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1.
Huan Jing Ke Xue ; 41(2): 554-563, 2020 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608714

RESUMO

To investigate the pollution characteristics and sources of organic aerosols at a background site of the Yangtze River Delta, day- and night- PM2.5 samples were collected from May 30th to August 15th, 2018 in Chongming Island, China and measured for their normal alkanes (n-alkanes) and polycyclic aromatic hydrocarbons (PAHs) content employing a GC-MS technique. Concentrations of PM2.5, n-alkanes, and PAHs during the entire sampling period were (33±21) µg·m-3, (26±44) ng·m-3, and (0.76±1.0) ng·m-3, respectively. During the entire campaign, 35% of the collected PM2.5 samples were of a particle loading larger than the first grade of the China National Air Quality Standard (35 µg·m-3), suggesting that further mitigation with respect to air pollution in Chongming Island remains imperative. In the period with a PM2.5 concentration higher than 35 µg·m-3, which was classified as the pollution period, concentrations of n-alkanes and PAHs were one order of magnitude higher than those in the period with PM2.5 less than 15 µg·m-3, which was classified as the clean period. During the entire campaign, OC was higher in the daytime than in the nighttime, mainly due to the daytime photooxidation that enhanced the formation of secondary organic aerosols. During the pollution period, concentrations of EC and other pollutants were higher in the nighttime than in daytime, mainly due to the transport of the inland pollutants by the nighttime land breeze. Such a diurnal difference was not observed for the pollutants in clean periods, mainly due to the relatively clean breeze from East China Sea that diluted the air pollution. Diagnostic ratios showed that 67% of n-alkanes in PM2.5 was derived from fossil fuel combustion. PMF analysis further showed that during the pollution period, vehicle exhausts and industrial emissions were the largest sources of PAHs, both accounting for 51% of the total in PM2.5. In contrast, during the clean periods ship emissions were the largest source, contributing about 45% of the total PAHs, exceeding the sum (38%) of vehicle and industrial emissions.

2.
Cancer Med ; 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32492289

RESUMO

Adult patients with relapsed or refractory T-cell acute lymphoblastic leukemia (R/R-T-ALL) have extremely poor prognosis, representing an urgent unmet medical need. Finding an optimal salvage regimen to bridge transplantation is a priority. The CAG (cytarabine, aclarubicin, and G-CSF) regimen was initially used by one group in China, showing unexpectedly promising results in 11 R/R-T-ALL patients. Here, we report the multicenter results of 41 patients who received the CAG regimen as salvage therapy. After one cycle of the CAG regimen, complete remission and partial remission were achieved in 33 (80.5%) and two (4.9%) patients, respectively. Failure to respond was observed in six patients (14.6%). Early T-cell precursor (ETP) (n = 26) and non-ETP (n = 15) patients had a similar CR rate (80.8% vs 80.0%, P = .95). Among 41 patients, allo-HSCT was successfully performed in 27 (66%) patients (22 in CR and 5 in non-CR). With a median follow-up time of 12 months, the estimated 2-year overall survival and event-free survival were 68.8% (95% CI, 47.3%-83.0%) and 56.5% (95% CI, 37.1%-71.9%), respectively. The CAG regimen was well-tolerated, and no early death occurred. Our multicenter results show that the CAG regimen is highly effective and safe, representing a novel choice for adult patients with R/R-T-ALL and providing a better bridge to transplantation.

