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Objective: To explore the characteristics and correlations of vaginal flora in women with cervical lesions. Methods: A total of 132 women, including 41 women diagnosed with normal cervical (NC), 39 patients with low-grade cervical intraepithelial neoplasia (CIN 1), 37 patients with high-grade cervical intraepithelial neoplasia (CIN 2/3) and 15 patients with cervical squamous cell carcinoma (SCC), who came from the gynecological clinic of Second Hospital of Shanxi Medical University during January 2018 to June 2018, were enrolled in this study according to the inclusive and exclusive criteria strictly. The vaginal flora was detected by 16S rDNA sequencing technology. Co-occurrence network analysis was used to investigate the Spearman correlations between different genera of bacteria. Results: The dominant bacteria in NC, CIN 1 and CIN 2/3 groups were Lactobacillus [constituent ratios 79.4% (1 869 598/2 354 098), 63.6% (1 536 466/2 415 100) and 58.3% (1 342 896/2 301 536), respectively], while Peptophilus [20.4% (246 072/1 205 154) ] was the dominant bacteria in SCC group. With the aggravation of cervical lesions, the diversity of vaginal flora gradually increased (Shannon index: F=6.39, P=0.001; Simpson index: F=3.95, P=0.012). During the cervical lesion progress, the ratio of Lactobacillus gradually decreased, the ratio of other anaerobes such as Peptophilus, Sneathia, Prevotella and etc. gradually increased, and the differential bacteria (LDA score >3.5) gradually evolved from Lactobacillus to other anaerobes. The top 10 relative abundance bacteria, spearman correlation coefficient>0.4 and P<0.05 were selected. Co-occurrence network analysis showed that Prevotella, Peptophilus, Porphyrinomonas, Anaerococcus, Sneathia, Atopobium, Gardnerella and Streptococcus were positively correlated in different stages of cervical lesions, while Lactobacillus was negatively correlated with the above anaerobes. It was found that the relationship between vaginal floras in CIN 1 group was the most complex and only Peptophilus was significantly negatively correlated with Lactobacillus in SCC group. Conclusions: The increased diversity and changed correlations between vaginal floras are closely related to cervical lesions. Peptophilus is of great significance in the diagnosis, prediction and early warning of cervical carcinogenesis.
Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Vagina/microbiologia , Neoplasias do Colo do Útero/genética , Colo do Útero , Lactobacillus/genéticaRESUMO
Objective: To investigate the breakthrough incidence of invasive fungal disease(IFD) and side effects of posaconazole as primary prophylaxis during induction chemotherapy for acute myeloid leukemia(AML). Methods: A total of 206 newly diagnosed AML patients admitted to our department during January 2016 and December 2018 were enrolled in the study. Exclusive criteria were as followings including patients diagnosed as acute promyelocytic leukemia; those who received intravenous antifungal therapy after admission or had history of IFD one month before induction chemotherapy, or those with functional insufficiency of vital organs and those older than 65. Forty-seven patients received posaconazole (posaconazole group), 61 cases received voriconazole (voriconazole group) and 98 cases did not receive any prophylaxis (control group) during induction chemotherapy. Prophylactic efficacy and safety between posaconazole and voriconazole were compared. Results: During induction chemotherapy, five possible cases of IFD occurred in posaconazole group (10.6%); while 11 cases (18.0%) were in voriconazole group including 7 possible, 3 probable and 1 proven. Thirty-five cases (35.7%) in control group were diagnosed as IFD including 19 possible, 11 probable and 5 proven ones. The incidences of IFD in posaconazole and voriconazole group were significantly lower than that in control group (P<0.05). The difference of posaconazole group and voriconazole group was not significant (P>0.05). The reported adverse events in posaconazole group were significantly lower than those in voriconazole group [12.8%(6/47) vs. 32.8%(20/61), P<0.05]. Conclusions: Posaconazole and voriconazole decrease IFD as primary prophylaxis during induction chemotherapy in patients with AML. The prophylactic effect of IFD with posaconazole is similar as voriconazole, but posaconazole shows better safety.
