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1.
Biosens Bioelectron ; 238: 115589, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37591158

RESUMO

Given the targeted binding ability and cleavage activity of the emerging CRISPR/Cas12a assay which transduces the target into its cleavage activity exhibited broadly prospective applications in integrated sensing and actuating system. Here, we elaborated a universal approach to quickly activate CRISPR/Cas12a for low-abundance biomarker detection based on the amplification strategy of a target-induced spherical nucleic acid enzyme (SNAzyme) network that could accelerate the output of activators. Specifically, multifunctional Y-shaped probes and hairpin probes (HPs, which contained the specific sequence of the activators of CRISPR/Cas12a and the substrate chain of DNAzyme) were rationally designed to construct SNAzyme. Target recognition induced disassembly of the Y-shaped probes, which released DNAzyme strands to active DNAzyme and accompanied by SNAzyme self-assembly into SNAzyme network. Interestingly, compared with randomly dispersed SNAzyme, the reaction kinetics of the SNAzyme network enhanced 1.6 times in response to Α-methyl acyl-CoA racemase (AMACR, a biomarker for prostate cancer), which was attributed to the promoted catalytic efficiency of DNAzyme by the confined SNAzyme network. Benefiting from these, the prepared biosensor based on electrochemiluminescence (ECL) platform by loading AuAg nanoclusters (AuAgNCs) into metal-organic framework-5 (MOF-5) exhibited satisfying detection performance for AMACR with a wide linear range (0.001 µg/mL to 100 µg/mL) and a low detection limit (1.0 × 10-4 µg/mL, which exhibited significant potential in clinical diagnoses.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Masculino , Humanos , Bioensaio , Catálise
2.
Acad Radiol ; 30 Suppl 1: S1-S13, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37393175

RESUMO

RATIONALE AND OBJECTIVES: To develop and evaluate a peritumoral radiomic-based machine learning model to differentiate low-Gleason grade group (L-GGG) and high-GGG (H-GGG) prostate lesions. MATERIALS AND METHODS: In this retrospective study, a total of 175 patients with prostate cancer (PCa) confirmed by puncture biopsy were recruited and included 59 patients with L-GGG and 116 patients with H-GGG. The original PCa regions of interest (ROIs) were delineated on T2-weighted (T2WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) maps, and then centra-tumoral and peritumoral ROIs were defined. Features were meticulously extracted from each ROI to establish radiomics models, employing distinct sequence datasets. Peritumoral radiomics models were specifically developed for both the peripheral zone (PZ) and transitional zone (TZ), utilizing dedicated PZ and TZ datasets, respectively. The performances of the models were evaluated by using the receiver operating characteristic (ROC) curve and precision-recall curve. RESULTS: The classification model with combined peritumoral features based on T2 + DWI + ADC sequence dataset demonstrated superior performance compared to the original tumor and centra-tumoral classification models. It achieved an area under the ROC curve (AUC) of 0.850 [95% confidence interval, 0.849, 0.860] and an average accuracy of 0.950. The combined peritumoral model outperformed the regional peritumoral models with AUC of 0.85 versus 0.75 for PZ lesions and 0.88 versus 0.69 for TZ lesions, respectively. The peritumoral classification models exhibit greater efficacy in predicting PZ lesions as opposed to TZ lesions. CONCLUSION: The peritumoral radiomics features showed excellent performance in predicting GGG in PCa patients and might be a valuable addition to the non-invasive assessment of PCa aggressiveness.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Aprendizado de Máquina
3.
Talanta ; 251: 123788, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35933847

RESUMO

As various aptasensors are adopted in clinical diagnosis, the development of convenient multiple-target determination is a field of ever-increasing interests. Herein, a label-free and amplified electrochemiluminescence (ECL) sensing platform was constructed to detect multiple targets of hemin, glucose and thrombin (TB) using peroxydisulfate (S2O82-) solution, which was one of the most convenient and economical ECL systems. It was worth mentioning that the target-induced bi-enzyme cascade catalysis reaction was developed to increase the ECL response strongly of S2O82- solution due to the production of (1O2)2* from the inter-reaction between reactive oxygen species (ROS) and sulfate radical (SO4•-). Specifically, with the layer-by-layer assembly of multi-walled carbon nanotubes (MWCNTs), glucose oxidase (GOx) and gold nanoparticles (AuNPs) as the interface, the guanine-rich (G-rich) thrombin aptamer (TBA) was anchored for hemin (target 1) detection, due to the electrocatalysis of hemin/G-quadruplex as a horseradish peroxidase mimicking DNAzyme (HRP-DNAzyme) towards dissolved oxygen for ROS generation. Second, in the presence of glucose (target 2), the ECL intensity was improved because glucose was the substrate of the bi-enzyme cascade catalysis reaction. Third, when TB (target 3) was sequentially incubated based on the above-mentioned aptasensor, the bi-enzyme catalysis was inhibited to decrease the ECL signal, due to the steric hindrance effect of the TB protein. As a result, the aptasensor achieved the nanomolar detection for hemin (3.33 nM), the micromolar detection for glucose (0.33 µM) and the femtomolar detection for TB (3.33 fM), respectively.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , DNA Catalítico , Nanopartículas Metálicas , Nanotubos de Carbono , DNA Catalítico/metabolismo , Técnicas Eletroquímicas , Glucose , Glucose Oxidase/metabolismo , Ouro , Guanina , Hemina , Peroxidase do Rábano Silvestre/metabolismo , Oxigênio , Espécies Reativas de Oxigênio , Trombina
4.
Front Oncol ; 12: 911426, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795067

