Adolescent ; Adult ; Aged ; Cystitis ; etiology ; prevention & control ; Female ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Hemorrhage ; etiology ; prevention & control ; Humans ; Injections, Intravenous ; Male ; Mesna ; administration & dosage ; therapeutic use ; Middle Aged ; Transplantation Conditioning ; methods ; Young Adult

microRNA (miRNA) are about 22 nucleotide (nt) endogenous small non-coding RNA that play an important role in regulation of gene expression at the post-transcriptional level. miRNA control the expression of genes involved in several biologic processes, including apoptosis, proliferation, differentiation and metabolism of cells. miRNA can also act as oncogenes or antioncogenes. Abnormal expression of miRNA is associated with chronic myelogenous leukemia (CML) and contributes to the pathogenesis, disease progression, and response to therapy of CML. They may also serve as the potential therapy targets in the disease. In this review, the most important findings about the biogenesis pathway and function of miRNA as well as the role of miRNA in the pathogenesis, drug-resistance and therapy of CML are discussed.
Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; MicroRNAs

Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; pathology ; prevention & control ; surgery ; Recurrence ; Transplantation, Homologous

OBJECTIVETo investigate the effect of miRNA-101 on the expression of the enhancer of zeste homolog 2 (EXH2) in human androgen-independent prostated cancer LNCaP cells.

METHODSWe divided LNCaP cells into a blank control, a negative control, and a miRNA-l01 transfection group, constructed the vector by transfecting synthetic miRNA-101 mimics into the LNCaP cells, and evaluated the efficiency of transfection by fluorescence microscopy. Then we determined the expression level of EZH2 mRNA by qRT-PCR in the three groups of cells and that of the EZH2 protein in the negative control and transfection groups by Western blot.

RESULTSGreen fluorescence signals were observed in over 70% of the LNCaP cells in the transfection group after 24 hours of transfection. At 72 hours, the expression of miRNA-101 was significantly upregulated in the transfected cells (P < 0.01), that of EZH2 mRNA was remarkably lower in the transfection group (0.01 ± 0.10) than in the blank control (0.95 ± 0.40) and negative control (0.86 ± 0.30) groups (both P < 0.01), and that of the EZH2 protein was increased in the negative control but decreased in the transfection group with the extension of culture time.

CONCLUSIONmiRNA-101, with its inhibitory effect on the expression of EZH2 in LNCaP cells, is a potential biotherapeutic for prostate cancer.

Androgens ; Cell Line, Tumor ; Enhancer of Zeste Homolog 2 Protein ; Genetic Vectors ; Humans ; Male ; MicroRNAs ; physiology ; Polycomb Repressive Complex 2 ; genetics ; metabolism ; Prostatic Neoplasms ; metabolism ; RNA, Messenger ; metabolism ; Transfection

In order to explore the influence of purified donor regulatory T cells (T(Reg) cells) infused after allogeneic bone marrow transplantation (allo-BMT) on GVHD and hematopoietic reconstitution of mice, an allo-BMT model of C(57)BL/6-->BALB/c mice was established. CD4(+)CD25(+)T(Reg) cells were purified through bead-magnetic activated cells separated from donor mice peripheral blood. The recipient mice were randomly divided into three groups: CD4(+)CD25(+) T cells, CD4(+)CD25(-) T cells and RPMI 1640 culture medium. These cells and RPMI 1640 were infused into recipient mice by caudal veins at about 6 to 8 hours after allo-BMT respectively. Incidence of GVHD, pathological lesion of liver, spleen, small intestine, survival time and hematopoietic reconstitution in the recipients were observed after allo-BMT. The results showed that the time for WBC > 1.0 x 10(9)/L was (8.14 +/- 3.26) days, (17.62 +/- 5.71) days, (19.81 +/- 6.77) days and the time for Plt > 20.0 x 10(9)/L was (5.29 +/- 1.34) days, (8.97 +/- 3.44) days, (9.52 +/- 3.92) days in T(Reg) positive cell group, T(Reg) negative cell group and the blank control group respectively, and the recovery times of WBC and Plt in T(Reg) positive cell group were faster than that in T(Reg) negative cell group and the blank control group (P < 0.05). The scores of GVHD were (1.33 +/- 0.58), (1.80 +/- 0.27), (1.93 +/- 0.45) in three groups of mice at about 15 days after allo-BMT, respectively, the GVHD in T(Reg) positive cell group was slighter than that in T(Reg) negative cell group and the blank control group (P < 0.05). It was found that GVHD pathologic manifestations of the liver, spleen and small intestine in T(Reg) positive cell group were slighter in a certain extent than those in other two groups at about (25 - 30) days after allo-BMT. The mean survival time in three groups was (41.45 +/- 17.88) days, (18.75 +/- 14.39) days and (25.67 +/- 16.84) days after allo-BMT, respectively, which in the T(Reg) positive cell group was significantly longer than that in other two groups (P < 0.05). It is concluded that donor-T(Reg) cell infusion can mitigate the GVHD so as to reach hematopoietic reconstitution and prolong survival time after allo-BMT in mice.
Animals ; Female ; Graft vs Host Disease ; immunology ; prevention & control ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Interleukin-2 Receptor alpha Subunit ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Random Allocation ; T-Lymphocytes, Regulatory ; immunology ; transplantation

