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<p><b>OBJECTIVE</b>To identify the characteristics of Chinese obesogenic environments at a provincial level, infer a spatial distribution map of obesity prevalence in 31 provinces, and provide a foundation for development of policy to reduce obesity in children and adolescents.</p><p><b>METHODS</b>After scanning obesity data on subjects aged 7-17 years from 12 provinces in the China Health and Nutrition Survey 2011 and environmental data on 31 provinces from the China Statistical Yearbook 2011 and other sources, we selected 12 predictors. We used the 12 surveyed provinces as a training sample to fit an analytical model with partial least squares regression and prioritized the 12 predictors using variable importance in projection. We also fitted a predictive model with Bayesian analysis.</p><p><b>RESULTS</b>We identified characteristics of obesogenic environments. We fitted the predictive model with a deviance information criterion of 61.96 and with statistically significant (P < 0.05) parameter estimates of intercept [95% confidence interval (CI): 329.10, 963.11], log(oil) (CI: 13.11, 20.30), log(GDP) (CI: 3.05, 6.93), log(media) (CI: -234.95, -89.61), and log(washing-machine) (CI: 0.92, 5.07). The total inferred average obesity prevalence among those aged 7-17 was 9.69% in 31 Chinese provinces in 2011. We also found obvious clustering in occurrences of obesity in northern and eastern provinces in the predicted map.</p><p><b>CONCLUSION</b>Given complexity of obesity in children and adolescents, concerted efforts are needed to reduce consumption of edible oils, increase consumption of vegetables, and strengthen nutrition, health, and physical activity education in Chinese schools. The northern and eastern regions are the key areas requiring intervention.</p>
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Objective To design and synthesize novel G protein-coupled lysophosphatidic acid 2(LPA2)receptor agonists with anti-radiation activity. Methods Nine new LPA2 receptor agonists(Ⅰ2-Ⅰ5 andⅡ1-Ⅱ5)were designed and synthesized using DBIBB as the lead compound. The anti-radiation activity was assayed by the MTS method using the human umbilical vein endothelial cells(HUVEC)irradiated with 8.0 Gy 60Coγray. Results and Conclusion Nine target compounds notreported in the literature were synthesized and their structures were confirmed by 1H NMR and MS. The results showed thatⅠ4 andⅡ1 have obvious anti-radiation ac-tivity,indicating that this kind of compounds is worth further studying.
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<p><b>BACKGROUND</b>Drug susceptibility assay is very important in tuberculosis therapy. Pyrazinamide is a first line antituberculosis drug and diagnosis of its resistance in Mycobacterium tuberculosis (M. tuberculosis) is difficult and time consuming by conventional methods. In this study, we aimed to evaluate the performance of the microscopic observation drug susceptibility (MODS) assay in the detection of pyrazinamide resistance in M. tuberculosis relative to the conventional Wayne assay and Lowenstein-Jensen (LJ) proportion method.</p><p><b>METHODS</b>M. tuberculosis clinical isolates (n = 132) were tested by the MODS and the Wayne assay: the results were compared with those obtained by the LJ proportion method. Mutations in the gene were identified by direct sequencing of the pncA genes of all isolates in which pyrazinamide resistance was detected by any of the three methods.</p><p><b>RESULTS</b>Compared to the LJ results, the sensitivity and specificity of the MODS assay were 97.8% and 96.5% respectively; the sensitivity and specificity of the Wayne assay were 87.0% and 97.7% respectively. Mutations in the pncA gene were found in 41 of 46 strains that were pyrazinamide resistant (3 tests), in 1 of the 4 strains (LJ only), in 42 of 48 strains (at least 1 test), but no mutations in 1 strain sensitive according to the MODS assay only. The MODS assay, Wayne assay and LJ proportion method provided results in a median time of 6, 7 and 26 days respectively.</p><p><b>CONCLUSIONS</b>MODS assay offers a rapid, simple and reliable method for the detection of pyrazinamide resistance in M. tuberculosis and is an optimal alternative method in resource limited countries.</p>
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Antituberculosos , Farmacologia , Testes de Sensibilidade Microbiana , Microscopia , Métodos , Mycobacterium tuberculosis , Pirazinamida , FarmacologiaRESUMO