RESUMO

Objective: To develop and validate a noninvasive radiomic-based machine learning (ML) model to identify P504s/P63 status and further achieve the diagnosis of prostate cancer (PCa). Methods: A retrospective dataset of patients with preoperative prostate MRI examination and P504s/P63 pathological immunohistochemical results between June 2016 and February 2021 was conducted. As indicated by P504s/P63 expression, the patients were divided into label 0 (atypical prostatic hyperplasia), label 1 (benign prostatic hyperplasia, BPH) and label 2 (PCa) groups. This study employed T2WI, DWI and ADC sequences to assess prostate diseases and manually segmented regions of interest (ROIs) with Artificial Intelligence Kit software for radiomics feature acquisition. Feature dimensionality reduction and selection were performed by using a mutual information algorithm. Based on screened features, P504s/P63 prediction models were established by random forest (RF), gradient boosting decision tree (GBDT), logistic regression (LR), adaptive boosting (AdaBoost) and k-nearest neighbor (KNN) algorithms. The performance was evaluated by the area under the ROC curve (AUC) and accuracy. Results: A total of 315 patients were enrolled. Among the 851 radiomic features, the 32 top features were derived from T2WI, in which the gray-level run length matrix (GLRLM) and gray-level cooccurrence matrix (GLCM) features accounted for the largest proportion. Among the five models, the RF algorithm performed best in general evaluations (microaverage AUC=0.920, macroaverage AUC=0.870) and provided the most accurate result in further sublabel prediction (the accuracies of label 0, 1, and 2 were 0.831, 0.831, and 0.932, respectively). In comparative sequence analyses, T2WI was the best single-sequence candidate (microaverage AUC=0.94 and macroaverage AUC=0.78). The merged datasets of T2WI, DWI, and ADC yielded optimal AUCs (microaverage AUC=0.930 and macroaverage AUC=0.900). Conclusions: The radiomic-based RF classifier has the potential to be used to evaluate the presurgical P504s/P63 status and further diagnose PCa noninvasively and accurately.

5.
Addict Biol ; 26(6): e13025, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33609013

RESUMO

Oxycodone is one of the most commonly used analgesics in the clinic. However, long-term use can contribute to drug dependence. Accumulating evidence of changes in DNA methylation after opioid relapse has provided insight into mechanisms underlying drug-associated memory. The neuropeptide oxytocin is reported to be a potential treatment for addiction. The present study sought to identify changes in global and synaptic gene methylation after cue-induced reinstatement of oxycodone conditioned place preference (CPP) and the effect of oxytocin. We analyzed hippocampal mRNA of synaptic genes and also synaptic density in response to oxycodone CPP. We determined the mRNA levels of DNA methyltransferases (Dnmts) and ten-eleven translocations (Tets), observed global 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) levels, and measured DNA methylation status of four synaptic genes implicated in learning and memory (Arc, Dlg1, Dlg4, and Syn1). Both synaptic density and the transcription of 15 hippocampal synaptic genes significantly increased following cue-induced reinstatement of oxycodone CPP. Oxycodone relapse was also related to markedly decreased 5-mC levels and decreased transcription of Dnmt1, Dnmt3a, and Dnmt3b; in contrast, 5-hmC levels and the transcription of Tet1 and Tet3 were increased. Oxycodone exposure induced DNA hypomethylation at the exons of the Arc, Dlg1, Dlg4, and Syn1 genes. Intracerebroventricular (ICV) administration of oxytocin (2.5 µg/µl) specifically blocked oxycodone relapse, possibly by inhibition of Arc, Dlg1, Dlg4, and Syn1 hypomethylation in oxycodone-treated rats. Together, these data indicate the occurrence of epigenetic changes in the hippocampus following oxycodone relapse and the potential role of oxytocin in oxycodone addiction.