4.
Sci Total Environ ; 683: 341-350, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31132713

RESUMO

The recent development of microwave radiation technology has increased the application possibilities of waste tobacco stems (WTSs). In this study, the morphology and microwave absorption properties of tobacco stem materials as well as the pyrolysis of the resultant biomass (BMTS) were studied via thermogravimetry-differential scanning calorimetry (TG-DSC), scanning electron microscopy (SEM), mercury intrusion porosimetry (MIP), and a vector network analysis (VNA). The results show that the BMTS pyrolysis involves four stages in air: dehydration, heat transfer, pyrolysis, and carbonisation, and it involves three stages in N2: moisture evaporation, de-volatilization, and charring. The microwave-assisted expansion of WTSs can improve the pore diameter and total porosity of the expanded tobacco stems (ETSs) and BMTS. The latter is a macroporous material with a total porosity of 78.2% and a probable pore size of 29.5 µm. Its pore size distribution ranges from 10.7 nm to 227 µm. The microwave absorption properties of the WTSs are affected by the moisture content, bulk density, and grain size; the properties can be enhanced by decreasing the grain size and increasing the moisture content and bulk density within the experimental range. The 3 dB bandwidth and amplitude vary by 0.45 MHz and - 0.406 dB per 1% increase in the moisture content of the materials, respectively. Our results demonstrate that tobacco stem materials with different moisture contents and grain sizes should be classified before the expansion or re-drying steps to ensure heating uniformity and product quality during the microwave radiation treatment.


Assuntos
Micro-Ondas , Caules de Planta/química , Tabaco/química , Varredura Diferencial de Calorimetria , Caules de Planta/efeitos da radiação , Porosidade , Pirólise , Termogravimetria , Tabaco/efeitos da radiação
5.
Lipids Health Dis ; 18(1): 118, 2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31122252

RESUMO

BACKGROUND: Fatty acid synthase (FASN) is overexpressed in most human carcinomas, including non-small cell lung cancer (NSCLC), and contributes to poor prognosis. An increasing number of studies have highlighted the potential function of FASN as both a biomarker and therapeutic target for cancers. However, the underlying molecular mechanisms of FASN in glucose metabolism and the malignant biological behavior of NSCLC remain the subjects of intensive investigation. METHODS: FASN expression was depleted by FASN-siRNA in A549 and NCI-H1299 cell lines to detect the function of glucose metabolism and the malignant biological behavior of NSCLC cells. Western-blot and qPCR were applied to determine the expressions of FASN, t-AKT, p-AKT, t-ERK, p-ERK, PKM2, HK2 and AZGP1. ATP and lactate were detected to determine the activation of glucose metabolism. CCK8 and transwell assays were used to detect the proliferation, invasion, and migration capacity of the two types of NSCLC cells. The xenograft mouse model was used to evaluate tumor weights after suppression of FASN. RESULTS: LV-FASN-siRNA and its control lentiviral vector were successfully transfected into the two types of NSCLC cells (A549 and NCI-H1299). LV-FASN siRNA significantly suppressed FASN expression in both NSCLC cell types, and expressions of p-AKT, p-ERK, PKM2, and AZGP1 were also significantly decreased. Notably, the levels of ATP and lactate were significantly decreased after transfection with LV-FASN siRNA. The proliferation of both NSCLC cell types was decreased after suppression of FASN. The invasion and migration capacity of A549, but not NCI-H1299, were inhibited following down-regulation of FASN. In vivo, inhibition of FASN caused a marked animal tumor weight loss. CONCLUSIONS: FASN was involved in glucose metabolism via down-regulation of the AKT/ERK pathway and eventually altered the malignant phenotype in lung cancer cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Ácido Graxo Sintase Tipo I/antagonistas & inibidores , Glucose/metabolismo , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Movimento Celular , Ácido Graxo Sintase Tipo I/metabolismo , Regulação Neoplásica da Expressão Gênica , Vetores Genéticos/metabolismo , Humanos , Lentivirus/genética , Neoplasias Pulmonares/genética , Camundongos Nus , Invasividade Neoplásica , Interferência de RNA , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Anal Chim Acta ; 1070: 112-122, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31103164