<p><b>OBJECTIVE</b>To construct a plasmid carrying granulysin (GLS) and to study the effect of the GLS on apoptosis, mitochondrial transmembrane potential and cytochrome C release of SMMC-7721 cells.</p><p><b>METHODS</b>The coding sequence of the GLS was amplified from the total RNA of human CTL cells, and it was inserted into pBudCE4.1 plasmid and then it was used to transfect SMMC-7721 cells. The expression of GLS was detected by RT-PCR and confirmed by immunocytochemistry method. Cell apoptosis was ascertained by Hoechst staining and electron microscopy; mitochondrial transmembrane potential was detected using Mitocapture and cytochrome C release was studied using Western blot.</p><p><b>RESULTS</b>Recombinant pBudCE4.1/GLS plasmid was successfully constructed. GLS protein was successfully expressed in the SMMC-7721 cells and it induced apoptosis of the SMMC-7721 cells, and at the same time, mitochondrial transmembrane potential was reduced and cytochrome C was released from mitochondria into the cytosol.</p><p><b>CONCLUSIONS</b>GLS gene carried by recombinant plasmid could express in SMMC-7721 cells and induce cells apoptosis. The change of mitochondrial transmembrane potential and the release of cytochrome C might be one of the key factors of apoptosis induced by GLS.</p>
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Humanos , Antígenos de Diferenciação de Linfócitos T , Farmacologia , Apoptose , Linhagem Celular Tumoral , Citocromos c , Metabolismo , Potencial da Membrana Mitocondrial , Mitocôndrias , Metabolismo , FisiologiaRESUMO
<p><b>BACKGROUND</b>Isocitrate lyase (ICL) was previously demonstrated to play a pivotal role in the intracellular metabolism of Mycobacterium tuberculosis (MTB). Presently several lines of evidence suggest that ICL from MTB (MTB-ICL) may play some roles in the interaction between MTB and host macrophage. However, there has been no research on the interaction between MTB-ICL and host macrophage.</p><p><b>METHODS</b>MTB-icl and M. smegmatis (MS)-icl genes were amplified by polymerase chain reaction (PCR) and cloned into the E. coli-mycobacterium shuttle plasmid pUV15 to obtain recombinant shuttle plasmids pMTB-icl and pMS-icl. Following transformation into MS by electroporation, the expression of pMTB-icl and pMS-icl was verified by reverse transcriptase (RT)-PCR. The expression of recombinant plasmids derived from pUV15 when rMS was phagocytized by macrophage was also verified via fluorescence microscope. Ms 1 - 2c, rMS-pUV15, rMS-pMS-icl and rMS-pMTB-icl were used to infect RAW264.7 cells and the survival of intracellular MS was monitored by bacterial culture at 0, 24 and 48 hours after infection. The culture supernatants from macrophage infected by Ms 1 - 2c, rMS-pUV15, rMS-pMS-icl and rMS-pMTB-icl were collected and the interferon (IFN)-gamma and nitric oxide (NO) concentrations were measured by ELISA or by Griess assay, respectively. The apoptosis of macrophage was assayed by the in situ TUNEL technique.</p><p><b>RESULTS</b>RT-PCR showed that both pMTB-icl and pMS-icl could be expressed in MS. Fluorescence microscopic observation showed that recombinant plasmids derived from pUV15 (pUV15-IG) could also be expressed in MS when MS were phagocytized by macrophage. Bacterial culture data demonstrated that rMS-pMTB-icl exhibited significantly increased intracellular survival in the murine macrophage cell line RAW264.7 compared with Ms 1 - 2c, rMS-pUV15 and rMS-pMS-icl. This increased intracellular survival was not accompanied by the upregulation of IFN-gamma and NO in host macrophage. But a lower apoptosis rate of macrophages infected with rMS-pMTB-icl was observed when compared with macrophages infected with other strains of MS.</p><p><b>CONCLUSIONS</b>MTB-ICL could promote the intracellular survival of MS. Suppressing the apoptosis of host macrophage may be one of the important mechanisms involved in this increased intracellular survival.</p>
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Animais , Apoptose , Genética , Fisiologia , Linhagem Celular , Marcação In Situ das Extremidades Cortadas , Interferon gama , Metabolismo , Isocitrato Liase , Genética , Metabolismo , Macrófagos , Biologia Celular , Metabolismo , Microbiologia , Viabilidade Microbiana , Microscopia de Fluorescência , Mycobacterium smegmatis , Genética , Mycobacterium tuberculosis , Genética , Óxido Nítrico , Metabolismo , Plasmídeos , Genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transformação GenéticaRESUMO
<p><b>BACKGROUND</b>The FIP1L1-PDGFRalpha fusion gene plays an important role in the pathogenesis of chronic eosinophilic leukemia (CEL) and is a direct therapeutic target of the tyrosine kinase inhibitor imatinib mesylate.</p><p><b>METHODS</b>In 24 hypereosinophilic syndromes (HES) patients, using reverse transcriptase-polymerase chain reaction (RT-PCR), nested PCR and sequence analysis, we investigated the frequency of FIP1L1-PDGFRalpha and other abnormalities of tyrosine kinase family genes like PDGFRalpha, PDGFRbeta, C-KIT, FGFR1, ABL and FLT3 as well as gene mutation "hotspots", like MPL515 and JAK2V617F, frequently involved in myeloproliferative diseases. Fluorescence in situ hybridization was used to confirm the 4q12 deletion.