Assuntos
Metilação de DNA/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Transtornos Relacionados com Narcóticos/fisiopatologia , Oxicodona/farmacologia , Ocitocina/farmacologia , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Animais , Condicionamento Clássico/efeitos dos fármacos , Sinais (Psicologia) , Metilação de DNA/fisiologia , Relação Dose-Resposta a Droga , Aprendizagem/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Transtornos Relacionados com Narcóticos/genética , RNA Mensageiro/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
6.
J Integr Med ; 17(3): 167-172, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30922849

RESUMO

BACKGROUND: Fire-needle acupuncture, an important kind of acupuncture therapy, has been clinically used to treat upper limb spastic paralysis (ULSP) after stroke. Clinical experience has indicated that fire-needle acupuncture treatment takes less time, requires fewer visits, and has more rapid results and fewer side effects compared to chemical medicine alternatives. This study will evaluate the effects of fire-needle acupuncture for ULSP in the context of standardized clinical research and provide high-quality data to inform clinical procedures and future study design. METHODS/DESIGN: A randomized controlled trial will be carried out to evaluate the effects of fire-needle acupuncture therapy in patients with ULSP from stroke. ULSP patients (n = 120) will be recruited at Changhai Hospital in Shanghai, China. Patients will be randomly divided into three groups, including fire-needle acupuncture group (FAG), filiform-needle acupuncture group (FFAG) and rehabilitation treatment group (RTG). During the 3-week treatment, the FAG will be treated every two days, while FFAG and RTG will be treated 5 d in a row and then rest for 2 d. The Simplified Fugl-Meyer Motor Function Scale and Modified Ashworth Scale will be used as the primary outcome measures. Statistical analysis will be conducted by an independent statistician. DISCUSSION: Through this study, the utility of fire-needle acupuncture in treating ULSP after stroke will be tested, and some specific claims of fire-needle acupuncture therapy will be evaluated, such as relieving spasm and muscular tension, improving activities of daily living, rapidity of response and less frequency of treatment compared with other treatments. TRIAL REGISTRATION: Chinese Clinical Trial Registry (identifier: ChiCTR-IOR-17013875; registration date: 28 December 2016).


Assuntos
Terapia por Acupuntura , Espasticidade Muscular/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Pontos de Acupuntura , Adulto , Idoso , China , Protocolos Clínicos , Feminino , Humanos , Pessoa de Meia-Idade , Espasticidade Muscular/etiologia , Espasticidade Muscular/fisiopatologia , Agulhas , Extremidade Superior/fisiopatologia , Adulto Jovem
7.
J Cell Biochem ; 118(12): 4568-4574, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28485890

RESUMO

We aimed to investigate whether the cardioprotective effect of estrogen is mediated by inhibiting the apoptosis induced by endoplasmic reticulum stress (ERS) and to explore the underlying signaling pathway responsible for this effect. The effect of estrogen on ERS apoptosis, the mechanism responsible for that effect, and the ERS signaling pathways were examined in human umbilical vein endothelial cells (HUVECs) and measured using Western blot, Hoechst stains and caspase-3 activity assay. In vitro, 10-8 mol/l estrogen directly inhibited the up-regulation of the ERS marker glucose-regulated protein 78 (GRP78) and ERS apoptosis marker C/EBP homologous protein (CHOP). ERS was induced using the ERS inducer tunicamycin (TM, 10 µmol/l) or dithiothreitol (DTT, 2 mmol/l) in HUVECs. Estrogen can also decrease the apoptosis cells mediated by ERS, based on the results of Hoechst stains. Protein expression in the three main ERS signaling pathways was upregulated in TM- or DTT-induced HUVEC ERS. Increases in p-PERK/PERK were the most obvious, and estrogen significantly inhibited the upregulation of p-PERK/PERK, p-IRE1/IRE1, and ATF6. These inhibitory effects were abolished by specific estrogen receptor antagonists (ICI182, 780, and G15) and inhibitors of the E2 post-receptor signaling pathway, including phosphoinositide 3-kinase (PI3K) inhibitor LY294002, p38-mitogen activated protein kinase (p38-MAPK) inhibitor SB203580, c-Jun N-terminal kinase (JNK) inhibitor SP600125 and extracellular signal-regulated kinases1/2 (ERK1/2) inhibitor U0126; of these inhibitors, LY294002 was the most effective. Further experiments showed that when the PI3K pathway was blocked, the inhibitory effect of estrogen on ERS apoptosis was reduced. Estrogen can prevent HUVEC apoptosis by inhibiting the ERS apoptosis triggered by the PERK pathway, which may protect vascular endothelial cells and the cardiovascular system. The main mechanism responsible for ERS inhibition is the activation of the PI3K-Akt pathway for the activated estrogen receptor. J. Cell. Biochem. 118: 4568-4574, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Estradiol/farmacologia , Estrogênios/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular , Chaperona BiP do Retículo Endoplasmático , Proteínas de Choque Térmico/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Fator de Transcrição CHOP/metabolismo
8.
Talanta ; 158: 142-151, 2016 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-27343588

