Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 144
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Medicine (Baltimore) ; 99(7): e19075, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049809

RESUMO

BACKGROUND: Accumulating pre-clinical and clinical studies suggested that the renin-angiotensin system blockers (RASBs) possess anti-carcinogenic properties, and their use is associated with favorable outcomes in many types of cancers. METHODS: A systematic literature search of relevant databases through January 2019 was conducted to identify studies assessing the RASBs on prognostic outcomes in digestive system malignancies patients on the basis of predetermined selection criteria for pooled hazard ratio (HR) with 95% confidence intervals (CIs). A total of 13 studies were included in the meta-analysis. RESULTS: The meta-analysis showed that the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) resulted in a significant improvement in overall survival (HR 0.79; 95%CI 0.70-0.89; P < .000), cancer-specific survival (HR 0.81; 95%CI 0.73-0.90; P < .000) and recurrence-free survival (HR 0.68; 95%CI 0.54-0.85; P = .001), but not progression-free survival (HR 0.88; 95%CI 0.73-1.07; P = .183) and disease-free survival (HR 0.50; 95%CI 0.11-2.39; P = .103). Subgroup analysis indicated that the use of RASBs has a significant improvement of overall survival (OS) in pancreatic cancer, liver cancer, and gastric cancer. Two studies evaluated the dose-response relationship between ACEIs/ARBs therapy and survival and showed higher doses and better survival [(1-364 defined daily doses: odds ratio (OR) 0.89, 95%CI 0.78-1.01, P = .076), (≥365 defined daily doses: OR 0.54, 95%CI: 0.24-1.24, P = .148]. CONCLUSIONS: Meta-analysis of studies supports a beneficial association between use of RASBs and survival of digestive system malignancies.

2.
J Alzheimers Dis ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32065788

RESUMO

Hyperphosphorylated tau is one of the key characteristics of Alzheimer's disease (AD), and tau pathology correlates with cognitive impairment in AD better than amyloid-ß (Aß) pathology. Thus, a complete understanding of the relevant factors involved in tau phosphorylation is important for AD treatment. APOEɛ4, the strongest genetic risk factor for AD, was found to be involved in tau pathology in frontotemporal dementia. This result indicated that apolipoprotein E (ApoE) may also participate in tau phosphorylation in AD. In the present study, we injected Aß oligomer (AßO) into the lateral ventricles of wild-type (WT) mice and apoE-/- mice to test the process of tau phosphorylation in the acute phase. We found that the phosphorylated tau and phosphokinase levels were higher in WT mice than in apoE-/- mice. These phenomena were also confirmed in vitro. ApoE ɛ4-treated apoE-/- neurons exhibited more phosphorylated tau than ApoE ɛ2- and ApoE ɛ3-treated neurons. We also found that AßO induced more serious inflammation in WT mice and in ApoE-positive cultured neurons. Anti-inflammatory treatment reduced the phosphorylated tau level induced by AßOs in ApoE-positive neurons. These results suggest that ApoE may facilitate the phosphorylation of tau induced by AßO via inflammation.

3.
Endocr Relat Cancer ; 27(3): 153-162, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31905165

RESUMO

HER2-positive breast cancer is a biologically and clinically heterogeneous disease. Based on the expression of hormone receptors (HR), breast tumors can be further categorized into HR positive and HR negative. Here, we elucidated the comprehensive somatic mutation profile of HR+ and HR- HER2-positive breast tumors to understand their molecular heterogeneity. In this study, 64 HR+/HER2+ and 43 HR-/HER2+ stage I-III breast cancer patients were included. Capture-based targeted sequencing was performed using a panel consisting of 520 cancer-related genes, spanning 1.64 megabases of the human genome. A total of 1119 mutations were detected among the 107 HER2-positive patients. TP53, CDK12 and PIK3CA were the most frequently mutated, with mutation rates of 76, 61 and 49, respectively. HR+/HER2+ tumors had more gene amplification, splice site and frameshift mutations and a smaller number of missense, nonsense and insertion-deletion mutations than HR-/HER2+ tumors. In KEGG analysis, HR+/HER2+ tumors had more mutations in genes involved in homologous recombination (P = 0.004), TGF-beta (P = 0.007) and WNT (P = 0.002) signaling pathways than HR-/HER2+ tumors. Moreover, comparative analysis of our cohort with datasets from The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium revealed the distinct somatic mutation profile of Chinese HER2-positive breast cancer patients. Our study revealed the heterogeneity of somatic mutations between HR+/HER2+ and HR-/HER2+ in Chinese breast cancer patients. The distinct mutation profile and related pathways are potentially relevant in the development of optimal treatment strategies for this subset of patients.