RESUMO

Capillary electrophoresis-systematic evolution of ligands by exponential enrichment (CE-SELEX) has proven to be an effective technique for aptamers selection. In this study, we present an online reaction based convenient single-step CE-SELEX (ssCE-SELEX) mode with human thrombin (H-Thr) as a model target. The selection progress was monitored through bulk Kd analysis, which showed more than a 1000-fold improvement over the initial library after two rounds of selection. Three selected candidate sequences presented high binding affinities against H-Thr with nanomolar (nM) Kd determined by nonequilibrium capillary electrophoresis of equilibrium mixtures (NECEEM, 56.4-177.1 nM) and CE based non-linear fitting (CE-NLF, 98.2-199.7 nM). They also exhibited high specificities towards H-Thr compared with bovine thrombin, IgG, lysozyme, and lactoferrin. Meanwhile, the Kd results by isothermal titration calorimetry (ITC) confirmed the effective CE in measuring the aptamer affinity. In addition, three candidates were applied as aptasensors in the AuNPs based colorimetric assay, which showed visible color change and good linear relationships (R2 > 0.93) with H-Thr concentration. Furthermore, molecular dynamics (MD) simulation was performed to validate the binding of the three candidates with H-Thr by binding sites and binding free energy. The ssCE-SELEX method avoids off-line incubation, saves time and sample, and may provide a universal and convenient method for aptamers selection.


Assuntos
Aptâmeros de Nucleotídeos/química , DNA de Cadeia Simples/química , Sistemas On-Line , Técnica de Seleção de Aptâmeros/métodos , Animais , Calorimetria , Bovinos , Eletroforese Capilar , Humanos , Imunoglobulina G/análise , Lactoferrina/análise , Ligantes , Muramidase/análise , Muramidase/metabolismo , Trombina/análise
7.
Sci Total Environ ; 682: 541-552, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31129542

RESUMO

A three-dimensional variational (3DVAR) lidar data assimilation method is developed based on the Community Radiative Transfer Model (CRTM) and Weather Research and Forecasting model coupled to Chemistry (WRF-Chem) model. A 3DVAR data assimilation (DA) system using lidar extinction coefficient observation data is established, and variables from the Model for Simulating Aerosol Interactions and Chemistry (MOSAIC) mechanism of the WRF-Chem model are employed. Hourly lidar extinction coefficient data from 12:00 to 18:00 UTC on March 13, 2018 at four stations in Beijing are assimilated into the initial field of the WRF-Chem model; subsequently, a 24 h PM2.5 concentration forecast is made. Results indicate that assimilating lidar data can effectively improve the subsequent forecast. PM2.5 forecasts without using lidar DA are remarkably underestimated, particularly during heavy haze periods; in contrast, forecasts of PM2.5 concentrations with lidar DA are closer to observations, the model low bias is evidently reduced, and the vertical distribution of the PM2.5 concentration in Beijing is distinctly improved from the surface to 1200 m. Of the five aerosol species, improvements of NO3- are the most significant. The correlation coefficient between PM2.5 concentration forecasts with lidar DA and observations at 12 stations in Beijing is increased by 0.45, and the corresponding average RMSE is decreased by 25 µg·m-3, which respectively compared to those without DA.

8.
Exp Ther Med ; 17(1): 519-524, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30651831

RESUMO

The diaphragmatic fatigue that results from airflow obstruction is associated with the severe morbidity of patients with chronic obstructive pulmonary disease. Astragaloside IV (AS-IV) has antioxidant, anti-apoptotic and anti-inflammatory activities in various cell types. The present study aimed to evaluate the protective effects of AS-IV in diaphragmatic muscle cells. Diaphragmatic muscle cells extracted from neonatal rats were treated with a series of AS-IV concentrations (5, 10 or 20 mg/l) and the AKT inhibitor GSK690693 in the presence of interleukin-8 (IL-8). Cell proliferation and AKT phosphorylation were measured using Cell Counting Kit-8 and western blot assays, respectively. Cell apoptosis and reactive oxygen species (ROS) production were evaluated using flow cytometric analysis. Caspase activity and concentrations of proinflammatory factors (tumor necrosis factor-α, IL-6 and IL-8) were assessed using a caspase colorimetric assay and ELISA, respectively. IL-8 treatment resulted in decreased rates of cell proliferation and increased rates of AKT phosphorylation, cell apoptosis, caspase 3/9 activity, ROS production and proinflammatory factor production. AS-IV and GSK690693 treatment reversed the effects of IL-8. The effects of AS-IV were dose-dependent. The present results suggested that AS-IV is a candidate for the treatment of diaphragmatic fatigue due to its antioxidant, anti-apoptotic and anti-inflammatory activity.

