RESUMO
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy, which is the most common and severe acute leukemia in adults. Its occurrence, development and prognosis are affected by many factors, and more research is still needed to further guide its treatment. Here, we found that roundabout3 (ROBO3) was associated with poor prognosis in AML through bioinformatics analysis. We then found that overexpression of ROBO3 promoted AML cell proliferation, adhesion and migration while knockdown of ROBO3 had opposite effects. We subsequently found that ROBO3 regulated CD34 expression in AML cells, and this regulatory effect may be achieved through the Hippo-YAP pathway. The inhibitors of this pathway, K-975 and verteporfin, showed an inhibitory effect on AML cells with high ROBO3 expression. ROBO3 was also found to be significantly increased in bone marrow samples from AML patients. Our research indicates that ROBO3 plays an important role in the development of AML, which suggests that ROBO3 can be a prognostic biomarker and potential therapeutic target for AML.
Assuntos
Leucemia Mieloide Aguda , Adulto , Humanos , Regulação para Cima , Leucemia Mieloide Aguda/patologia , Proliferação de Células , Linhagem Celular Tumoral , Apoptose , Receptores de Superfície Celular/metabolismoRESUMO
18Ni(300) maraging steel, which has exceptional strength and toughness, is used in the field of aviation and aerospace. In this paper, using a high-speed tribo-tester, tribological behaviors of 18Ni(300) maraging steel were investigated under high-speed dry sliding conditions. Morphology of the worn surfaces and the debris was analyzed by scanning electron microscope, and the oxides of worn surfaces caused by friction heat were detected by X-ray diffraction. The experiment results reveal that the friction coefficient of frictional pairs declines with increasing load and speed. With the speed and load increasing, oxides of the worn surfaces of 18Ni(300) maraging steel change from FeO to Fe3O4 and the wear mechanism converts from adhesive wear into severe oxidative or extrusion wear.
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OBJECTIVE: To make an epidemiological investigation on echinococcosis in Darlag County, Guoluo Tibetan Autonomous Prefecture of Qinghai Province. METHODS: Local participants were screened for echinococcosis using B ultrasound from August to September in 2007. IHA was carried out to detect antibody in human sera. Indirect ELISA using recombinant-AgB and Em18 antigen was conducted to further diagnose the human alveolar echinococcosis (AE) and cystic echinococcosis (CE) . The prevalence of echinococcosis in wild rodents, yaks, sheep and dogs was examined either by dissection or through slaughterhouses. Adult worms and hydatid cysts were detected by PCR-RFLP to discriminate 3 Echinococcus species and genotype of Eg. Dog feces were tested by double antibody sandwich ELISA method to confirm the coproantigen positive rate. RESULTS: 1723 people were examined by ultrasound and 236 were clinically diagnosed as hydatid diseases with an overall morbidity of 13.7%, of which 5.5% were CE and 8.2% were AE. Prevalence in males and females was 11.6% and 15.6% respectively with a statistically significant difference (chi2=7.0, P< 0.05) . Prevalence in herdsmen and monks/nuns was as high as 23.0% and 13.2%, respectively. Adult worms were found in 5 out of 9 stray dogs by necropsy. 27 of 239 pikas (Ochotona curzoniae) were infected by E. shiquicus (11.3%). CE prevalence in sheep and yaks was 26.4% and 5/16 respectively. The Eg genotype was G1 (sheep strain). CONCLUSION: Three species of Echinococcus, e.g. E. granulosus, E. multilocularis and E. shiquicus are all prevalent in Darlag County. The prevalence of both AE and CE in human population is high in the area. Domestic dogs are the primary definitive host for both E. granulosus and E. multilocularis.
Assuntos
Equinococose Hepática/epidemiologia , Equinococose Hepática/parasitologia , Equinococose Pulmonar/epidemiologia , Equinococose Pulmonar/parasitologia , Adolescente , Adulto , Idoso , Animais , Bovinos/parasitologia , Criança , Pré-Escolar , China/epidemiologia , Cães/parasitologia , Echinococcus/classificação , Echinococcus/isolamento & purificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Roedores/parasitologia , Ovinos/parasitologia , Inquéritos e Questionários , Adulto JovemRESUMO
AIM: To determine whether the use of a mixed polymeric micelle delivery system based on vitamin E succinate (VES)-grafted-chitosan oligosaccharide (CSO)/VES-grafted-chitosan (CS) mixed micelles (VES-g-CSO/VES-g-CS MM) enhances the delivery of C-DMSA, a theranostic fluorescent probe, for Hg2+ detection and detoxification in vitro and in vivo. METHODS: Mixed micelles self-assembled from two polymers, VES-g-CSO and VES-g-CS, were used to load C-DMSA and afforded C-DMSA@VES-g-CSO/VES-g-CS MM for cell and in vivo applications. Fluorescence microscopy was used to assess C-DMSA cellular uptake and Hg2+ detection in L929 cells. C-DMSA@VES-g-CSO/VES-g-CS MM was then administered intravenously. Hg2+ detection was assessed by fluorescence microscopy in terms of bio-distribution while detoxification efficacy in Hg2+-poisoned rat models was evaluated in terms of mercury contents in blood and in liver. RESULTS: The C-DMSA loaded mixed micelles, C-DMSA@VES-g-CSO/VES-g-CS MM, significantly enhanced cellular uptake and detoxification efficacy of C-DMSA in Hg2+ pretreated human L929 cells. Evidence from the reduction of liver coefficient, mercury contents in liver and blood, alanine transaminase and aspartate transaminase activities in Hg2+ poisoned SD rats treated with the mixed micelles strongly supported that the micelles were effective for Hg2+ detoxification in vivo. Furthermore, ex vivo fluorescence imaging experiments also supported enhanced Hg2+ detection in rat liver. CONCLUSION: The mixed polymeric micelle delivery system could significantly enhance cell uptake and efficacy of a theranostic probe for Hg2+ detection and detoxification treatment in vitro and in vivo. Moreover, this nanoparticle drug delivery system could achieve targeted detection and detoxification in liver.