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2.
Biomaterials ; 228: 119553, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31689672

RESUMO

Nuclear medicine imaging has been developed as a powerful diagnostic approach for cancers by detecting gamma rays directly or indirectly from radionuclides to construct images with beneficial characteristics of high sensitivity, infinite penetration depth and quantitative capability. Current nuclear medicine imaging modalities mainly include single-photon emission computed tomography (SPECT) and positron emission tomography (PET) that require administration of radioactive tracers. In recent years, a vast number of radioactive tracers have been designed and constructed to improve nuclear medicine imaging performance toward early and accurate diagnosis of cancers. This review will discuss recent progress of nuclear medicine imaging tracers and associated biomedical imaging applications. Radiolabeling nanomaterials for rational development of tracers will be comprehensively reviewed with highlights on radiolabeling approaches (surface coupling, inner incorporation and interface engineering), providing profound understanding on radiolabeling chemistry and the associated imaging functionalities. The applications of radiolabeled nanomaterials in nuclear medicine imaging-related multimodality imaging will also be summarized with typical paradigms described. Finally, key challenges and new directions for future research will be discussed to guide further advancement and practical use of radiolabeled nanomaterials for imaging of cancers.

3.
Exp Ther Med ; 18(2): 1350-1356, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31363375

RESUMO

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer accounting for ~80% of lung cancer cases. According to novel research, numerous microRNAs (miRs) have been suggested to function as important regulators of cancer. In addition, the expression of miR-140-5p is decreased in patients with NSCLC. Therefore, it is important to further elucidate the role of miR-140-5p in NSCLC. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used in order to investigate the expression of miR-140-5p in NSCLC tissues and matched normal tissues and to determine miR-140-5p levels following transfection with mimics into A549 lung cancer cells. Targetscan software was used to predict the oncogene target of miR-140-5p. This analysis revealed that YES proto-oncogene 1 (YES1) includes a target site for miR-140-5p binding. The results revealed that YES1 is a potential target gene of miR-140-5p, and this was further confirmed by the results of luciferase reporter assays, which demonstrated that miR-140-5p directly targeted the predicted binding site in the 3'-untranslated region of YES1. Cell Counting Kit-8 (CCK-8) and flow cytometry assays were performed to determine the levels of cell viability and apoptosis. Western blot assays was performed to investigate the expression levels of YES1 and proteins associated with apoptosis in A549 cells following transfection. The results revealed that miR-140-5p expression was significantly downregulated in NSCLC tissues compared with matched normal tissues. The expression of miR-140-5p was significantly increased following transfection with miR-140-5p mimics. The results of CCK-8 and flow cytometry assays indicated that miR-140-5p inhibited proliferation and induced apoptosis of tumor cells. Western blot analysis and RT-qPCR revealed that YES1 and B-cell lymphoma 2 (Bcl-2) mRNA and protein expression levels were markedly decreased in A549 cells, while Bcl-2 associated X (Bax) and caspase-3 expression levels increased significantly following transfection with miR-140-5p mimics compared with the negative control group. In conclusion, miR-140-5p may induce apoptosis in A549 cells by targeting YES1 and regulating the expression of apoptosis-associated proteins Bcl-2, Bax and caspase-3.

4.
Arch Virol ; 164(1): 41-50, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30232612

RESUMO

Foot-and-mouth disease virus (FMDV) exhibits high mutation rates during replication. In this study, an isolate of FMDV serotype Asia-1 was serially passaged in a BHK-21 cell monolayer and then adapted to serum-free BHK-21 cell suspension culture to produce a seed virus for production of an inactivated vaccine. Analysis of the sequence encoding the structural proteins of the virus at various passages showed the presence of overlapping peaks in sequencing electropherograms after nucleotide 619 of VP1 in viruses recovered from the fourth passage in suspension culture, suggesting the possible introduction of an insertion or deletion into this portion of the viral genome of our seed virus stock. To evaluate this phenomenon, a virus designated "Vac-Asia1-VDLV", was isolated by plaque purification from the tenth passage in suspension culture. Sequencing results showed that a 12-nt-long exogenous sequence was inserted into the 3' end of the VP1 coding region at the position where the original overlapping peaks were identified. Analysis of the host cell transcriptome showed that the 12-nt sequence was identical to a highly expressed sequence in BHK-21 cells, strongly suggesting that recombination between the FMDV genome and host cell mRNA produced the recombinant virus. A growth curve showed that the virus with the 12-nt insertion reached a peak earlier than the parental strain and that this virus had acquired the ability to bind to the cell surface by a mechanism that was not dependent on integrin or the heparan sulfate receptor. This novel pathogen-host cell recombination event is discussed in terms of the mechanism of viral RNA replication and the phenotypic constraints of FMDV biology and evolution.


