte development. Runx1 deficiencies resulted in immaturity and reduction of lymphocytes in mice. In this study, we found that runx1W84X/W84X mutation led to the reduction and disordering of B cells, as well as the failure of V(D)J rearrangements in B cells but not T cells, resulting in antibody-inadequate-mediated immunodeficiency in adult zebrafish. By contrast, T cell development was not affected. The decreased number of B cells mainly results from excessive apoptosis in immature B cells. Disrupted B cell development results in runx1W84X/W84X mutants displaying a similar phenotype to common variable immunodeficiency-a primary immunodeficiency disease primarily characterized by frequent susceptibility to infection and deficient immune response, with marked reduction of antibody production of IgG, IgA and/or IgM. Our studies demonstrated an evolutionarily conserved function of runx1 in maturation and differentiation of B cells in adult zebrafish, which will serve as a valuable model for the study of immune deficiency diseases and their treatments.

Effects of local elastic compression on muscle strength, electromyographic, and mechanomyographic responses in the lower extremity.

The purpose of this study was to investigate the effect of elastic compression on muscle strength, electromyographic (EMG), and mechanomyographic (MMG) responses of quadriceps femoris during isometric and isokinetic contractions. Twelve participants performed 5s isometric maximal voluntary contractions (MVC) and 25 consecutive and maximal isokinetic knee extensions at 60 and 300°/s with no (control, CC), medium (MC), and high (HC) compression applied to the muscle. The EMG and MMG signals were collected simultaneously with muscle isometric and isokinetic strength data. The results showed that the elevated compression did not improve peak torque, peak power, average power, total work, and regression of torque in the isometric and isokinetic contractions. However, the root mean squared value of EMG in both HC and MC significantly decreased compared with CC at 60 and 300°/s (p<0.01). Furthermore, the EMG mean power frequency in HC was significantly higher than that in CC at 60°/s (p<0.05) whereas no significant compression effect was found in the MMG mean power frequency. These findings provide preliminary evidence suggesting that the increase in local compression pressure may effectively increase muscle efficiency and this might be beneficial in reducing muscle fatigue during concentric isokinetic muscle contractions.