RESUMO
BACKGROUND: Gibberellins (GAs) can have profound effects on growth and development in higher plants. In contrast to their flowering-promotive role in many well-studied plants, GAs can repress flowering in woody perennial plants such as apple (Malus x domestica Borkh.). Although this effect of GA on flowering is intriguing and has commercial importance, the genetic mechanisms linking GA perception with flowering have not been well described. RESULTS: Application of a mixture of bioactive GAs repressed flower formation without significant effect on node number or shoot elongation. Using Illumina-based transcriptional sequence data and a newly available, high-quality apple genome sequence, we generated transcript models for genes expressed in the shoot apex, and estimated their transcriptional response to GA. GA treatment resulted in downregulation of a diversity of genes participating in GA biosynthesis, and strong upregulation of the GA catabolic GA2 OXIDASE genes, consistent with GA feedback and feedforward regulation, respectively. We also observed strong downregulation of numerous genes encoding potential GA transporters and receptors. Additional GA-responsive genes included potential components of cytokinin (CK), abscisic acid (ABA), brassinosteroid, and auxin signaling pathways. Finally, we observed rapid and strong upregulation of both of two copies of a gene previously observed to inhibit flowering in apple, MdTFL1 (TERMINAL FLOWER 1). CONCLUSION: The rapid and robust upregulation of genes associated with GA catabolism in response to exogenous GA, combined with the decreased expression of GA biosynthetic genes, highlights GA feedforward and feedback regulation in the apple shoot apex. The finding that genes with potential roles in GA metabolism, transport and signaling are responsive to GA suggests GA homeostasis may be mediated at multiple levels in these tissues. The observation that TFL1-like genes are induced quickly in response to GA suggests they may be directly targeted by GA-responsive transcription factors, and offers a potential explanation for the flowering-inhibitory effects of GA in apple. These results provide a context for investigating factors that may transduce the GA signal in apple, and contribute to a preliminary genetic framework for the repression of flowering by GAs in a woody perennial plant.
Assuntos
Regulação da Expressão Gênica de Plantas/genética , Giberelinas/metabolismo , Malus/crescimento & desenvolvimento , Reguladores de Crescimento de Plantas/metabolismo , Flores/genética , Flores/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Genes de Plantas/genética , Giberelinas/farmacologia , Malus/genética , Meristema/genética , Meristema/crescimento & desenvolvimento , Reguladores de Crescimento de Plantas/farmacologia , Transdução de Sinais/genética , Fatores de Transcrição/genéticaRESUMO
Mice with homozygous null mutations in the HDL receptor (scavenger receptor class B, type I, or SR-BI) and apolipoprotein E (apoE) genes [SR-BI/apoE double KO (SR-BI(-/-)/apoE(-/-) or dKO) mice] spontaneously develop occlusive, atherosclerotic coronary artery disease (CAD) and die prematurely (50% mortality at 42 d of age). Using microarray mRNA expression profiling, we identified genes whose expression in the hearts of dKO mice changed substantially during disease progression [at 21 d of age (no CAD), 31 d of age (small myocardial infarctions), and 43 d of age (extensive myocardial infarctions) vs. CAD-free SR-BI(+/-)/apoE(-/-) controls]. Expression of most genes that increased >sixfold in dKO hearts at 43 d also increased after coronary artery ligation. We examined the influence and potential mechanism of action of apolipoprotein D (apoD) whose expression in dKO hearts increased 80-fold by 43 d. Analysis of ischemia/reperfusion-induced myocardial infarction in both apoD KO mice and wild-type mice with abnormally high plasma levels of apoD (adenovirus-mediated hepatic overexpression) established that apoD reduces myocardial infarction. There was a correlation of apoD's ability to protect primary cultured rat cardiomyocytes from hypoxia/reoxygenation injury with its potent ability to inhibit oxidation in a standard antioxidation assay in vitro. We conclude that dKO mice represent a useful mouse model of CAD and apoD may be part of an intrinsic cardioprotective system, possibly as a consequence of its antioxidation activity.
