Single-Dose Administration of Recombinant Human Thrombopoietin Mitigates Total Body Irradiation-Induced Hematopoietic System Injury in Mice and Nonhuman Primates.

Purpose: Recombinant human thrombopoietin (rhTPO) has been evaluated as a therapeutic intervention for radiation-induced myelosuppression. However, the immunogenicity induced by a repeated-dosing strategy raises concerns about the therapeutic use of rhTPO. In this study, single-dose administration of rhTPO was evaluated for efficacy in the hematopoietic response and survival effect on mice and nonhuman primates exposed to total body irradiation (TBI).

Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation.

All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts.

[Protective effect of HS-6101 on rhesus monkeys with severe hematopoietic acute radiation sickness].

This study was purposed to investigate the protective effects of lipoprotein HS-6101(6101) on rhesus monkey total body irradiated with 7.0 Gy ⁶⁰Coγ-ray. A total of 30 health adult rhesus monkeys were randomly divided into symptomatic therapy (ST), WR2721 and HS-6101 30, 90 and 270 mg/kg groups (n = 6), the rhesus monkeys of each groups were injected with physiological saline 0.

The protein kinase C agonist prostratin induces differentiation of human myeloid leukemia cells and enhances cellular differentiation by chemotherapeutic agents.

As acute myeloid leukemia (AML) cells are characterized by uncontrolled self-renewal and impaired cellular differentiation, induction of terminal differentiation of leukemia cells by differentiating agents has been proposed as an attractive therapeutic strategy to treat AML. Here, we demonstrated that prostratin, a potent protein kinase C (PKC) activator, inhibited the growth of myeloid leukemia cells by a predominant G1 arrest with variable induction of apoptosis. Conversely, prostratin induced significant differentiation of AML cell lines and primary AML blasts as evidenced by morphology and immunophenotyping.

[Protective effects of WR2721 on early bone marrow hematopoietic function in mice exposed to 6.5 Gy of (60)Co γ-rays].

The aim of this study was to investigate the effect of WR2721(amifostine) against bone marrow hematopoietic damage of mice exposed to 6.5 Gy of (60)Co-γ ray. A total of 60 C57/BL6J mice was divided into 3 groups:normal group (mice were injected with physiological salt solution), irradiation group (mice were injected with physiologic salt solution before irradiation) and WR2721 group (mice were injected with WR2721 before irradiation).

Cylindroside A, a new triterpenoid saponin from Cylindrokelupha dalatensis and its cytotoxic activity.

A new triterpenoid saponin, named cylindroside A (1), was isolated from the seeds of Cylindrokelupha dalatensis (Kosterm.) T.L.

[Transfection of ECSOD to Rhesus bone marrow mesenchymal stem cells in vitro].

This study was aimed to investigate the biological effects of Rhesus bone marrow mesenchymal stem cells (R-BMMSC) transfected by adenovirus bearing extracellular superoxide dismutase gene (AD-ECSOD). Using density gradient centrifugation and adherent culture way, the R-BMMSC transfected by AD-ECSOD and reporter gene EGFP were isolated, cultured and purified; the transfection efficiency was detected by fluorescence microscopy and flow cytometry; the ECSOD protein expression in cell culture supernatant were detected by ELISA; the surface antigens on R-BMMSC (CD34, CD29, CD45, CD90, HLA-DR) were detected by flow cytometry; and differentiation capability of transfected R-BMMSC were detected by oil red O and alizarin staining; the proliferation capability of R-BMMSC was assay by MTT method. The results showed that the transfection efficiency of AD-ECSOD (MOI 500, 1 000, 1 500 and 2 000) for R-BMMSC was > 95%.

[Radiation protection effect of rhIL-12 on monkey hematopoietic system].

This study was aimed to investigate the radioprotective effects of recombinant human interleukin-12 (rhIL-12) on monkey hematopoietic system, and to provide experimental evidence for future clinical prophylaxis and treatment for patients who suffered from acute radiation syndrome. In in vitro study, the effect of rhIL-12 in different concentrations (0, 1, 5, 25, 125 and 625 ng/ml) on colony forming capacity of human or monkey bone marrow-derived mononuclear cells was examined in methylcellulose H4434 medium. In in vivo study, the acute radiation syndrome model was established in 11 Rhesus monkeys which received lethal total body irradiation by 6 Gy (60)Co γ in single time irradiation.