4.
J Med Chem ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31928004

RESUMO

Negative design is a group of virtual screening methods that aims at weeding out compounds with undesired properties during the early stages of drug development. These methods are mainly designed to predict three important types of pharmacological properties: drug-likeness, frequent hitters, and toxicity. In order to achieve high screening efficiency, most negative design methods are physicochemical property-based and/or substructure-based rules or filters. Such methods have advantages of simplicity and good interpretability, but they also suffer from some defects such as inflexibility, discontinuity, and hard decision-making. In this review, the advances in negative design for the evaluations of drug-likeness, frequent hitters, and toxicity are outlined. In addition, the related Web servers and software packages developed recently for negative design are summarized. Finally, future research directions in this field are discussed.

5.
Drug Discov Today ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31987936

RESUMO

One of the major challenges in early drug discovery is the recognition of frequent hitters (FHs), that is, compounds that nonspecifically bind to a range of macromolecular targets or false positives caused by various types of assay interferences. In this review, we survey the mechanisms underlying different types of FHs, including aggregators, spectroscopic interference compounds (i.e., luciferase inhibitors and fluorescent compounds), chemical reactive compounds, and promiscuous compounds. We also review commonly used experimental detection techniques and computational prediction models for FH identification. In addition, the rational applications of these computational filters are discussed. It is believed that, with the rational use of FH filters, the efficiency of drug discovery will be significantly improved.

6.
Chem Commun (Camb) ; 56(12): 1811-1814, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31950951

RESUMO

We developed a label-free homogeneous photoelectrochemical biosensing strategy based on the synergy of G-quadruplex/hemin catalysed electron donor consumption and the inner filter effect for highly selective and sensitive microRNA assay.

7.
J Chem Inf Model ; 60(1): 63-76, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31869226

RESUMO

Lipophilicity, as evaluated by the n-octanol/buffer solution distribution coefficient at pH = 7.4 (log D7.4), is a major determinant of various absorption, distribution, metabolism, elimination, and toxicology (ADMET) parameters of drug candidates. In this study, we developed several quantitative structure-property relationship (QSPR) models to predict log D7.4 based on a large and structurally diverse data set. Eight popular machine learning algorithms were employed to build the prediction models with 43 molecular descriptors selected by a wrapper feature selection method. The results demonstrated that XGBoost yielded better prediction performance than any other single model (RT2 = 0.906 and RMSET = 0.395). Moreover, the consensus model from the top three models could continue to improve the prediction performance (RT2 = 0.922 and RMSET = 0.359). The robustness, reliability, and generalization ability of the models were strictly evaluated by the Y-randomization test and applicability domain analysis. Moreover, the group contribution model based on 110 atom types and the local models for different ionization states were also established and compared to the global models. The results demonstrated that the descriptor-based consensus model is superior to the group contribution method, and the local models have no advantage over the global models. Finally, matched molecular pair (MMP) analysis and descriptor importance analysis were performed to extract transformation rules and give some explanations related to log D7.4. In conclusion, we believe that the consensus model developed in this study can be used as a reliable and promising tool to evaluate log D7.4 in drug discovery.

8.
J Cell Physiol ; 235(3): 2643-2654, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31517391

RESUMO

Cancer stem cells are undifferentiated cancer cells that have self-renewal ability, a high tumorigenic activity, and a multilineage differentiation potential. MicroRNAs play a critical role in regulating gene expression during carcinogenesis. Here, we investigated the role of miR-7 and the mechanism by which it is dysregulated in gastric cancer stem cells (GCSCs). The stem cell marker, CD44, was used to sort GCSCs by fluorescence-activated cell sorting. We found that CD44 (+) cells have higher invasiveness and form more number of sphere colonies than CD44 (-) cells. Quantitative real-time polymerase chain reaction (PCR) revealed that the miR-7-5p expression was remarkably downregulated in GCSCs but was significantly increased in the methionine-deprived medium. The downregulation of miR-7-5p results from the increased DNA methylation in the promoter region using the methylation-specific PCR. Overexpression of miR-7-5p reduced the formation of colony and decreased the invasion of GCSCs through targeting Smo and Hes1 and subsequent repressing Notch and Hedgehog signaling pathways in vitro. Notably, upregulating miR-7-5p inhibited the growth of tumor in the xenograft model. Hence, these data demonstrated that miR-7-5p represses GCSC invasion through inhibition of Smo and Hes1, which provides a potential therapeutic target of gastric cancer treatment.