Assuntos
Antioxidantes/metabolismo , Apolipoproteínas D/sangue , Doença da Artéria Coronariana/sangue , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Apolipoproteínas D/genética , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo , Hipóxia Celular/genética , Células Cultivadas , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Knockout , Infarto do Miocárdio/sangue , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Miócitos Cardíacos/patologia , Ratos Wistar , Receptores Depuradores Classe B/genética , Receptores Depuradores Classe B/metabolismoRESUMO
BACKGROUND: A long juvenile period between germination and flowering is a common characteristic among fruit trees, including Malus hupehensis (Pamp.) Rehd., which is an apple rootstock widely used in China. microRNAs (miRNAs) play an important role in the regulation of phase transition and reproductive growth processes. RESULTS: M. hupehensis RNA libraries, one adult and one juvenile phase, were constructed using tree leaves and underwent high-throughput sequencing. We identified 42 known miRNA families and 172 novel miRNAs. We also identified 127 targets for 25 known miRNA families and 168 targets for 35 unique novel miRNAs using degradome sequencing. The identified miRNA targets were categorized into 58 biological processes, and the 123 targets of known miRNAs were associated with phase transition processes. The KEGG analysis revealed that these targets were involved in starch and sucrose metabolism, and plant hormone signal transduction. Expression profiling of miRNAs and their targets indicated multiple regulatory functions in the phase transition. The higher expression level of mdm-miR156 and lower expression level of mdm-miR172 in the juvenile phase leaves implied that these two small miRNAs regulated the phase transition. mdm-miR160 and miRNA393, which regulate genes involved in auxin signal transduction, could also be involved in controlling this process. The identification of known and novel miRNAs and their targets provides new information on this regulatory process in M. hupehensis, which will contribute to the understanding of miRNA functions during growth, phase transition and reproduction in woody fruit trees. CONCLUSIONS: The combination of sRNA and degradome sequencing can be used to better illustrate the profiling of hormone-regulated miRNAs and miRNA targets involving complex regulatory networks, which will contribute to the understanding of miRNA functions during growth, phase transition and reproductive growth in perennial woody fruit trees.
Assuntos
Malus/crescimento & desenvolvimento , Malus/genética , MicroRNAs/química , MicroRNAs/genética , Estabilidade de RNA , Análise de Sequência de RNA , Flores/crescimento & desenvolvimento , Ontologia Genética , Germinação , Malus/fisiologia , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Reprodução , TranscriptomaRESUMO
Our previous studies showed that cell surface ß1,4-galactosyltransferase 1 (ß1,4GT1) negatively regulated cell survival through inhibition and modulation of the epidermal growth factor receptor (EGFR) signaling pathway in human hepatocellular carcinoma (HCC) SMMC-7721 cells. However, the underlying mechanism remains unclear. Here we demonstrated that ß1,4-galactosyltransferase 1 (ß1,4GT1) interacted with EGFR in vitro by GST pull-down analysis. Furthermore, we demonstrated that ß1,4GT1 bound to EGFR in vivo by co-immunoprecipitation and determined the co-localization of ß1,4GT1 and EGFR on the cell surface via confocal laser scanning microscopy analysis. Finally, using (125)I-EGF binding experiments and Western blot analysis, we found that overexpression of ß1,4GT1 inhibited (125)I-EGF binding to EGFR, and consequently reduced the levels of EGFR dimerization and phosphorylation. In contrast, RNAi-mediated knockdown of ß1,4GT1 increased the levels of EGFR dimerization and phosphorylation. These data suggest that cell surface ß1,4GT1 interacts with EGFR and inhibits EGFR activation.
Assuntos
Carcinoma Hepatocelular/metabolismo , Receptores ErbB/metabolismo , Neoplasias Hepáticas/metabolismo , Sequência de Bases , Western Blotting , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Primers do DNA , Imunofluorescência , Humanos , Imunoprecipitação , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/patologia , Microscopia Confocal , N-Acetil-Lactosamina Sintase , Ligação ProteicaRESUMO
In domesticated apple (Malus x domestica Borkh.) and other woody perennials, floral initiation can be repressed by gibberellins (GAs). The associated mechanism is a major unanswered question in plant physiology, and understanding organismal aspects of GA signaling in apple has important commercial applications. In plants, the major mechanism for elimination of GAs and resetting of GA signaling is through catabolism by GA2-oxidases (GA2ox). We found that the GA2ox gene family in apple comprises 16 genes representing eight, clearly defined homeologous pairs, which were named as MdGA2ox1A/1B to MdGA2ox8A/8B. Expression of the genes was analyzed in the various structures of the spur, where flowers are initiated, as well as in various structures of seedlings over one diurnal cycle and in response to water-deficit and salt stress. Among the results, we found that MdGA2ox2A/2B dominated expression in the shoot apex and were strongly upregulated in the apex after treatment with exogenous GA3, suggesting potential involvement in repression of flowering. Several MdGA2ox genes also showed preferential expression in the leaf petiole, fruit pedicel, and the seed coat of developing seeds, potentially representing mechanisms to limit diffusion of GAs across these structures. In all contexts studied, we documented both concerted and distinct expression of individual homeologs. This work introduces an accessible woody plant model for studies of GA signaling, GA2ox gene regulation, and conservation/divergence of expression of homeologous genes, and should find application in development of new cultivars of apple and other tree fruits.
