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1.
BMC Oral Health ; 21(1): 467, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556097

RESUMO

BACKGROUND: Dental caries have a serious impact on general health and well-being; however, there is a lack of relevant data on the development trends of dental caries in permanent teeth among 12-year-old children in China. We aim to assess long-term trends of dental caries in permanent teeth among 12-year-old children in China and identify the susceptible subgroups based on five consecutive national surveys from 1995 to 2014. METHODS: A total of 88 972 subjects were extracted from five consecutive national surveys (1995, 2000, 2005, 2010, 2014). Standardized dental examinations were conducted and the oral health status of each subject was recorded. The prevalence of Decayed, Missing and Filled teeth (DMF%), mean Decayed, Missing, Filled teeth score (DMFT) and Caries Filling Ratio (CFR) were used as measurement indicators. Cochran-Armitage trend test was used to evaluate the trends in DMF% and CFR, and multivariate linear regression was used to evaluate the trends in DMFT. RESULTS: A V-shaped fluctuating upward trend in DMF% during 1995-2014 was observed (Z = - 13.124, P < 0.001), and the DMF% in 1995-2014 was 21.1%, 15.9%, 16.2%, 21.9% and 24.3%. The trend in DMFT was approximately consistent with DMF% (ß = 0.057, P < 0.001), but the downward volatility appeared in 2014. The DMFT in 1995-2014 was 0.38, 0.28, 0.31, 0.66 and 0.54. A continuously fluctuant trend in CFR was observed during past two decades (Z = 1.927, P > 0.05), and the CFR in 1995-2014 was 17.4%, 22.8%, 19.3%, 23.4% and 15.6%. The DMF% and DMFT of rural children had a larger absolute increase than that of urban children during 1995-2014 (DMF%-urban: Z = - 0.242, P > 0.05; DMF%-rural: Z = - 19.036, P < 0.001; DMFT-urban: ß = 0.035, P < 0.001, DMFT-rural: ß = 0.077, P < 0.001). The DMF% and DMFT in girls were higher than that in boys at each survey year (P < 0.001). CFR of urban children was higher than that of rural children at each survey year (P < 0.001). CONCLUSIONS: Over the past 20 years, DMFT and DMF% of 12-year-old children in China presented V-shaped fluctuant upward trends, with a decline trend from 1995 to 2000 and an upward trend from 2000 to 2014. CFR had no significant improvement. The rural children and girls are the more vulnerable groups in the development of dental caries and need to pay priority. Our study supports the continuation of policies to improve children' oral health.


Assuntos
Cárie Dentária , Criança , China/epidemiologia , Índice CPO , Cárie Dentária/epidemiologia , Dentição Permanente , Feminino , Humanos , Masculino , Prevalência , População Rural
2.
Circ J ; 84(4): 616-625, 2020 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-32115441

RESUMO

BACKGROUND: Ischemic postconditioning (IPostC) is an endogenous protective mechanism to reduce ischemia-reperfusion (I/R) injury. However, whether IPostC protects aged cardiomyocytes against I/R injury is not fully understood. Considering the protective function of microRNA 30a (miR-30a) against ischemia-induced injury in H9C2 cells, its role in the protective effects of IPostC on I/R injury of aged cardiomyocytes was investigated further.Methods and Results:To mimic I/R and IPostC in vitro, the aged cardiomyocyte model for hypoxia postconditioning (HPostC) treatment was established by 9 days of incubation with 8 mg/mL D-galactose and then followed by exposure to hypoxic environment. HPostC significantly alleviated hypoxia/reoxygenation (H/R) injury and reduced autophagy of aged cardiomyocytes, as evidenced by decreased LC3B-II expression and increased p62 by Western blot. Quantified by quantitative real-time polymerase chain reaction (qRT-PCR), miR-30a was increased in aged cardiomyocytes treated with HPostC compared with I/R injury group. Overexpression of miR-30a by LV3-rno-miR-30a mimic promoted cardioprotective effect of HPostC in aged cardiomyocytes by suppressing BECN1-mediated autophagy, all of which was abrogated by knockdown of miR-30a expression. Epigenetic analyses demonstrated that HPostC reduced DNA methyltransferase 3b-mediated DNA hypomethylation levels at miR-30a promoter, leading to upregulation of miR-30a. CONCLUSIONS: HPostC protected aged cardiomyocytes survival against H/R injury via DNMT3b-dependent activation of miR-30a. miR-30a could be a potential therapeutic target for ischemic myocardial infarction.