9.
Brief Bioinform ; 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31885044

RESUMO

BACKGROUND: With the increasing development of biotechnology and information technology, publicly available data in chemistry and biology are undergoing explosive growth. Such wealthy information in these resources needs to be extracted and then transformed to useful knowledge by various data mining methods. However, a main computational challenge is how to effectively represent or encode molecular objects under investigation such as chemicals, proteins, DNAs and even complicated interactions when data mining methods are employed. To further explore these complicated data, an integrated toolkit to represent different types of molecular objects and support various data mining algorithms is urgently needed. RESULTS: We developed a freely available R/CRAN package, called BioMedR, for molecular representations of chemicals, proteins, DNAs and pairwise samples of their interactions. The current version of BioMedR could calculate 293 molecular descriptors and 13 kinds of molecular fingerprints for small molecules, 9920 protein descriptors based on protein sequences and six types of generalized scale-based descriptors for proteochemometric modeling, more than 6000 DNA descriptors from nucleotide sequences and six types of interaction descriptors using three different combining strategies. Moreover, this package realized five similarity calculation methods and four powerful clustering algorithms as well as several useful auxiliary tools, which aims at building an integrated analysis pipeline for data acquisition, data checking, descriptor calculation and data modeling. CONCLUSION: BioMedR provides a comprehensive and uniform R package to link up different representations of molecular objects with each other and will benefit cheminformatics/bioinformatics and other biomedical users. It is available at: https://CRAN.R-project.org/package=BioMedR and https://github.com/wind22zhu/BioMedR/.

10.
J Nurs Manag ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710410

RESUMO

AIM: To develop a mobile application (App) that enhances bed cleaning management. BACKGROUND: Bed cleaning affects clinical work in hospitals. The nursing department needed an App to enhance bed cleaning management, especially one on the status of all beds to be cleaned. METHODS: Bed-Cleaning App (BedCApp) was developed. Then, asurvey was administered to 50 BedCApp users. RESULTS: BedCApp helped the administrative staff and nurse managers in adjusting their workload effectively. A complete presentation of beds to be cleaned and reminders were found to be the most satisfactory features. The average time from receiving the notice to completing bed cleaning was shortenedby25.5 min. The user satisfaction survey comprised50 valid questionnaires, with a satisfaction rate of 3.6/5. CONCLUSION: BedCApp provides the actual workload status; therefore, the administrative staff and nurse managers can optimize the workload during rush hours. The software is user-oriented, with good user acceptance. IMPLICATIONS FOR NURSING MANAGEMENT: Proactive workload management would improve outcomes during rush hours and avoid interference in clinical care. The user interfaces for the elderly staff has special design-simple to use, larger font size than that in the interface for non-elderly staff, and workflow reminders.