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Antifúngicos/uso terapêutico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/prevenção & controle , Leucemia Mieloide Aguda/microbiologia , Triazóis/uso terapêutico , Antibioticoprofilaxia , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/tratamento farmacológico , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/microbiologia , Infecções Oportunistas/prevenção & controle , Estudos Retrospectivos , VoriconazolRESUMO
Objective: To analyze the prognostic impact of Ikaros family zinc finger 1(IKZF1) mutation on adult Philadelphia chromosome (Ph1) positive acute lymphoblastic leukemia (ALL) patients. Methods: IKZF1 mutation was detected in 63 adult Ph1 positive ALL patients at diagnosis using capillary electrophoresis. Recruited patients were treated in our center and other three hospitals in Ningbo from January 2014 to January 2017. Clinical data were collected and retrospectively analyzed. Results: Thirty-nine (61.9%) patients were positive IKZF1 mutation in this cohort. The white blood cell (WBC) count in IKZF1 mutation group was significantly higher than that of mutation negative group [(64.6±11.3)×10(9)/L vs. (33.7±5.6)×10(9)/L, P<0.05]. Patients with WBC count over 30×10(9)/L accounted for 56.4% in IKZF1 mutation group. Complete remission (CR) rate in the IKZF1 mutation group was also lower than that of negative group after induction chemotherapy (64.1% vs. 75.0%, P>0.05). IKZF1 was a negative prognostic factor but not independent factor for survival by univariate and multivariate analyses. Patients were divided into chemotherapy and allogeneic transplantation groups. The 3-year overall survival (OS) rate and 3-year leukemia-free survival (LFS) rate in IKZF1 mutation group were significantly lower than those of negative group in both transplantation group (42.3% vs. 59.3%; 31.2% vs. 50.0%; respectively, both P<0.05) and chemotherapy group (24.8% vs. 40.0%; 19.0% vs. 34.3%; respectively, both P<0.05). Conclusion: IKZF1 mutation is a poor prognostic factor for adult Ph1 positive ALL patients.
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Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Fator de Transcrição Ikaros , Prognóstico , Estudos Retrospectivos , Dedos de ZincoRESUMO
Numerous synthetic RNA-based controls for integrating sensing switches with function devices have been demonstrated in a variety of organisms for gene regulation. Although potential advantages of RNA-based genetic control strategies have been shown in clinical applications, successfully extending these engineered systems into medical applications has seldom been reported. Here, a synthetic RNA-based ribozyme system and its application in advancing rationally designed cellular therapy were described. The theophylline-responsive, ribozyme-based device provided a powerful platform for suicide gene expression regulation in tumor cells. Moreover, we demonstrate the ability of our synthetic controller to modulate effectively the viability of the cells in response to drug input. Our RNA-based regulatory system could dose-dependently fine-tune transgene expression in mammalian cells and address urgent limitations in existing genetic control strategies for gene- and cell-based therapies in the future.
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Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Genes Transgênicos Suicidas/genética , Engenharia Genética , Neoplasias Pulmonares/metabolismo , RNA Catalítico/genética , Teofilina/farmacologia , Células A549 , Broncodilatadores/farmacologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HeLa , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Timidina Quinase/genética , Timidina Quinase/metabolismoRESUMO
Correction for 'Real-space evidence of the equilibrium ordered bicontinuous double diamond structure of a diblock copolymer' by C. Y. Chu et al., Soft Matter, 2015, 11, 1871-1876.
RESUMO
The ordered bicontinuous double diamond (OBDD) structure has long been believed to be an unstable ordered network nanostructure, which is relative to the ordered bicontinuous double gyroid (OBDG) structure for diblock copolymers. Using electron tomography, we present the first real-space observation of the thermodynamically stable OBDD structure in a diblock copolymer composed of a stereoregular block, syndiotactic polypropylene-block-polystyrene (sPP-b-PS), in which the sPP tetrapods are interconnected via a bicontinuous network with Pn3Ìm symmetry. The OBDD structure underwent a thermally reversible order-order transition (OOT) to OBDG upon heating, and the transition was accompanied with a slight reduction of domain spacing, as demonstrated both experimentally and theoretically. The thermodynamic stability of the OBDD structure was attributed to the ability of the configurationally regular sPP block to form helical segments, even above its melting point, as the reduction of internal energy associated with the helix formation may effectively compensate the greater packing frustration in OBDD relative to that in the tripods of OBDG.
