1.STUDY ON THE EFFECTIVE FRACTIONS DEPRESSING BLOOD-LIPIDS FROM OATS
Jingxi SHI ; Zhonghan YANG ; Huisheng MEI
Acta Nutrimenta Sinica 1956;0(04):-
Four fractions (starches, water insoluble proteins, water soluble fractions and residue) were separated from oats by means of filtration and repeated high speed centrifugation, and the lipids were extracted by acid-hydrolysis as well. Then each group of experiment hyperlipemic mice, caused by high lipid diet, were fed with these fractions for 10 days respectively. The results showed that the effectiveness of the residue fraction which was rich in dietary celluloses and lipids was similar to the whole oats on depressing bl-ood-lipid and that the water insoluble proteins were effective too. The lip-ids, however,were important but not unique effective composition in the residue of oats.
2.Mesenchymal stem cells protecting multiple organ failure
Kaixun HU ; Shifu ZHAO ; Mei GUO ; Huisheng AI
Chinese Journal of Emergency Medicine 2009;18(6):607-610
Objective The patients with lethal irradiation after sucessful hematopoietic stem cells transplan-tation had blood recovery, but did not avoid to died of multiple organ failure(MOF). To overcome the block, the article investigated mechanisms of mesenchymal stem cells (MSCs) protecting lethal radiated mice from multiple organ failure after haploid bone marrow cells transplantation. Method BALB/c mice irradiated with 8Gy60COγ-rays were randomly divided into two groups: MSCs group, infused MSCs labeled with cm-DiI and bone marrow monocytes of CB6F1 mice; Control group, only infused bone marrow monocytes; normal group, mice were infused cm-DiI marked MSCs without irradiation. The distribution of MSCs and the serous densities of Il-2, Il-10 and TNF-α in the recipients were observed after transplantation. Results MSCs collected in the bone marrow and the intes-tine in normal group at 15 d,in MSCs group MSCs enriched the different organs at 3,15 and 30 d. MSCs regulated down the secretion of IL-2 and TNF-α,and up the IL-10 density. Conclusions MSCs protected mice from multiple organ failure through above effects and may be open a new treatment strategy on acute radiation syndrome by stem cells.
3.Effects of granulocyte colony-stimulating factor on central and peripheral lymphocyte subset reconstitution after sublethal irradiation in mice
Hongxia ZHAO ; Mei GUO ; Kaixun HU ; Huisheng AI
Chinese Journal of Radiological Medicine and Protection 2011;31(3):303-307
Objective To investigate the effects of recombinant human granulocyte colonystimulating factor(G-CSF) on central and peripheral lymphocyte subset reconstitution after a sublethal dose of irradiation. Methods Sixty female BALB/c mice were given a 6.0 Gy γ-ray total body irradiation (TBI) and randomly divided into 2 equal groups. The mice in G-CSF + TBI group were injected subcutaneously with recombinant human G-CSF 100 μg·kg-1·d-1 for 14 d and the mice in TBI group were injected subcutaneously with the same volume of phosphate buffered solution (PBS) once daily for 14 d. 7,14,21, and 28 d later the mice were killed and their thymus were taken out to prepare of the mononuclear cell suspension to analysis the percentage of thymic CD4 + CD8 + double positive, CD4 +CD8 - single positive, CD4 - CD8 + single positive and CD4 - CD8 - double negtive cells by flow cytometry. Peripheral blood samples were collected from the caudal vein twice a week, and the white blood cell(WBC) counts and absolute number of lymphocytes were assessed by automatic hemocyte analyzer. 14,28, and 60 d later blood samples were collected from angular vein to examine the peripheral lymphocyte subsets by flow cytometry. Cell counting kit-8 was used to detect lipopolysaccharide (LPS) or concanavalin A (ConA) stimulated splenic lymphocyte proliferation. Results The percentage of thymic CD4 + CD8 +double positive cells decreased 7 d after irradiation, rebounded at 14 d, decreased again at 21 d, and then got a permanent recovery. 28 d after irradiation the percentage of thymic CD4 + CD8 + double positive cells in the G-CSF + TBI group recovered to normal and was significantly higher than that of the TBI group (t =12. 22, P < 0. 05). 21d after irradiation the percentage of thymic CD4-CD8 + single positive cells of the G-CSF + TBI group was significantly higher than that of the TBI group (t = 3.77, P < 0. 05). The peripheral WBCs and lymphocytes decreased to the lowest levels 7 d after irradiation and then gradually increased, however, WBCs and lymphoeytes of the G-CSF + TBI group began to recover earlier and faster than the TBI group. The proportion of CD3 + CD8 + T cells of the G-CSF + TBI group was significantly higher than that of the TBI group 14 and 60 d after irradiation (t =4. 31,5.78, P <0.05). But there was no significant difference in the proportion of CD3 + CD4 + T cells between the two groups. The proportion of B lymphoeytes of the G-CSF + TBI group was significantly lower than that of the TBI group 14 d after irradiation(t =7.30, P <0.05), but it recovered quickly, and there were no significant differences in the proportion of B lymphoeytes between the two groups 28 and 60 d after irradiation. The proliferation indexes of splenic lymphocytes in response to LPS and ConA in the G-CSF + TBI group were 4. 37 and 2.98 times higher than those in the TBI group 14 d after irradiation. Conclusions G-CSF could accelerate the recovery of central and peripheral lymphocyte subsets, raise the absolute number of lymphocytes, and enhance their proliferative function, which contributes to the central and peripheral immune reconstitution after acute irradiation.