Assuntos
Autofagia , Senescência Celular , Metilação de DNA , Epigênese Genética , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Animais , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Hipóxia Celular , Linhagem Celular , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Regiões Promotoras Genéticas , Ratos , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais , DNA Metiltransferase 3B
3.
Beijing Da Xue Xue Bao Yi Xue Ban ; 47(3): 406-9, 2015 Jun 18.
Artigo em Zh | MEDLINE | ID: mdl-26080867

RESUMO

OBJECTIVE: To analyze the association between obesity and age at spermarche among Chinese Han boys aged 11-18 years . METHODS: The height, weight and status of the spermarche of Chinese Han boys aged 11-18 years were selected from the data of 2010 National Physical Fitness and Health Surveillance.The body mass index (BMI), prevalence of spermarche in each age group and ages at spermarche by BMI groups were calculated. Chi square test was used to analyze the differences of prevalences of spermarche among the boys with different BMIs across ages. U-test was used to compare the differences of age at spermarche between the boys who were obese and not. RESULTS: In the boys aged 12 and 17 years in urban areas and boys aged 13 years in rural areas, the differences of prevalences of spermarche among the normal weight, overweight and obesity groups were significant (P<0.05). The age at spermarche in the obesity group (13.90 years) was 0.1 years earlier than that in the non-obesity group (14.00 years) (P<0.05). CONCLUSION: Obesity may make the age at spermarche ahead of time.


Assuntos
Fatores Etários , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Maturidade Sexual , Adolescente , Povo Asiático , Estatura , Índice de Massa Corporal , Peso Corporal , Criança , Humanos , Masculino , Prevalência
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 30(2): 129-33, 2013 Apr.
Artigo em Zh | MEDLINE | ID: mdl-23568719

RESUMO

OBJECTIVE: To evaluate cyto- and molecular genetic characteristics of adult patients with acute lymphoblastic leukemia (ALL) and its prognostic significance. METHODS: Two hundred and seventeen adult patients with ALL were analyzed for cyto- and molecular genetic characteristics with combined conventional cytogenetics, fluorescence in situ hybridization (FISH), real-time quantitative PCR (qPCR) and nested PCR. Significance of genetic findings for prognosis was evaluated. RESULTS: t(9;22)(q34;q11)/BCR-ABL has been the most frequent abnormality found in the cohort (56.3%). And 22.4% of cases with BCR-ABL detected by FISH was negative by cytogenetic analysis. Ratio of patients in high-risk group increased with age; Patients with B-ALL had a higher risk group than the average-risk group (98.40% vs. 65.70%, P=0.000). The overall survival (OS) rates at 3-month (67.30% vs. 85.10%, P=0.042), 6-month (55.1% vs. 80.4%, P=0.008), 12-month (34.0% vs. 59.1%, P=0.017) and 24-month (13.0% vs. 36.6%, P=0.010) were lower in high-risk group than in average-risk group, with medium OS time (11 months, 95% CI 8.0-13.9) being significantly shorter compared with the average-risk group (19 months, 95%CI 10.8-27.1). CONCLUSION: Adult patients with ALL have unique cyto- and molecular genetic characteristics, which has important value for prognosis and guiding treatment. Moreover, combined cytogenetic and molecular genetic techniques can precisely define sub-groups of ALL patients.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(2): 311-318, 2023 Apr.
Artigo em Zh | MEDLINE | ID: mdl-37096499