RESUMO
Poly(3-hydroxybutyrate) (PHB) was accumulated in full-scale municipal waste activated sludge at pilot scale. After accumulation, the fate of the PHB-rich biomass was evaluated over two weeks as a function of initial pH (5.5, 7.0 and 10), and incubation temperature (25, 37 and 55°C), with or without aeration. PHB became consumed under aerobic conditions as expected with first order rate constants in the range of 0.19 to 0.55 d-1. Under anaerobic conditions, up to 63 percent of the PHB became consumed within the first day (initial pH 7, 55°C). Subsequently, with continued anaerobic conditions, the polymer content remained stable in the biomass. Degradation rates were lower for acidic anaerobic incubation conditions at a lower temperature (25°C). Polymer thermal properties were measured in the dried PHB-rich biomass and for the polymer recovered by solvent extraction using dimethyl carbonate. PHB quality changes in dried biomass, indicated by differences in polymer melt enthalpy, correlated to differences in the extent of PHB extractability. Differences in the expressed PHB-in-biomass melt enthalpy that correlated to the polymer extractability suggested that yields of polymer recovery by extraction can be influenced by the state or quality of the polymer generated during downstream processing. Different post-accumulation process biomass management environments were found to influence the polymer quality and can also influence the extraction of non-polymer biomass. An acidic post-accumulation environment resulted in higher melt enthalpies in the biomass and, consequently, higher extraction efficiencies. Overall, acidic environmental conditions were found to be favourable for preserving both quantity and quality after PHB accumulation in activated sludge.
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Polímeros , Esgotos , Esgotos/química , Ácido 3-Hidroxibutírico , Biomassa , Hidroxibutiratos/química , Hidroxibutiratos/metabolismo , Poliésteres/química , Poliésteres/metabolismoRESUMO
BACKGROUND: The results of clinical trials for Alzheimer's disease (AD) patients treated with Intravenous immunoglobulin (IVIG) revealed inconsistency in efficacy. OBJECTIVE: To explore the neuroprotective effects and possible mechanisms of different IVIG in 3xTg-AD mice. METHODS: 3-month-old 3xTg-AD mice were administered intraperitoneally with different IVIG (A/B/C) for 3 months and then the therapeutic effects were observed and tested at 9 months of age. The bioavailability of IVIG and Aß40/42 concentrations in parietotemporal cortex was measured by ELISA. Behavioral tests were performed to examine cognitive functions. Immunohistochemistry was utilized to examine the deposition of Aß, the phosphorylation of tau, the levels of GFAP and Iba-1 in the hippocampus. Proteomics, Luminex assay and parallel reaction monitoring were performed to identify and verify the proteins that showed a marked change in the hippocampus. RESULTS: IVIG-C was more effective than IVIG-A and IVIG-B in counteracting cognitive deficits, ameliorating Aß deposits and tau phosphorylation, attenuating the activation of microglia and astrocytes in the hippocampus and inhibiting the secretion of pro-inflammatory factors. IVIG-C affected innate immunity and suppressed the activation of antigen processing and presentation by MHC class I molecule (APP-MHC-I). CONCLUSION: The efficacy of different IVIG on AD was significantly different, and only IVIG-C has been confirmed to possess significant neuroprotective effects, which are related to the inhibition of APP-MHC-I. IVIG may be a potential therapeutic for AD but further research is needed to evaluate the functional of IVIG before clinical trials of AD treatment.