Assuntos
Vírus da Febre Aftosa/genética , Vírus da Febre Aftosa/fisiologia , RNA Mensageiro/genética , Animais , Proteínas do Capsídeo , Linhagem Celular , Cricetinae , Febre Aftosa/virologia , Regulação Viral da Expressão Gênica , Genoma Viral , Mutação , RNA Viral/genética , Recombinação Genética , Cultura de Vírus , Replicação Viral
5.
Chem Sci ; 9(6): 1701, 2018 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-30288250

RESUMO

[This corrects the article DOI: 10.1039/C7SC04813K.].

6.
Materials (Basel) ; 11(8)2018 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-30044416

RESUMO

Optical fibers and waveguides in general effectively control and modulate light propagation, and these tools have been extensively used in communication, lighting and sensing. Recently, they have received increasing attention in biomedical applications. By delivering light into deep tissue via these devices, novel applications including biological sensing, stimulation and therapy can be realized. Therefore, implantable fibers and waveguides in biocompatible formats with versatile functionalities are highly desirable. In this review, we provide an overview of recent progress in the exploration of advanced optical fibers and waveguides for biomedical applications. Specifically, we highlight novel materials design and fabrication strategies to form implantable fibers and waveguides. Furthermore, their applications in various biomedical fields such as light therapy, optogenetics, fluorescence sensing and imaging are discussed. We believe that these newly developed fiber and waveguide based devices play a crucial role in advanced optical biointerfaces.

7.
Chem Sci ; 9(5): 1330-1338, 2018 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-29675180

RESUMO

DNA methylation is an important epigenetic modification in human genomes. Herein, we develop a single quantum dot (QD)-based nanosensor for sensitive detection of DNA methylation at both CpG and non-CpG sites using tricyclic ligation chain reaction (LCR)-mediated QD-based fluorescence resonance energy transfer (FRET). We design two sets of DNA probes (X and Y, X' and Y') for methylated DNA assay. In the presence of thermostable DNA ligase, probes X and Y may adjacently hybridize with the methylated DNA to obtain the ligated XY products which may function as the templates for probes X' and Y' to generate the X'Y' products. The resultant X'Y' products may in turn act as the templates to ligate probes X and Y for the generation of XY products, consequently inducing tricyclic LCR amplification under thermal denaturation conditions to generate a large number of XY products. The subsequent hybridization of XY products with the capture and reporter probes results in the formation of sandwich hybrids which may assemble on the 605QD surface to obtain 605QD-oligonucleotide-Cy5 nanostructures, inducing efficient FRET from the 605QD to Cy5 and the emission of Cy5. This nanosensor can detect DNA methylation at single 5-methylcytosine (5-mC) resolution with a detection limit of as low as 1.0 aM and a large dynamic range of 7 orders of magnitude. Moreover, this nanosensor can distinguish as low as a 0.01% methylation level, and it can detect DNA methylation in human lung cancer cells as well, holding great potential for accurate epigenetic evaluation and early cancer diagnosis.

9.
Sci Total Environ ; 631-632: 745-754, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29544178

RESUMO

Monochloramine (NH2Cl) is widely used for secondary disinfection by water utilities. However, Edmonton field stormwater sampling results have shown that NH2Cl, because of its long-lasting property, can cause stormwater contamination through outdoor potable water uses during the summer season. To protect water sources, it is important to understand NH2Cl dissipation mechanisms in stormwater. Natural organic matter (NOM) is the dominant species that contributes to NH2Cl decay in stormwater. In this research, it is proposed that NOM reacted with both NH2Cl and free chlorine through rapid and long-term reactions during NH2Cl dissipation. Based on this assumption, a kinetic model was developed and applied to estimate the NH2Cl decay in real stormwater samples, and the modeling results matched experimental data well under all the conditions. Further, the stormwater dissolved organic matter (SWDOM) collected from different neighborhoods was analyzed by Fourier transform infrared (FTIR) and fluorescence excitation-emission matrix (EEM) techniques. Humic substances were found to be dominant in SWDOM, and the samples from different neighborhoods had similar organic constituents. After reaction with excess NH2Cl, 25%-41% SWDOM fluorophores converted to inorganic components, while most of DOM remained in organic form. Humic substances as the major components in SWDON, are the dominant precursors of disinfection by-products in chloramination. Therefore, the potential reaction products of stormwater humic substances with NH2Cl should also be of concern. This research provided a useful method to estimate the NH2Cl dissipation in stormwater, and the methodology can also be applied for stormwater NH2Cl decay studies in other cities. Further, it is believed the SWDOM analysis in this research will contribute to future studies of NH2Cl NOM reaction mechanisms in both storm sewers and drinking water distribution systems.