12.
Ying Yong Sheng Tai Xue Bao ; 30(10): 3292-3302, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31621215

RESUMO

Rice is one of the main crops in China. Therefore, it is important to understand the current status and influencing factors of nitrogen and phosphorus losses from paddy fields in China, which would facilitate assessing the potential of chemical fertilizer reduction in different rice cultivating regions. We summarized the current knowledge on nitrogen and phosphorus losses from surface runoff in major rice cultivating areas in China, as well as their influencing factors, such as rainfall, planting pattern, cultivation techniques, fertilization management, water management strategies, etc. The total nitrogen (TN) and total phosphorus (TP) losses from runoff in six major rice cropping areas ranged from 5.09 to 21.32 and 0.70 to 3.22 kg·hm-2, respectively. The highest losses of TN and TP were the South China double rice cropping area. The TN runoff losses were the lowest in the North China single rice cropping area, while the lowest TP runoff losses occurred in plateau single and double rice cropping area of the Southwest China. The peaks of TN and TP in surface water of paddy fields were generally higher than those of the runoff water based on farmers' conventional fertilization in different rice cropping areas. The peak period of nitrogen and phosphorus losses was in a week after rice fertilization. There could be a potential of 20% reduction of nitrogen and phospho-rus for farmers' conventional fertilization compared with the optimized fertilization. Among all the factors, rainfall and fertilization management were the main ones affecting the runoff losses of nitrogen and phosphorus in paddy fields. Fertilization management and water management strategies were the mostly controllable, including reduction of fertilizers, application of new fertilizers, replacement of chemical fertilizers by organic fertilizers, water-saving irrigation, etc. Overall, the risk of nitrogen and phosphorus losses in paddy fields was more prominent in the Southern China than in any other areas of China. Rice cultivation should be carried out in a more resource-efficient way to reduce nutrient loss. Future research should focus on non-point source pollution monitoring of paddy fields, nitrogen and phosphorus losses risk assessment, nitrogen and phosphorus losses characteristics and mechanisms, and new technologies for reducing chemical fertilization inputs and environmental risks.


Assuntos
Oryza , Fósforo , Agricultura , China , Monitoramento Ambiental , Fertilizantes , Nitrogênio
13.
J Magn Reson Imaging ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31625643

RESUMO

BACKGROUND: Adipose tissue is closely related to bone mass, bone quality, and bone fractures, but the connection between fat and bone is complex and gender-related. Fat-water magnetic resonance imaging (MRI) and MR spectroscopy (MRS) are very useful tools for identifying tissue fat. PURPOSE: To assess gender interactions between bone mineral density (BMD), bone marrow fat, and body mass index (BMI) in the elderly using fat-water MRI and MRS. STUDY TYPE: Prospective/cohort. POPULATION: Sixty-six women and 38 men (mean age, 62.3 years; range, 50-75 years), Asian. FIELD STRENGTH: A 1.5T MR equipped with a body and spine array coil. STEAM MRS and T2 * Dixon were performed. ASSESSMENT: Vertebral bone marrow fat ratio (MFR), BMI, and BMD were measured. Correlations between these variables and differences in bone density in MFR were assessed between participants, divided into three groups based on bone density. STATISTICAL TESTS: Multiple regression; Pearson tests; analysis of covariance; analysis of variance. RESULTS: Multiple regression analysis identified gender, vertebral bone MFR, and BMI as significant predictors of vertebral BMD (P < 0.001). Among the women, vertebral BMD was negatively correlated with vertebral MFR (P = 0.011), but among the men, it was positively correlated with BMI (P = 0.048), although this relationship was confounded by age and MFR. Moreover, vertebral bone marrow fat and BMI were indeed statistically uncorrelated in the elderly (P = 0.357 in women; P = 0.961 in men). DATA CONCLUSION: We found gender interactions between fat and bone in the elderly. Higher bone marrow fat was correlated with lower trabecular BMD in older women but not in men. On the other hand, the positive correlation between BMI and BMD was more pronounced in men than in women. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019.

14.
J Chem Inf Model ; 59(9): 3714-3726, 2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31430151

RESUMO

Aggregation has been posing a great challenge in drug discovery. Current computational approaches aiming to filter out aggregated molecules based on their similarity to known aggregators, such as Aggregator Advisor, have low prediction accuracy, and therefore development of reliable in silico models to detect aggregators is highly desirable. In this study, we built a data set consisting of 12 119 aggregators and 24 172 drugs or drug candidates and then developed a group of classification models based on the combination of two ensemble learning approaches and five types of molecular representations. The best model yielded an accuracy of 0.950 and an area under the curve (AUC) value of 0.987 for the training set, and an accuracy of 0.937 and an AUC of 0.976 for the test set. The best model also gave reliable predictions to the external validation set with 5681 aggregators since 80% of molecules were predicted to be aggregators with a prediction probability higher than 0.9. More importantly, we explored the relationship between colloidal aggregation and molecular features, and generalized a set of simple rules to detect aggregators. Molecular features, such as log D, the number of hydroxyl groups, the number of aromatic carbons attached to a hydrogen atom, and the number of sulfur atoms in aromatic heterocycles, would be helpful to distinguish aggregators from nonaggregators. A comparison with numerous existing druglikeness and aggregation filtering rules and models used in virtual screening verified the high reliability of the model and rules proposed in this study. We also used the model to screen several curated chemical databases, and almost 20% of molecules in the evaluated databases were predicted as aggregators, highlighting the potential high risk of aggregation in screening. Finally, we developed an online Web server of ChemAGG ( http://admet.scbdd.com/ChemAGG/index ), which offers a freely available tool to detect aggregators.

