Effect of Dimethyl Fumarate (DMF) on T-cell Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the effect and possible mechanism of dimethyl fumarate (DMF) on T-cell acute lymphoblastic leukemia (T-ALL), and provide experimental and theoretical basis for the clinical treatment of T-ALL.@*METHODS@#Jurkat cells were treated with different concentrations of DMF for 24 hours, and then the proportion and absolute count of Ki67-positive Jurkat cells were analyzed by flow cytometry. Meanwhile, the protein levels of nuclear factor-erythroid 2-related factor 2 (Nrf2) and E3 ubiquitin ligase HACE1 in Jurkat cells treated with DMF for 24 hours were evaluated by Western blot. Nrf2 proteins were co-immunoprecipitated in Jurkat cells, and then HACE1 protein was assessed by Western blot. Plasmids of Flag-Nrf2 and different gradients of Flag-HACE1 were transfected into HEK293T cells, and the levels of Flag-Nrf2 were detected by Western blot after 48 hours.@*RESULTS@#DMF could significantly inhibit the proportion and absolute count of Ki67-positive Jurkat cells, and DMF inhibited the proliferation of Jurkat cells in a dose-dependent manner (r=0.9595, r=0.9054). DMF could significantly up-regulate the protein levels of Nrf2 and E3 ubiquitin ligase HACE1 in Jurkat cells (P<0.01, P<0.01). HACE1 physically interacted with Nrf2 in Jurkat cells. Overexpression of Flag-HACE1 significantly increased the protein level of Flag-Nrf2 in a dose-dependent manner (r=0.9771).@*CONCLUSION@#DMF inhibits the proliferation of T-cell acute lymphoblastic leukemia cell. The mechanism may be that, DMF significantly up-regulates the protein levels of Nrf2 and E3 ubiquitin ligase HACE1, and HACE1 interacts with Nrf2 and positively regulates Nrf2 protein level.

Roles of NLRP1 in blood diseases / 中国实验血液学杂志

The inflammasome is a group of multiprotein complexes in the cytoplasm, which can activate caspase-1 that mediates the maturation and release of IL-1β, IL-18, IL-33 and other pro-inflammatory cytokines.NALP1 (NACHT leucine-rich-repeat protein 1), also known as NLRP1, is the first one of the identified complex inflammasomes with definite ligands mainly involved in the activation of inflammasome assembly and the formation of apoptotic bodies. Moreover, it was also found that NLRP1 plays an important biological role in the development of acute leukemia, the bone marrow hematopoietic stem cell apoptosis and other blood diseases. This review briefly summarizes the structure, activation mechanism, regulation and the role of NLRP1 in the hematopoietic system.

Effect of endothelial progenitor cell on hematopoietic reconstitution in allogeneic hematopoietic stem cell transplantation mouse model / 中华血液学杂志

<p><b>OBJECTIVE</b>To examine the effects of endothelial progenitor cell (EPC) on hematopoietic reconstitution in allogeneic hematopoietic stem cell transplantation (allo-HSCT) mouse model.</p><p><b>METHODS</b>Allo-HSCT mouse model was established with condition of BU/CY, in which C57BL/6 (H-2b) and BALB/c (H-2d) mice were used as donors and recipients respectively. Recipients were randomly divided into 4 groups: untreated group, BU/CY condition group, bone marrow transplantation (BMT) group and transplantation of BM cells combined with EPCs (combined transplantation) group. The pathological changes of BM cells following transplantation were dynamically observed. Changes of BM sinusoidal endothelium and angiogenesis were observed by MECA-32 antibody immunohistochemical staining. The proportion of intramedullary stem and progenitor cells and serum cytokines were analyzed by flow cytometry. The numbers of peripheral blood cells were also counted.</p><p><b>RESULTS</b>(1) Injuries of BM hematopoietic tissue, sinusoidal endothelium and vascular were less severe in combined transplantation group than of BMT group. (2) EPC infusion significantly increased BM hematopoietic stem cells 21 days after transplantation. The percentage of BM hematopoietic stem cells in combined transplantation group peaked on day +14, which was higher than of BMT group (0.1743 vs 0.0787) (P<0.05). The continuously increased percentage of BM hematopoietic progenitor cells in combined transplantation group was significantly higher than in BMT group on day +21 (0.4550 vs 0.3905) (P<0.05). (3) The number of peripheral white blood cells in combined transplantation group was always higher than of BMT group, which reached the peak on day +14 (0.74×10⁹/L to 0.47×10⁹/L) (P<0.05). The peak number of peripheral blood platelets on day +14 in combined transplantation group was significantly higher than of group BMT (1228.9×10⁹/L to 977.12×10⁹/L) (P<0.05).</p><p><b>CONCLUSION</b>Allo-HSCT combined with EPC infusion accelerated hematopoietic reconstitution compared with BMT alone in allo-HSCT mouse model.</p>

Construction and sequencing of full-length cDNA clone of swine vesicular disease virus strain HK'1/70 / 病毒学报

By RACE, 2 overlapping cDNA fragments (3'PCR and 5'PCR fragments) covering the full genome of swine vesicular disease virus strain HK'1/70 were amplified from total RNA extracted from experimentally infected suckling mice. These fragments were cloned into pGEM-T Easy vector, respectively. 5'PCR fragment was digested by enzymes of Aat II and BssH II, and the Aat II-BssH II-digested 5'PCR fragment was obtained and cloned into the recombinant pGEM-T Easy vector containing 3'PCR fragment,the recombinant plasmid encoding full-length cDNA of SVDV HK'I/70 strain was then obtained and sequenced. The results showed that the complete genome of HK'1/70 was 7401 nucleotides (nts) long (excluding the poly (A) tract) which encodes a single polyprotein of 2185 amino acids, a 5'u ntranslating region (UTR) of 743 nts, a 3'UTR of 102 nts and a poly (A) tail at least 74 adenines. T' promoter was added at the 5'e nd of the full-length cDNA and an additional Pspl406I restriction site was added at the 3'e nd of poly (A) tail. The nucleotide and amino acid sequences were compared and phylogenetic analysis was used to examine the evolutionary relationships. The results showed that HK'1 /70 belonged to the second antigenic group. SVD virus was antigenically closely related to Coxsackie B5 virus, and located on the branches of CB5 evolutionary tree. Successful construction of full-length cDNA clone of SVDV HK'1/70 strain lays foundation for rescuing SVDV effectively and enables further research of SVDV on molecular level.