4.Experimental study of MSCs promoting haploid hematopoietic stem cell transplantation in treatment for mice with acute radiation syrndrome
Kaixun HU ; Shifu ZHAO ; Mei GUO ; Huisheng AI
Chinese Journal of Radiological Medicine and Protection 2008;28(2):135-138
Objective To investigate the mechanism of mesenchymal stem cells in enhancing the effects of haploid matched bone marrow cells transplantation in mice with acute radiation syndrome(ARS).Methods The survival of mice infused with difierent levels of MSCs and bone marrow cells after 8 Gy TBl were examined.BALB/c female mice irradiated with 8 Gy of 60Co γ-rays were randomly divided into two groups,MSCs group,infused with MSCs of female CB6F1 mice labeled with cm-DiI and bone marrow monocytes of male CB6F1,Control group,only infused with bone marrow monocytes.Peripheral blood counts,T-lymphocyte subpopulation of peripheral blood cells,the sry-gene chimerism of bone marrow of the receiptors,the distribution of MSCs in the receiptors,the occurrence time of cGVHD,pathologic variety of medulla were observed.Resuits MSCs improved the survival of mice after 8 TBI,but 1.5×108/kg of MSCs increased the mortality of irradiated mice.In comparison with the control group,leukocytes and plastocytes recovered rapidly in MSCs group.Megacaryocytes in sternum marrows grew fastly in MSC group.The percent of CD3 and CD4 positive cells in the MSCs group were hisher than those in control post-transplantation.The sry-gene chimerism of bone marrow of the receiptors was higher in the MSCs group than that in the control at 30 d.The MSCs were distributed in intestine,thymus,bone marrow,liver,heart of the receiptors at 30 d.The cGVHD occurrence was 30 d later in MSCs group than that of the control.Conclusions MSCs could improve stem cell engraftment,enhance T-lymphocyte and plastocytes recevery,delay occurrence of cGVHD,repair injured organs and increase survivals.It is indicated that MSCs can enhance the treatment effects of haploid hematopoietic stem cells transplant for ARS.
