Neuronal EphA4 Regulates OGD/R-Induced Apoptosis by Promoting Alternative Activation of Microglia.

Accumulating evidence indicates that post-injury inflammation characterized by activated microglia contributes much to the neuropathology of ischemic injury. Several studies have demonstrated that microglia exhibit two entirely different functional activation states, referred to as classically activated (M1) and alternatively activated (M2) phenotype. Promoting microglial phenotype to switch from M1 dominant to M2 dominant might be a promising approach for handling ischemic injury. However, the comprehensive mechanism that underlines microglia polarization in ischemic brain remains unclear. Neuronal erythropoietin-producing human hepatocellular carcinoma cell receptor 4 (EphA4), the richest Eph receptor in the central nervous system (CNS), upregulate after ischemia and may have the potential to regulate microglia activation. We hypothesized that modulating EphA4/ephrin signaling could affect ischemic injury through controlling microglia polarization. We therefore knocked down neuronal EphA4 with short hairpin RNA (shRNA) and determined the role of EphA4/ephrin signaling in oxygen-glucose deprivation and reperfusion (OGD/R)-induced injury. We found that EphA4 shRNA treatment attenuated OGD/R-induced apoptosis and microglia proliferation. Neuronal EphA4 knockdown also promoted microglial M2 polarization, which reduced pro-inflammatory mediators and released anti-inflammatory cytokines as well as neurotrophic factors. We further revealed that EphA4 shRNA treatment functioned through RhoA/Rho-associated kinase 2 (ROCK2) signaling, a key mediator of microglia alternative activation. Together, these data suggested that blockage of EphA4/ephrin signaling between neuron and microglia decreased OGD/R-induced injury by promoting alternative activation of microglia via RhoA/ROCK2 signaling.

[Rhizosphere Microbial Diversity in Different Wetland Microcosms].

To investigate the rhizosphere microbial community structure characteristics in varying combinations of plants and filter materials in the process of aquaculture pond water treatment, six types of wetland microcosms were established using two kinds of plants (Zizania latifolia Turcz. and Sagittaria graminea) and two types of filter materials (garnet and magnetite). High-throughput sequencing technology was used to analyze the microbial structural features and composition diversity of the wetland rhizosphere. The results were as follows. The microorganisms recovered belonged to 52 phyla, 118 classes, 455 families, 905 genera, and 1426 species. Based on the Shannon index, Zizania latifolia Turcz. (average value: 5.77) had a higher capacity than Sagittaria graminea(average value: 5.29) in terms of microbial enrichment. However, the rate of Proteobacteria in the rhizosphere microorganism communities of the Sagittaria graminea and Zizania latifolia Turcz. microcosms were 61.97% and 51.78%, respectively, further showing that the roots of Sagittaria graminea in the wetland microcosms better enriched the Proteobacteria during the experimental period. The major bacterial groups of different plant roots were enriched with ß-Proteobacteria in the experiment. The results of this study provide a theoretical basis for species optimization in artificial wetland systems and best combination of wetland construction that will be useful for future investigations.

[Expression of Btk and NFκB in acute myeloid leukemia cells and its significance].

This study was purposed to investigate the expression of Btk and NFκB in acute myeloid leukemia (AML) cells and its significance. Bone marrow mononuclear cell specimens were taken from 14 AML patients who were in new diagnosis and complete remission respectively, the expressions of Btk and NFκB at mRNA and protein levels were detected by RT-PCR and Western blot, respectively. The results showed that Btk and NFκB expressed in all the samples at RNA and protein levels. At protein level, Btk and NFκB expressions were higher in the cells from newly diagnosed AML patients than that in the cells from patients in complete remission stage (P < 0.05). It is concluded that Btk and NFκB may play an important role in the development and progression of AML, they may be used as potential therapeutic targets of AML and used in predicting the prognosis.

[Research advance of p53 gene in mantle cell lymphoma].