RESUMO

OBJECTIVE: The leukemia cells from patients with T-cell acute lymphoblastic leukemia (T-ALL) were inoculated into NCG mice to establish a stable human T-ALL leukemia animal model. METHODS: Leukemia cells from bone marrow of newly diagnosed T-ALL patients were isolated, and the leukemia cells were inoculated into NCG mice via tail vein. The proportion of hCD45 positive cells in peripheral blood of the mice was detected regularly by flow cytometry, and the infiltration of leukemia cells in bone marrow, liver, spleen and other organs of the mice was detected by pathology and immunohistochemistry. After the first generation mice model was successfully established, the spleen cells from the first generation mice were inoculated into the second generation mice, and after the second generation mice model was successfully established, the spleen cells from the second generation mice were further inoculated into the third generation mice, and the growth of leukemia cells in peripheral blood of the mice in each group was monitored by regular flow cytometry to evaluate the stability of this T-ALL leukemia animal model. RESULTS: On the 10th day after inoculation, hCD45+ leukemia cells could be successfully detected in the peripheral blood of the first generation mice, and the proportion of these cells was gradually increased. On average, the mice appeared listless 6 or 7 weeks after inoculation, and a large number of T lymphocyte leukemia cells were found in the peripheral blood and bone marrow smear of the mice. The spleen of the mice was obviously enlarged, and immunohistochemical examination showed that hCD3+ leukemia cells infiltrated into bone marrow, liver and spleen extensively. The second and third generation mice could stably develop leukemia, and the average survival time was 4-5 weeks. CONCLUSION: Inoculating leukemia cells from bone marrow of patients with T-ALL into NCG mice via tail vein can successfully construct a patient-derived tumor xenografts (PDTX) model.


Assuntos
Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Animais , Camundongos , Xenoenxertos , Medula Óssea , Modelos Animais de Doenças , Linfócitos T , Camundongos SCID
6.
Acta Haematol ; 127(3): 152-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22286512

RESUMO

Imatinib resistance is an important hurdle in the treatment of chronic myeloid leukemia (CML), and CML patients with this drug resistance are often given a dismal prognosis. In this case report, an imatinib-refractory blast phase CML patient was treated with a combination of imatinib and nilotinib. A complete hematologic response was achieved within 3 months, the drug combination was well tolerated, and there was a relatively long bone-marrow complete remission. These results suggest that combining imatinib and nilotinib treatment may improve the outcome of imatinib-resistant CML patients in the blast phase. We hypothesize regarding the possible mechanism for the effectiveness of the drug combination by reviewing the recent literature.


Assuntos
Antineoplásicos/uso terapêutico , Crise Blástica/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Benzamidas , Resistencia a Medicamentos Antineoplásicos , Quimioterapia Combinada , Humanos , Mesilato de Imatinib , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino
7.
Beijing Da Xue Xue Bao Yi Xue Ban ; 44(3): 369-74, 2012 Jun 18.
Artigo em Zh | MEDLINE | ID: mdl-22692305

RESUMO

OBJECTIVE: To analyze HIV/AIDS related risk behaviors among unmarried outside school adolescents and the impact factors in outflow areas, in order to provide basis for related health education. METHODS: Using cluster sampling method, we investigated a vocational training center for all 15- to 24-year-old unmarried outside school youths in one county. The structured questionnaire based on the Theory of Reasoned Action was anonymous, which filled envelopes on the spot. A total of 1 800 questionnaires were recovered, and 1 712 questionnaires were valid. Epidata 3.0 was used for establishing a database and SPSS 13.0 for statistical analysis. RESULTS: (1) The incidence of HIV/AIDS risk behaviors of the outside school adolescents was high: 18.0% of the respondents had sexual behavior, 27.3% had never used condom when sexed in the past three months, 31.0% had multiple sexual partners, and 9.7% had drug abuse experience; the rate of HIV/AIDS-related knowledge was only 25.1%; peer environment of respondents was poor. (2) The use of condoms was correlated with those who had higher score of AIDS knowledge, and who could talk about condoms in sexual intercourse; The multiple sexual partners' behavior was correlated with age, friends who were themselves multiple sexual partners, high score of the attitude, and the subjective norm; The commercial sex was correlated with the family address, high score of the HIV/AIDS-related knowledge, friends who had commercial sex, the subjective norm and the intention of behavior, The drug abuse behavior was correlated with age, high score of the HIV/AIDS-related knowledge, drug abuse among their friends, the subjective norm, and the intention of behavior. (3) Subjective norms and behavioral intentions could better predict the occurrence of HIV/AIDS risk behaviors. CONCLUSION: The outside school adolescents are at risk in lack of HIV/AIDS-related knowledge and coping skills of negative peer pressure, so providing the related health education before they go and work outside their home is the "critical period".