5.Effect of granulocyte colony-stimulating factor on murine thymic emigration and subsets reconstitution after a sublethal dose of irradiation
Hongxia ZHAO ; Mei GUO ; Xuedong SUN ; Huisheng AI
Chinese Journal of Radiological Medicine and Protection 2011;31(6):657-662
Objective To investigate the effects of recombinant human granulocyte colonystimulating factor(G-CSF) on murine thymic emigration and subsets reconstitution after a sublethal dose of irradiaton.Methods Female BALB/c mice were irradiated with a 6.0 Gy of γ-ray total-body irradiation and then randomly divided into GCSF group and control group.For mice in the GCSF group,recombinant human G-CSF 100 μg · kg-1 · d-1 was injected subcutaneously once daily for 14 continuous days and mice in the control group were given the same volume of phosphate buffered solution (PBS).At 7,14,21 and 28 days later,mice were killed and thymus mononuclear cell suspension were analyzed by flow cytometry for the percentage of the four stages of thymic CD4 -CD8 - double negative cells (DN1-4) and the CD4 + CD8 + double positive ( CD4 + CD8 + DP),CD4 + CD8 - single positive ( CD4 + SP),CD4 -CD8 + single positive cells (CD8 + SP).Real-time PCR was used for detection and quantitation of murine T cell receptor rearrangement excision circles(sjTRECs) of the thymic cells of 30 and 60 d after irradiation.Results The percentage of thymic DN1 cells in GCSF group was significantly higher than that of the control group 7 d after irradiation (t =9.59,P < 0.05 ).21 d later,the proportion of thymic DN3 and DN4 cells were higher than those of the control group ( t =16.37,7.6,P < 0.05 ).The percentage of thymic CD4 + CD8 + DP cells decreased 7 d after irradiation,increased at 14 d,decreased again at 21 days,and then got a permanent recover.The percentage of thymic CD4 + CD8 + DP cells in the GCSF group recovered to normal and was significantly higher than that of the control group 28 days after irradiation (t =12.22,P< 0.05).The percentage of thymic CD8 + SP cells of the GCSF group was significantly higher than that of the control group 21 d after irradiation ( t =3.77,P < 0.05 ),while G-CSF had no obvious influence on the percentage of the thymic CD4 + SP cells.The sjTRECs copies in the GCSF group was significantly higher than that of the control group 30 d after irradiation ( t =5.95,P < 0.01 ),which disappeared 60 d later.Conclusions G-CSF could promote the proliferation and differentiation of thymic DN and DP cells,enhance the recent thymic emigrants and accelerate central immunologic reconstitution after acute irradiation.
6.Biological dose estimation by cytokinesis-block micronuclei assay for victims in Taiyuan radiation accident
Bo YAO ; Yufang LI ; Yan TAN ; Guangxian LIU ; Mei GUO ; Benrong HANG ; Huisheng AI
Chinese Journal of Radiological Medicine and Protection 2011;31(2):185-189
Objective To investigate the value of cytokinesis-block micronuclei(CBMN)assay in estimation of the biological doses of the victims of radiation accident.Methods Samples of peripheral blood were collected from the 5 victims(Subjects 1-5)at 16 h after the radiation accident of Taiyuan,Shanxi Province.And the peripheral blood samples and bone marrow sample were collected from the victim No.1 at 23 and 24 h after the radiation.Eight days after the accident Subject 1 underwent allogeneic peripheral blood hematopoietic stem cell transplantation.At difierent time points in the period of 1 year after the accident.peripheral blood samples were collected from these 5 victims.CBMN assay was conducted on the peripheral blood lymphocytes on the samples,and the biological doses were estimated based on the micronuclei(MN)frequencies.The nuclear division index(NDI)obtained from in vitro irradiation experiment using high dose of 60Coγ-rays was used to estimate the exposed doses for Subject 1. Dynamic arialysis of the MN frequency for the 5 victims was performed in the period of 1 year after the accident.Results The MN frequency of Subject 1 surpassed the value corresponding to the upper limit of the MN dose.effective curve.The dose range estimated bv the combination of the CBMN and NDI (CBMN+NDl)assay was 10-20 Gy for Subject 1.The doses estimated by MN frequency for Subjects 2,3,4,and 5 were 3.6,2.9,2.3,and 2.9 Gy,respectively.The estimated doses were in accordance with those estimated by physicat method.chromosome aberration analysis.and clinical symptoms.Prominent decrease of the MN frequency was observed at 26 d after the accident(18 d after the transplantation)for Subject 1(u=3.295,P<0.05).Gradual decrease of MN frequency was observed after the accident for Subjects 2,3,4,and 5.The MN frequencies 1 month after the accident of Subjects 3,4,and 5 were all significantly lower than those 16 h later(u=6.874,4.526,and 7.811,P<0.05).Conclusions Quick and accurate.CBMN assay reinforces and verifies the result of chromosome aberration analysis.The new index CBMN+NDI assay is of reference valne for estimating higher dose of irradiation.
