The aberrantly activated AURKB supports and complements the function of AURKA in CALR mutated cells through regulating the cell growth and differentiation.

Aurora kinase B (AURKB) was reported to assist Aurora kinase A (AURKA) to regulate cellular mitosis. AURKA has been found activated in myeloproliferative neoplasms (MPNs) patients with CALR gene mutation, however, it's unclear whether AURKB displays a compensatory function of AURKA in regulation of CALR mutant cell growth and differentiation. Here, we found that AURKB, similar with AURKA, was aberrantly activated in CALR mutant patients, and displayed a more tolerance to the aurora kinase inhibitor.

[Effects of Down-Regulation of on Differentiation and Apoptosis of MPN Cells with Gene Mutation and Survival of 6133/MPL Mice].

Objective: To investigate the effects of down-regulation of p21 activated kinase 1 (PAK1) on the proliferation, differentiation, and apoptosis of myeloproliferative neoplasm (MPN) cells (6133/MPL) with thrombopoietin receptor MPL mutation at codon 515 () and survival of 6133/MPL mice.

Methods: Interference with the protein level of in 6133/MPL cells was assessed using lentivirus-mediated shRNA transfection technology. CCK-8 assay was used to detect the effect of down-regulation of on the proliferation viability of 6133/MPL cells, and colony-forming ability was measured by cell counting.

Assessment of intestinal status in MPL mutant myeloproliferative neoplasms mice model.

The MPL mutation is a prevalent genetic mutation in patients with myeloproliferative neoplasms (MPN), and utilizing this mutation in mice model can provide important insights into the disease. However, the relationship between intestinal homeostasis and MPN mice model remains elusive. In this study, we utilized a retroviral vector to transfect hematopoietic stem cells with the MPL mutation, creating mutated MPN mice model to investigate their intestinal status.

Inhibition of PAK1 generates an ameliorative effect on MPLW515L mouse model of myeloproliferative neoplasms by regulating the differentiation and survival of megakaryocytes.

Most thrombopoietin receptor (MPL) mutations result in abnormal megakaryocyte expansion in the spleen or bone marrow (BM), leading to progressive fibrosis. It has been reported that p21 (Rac Family Small GTPase 1 [RAC1])-activated kinase 1 (PAK1) participates in the proliferation and differentiation of megakaryoblasts. PAK1 phosphorylation increased in patients with myeloproliferative neoplasms (MPNs) and murine MPN cells with the Mplw515l mutant gene in this study; however, the function of overactivated PAK1 in MPN cells remains unclear.

[Construction of a Mouse Model for Myeloproliferative Neoplasms and an Evaluation System].

Objective: To construct a myeloproliferative neoplasms (MPN) transplanted mouse model with or gene mutation, and establish a systematic evaluation system to verify the success of model construction.

Methods: The bone marrow c-kit cells of the mice were obtained by the following steps: The mice were killed by cervical dislocation, the femur, tibia and ilium were separated, and the bone marrow cells were collected. The c-kit cells were sorted after incubation with CD117 magnetic beads.

Targeting cyclin-dependent kinases 4/6 inhibits survival of megakaryoblasts in acute megakaryoblastic leukaemia.

Acute megakaryoblastic leukaemia (AMKL) is characterized by expansion of megakaryoblasts, which are hyper-proliferative cells that fail to undergo differentiation. Insight to the cell-cycle regulation revealed important events in early or late megakaryocytes (MKs) maturation; the cyclin-dependent kinases 4 and 6 (CDK4/6) have been reported to participate in the development of progenitor megakaryocytes, mainly by promoting cell cycle progression and DNA polyploidization. However, it remains unclear whether the continuous proliferation, but not differentiation, of megakaryoblasts is related to an aberrant regulation of CDK4/6 in AMKL.

[Experimental study of tissue-engineered bone constructed with simvastatin carried by PLGA/CPC and bone marrow stromal cells].

Purpose: To study the feasibility of tissue engineered bone constructed with simvastatin carried by PLGA/CPC and bone marrow stromal cells (BMSCs) and screen the effective drug loading of simvastatin.

Methods: Solvent casting-particle leaching technology combined with the phase separation process was used to prepare the different concentrations (simvastatin mass: 0.1, 0.

Over-expression of hypoxia-inducible factor-1 alpha in vitro protects the cardiac fibroblasts from hypoxia-induced apoptosis.

Objectives: A great number of studies indicate that cardiac fibroblasts are essential for maintaining the structure and function of heart. Hypoxia-inducible factor-1 alpha (HIF-1α) is a central transcriptional regulator of hypoxic response. The present study examined whether over-expression of HIF-1α could prevent hypoxia-induced injury in neonatal rat cardiac fibroblasts and, if so, its possible molecular targets.

Arsenic trioxide induces cardiac fibroblast apoptosis in vitro and in vivo by up-regulating TGF-β1 expression.

Arsenic trioxide (As2O3; ATO) is clinically effective in treating acute promyelocytic leukemia (APL); however, it frequently causes cardiotoxic effects. This study was designed to investigate whether ATO could induce apoptosis of cardiac fibroblasts (CFs) that play very important roles in maintaining the structure integrity and function of the heart. Cardiac fibroblasts from guinea pigs administered with ATO (1mg/kgbw) were used to test the pro-apoptotic role of ATO in vivo.

Arsenic-induced interstitial myocardial fibrosis reveals a new insight into drug-induced long QT syndrome.

Aims: Arsenic trioxide (ATO), an effective therapeutic agent for acute promyelocytic leukaemia, can cause sudden cardiac death due to long QT syndrome (LQTS). The present study was designed to determine whether ATO could induce cardiac fibrosis and explore whether cardiac fibroblasts (CFs) are involved in the development of LQTS by ATO.

Methods And Results: ATO treatment of guinea pigs caused substantial interstitial myocardial fibrosis and LQTS, which was accompanied by an increase in transforming growth factor β1(TGF-β1) secretion and a decrease in ether-à-go-go-related gene (HERG) and inward rectifying potassium channel (I(K1)) subunit Kir2.