Assuntos
Síndrome da Imunodeficiência Adquirida/epidemiologia , Infecções por HIV/epidemiologia , Comportamento Sexual/estatística & dados numéricos , Sexo sem Proteção/estatística & dados numéricos , Adolescente , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Fatores de Risco , Estudos de Amostragem , Parceiros Sexuais , Inquéritos e Questionários , Migrantes , Adulto Jovem
8.
Biomolecules ; 12(11)2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36359005

RESUMO

Genomic DNA damage occurs as an inevitable consequence of exposure to harmful exogenous and endogenous agents. Therefore, the effective sensing and repair of DNA damage are essential for maintaining genomic stability and cellular homeostasis. Inappropriate responses to DNA damage can lead to genomic instability and, ultimately, cancer. Protein post-translational modifications (PTMs) are a key regulator of the DNA damage response (DDR), and recent progress in mass spectrometry analysis methods has revealed that a wide range of metabolites can serve as donors for PTMs. In this review, we will summarize how the DDR is regulated by lipid metabolite-associated PTMs, including acetylation, S-succinylation, N-myristoylation, palmitoylation, and crotonylation, and the implications for tumorigenesis. We will also discuss potential novel targets for anti-cancer drug development.


Assuntos
Reparo do DNA , Neoplasias , Humanos , Processamento de Proteína Pós-Traducional , Dano ao DNA , Instabilidade Genômica , Neoplasias/genética , Lipídeos
9.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(1): 39-46, 2021 Jan.
Artigo em Zh | MEDLINE | ID: mdl-33441227

RESUMO

Objective To investigate the role of phosphatidylinositol 3-kinase (PI3K) isoforms in type III receptor tyrosine kinase KIT mutation-mediated signaling and cell proliferation. Methods The wild-type KIT and the common KIT mutations V560D and W557K558del in gastrointestinal stromal tumors (GIST) were stably expressed in BaF3 cells. The cells were treated with PI3K isoforms PI3Kα, PI3Kß and PI3Kδ specific inhibitors or pan PI3K inhibitor. The activation of KIT and its downstream signals was detected by immunoprecipitation and Western blot analysis. GIST-T1 cells were treated with the same drug, and the activation of KIT and its downstream signals was also detected by immunoprecipitation and Western blot analysis, and cell proliferation and apoptosis were detected by MTT assay and flow cytometry, respectively. Results Compared with the controls, in BaF3 cells expressing wild-type KIT and its mutants, the activation of KIT and its downstream signaling molecules AKT and ERK was inhibited the most by PI3Kδ specific inhibitor, followed by the specific inhibitors of PI3Kα and PI3Kß subtype. In GIST-T1 cells, the activation of KIT and its downstream signals was inhibited the most by PI3Kß specific inhibitor, followed by PI3Kδ and PI3Kα specific inhibitors. Conclusion In BaF3 cells, PI3Kδ subtype plays a major role in KIT activation and its downstream signal transduction, while in GIST-T1 cells, PI3Kß subtype plays a major role in KIT activation and its downstream signal transduction. These results indicate that PI3K isoforms play different roles in KIT mutation-mediated cell transformation depending on the host cells.


Assuntos
Fosfatidilinositol 3-Quinase , Fosfatidilinositol 3-Quinases , Mutação , Fosfatidilinositol 3-Quinases/genética , Inibidores de Fosfoinositídeo-3 Quinase , Isoformas de Proteínas/genética
10.
Front Psychiatry ; 12: 698562, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603100