9.
Int J Chron Obstruct Pulmon Dis ; 13: 2183-2190, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30140150

RESUMO

Purpose: Previous studies have described the incidence, risk factors, and outcomes for patients with acute exacerbations of COPD (AECOPD) developing acute kidney injury (AKI). However, little is known about the differences between community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) in patients with AECOPD. Thus, in this study, we compared prevalence, risk factors, and outcomes for these patients with CA-AKI and HA-AKI. Patients and methods: This study was conducted from January 2014 to January 2017, and data from adult inpatients with AECOPD were analyzed retrospectively. A total of 1,768 patients were included, 280 patients were identified with CA-AKI and 97 patients were with HA-AKI. Results: Prevalence of CA-AKI was 15.8% and that of HA-AKI was 5.5%, giving an overall AKI prevalence of 21.3%. Patients with CA-AKI had a higher prevalence of chronic kidney disease (CKD) and lower prevalence of chronic cor pulmonale than patients with HA-AKI. Risk factors for developing HA-AKI and CA-AKI were similar, such as being elderly, requirement for mechanical ventilation, and a history of coronary artery disease and CKD. Patients with HA-AKI were more likely to have stage 3 AKI and worse short-term outcomes. In comparison with patients with CA-AKI, those with HA-AKI were more likely to require non-invasive mechanical ventilation (31.3% versus 16.8%; P = 0.003) and had a longer duration of mechanical ventilation (11 days versus 8 days; P = 0.020), longer hospitalization (14 days versus 12 days; P = 0.038), and higher inpatient mortality (32.0% versus 13.2%; P < 0.001). Patients with HA-AKI had worse (multivariate-adjusted) inpatient survival than those with CA-AKI (hazard ratio, 1.7 [95% confidence interval, 1.03-2.81; P = 0.038] for the HA-AKI group). Conclusion: AKI was common in patients with AECOPD requiring hospitalization. CA-AKI was more common than HA-AKI but otherwise demonstrated similar demographics and risk factors. Nevertheless, patients with HA-AKI had worse short-term outcomes.


Assuntos
Lesão Renal Aguda/etiologia , Progressão da Doença , Hospitalização , Doença Pulmonar Obstrutiva Crônica/complicações , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/patologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Prevalência , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Retrospectivos , Fatores de Risco
10.
Antiviral Res ; 152: 84-93, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29421320

RESUMO

Human adenoviruses (HAdVs) usually cause mild respiratory infections, but they can also lead to fatal outcomes for immunosuppressive patients. Unfortunately, there has been no specific anti-HAdV drug approved for medical use. A better understanding of the nature of virus-host interactions during infection is beneficial to the discovery of potential antiviral targets and new antiviral drugs. In this study, a time-course transcriptome analysis of HAdV-infected human lung epithelial cells (A549 cells) was performed to investigate virus-host interactions, and several key host molecules involved in the HAdV infection process were identified. The RARß (retinoic acid receptor ß) molecule, one of the upstream regulatory factors of differentially expressed genes (DEGs), played important roles in HAdV replication. The results of reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting showed that RARß mRNA and protein were downregulated by HAdV infection in the A549 cells. The knockdown of RARß by RARß siRNA increased the HAdV production and the overexpression of RARß decreased the HAdV production. Furthermore, FDA-approved Tazarotene, which is an RAR selective agonist with relatively more selectivity for RARß, was found to inhibit HAdV replication in vitro. Taken together, our study presents a key host molecule in adenovirus infection, which could be developed as a potential host target to an anti-adenovirus drug. In addition, this study provides evidence for the re-exploitation of an FDA-approved small molecule for therapeutic applications in adenovirus replication.