RESUMO
Cholesterol 7α-hydroxylase (CYP7A1) is the initial and rate-limiting enzyme for bile acid synthesis. Transcription of the CYP7A1 gene is regulated by bile acids, nuclear receptors and cytokines. Fibroblast growth factor 7 (FGF7) secreted from activated hepatic stellate cells (HSC) during chronic liver fibrosis regulates hepatocyte survival and liver regeneration. In the carbon tetrachloride (CCl(4))-induced fibrotic mouse liver, we demonstrated that the expression of CYP7A1 was largely decreased while the expression of FGF7 was significantly increased. We further demonstrated that FGF7 inhibited CYP7A1 gene expression in hepatocytes. Knockdown study by short interfering RNA, kinase inhibition and phosphorylation assays revealed that the suppression of CYP7A1 expression by FGF7 was mediated by FGFR2 and its downstream JNK signaling cascade. The FGF7 neutralizing antibody restored CYP7A1 expression in Hep3B cells treated with conditioned medium from HSC. In summary, the data suggest that FGF7 is a novel regulator of CYP7A1 expression in hepatocytes and may prevent hepatocytes from accumulating toxic bile acids during liver injury and fibrosis.
Assuntos
Ácidos e Sais Biliares/biossíntese , Colesterol 7-alfa-Hidroxilase/genética , Fator 7 de Crescimento de Fibroblastos/fisiologia , Regulação Enzimológica da Expressão Gênica , Hepatócitos/enzimologia , Cirrose Hepática/enzimologia , Animais , Tetracloreto de Carbono/toxicidade , Linhagem Celular Tumoral , Colesterol 7-alfa-Hidroxilase/antagonistas & inibidores , Modelos Animais de Doenças , Fator 7 de Crescimento de Fibroblastos/farmacologia , Hepatócitos/efeitos dos fármacos , Humanos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , MAP Quinase Quinase 4/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , RNA Interferente Pequeno/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismoRESUMO
OBJECTIVES: To determine the prevalence and factors associated with histologic diagnoses of cervical intraepithelial neoplasia in women with ASC-US. METHOD: Sampling investigations were carried out on married women aged 25-54 in 12 districts in Beijing from April 2007 to November 2008. Further examinations and analyses were carried out on women with ASC-US in the cytological screening. RESULTS: Of 6,339 women, 9.6% suffered from cervical abnormalities in cytology; among them, 409 cases were ASC-US. Of the 409 ASC-US, 42.1% showed inflammation; 50.9% had CIN 1, 6.1% had CIN 2, and three cases had CIN 3, one of which was cervical cancer. Four hundred and four cases were subjected to detection for the human papillomaovirus (HPV) and the infection rate was 30.7%. Morbidity in the HPV infected patients that suffered from CIN 2 or higher was significantly higher than that in the uninfected population (chi2 = 26.685, p = 0.000). No statistical significance was found in the correlation between the pathological results of ASC-US and the loading dose of HPV infection (chi2 = 7.754, p = 0.458). CONCLUSION: The morbidity of CIN in women with ASCUS in Beijing is high, and women with ASC-US should be paid great attention, especially women who are infected with high-risk HPV.