RESUMO

Background: Binge drinking and smoking among adolescents are serious public concerns. However, very few studies have explored the reinforcement of bullying victimization by such behavior. Our study aimed at examining the individual and combined associations of smoking and bullying victimization with binge drinking among adolescents in Beijing, China. Methods: A total of 33,694 students aged 13-17 years old in Beijing, China were anonymously investigated via the cross-sectional Chinese Youth Risk Behavior Surveillance Survey from April to May 2014. A three-stage stratified sampling was used to select participants. Factors such as sociodemographic variables and indicators of smoking, bullying victimization, and binge drinking were analyzed with multiple logistic regressions, and joint and additive interaction effects were tested. Results: Overall, ever-drinking prevalence was 59.1% (boys: 64.4%; girls: 53.7%). Past 30-day binge drinking was 11.5% (boys: 15.6%; girls: 7.4%) and frequent binge drinking was 2.3% (boys: 3.3%; girls: 1.0%). Past 30-day smoking was 10.7% (boys: 16.4%; girls: 5.0%) and past 30-day bullying victimization was 48.7% (boys: 57.3%; girls: 40.1%). The combined effects of smoking and bullying victimization on occasional binge drinking (OR = 6.49, 95% CI = 5.60-7.52) and frequent binge drinking (OR = 10.32, 95% CI = 7.52-14.14) were significant, and the additive interaction effect was significant for current smoking and bullying victimization on frequent binge drinking (OR = 10.22, 95% CI = 9.43-11.07). The additive interaction effect for current smoking and bullying victimization on frequent binge drinking was significant among boys. Conclusion: Bullying victimization reinforced the association of smoking with frequent binge drinking, especially with findings specific to boys. Programs to prevent smoking or bullying or both may reduce binge drinking among adolescents in China.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32164156

RESUMO

This study explored factors affecting parents' intentions to use physical violence (PV) to discipline their children in the future. The theory of planned behavior (TPB) guided selection of variables. A sample of 1337 preschool children's parents from nine kindergartens located in a county of Henan Province, China were selected by stratified random cluster sampling. Data on parents' attitudes, subjective norms, and perceived behavioral control over PV, intentions to engage in PV to discipline their preschool children in the future, self-reported PV behavior toward their children during the past three months, and demographic characteristics were collected via a paper-based questionnaire. Multivariable logistic regression analyses examined putative predictors of parents' intentions to use physically violent discipline. Nearly three-quarters of the sample said they definitely will not use violent discipline, while 23.4% either said they would use it, or did not rule it out. Logistic regression analysis showed that parents' lower level of perceived behavioral control over using violence (OR 4.17; 95% CI: 2.659, 6.551), attitudes that support PV (OR 2.23; 95% CI: 1.555, 3.203), and having been physically violent with their children during the past three months (OR 1.62; 95% CI: 1.032, 2.556) were significantly associated with parents' tendency either to include, or not exclude, the use of violent discipline. Parents' subjective norms regarding PV had no significant impact on their intentions (p > 0.05). The influence of TPB constructs varied according to parents' gender. Intervention programs that aim to reduce violent discipline should focus both on increasing parents' perceived behavioral control over PV and changing their attitudes toward physically violent practices, especially among mothers and parents who have already used PV to discipline their children.


Assuntos
Maus-Tratos Infantis , Relações Pais-Filho , Abuso Físico , Atitude , Criança , Pré-Escolar , China , Feminino , Humanos , Intenção , Masculino , Pais
12.
Cell Biosci ; 10: 16, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32082541

RESUMO

BACKGROUND: KIT mutations are the predominant driver mutations in gastrointestinal stromal tumors (GISTs), and targeted therapy against KIT has improved treatment outcome dramatically. However, gaining secondary mutation of KIT confers drug resistance of GISTs leading to treatment failure. RESULTS: In this study, we found that secondary mutation of KIT dramatically increases the ligand-independent activation of the receptor and their resistance to the often used KIT inhibitor Imatinib in the treatment of GISTs. PI3 kinase plays essential roles in the cell transformation mediated by the primary mutation of KIT. We found that loss of PI3 kinase association, but not the inhibition of the lipid kinase activity of PI3 kinase, inhibits the ligand-independent activation of secondary mutations of KIT, and increases their sensitivity to Imatinib, and loss of PI3 kinase association inhibits secondary mutations of KIT mediated cell survival and proliferation in vitro. The in vivo assay further showed that the growth of tumors carrying secondary mutations of KIT is more sensitive to Imatinib when PI3 kinase association is blocked while inhibition of the lipid kinase activity of PI3 kinase cannot inhibit tumor growth, indicating that PI3 kinase is important for the drug resistance of secondary mutation of KIT independent of the lipid kinase activity of PI3 kinase. CONCLUSIONS: Our results suggested that PI3 kinase is necessary for the ligand-independent activation of secondary mutations of KIT, and loss of PI3 kinase association improves the sensitivity of secondary mutations to the targeted therapy independent of the lipid kinase activity of PI3 kinase.