10.
Oncol Lett ; 15(4): 5280-5284, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29552167

RESUMO

Nimotuzumab, a humanized IgG1 monoclonal antibody against epidermal growth factor receptor (EGFR), increases radiosensitivity in lung cancer. Cisplatin is an effective antitumor agent in lung cancer. In the present study, the antitumor activity of nimotuzumab combined with cisplatin was investigated in A549 lung cancer cells. Viability, cell cycle distribution and cyclin D1 expression were assessed following treatment with nimotuzumab alone, cisplatin alone, nimotuzumab in combination with cisplatin, and nimotuzumab followed sequentially by cisplatin. The inhibitory effect on cell viability of nimotuzumab sequentially followed by cisplatin was higher compared with cisplatin alone (82.17±1.62 vs. 56.97±1.42%). Compared with treatment by cisplatin alone, cell cycle analysis by flow cytometry demonstrated that the percentage of cells in the G0/G1 phase was increased when A549 cells were treated with nimotuzumab followed sequentially by cisplatin (P<0.01). However, the proportion of cells in G0/G1 phase was decreased when A549 cells were treated with nimotuzumab and cisplatin simultaneously compared with cisplatin alone (P<0.05). Cyclin D1 expression was decreased in all chemotherapy treatment groups; the most significant decrease was in A549 cells treated with nimotuzumab followed sequentially by cisplatin. Nimotuzumab may enhance the antitumor activity of cisplatin on A549 cells. The cell cycle arrest at G0/G1 observed may have been due to decreased cyclin D1 levels. Potential antagonism was identified when A549 cells were treated with nimotuzumab and cisplatin simultaneously, indicating that targeted therapy may be more effective when administered prior to conventional chemotherapy.

11.
Chem Commun (Camb) ; 54(13): 1583-1586, 2018 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-29368771

RESUMO

We develop a simple and label-free fluorescence method for the polynucleotide kinase (PNK) assay based on phosphorylation-triggered isothermal exponential amplification. This method exhibits ultrahigh sensitivity superior to most existing PNK assays. Importantly, this method enables sensitive detection of endogenous PNK activity at the single-cell level, holding great potential in clinical diagnosis and biomedical research.


Assuntos
Ensaios Enzimáticos/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Polinucleotídeo 5'-Hidroxiquinase/análise , DNA/química , DNA Polimerase I/química , Exodesoxirribonucleases/química , Fluorescência , Células HEK293 , Humanos , Limite de Detecção , Hibridização de Ácido Nucleico , Polinucleotídeo 5'-Hidroxiquinase/antagonistas & inibidores
12.
J Environ Manage ; 206: 51-59, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29055849

RESUMO

Many municipalities in Canada and all over the world use chloramination for drinking water secondary disinfection to avoid DBPs formation from conventional chlorination. However, the long-lasting monochloramine (NH2Cl) disinfectant can pose a significant risk to aquatic life through its introduction into municipal storm sewer systems and thus fresh water sources by residential, commercial, and industrial water uses. To establish general total active chlorine (TAC) concentrations in discharges from storm sewers, the TAC concentration was measured in stormwater samples in Edmonton, Alberta, Canada, during the summers of 2015 and 2016 under both dry and wet weather conditions. The field-sampling results showed TAC concentration variations from 0.02 to 0.77 mg/L in summer 2015, which exceeds the discharge effluent limit of 0.02 mg/L. As compared to 2015, the TAC concentrations were significantly lower during the summer 2016 (0-0.24 mg/L), for which it is believed that the higher precipitation during summer 2016 reduced outdoor tap water uses. Since many other cities also use chloramines as disinfectants for drinking water disinfection, the TAC analysis from Edmonton may prove useful for other regions as well. Other physicochemical and biological characteristics of stormwater and storm sewer biofilm samples were also analyzed, and no significant difference was found during these two years. Higher density of AOB and NOB detected in the storm sewer biofilm of residential areas - as compared with other areas - generally correlated to high concentrations of ammonium and nitrite in this region in both of the two years, and they may have contributed to the TAC decay in the storm sewers. The NH2Cl decay laboratory experiments illustrate that dissolved organic carbon (DOC) concentration is the dominant factor in determining the NH2Cl decay rate in stormwater samples. The high DOC concentrations detected from a downstream industrial sampling location may contribute to a high stormwater NH2Cl decay rate in this area.