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Doença de Alzheimer , Fármacos Neuroprotetores , Camundongos , Humanos , Animais , Imunoglobulinas Intravenosas/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Antígenos de Histocompatibilidade Classe I/uso terapêutico , Apresentação de Antígeno , Proteínas tau/metabolismo , Camundongos TransgênicosRESUMO
BACKGROUND: Acute myeloid leukemia (AML) is the most common type of acute leukemia and biologically heterogeneous diseases with poor prognosis. Thus, we aimed to identify prognostic markers to effectively predict the prognosis of AML patients and eventually guide treatment. METHODS: Prognosis-associated genes were determined by Kaplan-Meier and multivariate analyses using the expression and clinical data of 173 AML patients from The Cancer Genome Atlas database and validated in an independent Oregon Health and Science University dataset. A prognostic risk score was computed based on a linear combination of 5-gene expression levels using the regression coefficients derived from the multivariate logistic regression model. The classification of AML was established by unsupervised hierarchical clustering of CALCRL, DOCK1, PLA2G4A, FCHO2 and LRCH4 expression levels. RESULTS: High FCHO2 and LRCH4 expression was related to decreased mortality. While high CALCRL, DOCK1, PLA2G4A expression was associated with increased mortality. The risk score was predictive of increased mortality rate in AML patients. Hierarchical clustering analysis of the five genes discovered three clusters of AML patients. The cluster1 AML patients were associated with lower cytogenetics risk than cluster2 or 3 patients, and better prognosis than cluster3 patients (P values < 0.05 for all cases, fisher exact test or log-rank test). CONCLUSION: The gene panel comprising CALCRL, DOCK1, PLA2G4A, FCHO2 and LRCH4 as well as the risk score may offer novel prognostic biomarkers and classification of AML patients to significantly improve outcome prediction.
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Proteína Semelhante a Receptor de Calcitonina/genética , Proteínas de Ligação a Ácido Graxo/genética , Expressão Gênica , Fosfolipases A2 do Grupo IV/genética , Leucemia Mieloide Aguda/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Proteínas rac de Ligação ao GTP/genética , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidade , Análise Multivariada , Prognóstico , Fatores de Risco , Resultado do TratamentoRESUMO
Objective: To investigate the effect of red blood cell folate on the prognosis of high-risk human papillomavirus (HR-HPV) infection. Methods: A total of 564 participants with low-grade cervical intraepithelial neoplasias (CINâ ) were selected from the community-based married women cohort established in 2014. The general baseline information and factors related to HPV infection were collected. Meanwhile, HPV genotyping and levels of folate were measured. The subjects were divided into different levels of exposure group according to the folate levels and followed up for 24 months to observe the changes of HR-HPV infection status. There were four changes, including persistent infection, infection turned negative, from negative to positive and constant negative by comparing HR-HPV infection status at baseline and follow-up to 24 months. Results: 483 participators completed 24 months of follow-up observation, with a follow-up rate of 85.64% (483/564). The rates of persistent infection, infection turned negative, from negative to positive, and the constant negative were 52.45% (75/143), 47.55% (68/143), 19.71% (67/340), 80.29% (273/340), respectively. Our results demonstrated that the risk of persistent infection (aRR=2.50, 95%CI: 1.55-4.02) and from negative to positive (aRR=4.55, 95%CI: 2.52-8.23) in the low level of folate were significantly higher than that in the high level of folate, especially the risk of homotype persistent infection (aRR=2.72, 95%CI: 1.51-4.90). The risk of persistent infection (trend χ2=20.62, P<0.001), from negative to positive (trend χ2=31.76, P<0.001), persistent homotypic infection (trend χ2=20.09, P<0.001) increased with the decrease of red blood cell folate level. On the contrary, no similar results were found in persistent heterotypic infection. Conclusions: A low level of red blood cell folate could increase the risk of HR-HPV persistent infection and from negative to positive. In women with HR-HPV infection, the risk of persistent homotypic infection is higher.