Assuntos
Infecções por Adenoviridae/metabolismo , Adenovírus Humanos/fisiologia , Receptores do Ácido Retinoico/metabolismo , Replicação Viral/efeitos dos fármacos , Células A549 , Infecções por Adenoviridae/tratamento farmacológico , Infecções por Adenoviridae/genética , Infecções por Adenoviridae/virologia , Adenovírus Humanos/efeitos dos fármacos , Adenovírus Humanos/genética , Antivirais/farmacologia , Regulação para Baixo/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Humanos , Receptores do Ácido Retinoico/agonistas , Receptores do Ácido Retinoico/genética
11.
Interdiscip Sci ; 10(1): 126-130, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29380342

RESUMO

Essential hypertension (EH) has become a major chronic disease around the world. To build a risk-predicting model for EH can help to interpose people's lifestyle and dietary habit to decrease the risk of getting EH. In this study, we constructed a EH risk-predicting model considering both environmental and genetic factors with support vector machine (SVM). The data were collected through Epidemiological investigation questionnaire from Beijing Chinese Han population. After data cleaning, we finally selected 9 environmental factors and 12 genetic factors to construct the predicting model based on 1200 samples, including 559 essential hypertension patients and 641 controls. Using radial basis kernel function, predictive accuracy via SVM with function with only environmental factor and only genetic factor were 72.8 and 54.4%, respectively; after considering both environmental and genetic factor the accuracy improved to 76.3%. Using the model via SVM with Laplacian function, the accuracy with only environmental factor and only genetic factor were 76.9 and 57.7%, respectively; after combining environmental and genetic factor, the accuracy improved to 80.1%. The predictive accuracy of SVM model constructed based on Laplacian function was higher than radial basis kernel function, as well as sensitivity and specificity, which were 63.3 and 86.7%, respectively. In conclusion, the model based on SVM with Laplacian kernel function had better performance in predicting risk of hypertension. And SVM model considering both environmental and genetic factors had better performance than the model with environmental or genetic factors only.


Assuntos
Meio Ambiente , Hipertensão Essencial/genética , Predisposição Genética para Doença , Modelos Genéticos , Máquina de Vetores de Suporte , Humanos , Curva ROC , Fatores de Risco
12.
Sci Data ; 4: 170195, 2017 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-29257136

RESUMO

The early-matured japonica (Geng) rice variety, Suijing18 (SJ18), carries multiple elite traits including durable blast resistance, good grain quality, and high yield. Using PacBio SMRT technology, we produced over 25 Gb of long-read sequencing raw data from SJ18 with a coverage of 62×. Using Illumina paired-end whole-genome shotgun sequencing technology, we generated 59 Gb of short-read sequencing data from SJ18 (23.6 Gb from a 200 bp library with a coverage of 59× and 35.4 Gb from an 800 bp library with a coverage of 88×). With these data, we assembled a single SJ18 genome and then generated a set of annotation data. These data sets can be used to test new programs for variation deep mining, and will provide new insights into the genome structure, function, and evolution of SJ18, and will provide essential support for biological research in general.


Assuntos
Genoma de Planta , Oryza/genética , Análise de Sequência de DNA
13.
Leuk Lymphoma ; 58(2): 428-437, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27439454

RESUMO

Proteasome inhibitor bortezomib has proven efficacy against multiple myeloma. However, bortezomib activates the phosphatidylinositol 3-kinase/AKT (PI3K/AKT) pathway (which is essential to the development of myeloma), often resulting in drug resistance and disease recurrence. The addition of BKM120 significantly enhanced the apoptotic effects of bortezomib in both bortezomib-sensitive and bortezomib-resistant cells. Treatment with bortezomib alone increased the phosphorylation of AKT (P-AKT), whereas the addition of BKM120 markedly downregulated P-AKT in both bortezomib-sensitive and bortezomib-resistant cells. The clinical relevance of combined treatment with bortezomib and BKM120 was investigated in a xenograft mouse model and in myeloma patients, and the synergy of the combination was confirmed. In conclusion, the addition of BKM120 enhanced the sensitivity of myeloma cells to bortezomib.