Assuntos
Cloro , Poluentes Químicos da Água , Purificação da Água , Alberta , Cloraminas , Cidades , Desinfetantes , Desinfecção
13.
J Diabetes Sci Technol ; 12(2): 325-332, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29056082

RESUMO

BACKGROUND: The association of glucose variability (GV) with other glycemic measures is emerging as a topic of interest. The aim of this analysis is to study the correlation between GV and measures of glycemic control, such as glycated hemoglobin (HbA1c) and daily mean glucose (DMG). METHODS: Data from 5 phase 3 trials were pooled into 3 analysis groups: type 2 diabetes (T2D) treated with basal insulin only, T2D treated with basal-bolus therapy, and type 1 diabetes (T1D). A generalized boosted model was used post hoc to assess the relationship of the following variables with glycemic control parameters (HbA1c and DMG): within-day GV, between-day GV (calculated using self-monitored blood glucose and fasting blood glucose [FBG]), hypoglycemia rate, and certain baseline characteristics. RESULTS: Within-day GV (calculated using standard deviation [SD]) was found to have a significant influence on endpoints HbA1c and DMG in all 3 patient groups. Between-day GV from FBG (calculated using SD), within-day GV (calculated using coefficient of variation), and hypoglycemia rate were found to significantly influence the endpoint HbA1c in the T2D basal-only group. CONCLUSIONS: Lower within-day GV was significantly associated with improvement in DMG and HbA1c. This finding suggests that GV could be a marker in the early phases of new antihyperglycemic therapy development for predicting clinical outcomes in terms of HbA1c and DMG.


Assuntos
Glicemia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Hemoglobina A Glicada , Ensaios Clínicos Fase III como Assunto , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Estudos Retrospectivos
14.
J Investig Med ; 66(3): 661-668, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29167192

RESUMO

Data on cytokeratin-18 (K-18) and enhanced liver fibrosis (ELF) score in insulin-treated diabetes patients with non-alcoholic fatty liver disease (NAFLD) are limited. This study analyzed phase III data comparing basal insulin peglispro (BIL) and insulin glargine in type 1 (T1D), and type 2 diabetes (T2D) (insulin-naïve and insulin-treated). Alanine aminotransferase (ALT), K-18, ELF scores and liver fat content (LFC), measured by MRI, were obtained longitudinally. Baseline K-18 (U/L) was higher in T2D (range: 207‒247) than T1D (range: 148‒183), correlated with ALT in all populations (r (range) 0.264‒0.637, p<0.05), but with LFC only in T2D (r (range) 0.474‒0.586, p<0.05). K-18 increased significantly from baseline in BIL-treated, but not glargine-treated patients. Change from baseline (CFB) K-18 was significantly correlated with CFB in ALT in BIL-treated T2D populations. Baseline ELF scores were higher in T2D (range: 9.12‒9.20) than T1D (range: 8.24‒8.36), correlated with ALT in T1D only (0.209, p<0.05), and not correlated with LFC in any population. ELF scores increased significantly from baseline in BIL-treated but not glargine-treated patients. There were no correlations between CFB in LFC and ELF score at week 52 in any treatment group/population. In all BIL-treated populations, CFB in ALT and CFB in ELF score at week 52 were positively correlated. These data characterize associations of K-18 and ELF score with ALT and LFC in insulin-treated patients with T1D and T2D. Hepatopreferential insulins may be associated with increased K-18 and ELF scores but mechanisms and clinical significance are unknown. ClinicalTrials.gov identifiers are NCT01481779, NCT01435616, NCT01454284 and NCT01582451.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina/uso terapêutico , Queratina-18/sangue , Cirrose Hepática/sangue , Adiposidade , Adulto , Demografia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Cirrose Hepática/complicações , Masculino
15.
Environ Technol ; 39(8): 1007-1016, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28394201