Objective To investigate the distribution of water-borne fluoride and the current situation of endemic fluorosis in Yan'an city in 2006, and to evaluate the effect of water defluoridation project by improving driking water quality. Method In 2006 in Yan'an city, 5 samples from water source were collected in each selected village that was chosen according to 5 directions of East, West, South, North, and Central. Meanwhile, 1 sample from water source, 1 sample from water processing factory and 2 tap water samples were collected from each water defluoridation project. Water fluoride was determined by spectrophotometric method, teeth and skeletal fluorosis examination were performed by Dean method and "national criteria of endemic skeletal fluorosis diagnosis of China" in children aged 8-12 year and adults, respectively if water fluoride level > 1.00 mg/L Results Of 726 water samples from 293 villages tested, samples from 25 villages had higher fluoride( > 1.00 mg/L), and these villages covered a population of 11 610 people and most of these people were in Wuqi and Yanchuan counties. Water fluoride ranged from 0.10 mg/L to 3.50 mg/L, with median being 0.59 mg/L. Of 100 water samples from 25 water defluoridation projects, only 1 sample exceeded the national criteria in Yanchuan, and Wuqi counties, respectively,with fluoride level being 1.85 mg/L and 1.60 mg/L, respectively, and population exposed was 3083 and 708, respectively, with water fluoride ranged 0.30 - 2.00 mg/L In the examination of 1281 children aged 8 - 12, we detected 238 cases of dental fluorosis, and the detection rate reached 18.58%; 13 900 adults were checked, and 375 cases were confirmed of skeletal fluorosis, a detection rate reached 2.70%. Conclusions Yan'an has a wide range of water with high fluoride and severe fluorosis people. The water defluoridation projects need to be further improved. The task of prevention of endemic fluorosis is still arduous, and we should speed up the implementation of comprehensive water defluoridation measures.

Objective In this study,we investigated the relationship between oxidative stress,selenoproteins level and onset of Keshan disease (KD) through detecting the expression of 8-hydroxy-2-deoxy guanosine (8-OH-dG),thioredoxin reductase 1 (TrxR1) and glutathione peroxidase 1 (GPx1) in myocardial tissue.Methods Myocardium samples of autopsy patients including 8 cases of KD (KD group included 4 acute KD and 4 chronic KD) and 9 cases of non-KD (control group) were immunohistochemically stained for 8-OH-dG,TrxR1 and GPx1.The staining intensities subsequently quantified by using Olympus Image-Pro Plus 6.0 software.Results The positive rate of 8-OH-dG expression in myocardial nuclei was higher in the case group[(68.6 ± 20.4)％] than that of the control group[(2.4 ± 1.5)％,t =8.515,P ＜ 0.05].In addition,the positive rate of 8-OH-dG expression in acute KD[(91.7 ± 3.7)％] was significantly higher than that of chronic KD[(53.2 ± 7.9)％,t =6.409,P＜0.05].The distribution of TrxR1 and GPx1 was not associated with the distribution of myocardial damage.The expression of these two selenoproteins in KD group (401340 ± 59865,497590 ± 197082) were both lower than that of control group(2790300 ± 379298,1348400 ±615840; t =-28.493,-6.016,respectively,all P＜0.01).Conclusions Oxidative damage is detected in myocardium tissue of KD,and 8-OH-dG expression is associated with the degree of myocardial damage in KD.Selenoproteins,TrxR1 and GPx1,may be closely related to the pathogenesis of KD.

OBJECTIVETo observe the effect of donor CD4+;CD25+; regulatory T cells (TReg) on hematopoietic reconstitution, immune reconstitutuion and graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

METHODSThirty patients were divided into high TReg group (TReg> or =10.0 x 10(6) cells/kg, n=13) and low TReg group (TReg<10.0 x 10(6) cells/kg, n=17) according to the number of TReg in the grafts. Flow cytometry (FCM) was used to detect the TReg percentage in the grafts and recipients peripheral blood T lymphocyte subsets and TReg at different time points after allo-HSCT. The hematopoietic reconstitution, immune reconstitution, TReg reconstitution, incidence of GVHD and disease-free survival were compared between the two groups.

RESULTSThe high and low TReg groups showed similar WBC reconstitution time (+8.62-/+2.29 vs +8.88-/+2.71 days, P=0.778) and platelet reconstitution time (+12.69-/+5.74 vs +15.18-/+6.71 days, P=0.613). In high TReg group, the reconstitutions of CD4+;CD3+; and CD45RO+;CD4+; T cells on day 15 and CD3+; and CD4+;CD3+; T cells on day 30 were significantly accelerated in comparison with those of the low TReg group (with P values of 0.039, 0.024, 0.014, 0.020, respectively). TReg reconstitution 15 and 180 days following the surgery was significantly faster in high TReg group than in low TReg group (P=0.013, 0.005, respectively). The incidence of acute GVHD in high TReg group (61.54%) was obviously lower than that in low TReg group (94.12%, P=0.027). A negative correlation was found between the number of infused donor TReg and the severity of acute GVHD (rs=-0.393, P=0.032). The one-year disease-free survival rates of the high and low TReg groups were (60.40-/+16.10)% and (72.00-/+12.00)%, respectively, showing no significant difference between the two groups (P=0.818).

CONCLUSIONDonor TReg may promote immunological reconstitution and TReg reconstitution, and decrease the incidence of acute GVHD after allo-HSCT.

Blood Donors ; CD4-Positive T-Lymphocytes ; immunology ; Disease-Free Survival ; Graft vs Host Disease ; etiology ; immunology ; Hematopoiesis ; immunology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Interleukin-2 Receptor alpha Subunit ; immunology ; T-Lymphocytes, Regulatory ; immunology