Assuntos
Aminopiridinas/farmacologia , Bortezomib/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Morfolinas/farmacologia , Mieloma Múltiplo/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Concentração Inibidora 50 , Camundongos , Mieloma Múltiplo/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Exp Gerontol ; 83: 89-93, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27452792

RESUMO

Brain Erythropoietin (EPO), an important neurotrophic factor and neuroprotective factor, was found to be associated with aging. Studies found EPO expression was significantly decreased in the hippocampus of aging rat compared with that of the youth. But mechanisms of the decline of the brain EPO during aging remain unclear. The present study utilized a d-galactose (d-gal)-induced aging model in which the inducement of aging was mainly oxidative injury, to explore underlying mechanisms for the decline of brain EPO in aging rats. d-gal-induced aging rats (2months) were simulated by subcutaneously injecting with d-gal at doses of 50mg·kg(-1), 150mg·kg(-1) and 250mg·kg(-1) daily for 8weeks while the control group received vehicle only. These groups were all compared with the aging rats (24months) which had received no other treatment. The cognitive impairment was assessed using Morris water maze (MWM) in the prepared models, and the amount of ß-galactosidase, the lipid peroxidation product malondialdehyde (MDA) level and the superoxide dismutase (SOD) activity in the hippocampus was examined by assay kits. The levels of EPO, EPOR, p-JAK2 and hypoxia-inducible factor-2α (HIF-2α) in the hippocampus were detected by western blot. Additionally, the correlation coefficient between EPO/EPOR expression and MDA level was analyzed. The MWM test showed that compared to control group, the escape latency was significantly extended and the times of crossing the platform was decreased at the doses of 150mg·kg(-1) and 250mg·kg(-1) (p<0.05). Also, the amount of ß-galactosidase and the MDA level in the hippocampus were significantly increased but the SOD activity was significantly decreased (p<0.05, 0.01 and 0.01, respectively). Similar to aging rats, the expressions of EPO, EPOR, p-JAK2, and HIF-2αin the brain of d-gal-treated rats were significantly decreased (p<0.05) at 150mg·kg(-1) and 250mg·kg(-1). Interestingly, negative correlations were found between EPOR (r=-0.699, p<0.01), EPO (r=-0.701, p<0.01) and the MDA level. These results indicated that aging could result in the decline of EPO in the hippocampus and oxidative stress might be the main reason for the decline of brain EPO in aging rats, involved with the decrease of HIF-2α stability.


Assuntos
Envelhecimento , Eritropoetina/metabolismo , Hipocampo/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Estresse Oxidativo , Animais , Disfunção Cognitiva , Galactose , Modelos Lineares , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição/metabolismo , beta-Galactosidase/metabolismo
15.
Mol Clin Oncol ; 4(1): 107-113, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26870367

RESUMO

To define the role of autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (MM) in the era of novel agents, we analyzed follow-up data of patients treated by these agents alone or followed by ASCT. From January, 2008 to December, 2012, 136 patients with de novo MM, aged <65 years, completed bortezomib- or thalidomide-based induction therapy and 114 patients achieved at least a partial response (PR). A total of 42 patients underwent ASCT. After a median follow-up of 39 months (range, 5-74 months), the median progression-free survival (PFS) was 23 months in the non-ASCT group vs. 42 months in the ASCT group (P=0.001), and the 5-year overall survival (OS) rate was 58.9 vs. 81.2%, respectively (P=0.03). The multivariate analysis revealed that complete response (CR) and maintenance therapy (MT) were independent factors of improved OS in both groups. Moreover, a subgroup analysis was performed according to the response status to evaluate the role of ASCT and MT. In the CR subgroup, neither ASCT nor MT exerted a significant effect on PFS or OS. In the very good PR subgroup, ASCT after MT (ASCT/MT) significantly improved PFS, but not OS. In patients exhibiting PR, ASCT/MT significantly prolonged PFS and OS. Therefore, ASCT in the era of novel agents maintains an important role in younger MM patients, particularly those achieving a PR after induction therapy. Furthermore, MT is a key factor associated with long-term survival in all MM patients.