RESUMO

Benzimidazole is an important intermediate in industry and it is usually difficult to be degraded by many treatment technologies. Looking for a highly effective, environment-friendly degradation process for benzimidazole wastewater is of great significance to reduce pollution. Based on the structure of contaminants, the micro-electrolysis (ME) coupled with the Fenton technique was chosen to degrade the industrial benzimidazole wastewater. Special feeding was applied to maintain the suitable hydrogen peroxide (H2O2) concentration to produce the hydroxyl radicals (•OH) as much as possible and protect •OH from being quenched by excess H2O2 according to the reaction mechanism. The results showed that this combined technique was highly efficient to decompose benzimidazole compounds. More chemical oxygen demand (COD) could be reduced when flow control was used, compared to the flow not being controlled. The COD removal rate could reach 85.2% at optimal parameters. Then the effluent of this process was combined with the existing biochemical system for further degradation. The studies of Ultraviolet Spectrophotometry, Fourier Transform Infrared Spectroscopy and Liquid Chromatography Mass Spectrometry showed that both 2-(a-Hydroxyethyl) benzimidazole and 2-Acetylbenzimidazole were decomposed to the isopropanolamine and aniline after the ME treatment; then the intermediates were oxidized into oxalic acid after the Fenton reaction.


Assuntos
Benzimidazóis/química , Eliminação de Resíduos Líquidos , Águas Residuárias , Poluentes Químicos da Água/química , Peróxido de Hidrogênio , Resíduos Industriais , Ferro , Estrutura Molecular , Oxirredução
16.
Viral Immunol ; 31(1): 34-39, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28514189

RESUMO

The attenuated C-strain vaccine against classical swine fever virus (CSFV) is one of the safest and most effective attenuated vaccines. However, little is known of the host immune response after vaccination with the C-strain vaccine. Blood samples from vaccinated pigs were collected to evaluate the number of immune cells, the level of specific CSFV antibody, and related cytokines induced by the vaccination of C-strain vaccine. The C-strain nucleic acid was gradually removed and specific antibody to vaccine kept increasing; the amount of the lymphocyte, Tc cell, and Th cell increased; some inflammatory cytokines such as interleukin (IL)-1 and tumor necrosis factor-α mainly showed downregulated trends, but IL-6 and IL-8 were upregulated greatly; IL-2, IL-4, IL-5, IL-12p40, IL-13, interferon (IFN)-I, and Toll-like receptors (TLRs) kept high expression level after 28 days postvaccination (dpv); IFN-γ was upregulated slightly at 5 and 9 dpv, respectively. These results suggest that the C-strain vaccine induces a Th2 cell response to produce the specific antibody. The vaccine virus replicates at very low level. C-strain vaccine burden has close relationship with the expression of TLRs. The overexpression of TLRs initiates the innate immune system to clear up the vaccine. Meanwhile, ILs expressed by immune system induce the differentiation of B cells and produce specific antibody.


Assuntos
Vírus da Febre Suína Clássica/imunologia , Peste Suína Clássica/prevenção & controle , Citocinas/genética , Suínos/imunologia , Subpopulações de Linfócitos T/imunologia , Vacinação/veterinária , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Peste Suína Clássica/sangue , Peste Suína Clássica/imunologia , Regulação da Expressão Gênica , Cinética , Contagem de Linfócitos , Masculino , RNA Viral/análise , Suínos/virologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Receptores Toll-Like/genética , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Vacinas Virais/administração & dosagem
17.
Water Sci Technol ; 78(11): 2279-2287, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30699079

RESUMO

Monochloramine (NH2Cl), as the dominant disinfectant in drinking water chloramination, can provide long-term disinfection in distribution systems. However, NH2Cl can also be discharged into storm sewer systems and cause stormwater contamination through outdoor tap water uses. In storm sewer systems, NH2Cl dissipation can occur by three pathways: (i) auto-decomposition, (ii) chemical reaction with stormwater components, and (iii) biological dissipation. In this research, a field NH2Cl dissipation test was conducted with continuous tap water discharge into a storm sewer. The results showed a fast decrease of NH2Cl concentration from the discharge point to the sampling point at the beginning of the discharge period, while the rate of decrease decreased as time passed. Based on the various pathways involved in NH2Cl decay and the field testing results, a kinetic model was developed. To describe the variation of the NH2Cl dissipation rates during the field testing, a time coefficient fT was introduced, and the relationship between fT and time was determined. After calibration through the fT coefficient, the kinetic model described the field NH2Cl dissipation process well. The model developed in this research can assist in the regulation of tap water outdoor discharge and contribute to the protection of the aquatic environment.


