Combining the novel FLT3 and MERTK dual inhibitor MRX-2843 with venetoclax results in promising antileukemic activity against FLT3-ITD AML.

FMS-like tyrosine kinase 3 (FLT3) mutations occur in approximately one third of acute myeloid leukemia (AML) patients. FLT3-Internal tandem duplication (FLT3-ITD) mutations are the most common FLT3 mutations and are associated with a poor prognosis. Gilteritinib is a FLT3 inhibitor that is US FDA approved for treating adult patients with relapsed/refractory AML and a FLT3 mutation.

Comprehensive analysis of transcriptomics and metabolomics to understand tail-suspension-induced myocardial injury in rat.

Background/aims: The effect and underlying mechanism of microgravity on myocardium still poorly understood. The present study aims to reveal the effect and underlying mechanism of tail-suspension-induced microgravity on myocardium of rats.

Methods: Tail-suspension was conducted to simulate microgravity in rats.

Venetoclax enhances DNA damage induced by XPO1 inhibitors: A novel mechanism underlying the synergistic antileukaemic effect in acute myeloid leukaemia.

Acute myeloid leukaemia (AML) is a highly heterogeneous haematologic malignancy with poor prognosis. We previously showed synergistic antileukaemic interaction between exportin 1 (XPO1) inhibitor KPT-330 (Selinexor) and Bcl-2 inhibitor venetoclax (ABT-199) in preclinical models of AML, which was partially meditated by Mcl-1, although the full mechanism of action remains unknown. In this study, using real-time RT-PCR and Western blot analysis, we show that inhibition of XPO1 via KPT-330 or KPT-8602 (Eltanexor) decreases the mRNA and protein levels of c-Myc, CHK1, WEE1, RAD51 and RRM2.

Cotargeting of Bcl-2 and Mcl-1 shows promising antileukemic activity against AML cells including those with acquired cytarabine resistance.

Acute myeloid leukemia (AML) remains a clinical challenge. Venetoclax is an effective Bcl-2 selective inhibitor approved by the U.S.

Is autonomic modulation different between European and Chinese astronauts?

Purpose: The objective was to investigate autonomic control in groups of European and Chinese astronauts and to identify similarities and differences.

Methods: Beat-to-beat heart rate and finger blood pressure, brachial blood pressure, and respiratory frequency were measured from 10 astronauts (five European taking part in three different space missions and five Chinese astronauts taking part in two different space missions). Data recording was performed in the supine and standing positions at least 10 days before launch, and 1, 3, and 10 days after return.

Genetic influence on baroreflex sensitivity in normotensive young men.

Background: The dysfunction of baroreflex plays an important role in the pathogenesis of essential hypertension. Recent studies suggest that approximately 40% of the variation in baroreflex sensitivity (BRS) may be accounted for by genetic factors. However, only a few such genetic polymorphisms have been explicitly identified.