Assuntos
Neoplasias de Células Escamosas/epidemiologia , Teste de Papanicolaou , Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal/estatística & dados numéricos , Adulto , China/epidemiologia , Comorbidade , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/diagnóstico , Infecções por Papillomavirus/diagnóstico , Prevalência , Fatores de Risco , População Urbana/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Displasia do Colo do Útero/diagnósticoRESUMO
The purpose of this study is to examine knowledge of cervical cancer and the relationship between knowledge of human papillomavirus (HPV) infection and cervical disease in a largely representative Beijing population. A questionnaire-based survey was conducted in a Beijing population sample of married women ages 25 to 54 years (n = 6,339), evaluating knowledge and relevant factors with regard to cervical cancer. Knowledge levels were low; only 52.5% (n = 3,328) of the respondents knew that cervical cancer can be detected in its early stage. Only 26.9% reported that human HPV infections were risk factors for cervical cancer. The level of knowledge was lower among older, with less education, less income, unstable profession, and non-Beijing Hukou women (all P < 0.01). An increasing level of knowledge may impact positively on intentions to participate in cervical cancer screening. Education schemes to improve knowledge of cervical cancer should be performed in a multimodel, multichannel method.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Programas de Rastreamento , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Idoso , Escolaridade , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Infecções por Papillomavirus/virologia , Fatores de Risco , Inquéritos e Questionários , Neoplasias do Colo do Útero/virologiaRESUMO
OBJECTIVE: To investigate subtype of HPV infection among women at age of 25 to 54 years in Beijing. METHODS: From Sept. 2006 to Dec. 2008, 5552 reproductive women at age of 25 to 54 years classified into each 5-year as group were screened. Each participant completed a questionnaire and a sample of exfoliated cervical cells for liquid-based cytology and HPV subtype gene testing was performed. RESULTS: The overall prevalence of HPV was 6.68% (371/5552). High-risk HPV and Low-risk HPV prevalence were 5.76% (320/5552) and 2.00% (111/5552), respectively. The most common HPV types were HPV16 (2.61%, 145/5552), HPV58 (0.97%, 54/5552), HPV33 (0.85%, 47/5552), HPV43 (0.74%, 41/5552) and HPV56 (0.70%, 39/5552). There were two peaks of HPV prevalence: groups of 30 - 34 years and 40 - 44 years. CONCLUSION: The most common HPV subtypes in Beijing were HPV 16, 58, 33 and 43 and HPV prevalence showed a bi-modal age-specific curve.
Assuntos
Papillomaviridae/classificação , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Distribuição por Idade , Fatores Etários , China/epidemiologia , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Humanos , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Prevalência , Fatores de Risco , Inquéritos e Questionários , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/virologia , Esfregaço VaginalRESUMO
Many apple cultivars are subject to biennial fluctuations in flowering and fruiting. It is believed that this phenomenon is caused by a repressive effect of developing fruit on the initiation of flowers in the apex of proximal bourse shoots. However, the genetic pathways of floral initiation are incompletely described in apple, and the biological nature of floral repression by fruit is currently unknown. In this study, we characterized the transcriptional landscape of bourse shoot apices in the biennial cultivar, 'Honeycrisp', during the period of floral initiation, in trees bearing a high fruit load and in trees without fruit. Trees with high fruit load produced almost exclusively vegetative growth in the subsequent year, whereas the trees without fruit produced flowers on the majority of the potential flowering nodes. Using RNA-based sequence data, we documented gene expression at high resolution, identifying >11,000 transcripts that had not been previously annotated, and characterized expression profiles associated with vegetative growth and flowering. We also conducted a census of genes related to known flowering genes, organized the phylogenetic and syntenic relationships of these genes, and compared expression among homeologs. Several genes closely related to AP1, FT, FUL, LFY, and SPLs were more strongly expressed in apices from non-bearing, floral-determined trees, consistent with their presumed floral-promotive roles. In contrast, a homolog of TFL1 exhibited strong and persistent up-regulation only in apices from bearing, vegetative-determined trees, suggesting a role in floral repression. Additionally, we identified four GIBBERELLIC ACID (GA) 2 OXIDASE genes that were expressed to relatively high levels in apices from bearing trees. These results define the flowering-related transcriptional landscape in apple, and strongly support previous studies implicating both gibberellins and TFL1 as key components in repression of flowering by fruit.