Assuntos
Cloraminas/análise , Eliminação de Resíduos Líquidos/estatística & dados numéricos , Águas Residuárias/química , Poluentes da Água/análise , Desinfetantes/análise , Desinfecção , Água Potável , Monitoramento Ambiental , Águas Residuárias/estatística & dados numéricos
18.
Biomark Med ; 11(11): 991-1001, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29160108

RESUMO

AIM: To characterize the effects of hepato-preferential basal insulin peglispro (BIL) and insulin glargine on insulin resistance (lipoprotein insulin resistance index [LP-IR]) and inflammation (GlycA), and to explore the biological implications. METHODS: This substudy included 847 patients with Type 1 diabetes (T1D) or Type 2 diabetes (T2D) in four cohorts of the BIL development program. LP-IR and GlycA were measured before and after insulin treatment. Correlations between LP-IR, GlycA, clinical parameters and liver biomarkers were assessed. RESULTS: LP-IR and GlycA were higher in T2D than T1D. LP-IR increased in patients switched from basal insulins to BIL but not in insulin-naive patients. GlycA decreased in T2D patients treated with BIL and T1D patients treated with glargine. CONCLUSION: These exploratory analyses help to characterize differences in biological effects between BIL and glargine treatment.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Insulina Glargina/administração & dosagem , Resistência à Insulina , Lipoproteínas/sangue , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Chem Commun (Camb) ; 53(83): 11496-11499, 2017 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-28990029

RESUMO

We develop an antibody-free fluorescence method for the epidermal growth factor receptor (EGFR) assay using aptamer-based target-/probe-mediated cyclic signal amplification. The method is highly sensitive with a detection limit of 0.16 fM, and it can be applied to detect EGFR in lung cancer cells, holding great potential in clinical diagnosis.


Assuntos
Receptores ErbB/química , Neoplasias Pulmonares/metabolismo , Células A549 , Aptâmeros de Nucleotídeos/metabolismo , Humanos , Limite de Detecção , Neoplasias Pulmonares/química , Sensibilidade e Especificidade
20.
Anal Chem ; 89(22): 12408-12415, 2017 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-29083155

RESUMO

DNA methyltransferases (MTases) may specifically recognize the short palindromic sequences and transfer a methyl group from S-adenosyl-l-methionine to target cytosine/adenine. The aberrant DNA methylation is linked to the abnormal DNA MTase activity, and some DNA MTases have become promising targets of anticancer/antimicrobial drugs. However, the reported DNA MTase assays often involve laborious operation, expensive instruments, and radio-labeled substrates. Here, we develop a simple and label-free fluorescent method to sensitively detect DNA adenine methyltransferase (Dam) on the basis of terminal deoxynucleotidyl transferase (TdT)-activated Endonuclease IV (Endo IV)-assisted hyperbranched amplification. We design a hairpin probe with a palindromic sequence in the stem as the substrate and a NH2-modified 3' end for the prevention of nonspecific amplification. The substrate may be methylated by Dam and subsequently cleaved by DpnI, producing three single-stranded DNAs, two of which with 3'-OH termini may be amplified by hyperbranched amplification to generate a distinct fluorescence signal. Because high exactitude of TdT enables the amplification only in the presence of free 3'-OH termini and Endo IV only hydrolyzes the intact apurinic/apyrimidinic sites in double-stranded DNAs, zero background signal can be achieved. This method exhibits excellent selectivity and high sensitivity with a limit of detection of 0.003 U/mL for pure Dam and 9.61 × 10-6 mg/mL for Dam in E. coli cells. Moreover, it can be used to screen the Dam inhibitors, holding great potentials in disease diagnosis and drug development.


Assuntos
Escherichia coli/enzimologia , DNA Metiltransferases Sítio Específica (Adenina-Específica)/análise , Inibidores Enzimáticos/farmacologia , Escherichia coli/citologia , Fluoruracila/farmacologia , DNA Metiltransferases Sítio Específica (Adenina-Específica)/antagonistas & inibidores , DNA Metiltransferases Sítio Específica (Adenina-Específica)/metabolismo
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