RhG-CSF improves radiation-induced myelosuppression and survival in the canine exposed to fission neutron irradiation.

Fission-neutron radiation damage is hard to treat due to its critical injuries to hematopoietic and gastrointestinal systems, and so far few data are available on the therapeutic measures for neutron-radiation syndrome. This study was designed to test the effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in dogs which had received 2.3 Gy mixed fission-neutron-γ irradiation with a high ratio of neutrons (~90%).

[New advance of research on therapy of severe acute radiation sickness with mesenchymal stem cells].

Mesenchymal stem cells (MSC) are a kind of non-hematopoietic adult stem cells with self-renewal and multilineage differentiation potential, which have special biological characteristics, such as secreting various cytokines, promoting hematopoiesis, accelerating stem cells homing and reconstructing hematopoietic microenvironment. MSC are collected and amplified easily, and can be transfected by exogenous gene. Many reports indicated that MSC were applied in therapy for variety of tissues and organs injury, meanwhile the treatment for acute radiation sickness has made significant progress.

[Effect of rhG-CSF on blood coagulation in beagles irradiated by 2.3 Gy neutron].

The aim of this study was to investigate the effect of recombinant human granulocyte stimulating factor (rhG-CSF) on blood coagulation of beagles irradiated by 2.3 Gy neutron so as to provide new therapy for blood coagulation disorder after neutron irradiation. 10 beagles were exposed to 2.

Fluacrypyrim, a novel STAT3 activation inhibitor, induces cell cycle arrest and apoptosis in cancer cells harboring constitutively-active STAT3.

STAT3 protein has an important role in oncogenesis and is a promising anticancer target. Herein, we demonstrate that a novel small molecule fluacrypyrim (FAPM) inhibits the growth of leukemia cells by a predominant G1 arrest with significant decrease of the protein and mRNA levels of cyclin D1. As cyclin D1 is transcriptionally regulated by STAT3, FAPM is then shown to markedly inhibit the STAT3 phosphorylation with marginal effect on the other signal transducers and activators of transcription, and without effect on phosphoinositide-3-kinase and mitogen-activated protein kinase pathways.

[Jak/STAT signaling pathway of IL-11 in the protection of intestinal epithelial cells from neutron radiation].

Aim: To explore the effect of IL-11 on the activation of Jak/STAT pathway and the expressions of Bax and Bcl-2 in the intestinal epithelial cells exposed to neutron radiation.

Methods: The BALB/c mice and IEC-6, irradiated by 4 Gy neutron with or without IL-11 treatment, served as in vivo and in vitro model seperately. The changes of the intestines, activity of Jak1 and STAT3 and expressions of Bax and Bcl-2 were observed by HE staining, Western blot, EMSA, immunohistochemistry and image analysis.

[Mesenchymal stem cells applied in therapy for acute radiation injury].

Mesenchymal stem cells are a kind of non-hematopoietic adult stem cells with selfrenewal and multilineage differentiation potential, which have special biological characteristics, such as secreting hematopoietic growth factors, reconstructing hematopoietic microenvironment, low immunogenicity, and can be transfected and expressed by exogenous gene. This article summarizes the biological characteristics of MSCs and their models of application to acute radiation disease in animals.

[Effect of IL-2 on the growth and apoptosis of intestinal epithelial cells radiated by neutron and mechanisms of IL-2 on the injured IEC-6].

Aim: To observe the effect of neutron radiation on intestinal epithelial cells 6 (IEC-6), to study the effect of IL-2 on the proliferation and recovery of neutron-injured IEC-6, and to investigate the regulatory mechanisms of IL-2 on the injured IEC-6.

Methods: 4Gy-neutron-injured IEC-6 were treated by IL-2, with or without the blocking agent JAK(1) (A77-1726). The change of proliferative activity and death manner of the treated IEC-6 were detected by MTT colorimetry and flow cytometry at 10, 15, 30 minutes and 1, 3, 6, 12, 24, 48, 72 hours respectively.

Effect of recombinant human interleukin-11 on expressions of interleukin-11 receptor alpha-chain and glycoprotein 130 in intestinal epithelium cell line-6 after neutron irradiation.