16.
Proc Natl Acad Sci U S A ; 113(5): 1327-32, 2016 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-26768847

RESUMO

Polyploidy is much rarer in animals than in plants but it is not known why. The outcome of combining two genomes in vertebrates remains unpredictable, especially because polyploidization seldom shows positive effects and more often results in lethal consequences because viable gametes fail to form during meiosis. Fortunately, the goldfish (maternal) × common carp (paternal) hybrids have reproduced successfully up to generation 22, and this hybrid lineage permits an investigation into the genomics of hybridization and tetraploidization. The first two generations of these hybrids are diploids, and subsequent generations are tetraploids. Liver transcriptomes from four generations and their progenitors reveal chimeric genes (>9%) and mutations of orthologous genes. Characterizations of 18 randomly chosen genes from genomic DNA and cDNA confirm the chimera. Some of the chimeric and differentially expressed genes relate to mutagenesis, repair, and cancer-related pathways in 2nF1. Erroneous DNA excision between homologous parental genes may drive the high percentage of chimeric genes, or even more potential mechanisms may result in this phenomenon. Meanwhile, diploid offspring show paternal-biased expression, yet tetraploids show maternal-biased expression. These discoveries reveal that fast and unstable changes are mainly deleterious at the level of transcriptomes although some offspring still survive their genomic abnormalities. In addition, the synthetic effect of genome shock might have resulted in greatly reduced viability of 2nF2 hybrid offspring. The goldfish × common carp hybrids constitute an ideal system for unveiling the consequences of intergenomic interactions in hybrid vertebrate genomes and their fertility.


Assuntos
Cruzamentos Genéticos , Carpa Dourada/genética , Ploidias , Animais , Cromossomos , Perfilação da Expressão Gênica , Hibridização in Situ Fluorescente
17.
Gene ; 575(2 Pt 3): 695-701, 2016 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-26410414

RESUMO

Microsatellites or simple sequence repeats (SSRs) are known to present ubiquitously in genomes of eukaryotes and prokaryotes, as well as viruses. A comprehensive analysis of microsatellites and compound microsatellites (CM) was performed for 67 T4-like bacteriophage genomes. We found that the number of repeats was generally proportional to the size of the genome. CM were more abundant in genic regions, while their relative abundance was higher in intergenic regions. Meanwhile, the number of CM rapidly decreased with the increase of complexity but gradually increased with higher dMAX (maximum distance between any two adjacent microsatellites). (A)n/(T)n, (AT)n/(TA)n and (AAG)n were the most abundant repeats of mono-, di- and trinucleotide microsatellites, respectively. The number of microsatellites in reference sequences was significantly lower than that in corresponding random sequences. This result was mainly attributed to mono- and dinucleotide repeats which hardly exceeded 6bp in T4-like viruses. These observations may be helpful to understand the distribution of microsatellites and viral genetic diversity in T4-like viruses.


Assuntos
Bacteriófago T4/genética , Repetições de Microssatélites , DNA Viral/análise , Variação Genética , Tamanho do Genoma
18.
BMC Genomics ; 16: 414, 2015 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-26016565

RESUMO

BACKGROUND: Enterococcus faecalis and Enterococcus faecium are typical enterococcal bacterial pathogens. Antibiotic resistance means that the identification of novel E. faecalis and E. faecium phages against antibiotic-resistant Enterococcus have an important impact on public health. In this study, the E. faecalis phage IME-EF4, E. faecium phage IME-EFm1, and both their hosts were antibiotic resistant. To characterize the genome termini of these two phages, a termini analysis theory was developed to provide a wealth of terminal sequence information directly, using only high-throughput sequencing (HTS) read frequency statistics. RESULTS: The complete genome sequences of phages IME-EF4 and IME-EFm1 were determined, and our termini analysis theory was used to determine the genome termini of these two phages. Results showed 9 bp 3' protruding cohesive ends in both IME-EF4 and IME-EFm1 genomes by analyzing frequencies of HTS reads. For the positive strands of their genomes, the 9 nt 3' protruding cohesive ends are 5'-TCATCACCG-3' (IME-EF4) and 5'-GGGTCAGCG-3' (IME-EFm1). Further experiments confirmed these results. These experiments included mega-primer polymerase chain reaction sequencing, terminal run-off sequencing, and adaptor ligation followed by run-off sequencing. CONCLUSION: Using this termini analysis theory, the termini of two newly isolated antibiotic-resistant Enterococcus phages, IME-EF4 and IME-EFm1, were identified as the byproduct of HTS. Molecular biology experiments confirmed the identification. Because it does not require time-consuming wet lab termini analysis experiments, the termini analysis theory is a fast and easy means of identifying phage DNA genome termini using HTS read frequency statistics alone. It may aid understanding of phage DNA packaging.