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Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Estudos de Coortes , Eritrócitos , Feminino , Ácido Fólico , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Infecção Persistente , PrognósticoRESUMO
Objective: To investigate the diagnostic value of different vaginal micro-environmental factors in low-grade cervical intraepithelial neoplasia (CIN â ) and determine the optimal model in high-risk human papillomavirus (HR-HPV) infection. Methods: A total of 926 women, including 623 with normal cervical (NC) condition and 303 CINâ patients, had undergone pathological examinations, and were enrolled in the study. All the women were from a community previously established cohort. Vaginal cleanliness, pH, H2O2, ß-glucuronidase, coagulase, sialidase, and leukocyte esterase (LE) were detected by the combined detection method aerobic vaginitis/bacterial vaginosis in vaginal secretions. HPV genotyping was performed by using the flow-through hybridization technology. The data were analyzed by SAS 9.2 and SPSS 23.0. Results: The vaginal cleanliness, pH, sialidase, and LE were determined as the representative vaginal micro-environment factors by principal component analysis. Based on logistic regression theory to analyze the ROC curve, the results showed that the highest sensitivity was with pH value (76.2%), and the highest specificity was with sialidase (90.9%). The area under ROC curve were higher in combination detection modes of sialidase+LE (0.714), pH+sialidase+LE (0.719), vaginal cleanness+sialidase+LE (0.713) and pH+vaginal cleanness+sialidase+LE (0.709). According to HR-HPV infection status, the TOPSIS method was used to analyze the combined detection optimal model. Specifically, we found that the best diagnostic model was pH+sialidase +LE (Ci=0.585) in the HR-HPV positive group and vaginal cleanness+sialidase+LE (Ci=0.641) in the negative group. Conclusions: The combined detection of vaginal microenvironment factors could be used for auxiliary diagnosis for CINâ . It would be more effective when detecting pH, sialidase, and LE in HR-HPV positive women while vaginal cleanness, sialidase, and LE in HR-HPV negative women at the same time.
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Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Peróxido de Hidrogênio , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Microambiente Tumoral , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal , Displasia do Colo do Útero/diagnósticoRESUMO
Objective: To investigate the effects of polycyclic aromatic hydrocarbons (PAHs) exposure on the prognosis of high risk human papillomavirus (HR-HPV) infection. Methods: In this prospective study, 564 patients with low-grade cervical intraepithelial neoplasia confirmed by pathology were selected from the natural cohort population established by our research group in Shanxi province in 2014. Based on the baseline data of demographic characteristics and factors related to HPV infection, the concentrations of 1-hydroxypyrene in urine samples of the patients were determined by high performance liquid chromatography to define the exposure level of PAHs. At baseline survey and follow-up after 24 months, flow-through hybridization was used to detect HPV infection types, and to evaluate the prognosis of HR-HPV (persistent infection, negative conversion, positive conversion and persistent negative status). Results: Of the 564 subjects, 483 completed the follow-up, with a follow-up rate of 85.6% (483/564). Among them, the persistent infection rate was 52.4% (75/143), the persistent homotype infection rate was 35.7% (51/143), the negative conversion rate was 47.6% (68/143), the positive conversion rate was 19.7% (67/340), and the persistent negative rate was 80.3% (273/340). The follow-up results showed that the persistent infection rate (aRR=3.22, 95%CI: 1.85-5.62) and positive conversion rate (aRR=2.84, 95%CI: 1.64-4.94) of HR-HPV in high PAHs exposure group were higher than those in low PAHs exposure group, while the persistent negative rate (aRR=0.55, 95% CI: 0.43-0.70) of HR-HPV in high PAHs exposure group were lower than those in low PAHs exposure group. Based on restrictive cubic spline analysis, the results showed that the effects of PAHs exposure on persistent HR-HPV infection and persistent homotype infection showed an ascending linear dose-response relationship, while on HR-HPV positive conversion and persistent negative status showed an ascending and declining nonlinear dose-response relationship respectively (P<0.01). Conclusions: High PAHs exposure could promote persistent HR-HPV infection and persistent homotypic infection. Reducing PAHs exposure might conducive to HR-HPV continuous negative maintenance. Active prevention and control of PAHs exposure is of great significance to prevent HR-HPV infection and persistent infection.