Aim: To explore the effect of recombinant human interleukin-11 (rhIL-11) on the expressions of interleukin-11 receptor alpha-chain (IL-11Ralpha) and an additional signal transducer glycoprotein 130 (gp130) in intestinal epithelium cell line-6 (IEC-6) after neutron irradiation.

Methods: Cultured IEC-6 cells were exposed to 4.0Gy neutron and treated with 100 ng/mL rhIL-11 12 h prior to or immediately after irradiation.

[Studies on peripheral blood & pathological index in inflammatory bowel disease of rats with clyster No. 1].

Objective: To observe the effect of the clysters No. 1 of Traditional Chinese Medicine (TCM) in inflammatory bowel disease on rats and search the new way and evidence for IBD cures.

Method: The rats were divided into four groups: normal control group (I), model control group (II), Sulfasalazine( SASP) treating control group (III) and traditional Chinese medicine clysters No.

[An experimental study of the effect of IL-2 on the growth of irradiated intestinal epithelial cells].

Aim: To observe the effect of ionizing radiation on intestinal epithelial cells 6 (IEC-6) and the effect of IL-2 on the proliferation and recovery of radiation-injured IEC-6 cells.

Methods: IEC-6 cells exposed to 4, 8 and 12 Gy gamma ray were analyzed with MTT colorimetry, light microscopy, electron microscopy, DNA gel electrophoresis and flow cytometry at 3, 6, 9, 12 hours and 1, 2, 3 days after radiation. Proliferation of 8 Gy gamma ray-irradiated IEC-6 cells which was treated with IL-2 was detected by MTT colorimetry at 3, 6, 9, 12 and 24 hours after irradiation.

[Expression of human HSF in E. coli and its effects on mobilization of hematopoietic stem cells in rhesus monkeys].

Objective: To study the expression of hHSF in E. coli and its effect on the mobilization of hematopoietic stem/progenitor cells.

Methods: The hHSF gene was obtained by overlapping PCR and cloned into the vector pET30a to yield pET30a-hHSF, which was transformed into E.

[Radioprotection of recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor on peripheral lymphocytes of rhesus monkey irradiated by 3.0 Gy gamma-rays].

Objective: To observe the radioprotection of recombinant human interleukin-3 (rhIL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and rhIL-3 (rhIL-3+GM-CSF) on peripheral lymphocytes of rhesus monkey irradiated by 3.0 Gy gamma-rays, and attempt to provide evidence of cytokines used effectively in the therapy of acute radiation sickness.

Methods: Thirty rhesus monkey used in the experiment were randomly divided into six groups of rhIL-3 20 microg.

[The effects of rhG-CSF and rhSCF on peripheral blood leukocytes and CFU-GM in rhesus monkeys].

To evaluate the effects of rhG-CSF and rhSCF on mobilization of the peripheral blood stem cells, 15 monkeys were divided into control, rhG-CSF 10 micro g/(kg x day) and rhG-CSF 10 micro g/(kg x day) + rhSCF 50 micro g/(kg x day) treated groups. Monkeys were administered with vehicle, rhG-CSF and rhG-CSF + rhSCF subcutaneously once daily for 14 days, respectively. The results showed that the highest counts of leukocyte of rhG-CSF treated group were 411% of baseline value on day 7 after administration, compared with that of rhG-CSF + rhSCF treated group which were 538% on day 9.

Therapeutic Effects of rhIL-11 on Irradiation-Induced Myelosuppression in Rhesus Monkeys.

The efficacy of rhIL-11 in treating thrombocytopenia and neutropenia in gamma-irradiated rhesus monkeys and the variation in curative effect due to difference of administration times were studied. Healthy rhesus monkeys were exposed to 3.0 Gy (60)Co total body irradiation (TBI) to result in pancytopenia for three weeks.

[Direct Injection of Plasmid DNA Expressing IL-6 Gene Improves Recovery of Thrombocytopoiesis in Irradiated Mice].

Hemorrhage is one of major clinical features of the patients exposed to large dose of ionizing radiation and a sudden decrease of peripheral platelet counts in hemorrhage complication may bring the patients into life-threatening situation. Cytokines had been used to improve thrombocytopoiesis in various radiation induced thrombocytopenia. Current measures for this purpose involve repeated injection of recombinant cytokines, which bring much inconvenient and agony to the patients, or gene therapy with viral vectors that could not obviate the risk of infection.