13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(6): 1598-1603, 2018 Dec.
Artigo em Zh | MEDLINE | ID: mdl-30501690

RESUMO

OBJECTIVES: To explore the clinical significance of clonal evolution of additional chromosomal 8 in CML progression. METHODS: An unusual case with the clonal evolution from trisomy 8 to tetrasomy 8 accompanied by 2 time of CML blast crisis (BC) was reported. RESULTS: This patient suffered from 2 time of CML blast crisis and the additional chromosome 8 aberrations were accompanied. Trisomy 8 and tetrasomy 8 were detected at first CML blast crisis and second CML blast crisis, respectively. After tetrasomy 8 was developed, the c-Myc was over-expressed and the central nervous system leukemia happened in this case. Only high dose Ara-C and MTX regimen could induce remission for a short period. CONCLUSION: These findings suggested that additional chromosome 8 aberrations are important marker for poor prognosis of CML patients and contribute to a poor prognosis.


Assuntos
Cromossomos Humanos Par 8 , Evolução Clonal , Crise Blástica , Aberrações Cromossômicas , Progressão da Doença , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva
14.
Placenta ; 46: 49-62, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27697222

RESUMO

Inflammation and dysregulated lipid metabolism are involved in the pathogenesis of preeclampsia, and fatty acid binding protein 4 (FABP4) is known to regulate both inflammation and lipid metabolism. In the present study, we elucidated the role of FABP4 using in vitro and in vivo models of preclampsia. We found increased expression of FABP4 in the placenta of preeclamptic rats, which was further confirmed in HTR-8 cells, an extravillous trophoblast cell line, treated with L-NAME. Overexpression of FABP4 in HTR-8 cells resulted in upregulated expression of pro-inflammatory cytokines IL-6 and TNF-α, and increased lipid accumulation, suggesting that FABP4 plays a role in preeclampsia. Furthermore, downregulation of methylation in the promotor resulted in increased FABP4 expression, which was mediated by downregulated DNA methyltransferase 1 (DNMT1). Bioinformatics analysis showed that miR-148a/152 regulated the expression of DNMT1, and additional in vitro studies revealed that miR-148a/152 inhibited DNMT1 expression by directly binding to its 3'-UTR. Interestingly, DNMT1 enhanced the expression of miR-148a/152 by downregulation of methylation in its promotor. Taken together, our results showed that FABP4 may be involved in the pathogenesis of preeclampsia, and the expression of FABP4 is enhanced by miR-148a/152 mediated inhibition of DNMT1 expression.


Assuntos
DNA (Citosina-5-)-Metiltransferases/metabolismo , Proteínas de Ligação a Ácido Graxo/metabolismo , MicroRNAs/metabolismo , Pré-Eclâmpsia/etiologia , Animais , Citocinas/metabolismo , DNA (Citosina-5-)-Metiltransferase 1 , Modelos Animais de Doenças , Feminino , Metabolismo dos Lipídeos , Metilação , NG-Nitroarginina Metil Éster , Placenta/metabolismo , Pré-Eclâmpsia/metabolismo , Gravidez , Regiões Promotoras Genéticas , Ratos Sprague-Dawley , Regulação para Cima
15.
FEBS Lett ; 589(24 Pt B): 3998-4009, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26606905

RESUMO

Homocysteine (Hcy) is an independent risk factor for atherosclerosis, but the underlying molecular mechanisms are not known. We investigated the effects of Hcy on fatty acid-binding protein 4 (FABP4), and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased FABP4 expression and decreased methylation. The FABP4 expression and DNA methylation was assessed in the aorta of ApoE(-/-) mice fed high-methionine diet for 20weeks. Over-expression of FABP4 enhanced accumulation of total cholesterol and cholesterol ester in foam cells. The up-regulation of DNA methyltransferase 1 (DNMT1) promoted the methylation process and decreased FABP4 expression. These data suggest that FABP4 plays a key role in Hcy-mediated disturbance of lipid metabolism and that DNMT1 may be a novel therapeutic target in Hcy-related atherosclerosis.