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Infecções por Papillomavirus , Hidrocarbonetos Policíclicos Aromáticos , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Estudos de Coortes , Feminino , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Prognóstico , Estudos ProspectivosRESUMO
Objective: To investigate the clinical characteristics and prognosis in adult acute myeloid leukemia (AML) patients with FLT3-ITD and CEBPA double-mutated (CEBPAdm) co-mutation. Methods: Clinical data and prognostic factors were retrospectively analyzed in adult AML patients with FLT3-ITD and CEBPAdm co-mutation at The First Affiliated Hospital of Zhengzhou University from January 2016 to September 2018. Results: Among 599 non-acute promyelocytic leukemia (APL) patients, 268 received gene mutation detection, who were divided into 4 groups including 19 FLT3-ITD positive (FLT3-ITD(+)) and CEBPAdm positive (CEBPAdm(+)) cases (group A) , 84 FLT3-ITD(+) and CEBPAdm(-) cases (group B) , 95 FLT3-ITD(-) and CEBPAdm(+) cases (group C) , 70 double negative mutation cases (group D) . Gender, platelet count, FAB classification, induction treatment regimen and fusion gene mutation were comparable among four groups (P>0.05) , while age onset, peripheral white blood cell (WBC) count, hemoglobin, percentage of blasts in peripheral blood, percentage of blasts in bone marrow, complete remission rate (CR(1) rate) after the first induction chemotherapy, the relapse rate, the median progression-free survival (PFS) time, and median overall survival (OS) time were significantly different between groups (P<0.05) . When compared in pairs, gender, age onset, hemoglobin, platelet count, FAB classification in group A were not statistically different compared to group B, C and D (P>0.05) , while patients in group A had higher WBC count, blasts in peripheral blood, minimal residual disease (MRD) in bone marrow. The CR(1) rates of group A, B, C, and D were 50.0%ã32.4%ã59.8%ã39.0% respectively (P=0.003) , and the relapse rates were 55.6%, 50.0%, 21.1%, 40.0% (P<0.001) . As to survival, the median OS in each group was 6.25, 3.0, 15.5, 10.5 months respectively (P<0.001) , and the median PFS was 5.0, 4.0, 10.0, 6.7 months (P=0.032) . Conclusion: Adult AML patients with FLT3-ITD and CEBPAdm co-mutation have a higher leukemia load and low CR(1) rate, which translates into poor prognosis with high relapse rate and short survival time.
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Proteínas Estimuladoras de Ligação a CCAAT/genética , Leucemia Mieloide Aguda , Tirosina Quinase 3 Semelhante a fms/genética , Adulto , Humanos , Leucemia Mieloide Aguda/genética , Mutação , Prognóstico , Indução de Remissão , Estudos RetrospectivosRESUMO
Transcription factor IID (TFIID) binds to the TATA box promoter element and regulates the expression of most eukaryotic genes transcribed by RNA polymerase II. Complementary DNA (cDNA) encoding a human TFIID protein has been cloned. The human TFIID polypeptide has 339 amino acids and a molecular size of 37,745 daltons. The carboxyl-terminal 181 amino acids of the human TFIID protein shares 80% identity with the TFIID protein from Saccharomyces cerevisiae. The amino terminus contains an unusual repeat of 38 consecutive glutamine residues and an X-Thr-Pro repeat. Expression of DNA in reticulocyte lysates or in Escherichia coli yielded a protein that was competent for both DNA binding and transcription activation.