Assuntos
Flores , Frutas , Regulação da Expressão Gênica de Plantas , Malus , Brotos de Planta/fisiologia , Flores/genética , Flores/fisiologia , Frutas/genética , Frutas/fisiologia , Malus/genética , Malus/fisiologia , Proteínas de Plantas/genéticaRESUMO
OBJECTIVE: To investigate the characteristic of precancerous conditions of cervical intraepithelial neoplasia (CIN) and its related high-risk factors among the married women in Beijing, China. METHODS: Based upon the method of cross-sectional survey, 6339 married women at reproductive age from 25 to 54 years old were selected randomly in a total of 137 communities of 12 districts or counties in Beijing from March 2007 to September 2008. The interview was carried out with unified questionnaires and gynecological examinations. And the cervical Pap smear was used for liquid-based cytological examination and the cervical secretion for detection of high-risk human papillomavirus (HPV) DNA. Furthermore, the women with abnormal cervical cytology received colposcopy and cervical biopsy. RESULTS: (1) Among 6, 339 study subjects, 374 cases had CIN and the prevalence rate was 5.9%; (2) For the cases with cervical cytology positive results, cervical biopsy showed an elevated level of abnormal cytology and an increased incidence of cervical lesions; (3) The peak age of CIN prevalence was 30 to 34 years old and there was a high grade of cervical neoplasia; (4) Among the population, the infection rate of high-risk HPV was 9.9% and the infection rate of high-risk HPV in positive cytological group (41.2%) was significantly higher than that in negative cytological group (6.6%); (5) The infection rate and DNA load of high-risk HPV increased following the severity grade of CIN. CONCLUSION: In Beijing, married women at 30 to 34 years old are the high-risk group in CIN incidence and the infection of high-risk HPV is an independent risk factor. Liquid-base cytology combined with high-risk HPV DNA test is a viable method to discover CIN in time and prevent the incidence of cervical cancer.
Assuntos
Lesões Pré-Cancerosas/epidemiologia , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Medição de Risco , Inquéritos e Questionários , Doenças do Colo do Útero/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: to investigate high risk factors associated with cervical intraepithelial neoplasia (CIN) in married women aged 25 to 54 years in Beijing. METHODS: from Mar. 2007 to Sep. 2008, 6339 married women at age of 25 to 54 years were selected randomly by cross sectional survey in a total of 137 communities of 12 districts or counties in Beijing. The interview was carried out with unified questionnaires, gynecological examination. The cervical smear cytology and high-risk human papillomavirus (HR-HPV) infection of cervical secretion were detected. Women with abnormal cervical cytology underwent colposcopy and cervical biopsy. Odd ratio (OR) and 95% confidence interval (CI) of related high risk factors with CIN were studied by logistic regression analysis. RESULTS: among 6339 women, the prevalence rate of CIN including 4 squamous cell carcinoma (SCC) was 5.90% (374/6339). By multinomial regression analysis, HR-HPV infection (95%CI: 9.953 - 15.811), History of trichomonas vaginitis (95%CI: 1.046 - 2.104), oral contraceptives (95%CI: 1.087 - 1.806), age less than 45 years old (95%CI: 1.069 - 1.828) were related with CIN. CONCLUSION: infection rate of HR-HPV is an independent risk factor of CIN, however, the history of trichomonas vaginitis, oral contraceptives and age less than 45 years old are related risk factors of CIN.
Assuntos
Carcinoma de Células Escamosas/epidemiologia , Infecções por Papillomavirus/complicações , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Adulto , Fatores Etários , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/virologia , China/epidemiologia , Anticoncepcionais Femininos , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/etiologia , Lesões Pré-Cancerosas/virologia , Análise de Regressão , Fatores de Risco , Inquéritos e Questionários , Vaginite por Trichomonas/complicações , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Displasia do Colo do Útero/etiologia , Displasia do Colo do Útero/virologiaRESUMO
OBJECTIVE: To investigate prevalence of cervical intraepithelial neoplasia (CIN) among the married women aged 25-54 years in Beijing. METHODS: With method of cross sectional survey, 6339 married women at age of 25 to 54 years were selected randomly in 137 communities of 12 districts or counties in Beijing from March 2007 to September 2008. The cervical smear cytology and high-risk human papillomavirus (HPV) infection of cervical secretion were detected. Women with abnormal cervical cytology were underwent colposcopy and cervical biopsy. RESULTS: Among 6339 women, 9.58% (607/6339) cases had abnormal cytological results, the colposcopy and cervical biopsy showed the rate of CIN was 5.84% (370/6339) in total selected women and 60.96% (370/607) in women with abnormal cervical cytology, including 4.65%(295/6339) in CIN I, 0.80% (51/6339) in CIN II, 0.38% (24/6339) in CIN III; 0.06% (4/6339) in early invasive carcinoma (SCC). Based on geographical distribution, the rate of cervical lesions was 4.46% (42/942) in urban areas, 6.27% (188/3000) in suburbs and 6.01% (144/2397) in outer suburbs (P > 0.05). CONCLUSION: It was found that the incidence of CIN was 5.84% in married women aged 25-54 years in Beijing, which did not show significant prevalence in urban, suburb and outer suburbs region.