Assuntos
Aorta/metabolismo , Aterosclerose/metabolismo , Metilação de DNA , Proteínas de Ligação a Ácido Graxo/metabolismo , Hiper-Homocisteinemia/etiologia , Metionina/intoxicação , Proteínas Repressoras/metabolismo , Animais , Aorta/enzimologia , Aorta/patologia , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Aterosclerose/etiologia , Linhagem Celular Tumoral , Colesterol/sangue , Colesterol/metabolismo , Dieta/efeitos adversos , Proteínas de Ligação a Ácido Graxo/genética , Células Espumosas/enzimologia , Células Espumosas/metabolismo , Células Espumosas/patologia , Regulação da Expressão Gênica , Genes Reporter , Humanos , Hiper-Homocisteinemia/metabolismo , Hiper-Homocisteinemia/patologia , Hiper-Homocisteinemia/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Monócitos/enzimologia , Monócitos/metabolismo , Monócitos/patologia , Regiões Promotoras Genéticas , Proteínas Repressoras/genética
16.
PLoS One ; 9(7): e101432, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25068885

RESUMO

Traditional Chinese medicine (TCM) is one of the oldest East Asian medical systems. The present study adopted a systems biology-based approach to provide new insights relating to the active constituents and molecular mechanisms underlying the effects of dragon's blood (DB) tablets for the treatment of colitis. This study integrated chemical analysis, prediction of absorption, distribution, metabolism, and excretion (ADME), and network pharmacology. Firstly, a rapid, reliable, and accurate ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method was employed to identify 48 components of DB tablets. In silico prediction of the passive absorption of these compounds, based on Caco-2 cell permeability, and their P450 metabolism enabled the identification of 22 potentially absorbed components and 8 metabolites. Finally, networks were constructed to analyze interactions between these DB components/metabolites absorbed and their putative targets, and between the putative DB targets and known therapeutic targets for colitis. This study provided a great opportunity to deepen the understanding of the complex pharmacological mechanisms underlying the effects of DB in colitis treatment.


Assuntos
Colite/terapia , Medicina Tradicional Chinesa , Biologia de Sistemas , Humanos , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
17.
PLoS One ; 8(9): e73865, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24040098

RESUMO

SIL-TAL1 rearrangement is common in T-cell acute lymphoblastic leukemia (T-ALL), however its prognostic implication remains controversial. To investigate the clinical characteristics and outcome of this subtype in Chinese population, we systemically reviewed 62 patients with newly diagnosed T-ALL, including 15 patients with SIL-TAL1 rearrangement. We found that SIL-TAL1(+) T-ALL was characterized by higher white blood cell count (P = 0.029) at diagnosis, predominant cortical T-ALL immunophenotype (P = 0.028) of the leukemic blasts, and a higher prevalence of tumor lysis syndrome (TLS, P<0.001) and disseminated intravascular coagulation (DIC, P<0.001), which led to a higher early mortality (P = 0.011). Compared with SIL-TAL1(-) patients, SIL-TAL1(+) patients had shorter relapse free survival (P = 0.007) and overall survival (P = 0.002). Our NOD/SCID xenotransplantation model also demonstrated that SIL-TAL1(+) mice models had earlier disease onset, higher leukemia cell load in peripheral blood and shorter overall survival (P<0.001). Moreover, the SIL-TAL1(+) mice models exerted a tendency of TLS/DIC and seemed vulnerable towards chemotherapy, which further simulated our clinical settings. These data demonstrate that SIL-TAL1 rearrangement identifies a distinct subtype with inferior outcome which could allow for individual therapeutic stratification for T-ALL patients.