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Regiões Promotoras Genéticas , Saccharomyces cerevisiae/genética , Fatores de Transcrição/genética , Transcrição Gênica , Sequência de Aminoácidos , Clonagem Molecular , Escherichia coli/genética , Expressão Gênica , Células HeLa/metabolismo , Humanos , Dados de Sequência Molecular , Proteínas Recombinantes/metabolismo , Reticulócitos/metabolismo , Homologia de Sequência do Ácido Nucleico , Fator de Transcrição TFIID , Fatores de Transcrição/metabolismoRESUMO
OBJECTIVE: Coronary calcification detected by CT is a marker for atherosclerotic disease with prognostic significance. However, potentially unstable plaque is characterized by a high lipid content rather than calcification, which may make detection using the calcium score difficult. To assess the prevalence and severity of atherosclerotic disease in patients without coronary calcification, we evaluated findings in patients with a normal calcium score undergoing coronary CT angiography (CTA). MATERIALS AND METHODS: Data from 794 consecutive coronary CTA examinations performed between February 2005 and May 2007 were reviewed. The calcium scores were determined as part of coronary CTA examinations, and calcium was quantified according to the Agatston method. Patients underwent coronary CTA because of high risk for coronary artery disease (53%) or atypical symptoms or abnormal stress test results (47%). On coronary CTA, plaque was characterized as mild disease without hemodynamically significant stenosis, moderate disease without hemodynamically significant stenosis, moderate stenosis (50-70% luminal narrowing), or severe stenosis (> 70% luminal narrowing). RESULTS: Of the 729 patients included in the study, 325 (45%) had a normal calcium score. Of these, 167 (51%) had noncalcified plaque on coronary CTA. Twelve (3.7%) of those with a normal calcium score had at least moderate stenosis, five (1.5%) of whom had severe stenosis. Eight of the 12 patients with significant stenosis underwent invasive angiography and coronary stenting. CONCLUSION: A considerable atheroma burden including significant stenoses may be present in patients with no coronary calcification. Although the calcium score does add prognostic value to standard risk factors and serum markers, imaging the vessel wall directly may be helpful to identify noncalcified plaque and guide therapy.
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Calcinose/diagnóstico por imagem , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
AIMS: To investigate the antibacterial mechanism of carvacrol and thymol against Escherichia coli. METHODS AND RESULTS: The time-kill curve results showed that carvacrol and thymol at 200 mg l(-1) could inhibit the growth of E. coli. Flow cytometry and fluorescent dyes were used to explore the effect of two components on membrane permeability and membrane potential. In membrane permeability experiment, the mean fluorescence intensity of cells treated with 200 mg l(-1) carvacrol or thymol were lower than nonexposed cells. The ratio of red to green fluorescence intensity of DiOC2(3) reflected the change of membrane potential. Carvacrol and thymol at 200 mg l(-1) caused the ratio of red/green decreasing from 0.42 of control to 0.08 and 0.07, respectively. CONCLUSIONS: Carvacrol and thymol had desired antimicrobial effect on E. coli. The antibacterial effects were attributed to their ability to permeabilize and depolarize the cytoplasmic membrane. SIGNIFICANCE AND IMPACT OF THE STUDY: This study showed the potential use of flow cytometry as a suitable method to investigate the mode of antibacterial action of essential oil components.
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Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Monoterpenos/farmacologia , Timol/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Cimenos , Citometria de Fluxo , Potenciais da Membrana/efeitos dos fármacosRESUMO
OBJECTIVE: Circular RNAs (circRNAs) have been known as important regulators in tumorigenesis. Whether circRNAs are involved in papillary thyroid carcinoma (PTC) requires to be determined. In the present study, we aimed to investigate the expression and function of has_circ_0008274 in PTC. PATIENTS AND METHODS: Tissue expression of has_circ_0008274 was evaluated in Gene Expression Omnibus datasets (GSE93522). Real-time PCR assays were used to detect the expression of has_circ_0008274 in human PTC tissues and cell lines. The correlation of has_circ_0008274 expression with clinicopathological factors was statistically analyzed. The MTT assay, colony formation assay, transwell assays were performed to analyze and compare cell viability and invasion. Western blot analysis was used to quantify the expression of AMPK/mTOR signaling pathway proteins. RESULTS: We found that has_circ_0008274 was significantly upregulated in PTC tissues, and the level of has_circ_0008274 was negatively associated with TNM stage and lymph node metastasis. Loss-of-function assay indicated that knockdown of has_circ_0008274 suppressed PTC cells proliferation and invasion in vitro. Mechanistically, has_circ_0008274 could inhibit the activation of AMPK/mTOR signaling pathway, which was demonstrated by measuring the expression levels of p-AMPK and p-mTOR. CONCLUSIONS: These results demonstrate that increased has_circ_0008274 expression modulates has_circ_0008274 to enhance PTC cells proliferation and invasion. Has_circ_0008274/ AMPK/mTOR axis may be a novel therapeutic candidate target in PTC treatment.