Assuntos
Lesões Pré-Cancerosas/epidemiologia , Displasia do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal , Adulto , Biópsia/métodos , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , China/epidemiologia , Colposcopia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/virologia , Prevalência , Fatores de Risco , Estudos de Amostragem , Inquéritos e Questionários , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologiaRESUMO
PDZK1 is a scaffold protein containing four PDZ protein interaction domains, which bind to the carboxy termini of a number of membrane transporter proteins, including ion channels (e.g., CFTR) and cell surface receptors. One of these, the HDL receptor, scavenger receptor class B type I (SR-BI), exhibits a striking, tissue-specific dependence on PDZK1 for its expression and activity. In PDZK1 knockout (KO) mice there is a marked reduction of SR-BI protein expression (approximately 95%) in the liver, but not in steroidogenic tissues or, as we show in this report, in bone marrow- or spleen-derived macrophages, or lung-derived endothelial cells. Because of hepatic SR-BI deficiency, PDZK1 KO mice exhibit dyslipidemia characterized by elevated plasma cholesterol carried in abnormally large HDL particles. Here, we show that inactivation of the PDZK1 gene promotes the development of aortic root atherosclerosis in apolipoprotein E (apoE) KO mice fed with a high fat/high cholesterol diet. However, unlike complete SR-BI-deficiency in SR-BI/apoE double KO mice, PDZK1 deficiency in PDZK1/apoE double knockout mice did not result in development of occlusive coronary artery disease or myocardial infarction, presumably because of their residual expression of SR-BI. These findings demonstrate that deficiency of an adaptor protein essential for normal expression of a lipoprotein receptor promotes atherosclerosis in a murine model. They also define PDZK1 as a member of the family of proteins that is instrumental in preventing cardiovascular disease by maintaining normal lipoprotein metabolism.
Assuntos
Aterosclerose/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lipoproteínas/metabolismo , Animais , Aorta/metabolismo , Aorta/patologia , Apolipoproteínas E/deficiência , Apolipoproteínas E/metabolismo , Aterosclerose/sangue , Antígenos CD36/metabolismo , Dieta , Células Endoteliais/metabolismo , Immunoblotting , Peptídeos e Proteínas de Sinalização Intracelular/deficiência , Lipídeos/sangue , Macrófagos/metabolismo , Proteínas de Membrana , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND/AIMS: The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, which plays an essential role in the regulation of enterohepatic circulation and lipid homeostasis. Here we investigated whether WAY-362450, a synthetic potent FXR agonist, could protect against non-alcoholic steatohepatitis (NASH) in mice fed a methionine and choline-deficient (MCD) diet. METHODS: Male C57BL/6 mice on the MCD diet were treated with or without WAY-362450 (30 mg/kg) for 4 weeks. RESULTS: The elevations of serum ALT and AST activities induced by the MCD diet were decreased with WAY-362450 treatment. In terms of liver histology, while WAY-362450 treatment showed no impact on hepatic triglyceride accumulation, it significantly reduced inflammatory cell infiltration and hepatic fibrosis. The reduction in inflammatory cell infiltration correlated with deceased serum levels of keratinocyte derived chemokine (mKC) and MCP 1 and decreased hepatic gene expression of MCP-1 and VCAM-1. The reduction of hepatic fibrosis by WAY-362450 treatment corresponded to a reduction in hepatic gene expression of fibrosis markers. The positive effects of WAY-362450 were FXR-dependent since no protection was observed in MCD diet-fed FXR deficient mice. CONCLUSIONS: These findings demonstrate that FXR agonists may be useful for the treatment of non-alcoholic steatohepatitis.
Assuntos
Azepinas/farmacologia , Fígado Gorduroso/tratamento farmacológico , Hepatite/prevenção & controle , Indóis/farmacologia , Cirrose Hepática Experimental/prevenção & controle , Receptores Citoplasmáticos e Nucleares/agonistas , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Quimiocina CCL2/sangue , Quimiocinas/sangue , Deficiência de Colina/complicações , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Hepatite/etiologia , Lipídeos/sangue , Cirrose Hepática Experimental/etiologia , Masculino , Metionina/deficiência , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Citoplasmáticos e Nucleares/deficiência , Receptores Citoplasmáticos e Nucleares/genética , Triglicerídeos/metabolismoRESUMO
C-reactive protein (CRP), a human acute-phase protein, is a risk factor for future cardiovascular events and exerts direct pro-inflammatory and pro-atherogenic properties. The farnesoid X receptor (FXR), a member of the nuclear hormone receptor superfamily, plays an essential role in the regulation of enterohepatic circulation and lipid homeostasis. In this study, we report that two synthetic FXR agonists, WAY-362450 and GW4064, suppressed interleukin-6-induced CRP expression in human Hep3B hepatoma cells. Knockdown of FXR by short interfering RNA attenuated the inhibitory effect of the FXR agonists and also increased the ability of interleukin-6 to induce CRP production. Furthermore, treatment of wild type C57BL/6 mice with the FXR agonist, WAY-362450, attenuated lipopolysaccharide-induced serum amyloid P component and serum amyloid A3 mRNA levels in the liver, whereas no effect was observed in FXR knockout mice. These data provide new evidence for direct anti-inflammatory properties of FXR.
Assuntos
Reação de Fase Aguda/imunologia , Proteína C-Reativa/antagonistas & inibidores , Proteínas de Ligação a DNA/fisiologia , Interleucina-6/fisiologia , Receptores Citoplasmáticos e Nucleares/fisiologia , Fatores de Transcrição/fisiologia , Reação de Fase Aguda/genética , Animais , Proteína C-Reativa/biossíntese , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/agonistas , Proteínas de Ligação a DNA/genética , Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/genética , Receptores Citoplasmáticos e Nucleares/agonistas , Receptores Citoplasmáticos e Nucleares/genética , Fatores de Transcrição/agonistas , Fatores de Transcrição/genéticaRESUMO
OBJECTIVE: To investigate high risk human papillomavirus (HR-HPV) prevalence among married women in Beijing and to study the high risk factors. METHODS: During March 2007 to September 2008, a total of 6185 married women sampled from 137 communities in 12 districts were screened by HR-HPV DNA test and cytological test. The interview was carried out with unified questionnaires. The database was set up and twice entered in EpiData 3.0. After checked up, the data were analyzed in SPSS 15.0. RESULTS: (1) The HR-HPV infection rate was 9.89%. The HR-HPV infection rate of the city zone, the suburb and the exurb were 9.34%, 10.51% and 9.51% (P > 0.05). The HR-HPV infection rate of the native and the outlander were 9.53%, 11.30% (P < 0.05). (2) The age distribution of HR-HPV infection was that the rate was around 10% among 25 to 44 age groups, which was the highest (11.21%) in 30 to 34 age group; then the rate was descended as the age raising, the rate of 50 to 54 age group was the lowest (7.78%). (3) Multiple logistic regression showed that the related risk factors of HR-HPV infection mainly included 1000 RMB and above of family income per person per month, possessing more than 1 sexual partner of her husband, outlander and high levels of education. (4) The prevalence of cervical intraepithelial neoplasia (CIN) in HR-HPV positive group was significantly higher than that in HR-HPV negative group (29.76% vs 3.32%, P < 0.01). CONCLUSIONS: (1) The HR-HPV infection rate among aged 25 to 54 years was 9.9% and there was no significant difference in area distribution. (2) The high risk population which should strengthen screening was the married bearing-age women with high level of family income, outlander, high levels of education and her husband possessing more than 1 sexual partner. (3) HR-HPV infection is the main risk factor for CIN and cervical cancer, while does not provide a causal relationship with them. The high risk population should be checked regularly to understand the development of HR-HPV infection and CIN incidence.
Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Pequim , Estudos Epidemiológicos , Feminino , Humanos , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/diagnóstico , Displasia do Colo do Útero/virologiaRESUMO
AIMS: In China, more and more research on the management of urinary incontinence (UI) is being conducted; a robust questionnaire to evaluate the symptoms and impact of UI will be very helpful. Thus, the Chinese version of The International Consultation on Incontinence Questionnaire (ICIQ) was developed. METHODS: Initial translation and back translation of the ICIQ-UI short form, the ICIQ-FLUTS, the ICIQ-FLUTS long form, the ICIQ-LUTSqol, and the ICIQ-FLUTSsex were completed by native Chinese and English speaker, respectively. Then, the psychometric properties of the Chinese version of the five ICIQ modules, including the content/face validity, internal consistency, and test-retest reliability were examined. RESULTS: The back translation of the questionnaires was consistent with the original English questionnaires. The Chinese version of the five ICIQ modules was easily completed, and the missing data were less than 2.5%. The Cornbach's alpha coefficient was 0.71-0.96. In the test-retest, the agreement rate of the two tests exceeded 95% and the kappa values were 0.72-0.93 (P < 0.001). CONCLUSIONS: The Chinese version of the five ICIQ modules was easily understood, and had adequate internal consistency and reliability. It can be used in the study of Chinese-speaking groups around the world.