Mantle cell lymphoma(MCL) is an independent uncommon subtype of B-cell non-Hodgkin's lymphoma (NHL) according to World Health Organization classification of hematopoietic and lymphoid tissue tumors. The genetic hallmark of MCL is the chromosomal translocation t(11;14)(q13;q32) that leads to upregulation of cyclin D1, an important regulator of the G(1) phase in the cell cycle. This genetic aberration is virtually present in all cases of MCL. It is characterized by distinct clinical features and outcome which is affected by a series of additional genetic aberration including the genomic guardian-P53 gene. This article reviews the effects of P53 gene aberrations including P53 deletion, mutation and their mutual relationship in MCL, and novel therapeutic regimens for MCL patients with P53 aberrations.

Prolonged chronic phase in chronic myelogenous leukemia after homoharringtonine therapy.

BACKGROUND: Homoharringtonine (HHT) is effective in treating late stage chronic myelogenous leukaemia (CML), but little is known about long term maintenance during complete cytogenetic response. Long term efficacy and toxicity profiles of low dose HHT were evaluated in this study. METHODS: One hundred and six patients with CML received 1.5 mg/m(2) of HHT alone by continuous daily infusion for seven to nine days every four weeks. Of 79 patients in the control group, 31 were treated with interferon alpha (IFN-alpha) and 48 with hydroxycarbamide. For 17 patients who failed to achieve cytogenetic response within 12 months' treatment of IFN-alpha, HHT was administered. Quantitative RT-PCR was used to detect the BCR-ABL mRNA expression in 36 Philadelphia positive CML patients enrolled after 2007. Haematological and cytogenetic responses were evaluated in all patients at the 12th month of follow-up. Long term efficacy was assessed in a follow-up with a median time of 54 months (12 months-98 months). RESULTS: After 12 months of therapy, cytogenetic response rate of the HHT, IFN-alpha and hydroxycarbamide groups were 39/106, 14/31 and 3/48, and corresponding molecular cytogenetic response rates 6/18, 3/8 and 0. Of the 17 patients who received HHT as salvage treatment, 6 achieved cytogenetic response (3 major). At the 48 months' follow-up, cytogenetic response was maintained in 32/39 patients treated with HHT. Patients who had cytogenetic response in HHT group or treated with IFN-alpha also showed longer median chronic durations, which were 45 months (12 months-98 months) and 49 months (12 months-92 months) respectively, indicating a longer survival time. CONCLUSIONS: Low dose HHT alone showed considerable short term and long term efficacy in the treatment of late stage CML. It may also be a good choice for patients who have failed imatinib, IFN-alpha treatment or haematopoietic stem cell transplantation or cannot afford these treatments.

[Short term high-dose dexamethasone therapy in previously untreated idiopathic thrombocytopenic purpura].

OBJECTIVE: To observe the long-term effect of short interim high-dose dexamethasone (HD-DXM)in previously untreated patients affected by idiopathic thrombocytopenic purpura(ITP) and investigate the action of maintenance treatment. METHODS: 40 mg/d of dexamethasone was given in a 4-day pulse every 14 days for 3 cycles to 45 patients with ITP. Among them, 22 cases were given routinely dexamethasone of 0.035 mg x kg(-1) x d(-1) for maintenance treatment between courses of high-dose dexamethasone (HD-DXM + RM group)and 23 cases were given dexamethasone of 0.035 mg x kg(-1) x d(-1) only when the platelet count was lower than 20 x 10(9)/L (HD-DXM + SM group). As a control group, another 22 cases were given routine dosage of prednisone (control group). RESULTS: (1) At the end of the third cycle, the effective rate in the HD-DXM + RM group was 81.8% (18/22), which was higher than 65.2% (15/23) of the HD-DXM + SM group and 63.6% (14/22) of the control group. (2) Among the HD-DXM group patients, the effective rate at the end of the third cycle was higher than that at the end of first and second cycles. (3) The effective rate of HD-DXM + RM group was higher than that of HD-DXM + SM group. (4) At the time of 1, 2, 3, and 4 months after the end of the last cycle of HD-DXM, the relapse rates in HD-DXM + RM group were 16.7%, 16.7%, 27.8% and 33.3% respectively, which were lower than that of HD-DXM + SM group and control group respectively. CONCLUSIONS: A schedule of 3 cycles of HD-DXM pulses with an interval of 2 weeks between cycles is an effective method for previously untreated ITP patients and maintenance treatment with small-dose dexamethasone between high-dose dexamethasone contributes to improve the long-term curative effect.