15.
BMC Plant Biol ; 19(1): 315, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307378

RESUMO

BACKGROUND: Abaxially anthocyanic leaves of deeply-shaded understorey plants play important ecological significance for the environmental adaption. In contrast to the transient pigmentation in other plants, anthocyanins are permanently presented in these abaxially red leaves, however, the mechanism for the pigment maintenance remains unclear. In the present study, we investigated phenolic metabolites that may affect pigment stability and degradation in Excoecaria cochinchinensis (a bush of permanently abaxial-red leaves), via a comparison with Osmanthus fragrans (a bush of transiently red leaves). RESULTS: High levels of galloylated anthocyanins were identified in the Excoecaria but not in the Osmanthus plants. The galloylated anthocyanin showed slightly higher stability than two non-galloylated anthocyanins, while all the 3 pigments were rapidly degraded by peroxidase (POD) in vitro. High levels of hydrolysable tannins [mainly galloylglucoses/ellagitannins (GGs/ETs)] were identified in Excoecaria but none in Osmanthus. GGs/ETs showed inhibition effect on POD, with IC50 ranged from 35.55 to 83.27 µM, correlated to the markedly lower POD activities detected in Excoecaria than in Osmanthus. Strong copigmentation was observed for GGs/ETs and anthocyanins, with more than 30% increase in the red intensity of non-galloylated anthocyanin solutions. In the leaf tissue, the hydrolysable tannins were observed to be co-localized with anthocyanins at the abaxial layer of the Excoecaria leaves, correlated to the low POD activity, more acidity and increased red intensity of the tissue. CONCLUSION: The results suggest that the Excoecaria leaves accumulate a distinct group of phenolic metabolites, mainly GGs/ETs, at the abaxial layer, which prevent anthocyanin degradation and increase the pigment stability, and consequently lead to the permanent maintenance of the red leaves.


Assuntos
Antocianinas/metabolismo , Euphorbiaceae/metabolismo , Taninos Hidrolisáveis/metabolismo , Peroxidase/antagonistas & inibidores , Pigmentação , Folhas de Planta/metabolismo , Euphorbiaceae/enzimologia , Oleaceae/metabolismo , Peroxidase/metabolismo , Folhas de Planta/crescimento & desenvolvimento
16.
Bot Stud ; 60(1): 10, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31267253

RESUMO

BACKGROUND: Haworthia are desert succulents belonging to the Asphodelaceae family. Haworthia species are cultivated commercially as ornamentals and some rare species are quite valuable at retail market but growth slowly and difficult to propagation. However, an efficient micropropagation protocol was remained insufficient. RESULTS: The organogenic cultures obtained from inflorescence explants were cultured on Murashige and Skoog (MS) medium supplemented with various combinations of 6-benzylaminopurine (BA) and α-naphthalene acetic acid (NAA) under a light intensity of 10 µmol m-2 s-1 or 45 µmol m-2 s-1. The highest callus proliferation index (93.15%) with 1.0 mg L-1 BA + 0.1 mg L-1 NAA under a light intensity of 10 µmol m-2 s-1. The best shoot proliferation rates were on media with either 1 mg L-1 BA + 0-0.4 mg L-1 NAA (65.57-81.01%) under a light intensity of 45 µmol m-2 s-1. The highest root length (15.57 mm) and the highest rooting frequency (17 roots per shoot) were obtained when adventitious shoots were inoculated on MS medium with 0.4 mg L-1 NAA + 0.4 mg L-1 IBA. The survival rate of the transplanted plantlets was about 100%. The efficient micropropagation protocol proliferated Haworthia regenerate plants from inflorescence within 11 weeks. CONCLUSIONS: The present study determined the best combination of light intensity and plant growth regulators (PGRs) for improved organogenesis of Haworthia during propagation by tissue culture. This optimized protocol showed light intensity is an important factor for efficient callus or shoot regeneration. These results indicate that it will be useful to optimize the light conditions for future commercial cultivation, germplasm conservation, genetic engineering and molecular biology research of this ornamental plant.