Assuntos
Pesquisa Biomédica/métodos , Inquéritos e Questionários , Incontinência Urinária/diagnóstico , China , Compreensão , Indicadores Básicos de Saúde , Humanos , Idioma , Psicometria , Reprodutibilidade dos TestesRESUMO
Trehalose (α-D-glucopyranosyl α-D-glucopyranoside) is a non-reducing disaccharide that serves as a carbon source and stress protectant in apple trees. Trehalose-6-phosphate (T6P) is the biosynthetic precursor of trehalose. It functions as a crucial signaling molecule involved in the regulation of floral induction, and is closely related to sucrose. Trehalose-6-phosphate synthase (TPS) family members are pivotal components of the T6P biosynthetic pathway. The present study identified 13 apple TPS family members and characterized their expression patterns in different tissues and in response to exogenous application of sucrose during floral induction. 'Fuji' apple trees were sprayed with sucrose prior to the onset of floral induction. Bud growth, flowering rate, and endogenous sugar levels were then monitored. The expression of genes associated with sucrose metabolism and flowering were also characterized by RT-quantitative PCR. Results revealed that sucrose applications significantly improved flower production and increased bud size and fresh weight, as well as the sucrose content in buds and leaves. Furthermore, the expression of MdTPS1, 2, 4, 10, and 11 was rapidly and significantly up-regulated in response to the sucrose treatments. In addition, the expression levels of flowering-related genes (e.g., SPL genes, FT1, and AP1) also increased in response to the sucrose sprays. In summary, apple TPS family members were identified that may influence the regulation of floral induction and other responses to sucrose. The relationship between sucrose and T6P or TPS during the regulation of floral induction in apple trees is discussed.
Assuntos
Flores/crescimento & desenvolvimento , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Glucosiltransferases/biossíntese , Malus/crescimento & desenvolvimento , Proteínas de Plantas/biossíntese , Sacarose/farmacologia , Flores/genética , Glucosiltransferases/genética , Malus/genética , Proteínas de Plantas/genética , Fosfatos Açúcares/genética , Fosfatos Açúcares/metabolismo , Trealose/análogos & derivados , Trealose/genética , Trealose/metabolismoRESUMO
BACKGROUND: Normal chow (low fat)-fed mice deficient in both the HDL receptor SR-BI and apolipoprotein E (SR-BI/apoE dKO) provide a distinctive model of coronary heart disease (CHD). They exhibit early-onset hypercholesterolemia characterized by unesterified cholesterol-rich abnormal lipoproteins (lamellar/vesicular and stacked discoidal particles), occlusive coronary atherosclerosis, spontaneous myocardial infarction, cardiac dysfunction, and premature death ( approximately 6 weeks of age). Mice in which similar features of CHD could be induced with a lipid-rich diet would represent a powerful tool to study CHD. METHODS AND RESULTS: To generate a diet-inducible model of CHD, we bred SR-BI-deficient (SR-BI KO) mice with hypomorphic apolipoprotein E mice (ApoeR61(h/h)) that express reduced levels of an apoE4-like murine apoE isoform and exhibit diet-induced hypercholesterolemia. When fed a normal chow diet, SR-BI KO/ApoeR61(h/h) mice did not exhibit early-onset atherosclerosis or CHD; the low expression level of the apoE4-like murine apoE was atheroprotective and cardioprotective. However, when fed an atherogenic diet rich in fat, cholesterol, and cholate, they rapidly developed hypercholesterolemia, atherosclerosis, and CHD, a response strikingly similar to that of SR-BI/apoE dKO mice fed a chow diet, and they died 32+/-6 days (50% mortality) after initiation of the high-fat feeding. CONCLUSIONS: The SR-BI KO/ApoeR61(h/h) mouse is a new model of diet-induced occlusive coronary atherosclerosis and CHD (myocardial infarction, cardiac dysfunction and premature death), allowing control of the age of onset, duration, severity, and possibly regression of disease. Thus, SR-BI KO/ApoeR61(h/h) mice have the potential to contribute to our understanding of CHD and its prevention and treatment.