Assuntos
Proteínas de Fusão Oncogênica/genética , Translocação Genética , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Modelos Animais de Doenças , Coagulação Intravascular Disseminada/etiologia , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Fenótipo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Prognóstico , Proteína FUS de Ligação a RNA/genética , Proteína FUS de Ligação a RNA/metabolismo , Estudos Retrospectivos , Síndrome de Lise Tumoral/etiologia , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
18.
Med Oncol ; 29(2): 1102-4, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21359860

RESUMO

Here, we report a Philadelphia chromosome-positive chronic myeloid leukemia case with the longest chronic phase and overall survival to our knowledge ever reported in the medical literature. During the 33-year chronic phase, he was asymptomatic without any treatment and had normal blood cell values. BCR-ABL silencing might be referred to the uncommon long-term survivor.


Assuntos
Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Cromossomo Filadélfia , Sobreviventes , Adulto , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Adulto Jovem
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(4): 812-7, 2012 Aug.
Artigo em Zh | MEDLINE | ID: mdl-22931634

RESUMO

This study was aimed to investigate the expression characteristics of two transcriptional factors in Ikaros family, Ikaros and Helios isoforms and their mechanism, as well as their correlation with clinical parameters, which play important roles in transcriptional regulation of hematopoiesis. Expression of Ikaros and Helios isoforms in a total of 163 patients with leukemia and correlations between Ikaros and Helios isoforms were analyzed by PCR. The results showed that different expression patters of Ikaros and Helios isoforms existed in leukemia patients, that is, Ikaros isoform (Ik-6) was predominantly expressed in acute lymphoblastic leukemia (ALL) with BCR/ABL fusion gene, while Helios isoform (He-i) was overexpressed in T-cell ALL patients. The results of cloning and sequencing demonstrated that the isoforms of Ikaros and Helios had different genetic alterations. The statistical correlation between these two isoforms not was found in this study, although interaction between Ikaros and Helios has been reported. It is concluded that although Ikaros and Helios belong to the same family with similar structure of zinc fingers, their isoforms have different expression profile, specific genetic alterations, and different clinical relevance in patients with leukemia. The connection and interaction between Ik-6 and He-i needs further research.


Assuntos
Fator de Transcrição Ikaros/metabolismo , Leucemia/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Perfilação da Expressão Gênica , Humanos , Fator de Transcrição Ikaros/genética , Leucemia/genética , Masculino , Pessoa de Meia-Idade , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Adulto Jovem
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(5): 1110-6, 2012 Oct.
Artigo em Zh | MEDLINE | ID: mdl-23114129

RESUMO

This study was purposed to investigate the incidence of mixed lineage leukemia (MLL) gene rearrangement and partner gene types as well as the clinical features and prognosis of acute leukemia (AL) with this rearrangement through detection in adult AL using combination of 3 techniques, and to evaluate the clinical value of this combination detection. The MLL gene rearrangement in 183 cases of adult AL was detected by combination of conventional cytogenetics, split signal FISH and multiplex nested PCR. The results showed that the incidence of MLL rearrangements in adult patients with AL was low (8.2%), and MLL-AF4 fusion gene was most common and predominant in acute lymphoblastic leukemia (ALL), while the MLL-AF6 and MLL-AF9 were most frequent in acute myeloid leukemia (AML). Extramedullary involvements were found in 40% of MLL-rearranged AL patients, and 33.3% of patients with MLL-rearranged AL reached to complete remission within 30 days during induction chemotherapy. In addition, in this cohort of MLL-rearranged adult AL patients, the 3-month relapse rate and 6-month overall survival rate were 50.0% and 50.0% respectively. It is concluded that the rate of missed diagnosis of CC technique for patients with MLL-rearranged AL reached to 60% in this study, while the combination of CC, FISH and multiplex nested PCR has been confirmed to have important significance for evaluating prognosis and conducting clinical therapy of patients with MLL-rearranged AL.


Assuntos
Rearranjo Gênico , Leucemia Mieloide Aguda/genética , Proteína de Leucina Linfoide-Mieloide/genética , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Fusão Oncogênica/genética , Adulto Jovem
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