17.
Oncol Lett ; 18(1): 891-897, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31289567

RESUMO

Ketoconazole, an antifungal agent, has been used to inhibit hormone synthesis in types of prostate and breast cancer. Immunomodulatory proteins of Ganoderma microsporum (GMI) inhibit the tumor necrosis factor-α- and epidermal growth factor-induced metastatic ability of lung cancer cells. Cutaneous malignant melanoma is a highly invasive and metastatic skin cancer. However, to the best of our knowledge, there is limited understanding regarding the effects of ketoconazole and GMI on melanoma. The current study aimed to investigate the inhibitory effects of GMI combined with ketoconazole on melanoma survival and metastasis. The effects of GMI combined with ketoconazole on the viability, migration and protein expression of melanoma cells were determined by MTT assay, Boyden chamber assay and western blot analysis, respectively. The expression of monocyte chemoattractant protein-1 (MCP-1) was investigated by enzyme-linked immunoabsorbent assay. The present results indicate that ketoconazole enhances the GMI-induced decrease in proliferation and migration of A375.S2 melanoma cells in a concentration-dependent manner. Ketoconazole was identified to reduce the level of GMI-induced phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK)-α and autophagy; however, ketoconazole did not affect p-AMPK-ß levels in A375.S2 cells. In addition, ketoconazole and dorsomorphin dihydrochloride, an AMPK inhibitor, were revealed to reduce MCP-1 secretion in A375.S2 cells. In summary, the present study revealed that ketoconazole enhances GMI-inhibited proliferation and migration of A375.S2 melanoma cancer cells, and inhibits the secretion of MCP-1.

18.
Biosens Bioelectron ; 141: 111395, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31195203

RESUMO

Photoelectrochemical (PEC) methods have recently witnessed ever expanding application in bioanalysis, but it is still desirable to further simplify the sensing procedures and develop simple and reliable PEC biosensing approaches. Herein, we proposed a truly label-free and immobilization-free PEC sensing platform, utilizing solution-phase methylene blue (MB) as the signal probe, and bare indium tin oxide (ITO) glass as the photoelectrode. Based on the diffusivity difference between free MB molecules and MB intercalated in DNA G-quadruplex, the activity and inhibition of DNA adenine methyltransferase (Dam), a proof-of-concept methyltransferase (MTase), is quantitatively analyzed. By taking advantage of the endonuclease-catalyzed cleavage of the Dam-methylated hairpin DNA probe, as well as the KF polymerase/Nt.AlwI endonuclease-aided signal amplification, highly sensitive and specific PEC detection of Dam activity has been achieved. Moreover, this approach can be easily extended to assay other types of MTase by choosing the appropriate methylation-sensitive endonucleases. The as-proposed strategy has also been successfully applied to analyze Dam spiked in human serum samples and to assess the inhibitory effects of antibiotics on Dam activity. More importantly, this label-free and truly immobilization-free PEC biosensing strategy shows additional merits of simplicity and satisfactory repeatability, due to the elimination of both labelling and immobilization procedures, making it a promising candidate for the application in highly sensitive, facile and reliable bioanalysis and drug screening.


Assuntos
Técnicas Biossensoriais/instrumentação , Substâncias Intercalantes/química , Azul de Metileno/química , DNA Metiltransferases Sítio Específica (Adenina-Específica)/sangue , Metilação de DNA/efeitos dos fármacos , Técnicas Eletroquímicas/instrumentação , Eletrodos , Ensaios Enzimáticos/instrumentação , Desenho de Equipamento , Humanos , Luz , DNA Metiltransferases Sítio Específica (Adenina-Específica)/análise , DNA Metiltransferases Sítio Específica (Adenina-Específica)/antagonistas & inibidores , Soluções , Compostos de Estanho/química
19.
Ann Transl Med ; 7(8): 179, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31168460