7.Bone marrow mesenchymal stem cells transplantation for the treatment of sclerodermatous chronic graft-versus-host disease: Immunologic mechanism changes in 4 cases
Hong ZHOU ; Mei GUO ; Qiyun SUN ; Shan HUANG ; Zhuo YANG ; Chunjing BIAN ; Yang ZENG ; Huisheng AI ; Chunhua ZHAO
Chinese Journal of Tissue Engineering Research 2010;14(10):1885-1891
BACKGROUND:The immunomodulatory ability of bone marrow mesenchymal stem cells(BMSCs)gives it a promising future in treating graft-versus-host disease(GVHD),especially with previous success in treating patients with acute GVHD.However,there are fewer reports concerning BMSCs in treating chronic GVHD,particularly for sclerodermatous chronic graft-versus-host disease(ScGVHD).OBJECTIVE:To evaluate the efficacy and safety of treatment of BMSCs for ScGVHD,and to primarily explore the immunological mechanism of clinical efficacy.METHODS:Four ScGVHD patients at the Affiliated Hospital of Academy of Military Medicine Science,between September 2006 and August 2008,were enrolled for this trial.The median patient age was 41 years,1 female and 3 male.The patients received BMSCs infusion at a dose of(1.0~2.0)×10~7 cells every time by intrabone marrow injection from the anterosuperior iliac spine and BMSCs from the same donor for the same patient were infused more than once.Concomitant medications for ScGVHD were individualized for each patient,but all were current standard medicines and the doses were significantly tapered.RESULTS AND CONCLUTION:After BMSCs infusion,the ratio of Th1 to Th2 was dramatically overturned,with an increase of Th1 and a decrease of Th2 reaching at a new balance.Correspondingly,symptoms of all the four patients gradually improved.During the course of BMSCs treatment,the life signs and laboratory results from the recipients remained normal.By the time of this report,there has been no recurrence of leukemia in the four patients.Although this study alone cannot guarantee the application of BMSCs in ScGVHD,the results are strongly in favor of the idea that the BMSCs treatment for ScGVHD patients is therapeutically practical without any detectable side effects,which may provide a new insight into the matter of treating ScGVHD clinically,thus will greatly increase the survival rate of leukemia after allogeneic bone marrow transplantation.
8.Mismatched donor cell infusion-related syndrome following microtransplant in patients with acute myeloid leukemia.
Bo CAI ; Xiaoyan ZOU ; Xin NING ; Tieqiang LIU ; Bingxia LI ; Yaqing LEI ; Jianhui QIAO ; Kaixun HU ; Yangyang LEI ; Zhiqing LIU ; Bo YAO ; Huisheng AI ; Yi WANG ; Changlin YU ; Mei GUO
Chinese Medical Journal 2023;136(7):815-821
BACKGROUND:
Immunotherapies such as adoptive immune cell infusion and immune-modulating agents are widely used for cancer treatment, and the concomitant symptoms, including cytokine release syndrome (CRS) or immune-related adverse events (irAEs), are frequently reported. However, clinical manifestations induced by mismatched donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell (GPBMC) infusion in patients receiving microtransplant (MST) have not yet been well depicted.
METHODS:
We analyzed 88 cycles of mismatched GPBMC infusion in patients with acute myeloid leukemia receiving MST and 54 cycles of chemotherapy without GPBMC infusion as a comparison. Clinical symptoms and their correlation with clinical features, laboratory findings, and clinical response were explored.
RESULTS:
Fever (58.0% [51/88]) and chills (43.2% [38/88]) were the significant early-onset symptoms after GPBMC infusion. Patients possessing less human leukocyte antigen-matching loci with the donor or those with unrelated donors experienced more chills (3 [2-5] loci vs. 5 [3-5] loci, P = 0.043 and 66.7% [12/18] vs. 37.1% [26/70], P = 0.024). On the other hand, those with decreased CD4 + /CD8 + T-cell ratio developed more fever (0.8 [0.7-1.2] vs. 1.4 [1.1-2.2], P = 0.007). Multivariable analysis demonstrated that younger patients experienced more fever (odds ratio [OR] = 0.963, 95% confidence interval [CI]: 0.932-0.995, P = 0.022), while patients with younger donors experienced more chills (OR = 0.915, 95% CI: 0.859-0.975, P = 0.006). Elevated ultra-sensitive C-reactive protein levels in the absence of cytokine storm were observed following GPBMC infusion, which indicated mild and transient inflammatory response. Although no predictive value of infusion-related syndrome to leukemia burden change was found, the proportion of host pre-treatment activated T cells was positively correlated with leukemia control.
CONCLUSIONS
Mismatched GPBMC infusion in MST induced unique infusion-related symptoms and laboratory changes, which were associated with donor- or recipient-derived risk factors, with less safety and tolerance concerns than reported CRS or irAEs.
Humans
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Leukocytes, Mononuclear
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Hematopoietic Stem Cell Transplantation/adverse effects*
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Leukemia, Myeloid, Acute/therapy*
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Unrelated Donors
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Granulocyte Colony-Stimulating Factor
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Graft vs Host Disease