Assuntos
Regulação Neoplásica da Expressão Gênica , RNA Circular/metabolismo , Transdução de Sinais/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Adulto , Linhagem Celular Tumoral , Proliferação de Células/genética , Conjuntos de Dados como Assunto , Feminino , Técnicas de Silenciamento de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , RNA Circular/genética , Serina-Treonina Quinases TOR/metabolismo , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/cirurgia , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Regulação para CimaRESUMO
It is commonly accepted that high salt concentrations negatively affect microbial activity in biological wastewater treatment reactors such as upflow anaerobic sludge blanket (UASB) reactors. Microbial aggregation in such reactors is equally important. It is well documented that anaerobic granules, when exposed to high salinity become weak and disintegrate, causing wash-out, operational problems and decreasing process performance. In this research, the possibility of microbial granule formation from dispersed biomass was investigated at salinity levels of 5 and 20 g Na+/L. High removal efficiencies of soluble influent organics were achieved at both salinity levels and this was accompanied by fast and robust formation of microbial granules. The process was found to be stable for the entire operational period of 217 days. As far as we know this is the first time it has been demonstrated that stable granule formation is possible at a salinity level as high as 20 g Na+/L. Methanosaeta was identified as the dominant methanogen at both salinity levels. Streptococcus spp. and bacteria belonging to the family Lachnospiraceae were identified as the dominant microbial population at 5 and 20 and g Na+/L, respectively.
Assuntos
Reatores Biológicos/microbiologia , Salinidade , Gerenciamento de Resíduos/métodos , Anaerobiose , Bactérias , Methanosarcinaceae/isolamento & purificação , Esgotos , Cloreto de Sódio , Águas ResiduáriasRESUMO
Objective: To investigate the impact of FLT3-ITD and DNMT3A R882 double mutations to the prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: FLT3-ITD, DNMT3A, C-kit, CEBPA, FLT3-TKD and NPM1 mutations were detected in 206 newly diagnosed AML patients by Sanger sequencing (M(3) and those received FLT3 inhibitor were excluded). Clinical data of AML patients were retrospectively analyzed to compare the prognosis of each gene mutation group. Results: â Of 206 patients, 104 were male and 102 female with a median age of 38 (3-63) years, including 6 cases of M(0), 24 cases of M(1), 56 cases of M(2), 39 cases of M(4), 63 cases of M(5), 6 cases of M(6) and 12 unclassified cases. â¡All 206 patients were divided into four groups according to the mutation gene at the time of diagnosis: FLT3-ITD(+) DNMT3A R882(+) group (group A), FLT3-ITD(+) DNMT3A R882(-) group (group B), FLT3-ITD(-) DNMT3A R882(+) group (group C) and FLT3-ITD(-) DNMT3A R882(-) groups (group D). Gender, leukocyte count at diagnosis, chromosome karyotype, the median age, FAB classification, disease status prior to transplantation, type of donor, conditioning regimen and GVHD were not significantly different between four groups (P>0.05). â¢The 2-year cumulative recurrence rate (CIR) of group A was significantly higher than that of other groups [group A (72.2±2.6)%, group B (38.6±0.6)%, group C (36.8±1.6)%, group D (27.8±0.1)%, respectively, P<0.05], while the 2-year overall survival (OS) rate and 2-year leukocyte-free survival (LFS) rate were lower than those of other groups [group A (30.9±13.3)%, (11.3±10.2)%; group B (67.5±7.8)%, (47.9±8.4)%; group C (61.4±12.4)%, (56.8±12.5)%; group D (80.1±3.7)%, (79.7±3.6)%, respectively, P<0.05]. Conclusion: AML patients with FLT3-ITD and DNMT3A R882 double mutations had a very high CIR and low OS, LFS after transplantation.