RESUMO

Background: The complexity of breast cancer at the clinical, morphological and genomic levels has been extensively studied in the western population. However, the mutational genomic profiles in Chinese breast cancer patients have not been explored in any detail. Methods: We performed targeted sequencing using a panel consisting of 33 breast cancer-related genes to investigate the genomic landscape of 304 consecutive treatment-naïve Chinese breast cancer patients at Guangdong Provincial People's Hospital (GDPH), and further compared the results to those in 453 of Caucasian breast cancer patients from The Cancer Genome Atlas (TCGA). Results: The most frequently mutated gene was TP53 (45%), followed by PIK3CA (44%), GATA3 (18%), MAP3K1 (10%), whereas the copy-number amplifications were frequently observed in genes of ERBB2 (24%), MYC (23%), FGFR1 (13%) and CCND1 (10%). Among the 8 most frequently mutated or amplified genes, at least one driver was identifiable in 87.5% (n=267) of our GDPH cohort, revealing the significant contribution of these known driver genes in the development of Chinese breast cancer. Compared to TCGA data, the median age at diagnosis in our cohort was significantly younger (48 vs. 58 years; P<0.001), while the distribution of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) statuses were similar. The largest difference occurred in HR+/HER2- subtype, where 8 of the 10 driver genes compared had statistically significant differences in their frequency, while there were differences in 2 of 10 driver genes among the TNBC and HR+/HER2+ group, but none in the HR-/HER2+ patients in our cohort compared to the TCGA data. Collectively, the most significant genomic difference was a significantly higher prevalence for TP53 and AKT1 in Chinese patients. Additionally, more than half of TP53-mutation HR+/HER2- Chinese patients (~60%) are likely to harbor more severe mutations in TP53, such as nonsense, indels, and splicing mutations. Conclusions: We elucidated the mutational landscape of cancer genes in Chinese breast cancer and further identified significant genomic differences between Asian and Caucasian patients. These results should improve our understanding of pathogenesis and/or metastatic behavior of breast cancer across races/ethnicities, including a better selection of targeted therapies.

20.
Int J Syst Evol Microbiol ; 69(8): 2471-2476, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31180314

RESUMO

A nitrite-tolerant denitrifying bacterium, strain GL14T, was isolated from the nitrification/denitrification bioreactor in our laboratory. Strain GL14T was Gram-stain-negative, rod-shaped, non-spore-forming, facultatively anaerobic and motile by means of a single polar flagellum. Phylogenetic analyses based on 16S rRNA gene sequences indicated that it was assigned to the genus Pseudomonas with highest 16S rRNA gene sequence similarity (98.77 %) to Pseudomonas xanthomarina DSM 18231T and Pseudomonassongnenensis NEAU-ST5-5T, followed by Pseudomonasstutzeri ATCC 17588T (98.42 %), Pseudomonaskunmingensis HL22-2T (98.29 %) and Pseudomonaszhaodongensis NEAU-ST5-21T (98.22 %). Phylogenetic analysis based on both concatenated sequences of the 16S rRNA gene and two housekeeping genes (gyrB and rpoD) and genome sequences further clarified the intrageneric phylogenetic position of strain GL14T. The DNA G+C content of GL14T was 63.1 mol%. The results of digital DNA-DNA hybridization (highest 24.2 % of DNA-DNA relatedness) based on the Genome-to-Genome Distance Calculator and average nucleotide identity analyses (highest 80.23 %) confirmed that the strain was distinctly delineated from known species of the genus Pseudomonas. The major fatty acids were summed feature 8 (C18 : 1ω7c/C18 : 1ω6c), C16 : 0, summed feature 3 (C16 : 1ω7c/C16 : 1ω6c), C17 : 0cyclo and C12 : 0. The respiratory quinone was ubiquinone Q-9. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Based on the phylogenetic, genomic, phenotypic and chemotaxonomic analyses, it was concluded that strain GL14T represents a novel species of the genus Pseudomonas, for which the name Pseudomonas nitrititolerans sp. nov. is proposed. The type strain is GL14T (=CGMCC 1.13874T=NBRC 113853T).


Assuntos
Reatores Biológicos/microbiologia , Nitritos/metabolismo , Filogenia , Pseudomonas/classificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Desnitrificação , Ácidos Graxos/química , Genes Bacterianos , Nitrificação , Hibridização de Ácido Nucleico , Fosfolipídeos/química , Pseudomonas/isolamento & purificação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA