Drug resistance and relapse are two major causes for treatment failure of leukemia, but their mechanisms remain elusive. Recently, increasing evidence shows that there is a subset of leukemia stem cells apart from immature leukemia cells in leukemia patients. These malignant stem cells do not response to routine chemotherapeutic agents, and may be the source of drug resistance and relapse of leukemia. Permanent cure of leukemia need elimination of these leukemia stem cells. We describe molecular characteristics of leukemia stem cells and possible target therapeutic strategies in this review.

AIM: To explore the effect of berbamine(BER) on apoptosis in K562 cells and its possible molecular mechanisms. METHODS: The apoptosis rate was measured by flow cytometry while electron microscopy and DNA electrophoresis were used to evaluate the characteristic changes of apoptosis, RT-PCR and Western blot were used to examine the expression levels of apoptosis related gene bcr/abl and BCR/ABL protein. RESULTS: By FCM, the apoptosis rate of K562 cells treated with 8.0 mg/L BER for 24 h and 72 h increased from (29.20?3.82)% to (61.77?4.35)% (P

AIM: To study whether caspase-3,8 is activated during azurin-induced apoptosis in U2OS cells. METHODS: AnnexinV /PI method was used to detect apoptosis. The changes of procaspase-3 were analyzed by Western blot, the changes of caspase-3 mRNA were detected by semi-quantitative RT-PCR, and caspase-3 relative activity was determined by colorimetric assay. RESULTS: After U2OS cells were treated with 0, 25, 50, 100, 200, 500 mg/L azurin for 24 h, respectively, the level of procaspase-3 protein decreased and the level of caspase-3 mRNA increased as azurin concentration increased. When the cells were treated with 100 mg/L azurin for 6, 12, 24, 48 h , respectively, the caspase-3 activity began to rise from 6 h,reached the peak at 24 h,and was still higher than the control group at 48 h ( P

Non-coding RNAs ( ncRNA ), including ribosomal RNA( rRNA), transfer RNA( tRNA), MicroRNA ( miRNA), long noncoding RNA(lncRNA) and small nucleolar RNA(snoR-NA), are a class of RNA that have multiple functions and are not translated to proteins. MicroRNA and lncRNA are involved in the injury, remodeling and aging of blood vessels, and it is necessary to understand the regulatory roles of MicroRNA and lncRNA in these processes. It is reported that MicroRNA and lncRNA are not only participated in the regulation of oxidative response, inflammation, cell proliferation and migration, and phenotype transition, they are also involved in the regulation of gene expression by conducting different mechanisms, including transcriptional regulation, post-transcriptional modification and chromatin remodeling. These aspects of regulation by MicroRNA and lncRNA are related to cardiovascular diseases, such as ath-erosclerosis, hypertension, myocardial infarction, stroke, pul-monary hypertension and diabetes, and thus provide a new way for genetic diagnosis and therapy of cardiovascular diseases.

OBJECTIVE To explore the characteristic of nosocomial infection and formulate the effective measures of nosocomial infection management. METHODS According to the underlying disease condition and method ICD10,the infection data were to classifed and colleced which including of 160 795 cases during 2003-2006.Then the prospective and retrospective investigation were done for studying the nosocomial infection condition. RESULTS The nosocomial infection rate was 4.69%. The highest infection rate was caused by hematological disease (15.43%). By site of infection the upper respiratory infection rate was 35.34%,the lower respiratory infection rate was 28.22%,the gastrointestinal infection rate was 6.82%,and the intra-abdominal infection was 3.75%. In these infection cases,G-bacteria infection occupied 58.35% (which ranked No.1 in all pathogens),and the fungal infection occupied 17.09%. CONCLUSIONS In order to reduce the infection rate,we must enhance the work of preventing the key diseases,standard the measures of disinfection and isolation,increaseing the quarantine inspection rate and applying antibiotic according to the results of antifugal susceptibility testing.

AIM: To determine the role of Fas antigen and caspase-8 in modulating apoptosis of osteosarcoma cells induced by bacterial redox protein azurin. METHODS: The human osteosarcoma cell line U2OS was treated with bacterial redox protein azurin (150 mg/L) for 6, 12, 24 and 48 h, respectively. Cell immunohistochemistry and quantitative image pattern analysis were applied for detecting the expression of Fas antigen. Caspase-8 activity was detected using caspase-8 fluorescent assay kit. The apoptotic rate was measured by FCM. RESULTS: Compared with the control group, the expression of Fas antigen and activity of caspase-8 significantly increased in U2OS cells treated with 150 mg/L azurin (P

Objective To evaluate clinical efficacy and safety of loratadine combined with desloratadine in the treatment of chronic spontaneous urticaria(CSU)in children. Methods A total of 177 children with CSU were enrolled into this study, and randomly and equally divided into 3 groups:combination group treated with an age?based dose of desloratadine tablet every morning and a weight?based dose of loratadine tablet before sleep every night for consecutive 28 days, loratadine group treated with a half tablet of placebo(starch tablet)every morning and oral loratadine tablet before sleep every night for consecutive 28 days, and desloratadine group treated with a half tablet of placebo (starch tablet) every morning and oral desloratadine tablet before sleep every night for 28 consecutive days. Possible adverse reactions were observed and recorded after the start of treatment, and therapeutic effects were evaluated at the end of treatment. Results A total of 166 patients completed the trial, including 55 in the combination group, 56 in the loratadine group and 55 in the desloratadine group. After 28?day treatment, the total response rate was significantly higher in the combination group(90.9%, 50/55)than in the loratadine group (71.4%[40/56],χ2=6.865, P<0.05)and desloratadine group(74.5%[41/55],χ2=5.153, P<0.05). No significant difference in the incidence of adverse reactions was observed among the combination group (10.9%[6/55]), loratadine group (8.9%[5/56]) and desloratadine group (9.1%[5/55], P > 0.05). Conclusion Combination of loratadine and desloratadine was superior to loratadine or desloratadine alone in the treatment of childhood CSU, and there was no significant difference in the incidence of adverse reactions among the 3 treatment groups.

OBJECTIVETo investigate the effects of the γ isoform of Ca(2+)/calmodulin-dependent protein kinase II (CaMKIIγ) on colorectal cancer (CRC) cell growth in vitro and in vivo and explore the mechanisms.

METHODSThe mRNA levels of CaMKIIγ in 5 CRC cell lines, tumor tissues and matched adjacent tissues from 20 CRC patients were examined by semi-quantitative RT-PCR. The lentiviral vector pLenti6.3-MCS-IRES2-eGFP was used to generate the lentivirus particle Lenti-CaMKIIγ for transfecting SW620 cells. The proliferation ability of the transfected SW620-CaMKIIγ cells was assessed by growth curve and colony formation assay. The expression of IKKα, IKKβ, IKKγ, p-IKKα/β, p-IκB andIκB of the transfected cells were determined by Western blotting, and the expression and localization of nuclear factor-κB (NF-κB) p65 were detected by immunofluorescence. In nude mouse models bearing the transfected SW620-CaMKIIγ cell xenograft, the tumor volume was measured twice a week.

RESULTSCaMKIIγ mRNA showed high expressions in the 5 colorectal cancer cell lines. Eighteen of the 20 tumor tissues showed higher expressions of CaMKIIγ than the adjacent non-tumor tissues. The proliferation of transfected SW620-CaMKIIγ cells was enhanced significantly. CaMKIIγ activated NF-κB signaling pathway and led to NF-κB p65 nuclear translocation. In the tumor-bearing mouse model, the volume of the tumors generated by the transfected SW620-CaMKIIγ cells was 1.46- and 1.68-fold higher than that of the tumors with the control cells at the 8th and 12th day, respectively.

CONCLUSIONCaMKIIγ can effectively promote the growth of colorectal cancer cells in vitro and in vivo by activating NF-κB signaling pathway.

Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Colorectal Neoplasms ; metabolism ; pathology ; Humans ; NF-kappa B ; metabolism ; RNA, Messenger ; genetics ; Signal Transduction ; Up-Regulation

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by a chromosome translocation that generates the Bcr-Abl oncogene encoding a constitutive kinase activity. Despite remarkable success in controlling CML at chronic phase by Bcr-Abl tyrosine kinase inhibitors (TKIs), a significant proportion of CML patients treated with TKIs develop drug resistance due to the inability of TKIs to kill leukemia stem cells (LSCs) that are responsible for initiation, drug resistance, and relapse of CML. Therefore, there is an urgent need for more potent and safer therapies against leukemia stem cells for curing CML. A number of LSC-associated targets and corresponding signaling pathways, including CaMKII-γ, a critical molecular switch for co-activating multiple LSC-associated signaling pathways, have been identified over the past decades and various small inhibitors targeting LSC are also under development. Increasing evidence shows that leukemia stem cells are the root of CML and targeting LSC may offer a curable treatment option for CML patients. This review summarizes the molecular biology of LSC and its-associated targets, and the potential clinical application in chronic myeloid leukemia.
Animals ; Chemokines ; metabolism ; Epigenesis, Genetic ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; metabolism ; pathology ; Neoplastic Stem Cells ; metabolism ; pathology ; Transcription Factors ; metabolism ; Tumor Microenvironment

OBJECTIVETo investigate the molecular?mechanisms by which triptolide induces apoptosis of human acute T lymphocytic leukemia Jurkat cells.

METHODSMTT assay was employed to detect the proliferation inhibition of Jurkat cells by triptolide, and the IC50 was calculated by OriginPro8. Flow cytometry was used to analyze apoptosis of Jurkat cells. Np9 mRNA levels were detected by RT-PCR and analyzed quantitatively by Kodak 1D 3.6 software. Correlation between the inhibition of Np9 transcription and the cell apoptosis was analyzed by SPSS 19.0.Western blotting was employed to determine Np9 downstream signaling molecules c-myc, β-catenin, ERK, AKT and Notch1 protein level in Jurkat cells after exposure to different concentrations of triptolide for 48 h.

RESULTSTriptolide treatment resulted in dose-dependent inhibition of Jurkat cells proliferation and its IC50 was 12.7 nmol/L. Triptolide induced apoptosis of Jurkat cells in dose- dependent manner. Furthermore, triptolide inhibited Np9 mRNA transcription level in Jurakt cells in a dose-dependent manner. There was a correlation between the triptolide-mediated the apoptosis and the inhibition of Np9 transcription of Jurkat cells (R(2)=0.907). Western blotting results displayed that triptolide inhibited transcription levels of Np9 mRNA with a concomitant decrease of its downstream signaling molecules c-myc, β-catenin, ERK, AKT and Notch1 at protein levels.

CONCLUSIONInhibition of HERV-K Np9 mRNA and its downstream signaling molecules c-myc, β-catenin, ERK, Akt and Notch1 protein might be one of important molecular?mechanisms by which triptolide induces apoptosis of human acute T lymphocytic leukemia Jurkat cells.

Apoptosis ; drug effects ; Diterpenes ; pharmacology ; Endogenous Retroviruses ; genetics ; Epoxy Compounds ; pharmacology ; Flow Cytometry ; Gene Products, env ; genetics ; Humans ; Jurkat Cells ; drug effects ; Phenanthrenes ; pharmacology ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; pathology ; Transcription, Genetic