</p><p><b>RESULTS</b>The FIP1L1-PDGFRalpha fusion transcript was found in 8 (33%) of 24 patients with HES, corresponding to the chromosome 4q12 deletion identified by FISH. The FIP1L1-PDGFRalpha-associated patients diagnosed with CEL, frequently had hepatosplenomegaly, eosinophil-related tissue damage, anemia, thrombocytopenia, myelofibrosis and a short overall survival time. Nevertheless, imatinib mesylate induced rapid and complete hematological responses in treated FIP1L1-PDGFRalpha cases, followed by molecular remission and reversal of myelofibrosis. FIP1L1-PDGFRalpha fusion could co-exist with other mutations of tyrosine kinase family genes, like FLT3 or PDGFRbeta. We also demonstrated that the SNPs of PDGFRbeta were associated with selective splicing of exon 19 in case 20.</p><p><b>CONCLUSIONS</b>Correlating the CEL genotype with phenotype, FIP1L1-PDGFRalpha emerges as a relatively homogeneous clinicobiological entity that co-exists with other abnormalities of tyrosine kinase family genes. It reflects the disease progression and there is a good response to imatinib. Detection of the FIP1L1-PDGFRalpha fusion gene is valid for both CEL diagnosis and therapy surveillance.</p>
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Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antineoplásicos , Usos Terapêuticos , Benzamidas , Doença Crônica , Progressão da Doença , Genótipo , Síndrome Hipereosinofílica , Tratamento Farmacológico , Genética , Patologia , Mesilato de Imatinib , Hibridização In Situ , Mutação , Proteínas Oncogênicas v-abl , Genética , Proteínas de Fusão Oncogênica , Genética , Fenótipo , Piperazinas , Usos Terapêuticos , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-kit , Genética , Pirimidinas , Usos Terapêuticos , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas , Genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tirosina Quinase 3 Semelhante a fms , Genética , Fatores de Poliadenilação e Clivagem de mRNA , GenéticaRESUMO
<p><b>OBJECTIVE</b>To review recent developments in therapeutic DNA vaccines against tuberculosis.</p><p><b>DATA SOURCES</b>The data used in this review were obtained mainly from the studies of therapeutic DNA vaccines against tuberculosis reported from 2000 to 2006.</p><p><b>STUDY SELECTION</b>Relevant articles about studies of therapeutic DNA vaccines against tuberculosis were selected.</p><p><b>DATA EXTRACTION</b>Data were mainly extracted from the 32 articles listed in the reference section of this review.</p><p><b>RESULTS</b>Some DNA vaccines which previously showed to induce protective immunity against infection by Mycobacterium tuberculosis in a prophylactic manner are also surprisingly effective when used therapeutically, including persistent Mycobacterium tuberculosis and multidrug-resistant tuberculosis which are refractory to immune system and antibacterial chemotherapy alone. When used in combination with antibacterial drugs, therapeutic DNA vaccines could effectively eliminate residual bacteria in infected animals and shorten the therapy course of conventional chemotherapy. Detailed studies demonstrated that therapeutic effects of DNA vaccines may at least partly be due to the restoration of the Th(1)/Th(2) balance. Some problems have also emerged along with these exciting results.</p><p><b>CONCLUSIONS</b>Therapeutic DNA vaccine is a promising strategy against tuberculosis, however developing an ideal DNA vaccine for therapy of tuberculosis will require further development.</p>
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Humanos , Tuberculose , Terapêutica , Vacinas contra a Tuberculose , Usos Terapêuticos , Vacinas de DNA , Usos TerapêuticosRESUMO
<p><b>OBJECTIVE</b>To study the feasibility of magnetron sputtering Cr-Ti-Al-N complex coating as an interlayer on titanium to enhance the titanium-ceramic binding strength.</p><p><b>METHODS</b>With a three-point bending test according to ISO 9693, the binding strength of Duceratin (Degussa) to titanium substrate prepared with 4 different surface treatments (polishing, polishing and megnetron sputtering Cr, Ti, Al, and N complex coating, sandblasting, sandblasting and coating) was evaluated. Ti/porcelain interface and fractured Ti surface were examined using scanning electron microscopy with energy-dispersive spectrometry (EDS).</p><p><b>RESULTS</b>The binding strength of polished and coated titanium/Duceratin was significantly higher than polished titanium group (P<0.05). The binding strength of sandblasted and coated titanium/Duceratin did not differ significantly from that of sandblasted titanium group (P>0.05), and the strength in the two sandblasted titanium groups was significantly higher than that in polished and coated titanium group (P<0.05).</p><p><b>CONCLUSION</b>Megnetron sputtering Cr-Ti-Al-N complex on polished titanium can increase the titanium/porcelain binding strength. Megnetron sputtering coating is a promising Ti/porcelain interlayer.</p>