Assuntos
Bacteriófagos/genética , Enterococcus/virologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Sequências Repetidas Terminais , Farmacorresistência Bacteriana , Enterococcus/isolamento & purificação , Enterococcus faecalis/isolamento & purificação , Enterococcus faecalis/virologia , Enterococcus faecium/isolamento & purificação , Enterococcus faecium/virologia , Genoma Viral , Humanos , Modelos Genéticos , Modelos Estatísticos
19.
J Renin Angiotensin Aldosterone Syst ; 16(4): 858-71, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25208931

RESUMO

BACKGROUND: Aldosterone synthase (CYP11B2) is one of the most studied candidate genes related to essential hypertension (EH) and left ventricular hypertrophy (LVH). Some studies have focused on the relationship between -344C/T polymorphism (rs1799998) in the CYP11B2 gene and LVH, but the results are controversial. This meta-analysis is purposed to reveal the relationship between the -344C/T and the left ventricular structure and function, including left ventricular end diastolic dimension (LVEDD), left ventricular end systolic diameter (LVESD), left ventricular mass/left ventricular mass index (LVM/LVMI), left ventricular posterior wall thickness (LVPWT), and interventricular septal wall thickness (IVS). METHODS: A literature search of PubMed and Embase databases was conducted on articles published before January 27, 2014. The odds ratios with 95% confidence intervals were calculated. Heterogeneity analyses were performed using meta-regression. Tests for publication bias were also performed and biased studies should be removed from subsequent analyses. RESULTS: There were 20 studies with a total of 6780 subjects meeting the inclusion criteria. The main finding was that concentration levels of LVEDD and LVESD were higher in CC homozygous individuals than in TT homozygous individuals in the whole group. In the Asian subgroup, TT homozygous individuals had larger IVS than CC homozygous individuals. In the Caucasian normotension subgroup, CC homozygous individuals had larger LVM/LVMI than TT homozygous individuals. In the Asian essential hypertension subgroup, TT homozygous individuals had larger LVPWT values than CC homozygous individuals. CONCLUSIONS: The present findings support the hypothesis that CC homozygous individuals may have greater left ventricular diameters (LVEDD and LVESD) regardless of their ethnicities or physical conditions.


Assuntos
Citocromo P-450 CYP11B2/genética , Ecocardiografia , Estudos de Associação Genética , Predisposição Genética para Doença , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/enzimologia , Polimorfismo de Nucleotídeo Único/genética , Diástole , Ventrículos do Coração/patologia , Ventrículos do Coração/fisiopatologia , Homozigoto , Humanos , Tamanho do Órgão , Análise de Regressão , Sístole
20.
FEBS Open Bio ; 4: 185-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24649400

RESUMO

Extensive simple sequence repeat (SSR) surveys have been performed for eukaryotic prokaryotic and viral genomes, but information regarding SSRs in viroids is limited. We undertook a survey to examine the presence of SSRs in viroid genomes. Our results show that the distribution of SSRs in viroids may influence secondary structure, and that SSRs could play a role in generating genetic diversity. We also discuss the potential evolutionary role of repeated sequences in the viroid genome. This is the first report of SSR loci in viroids, and our study could be helpful in understanding the structure and evolution of viroid genomes.

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