RESUMO

A novel and highly sensitive electrochemiluminescence (ECL) biosensing system was designed and developed for individual detection of different organophosphorous pesticides (OPs) in food samples. Bimetallic Pt-Au nanoparticles were electrodeposited on multi-walled carbon nanotubes (MWNTs)-modified glass carbon electrode (GCE) to increase the surface area of electrode and ECL signals of luminol. Biocomposites of enzymes from acetylcholinesterase and choline oxidase (AChE and ChOx) were immobilized onto the electrode surface to produce massive hydrogen peroxides (H2O2), thus amplifying ECL signals. Based on the dual-amplification effects of nanoparticles and H2O2 produced by enzymatic reactions, the proposed biosensor exhibits highly sensitivity. The proposed biosensing approach was then used for detecting OPs by inhibition of OPs on AChE. Under optimized experimental conditions, the ECL intensity decreased accordingly with the increase in concentration of OPs, and the inhibition rates of OPs were proportional to their concentrations in the range of 0.1-50nmolL(-1) for malathion, methyl parathion and chlorpyrifos, with detection limit of 0.16nmolL(-1), 0.09nmolL(-1) and 0.08nmolL(-1), respectively. The linearity range of the biosensor for pesticide dufulin varied from 50 to 500nmolL(-1), with the detection limit of 29.7nmolL(-1). The resulting biosensor was further validated by assessment of OPs residues in cabbage, which showed a fine applicability for the detection of OPs in the realistic sample.


Assuntos
Técnicas Biossensoriais , Praguicidas/análise , Acetilcolinesterase/química , Oxirredutases do Álcool/química , Benzotiazóis/análise , Benzotiazóis/química , Brassica/química , Clorpirifos/análise , Clorpirifos/química , Inibidores da Colinesterase/análise , Inibidores da Colinesterase/química , Técnicas Eletroquímicas , Eletrodos , Enzimas Imobilizadas/química , Ouro/química , Peróxido de Hidrogênio/química , Malation/análise , Malation/química , Metil Paration/análise , Metil Paration/química , Nanotubos de Carbono/química , Praguicidas/química , Platina/química
9.
Yao Xue Xue Bao ; 51(3): 450-4, 2016 03.
Artigo em Chinês | MEDLINE | ID: mdl-29859028

RESUMO

In this study, we developed a sensitive and rapid HPLC-MS/MS method for the determination of trans-ferulic acid(trans-FA) in plasma samples, and investigated the pharmacokinetics characteristics in healthy volunteers. The plasma samples were extracted with acetic ether, and then separated on a Hedera ODS-2 column with a mobile phase of methanol and 5 mmol·L(-1) ammonium acetate buffer solution containing 0.05% acetic acid(34∶66) at a flow rate of 0.4 m L·min(-1). Electrospray ionization source was applied and operated in the positive ion mode using MRM. The method exhibited a good linearity over the concentration range of 0.1-5 ng·m L(-1)(r ≥ 0.999 2). The values on both the occasions(intra- and inter-day) were all within 9.2%, and the accuracy was 95.4%-111.4%. No matrix effect and carry-over effect were observed. Trans-FA was stable in human plasma under different storage conditions. The developed HPLC-MS/MS method is rapid, sensitive, accurate, and reproducible, and suitable for the pharmacokinetic study of trans-FA in healthy Chinese volunteers.


Assuntos
Ácidos Cumáricos/sangue , Ácidos Cumáricos/farmacocinética , Cromatografia Líquida de Alta Pressão , Humanos , Plasma , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem
10.
Epilepsia ; 55(8): 1301-6, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24861996

RESUMO

OBJECTIVE: This study explored the association between the risk of carbamazepine (CBZ)-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and CBZ dose, dose-adjusted concentration, and ABCB1, CYP3A4, EPHX1, FAS, SCN1A, MICA, and BAG6 polymorphisms in patients of Han ethnicity with epilepsy who were living in northeastern China. MATERIALS AND METHODS: We determined the genotypes of patients with CBZ-SJS/TEN and CBZ-tolerant patients, who were used as controls, for ABCB1, CYP3A4, EPHX1, FAS, SCN1A, MICA, and BAG6 polymorphisms by polymerase chain reaction (PCR) amplification and direct sequencing. We measured the steady-state serum CBZ concentrations using fluorescence polarization immunoassay for the control patients. RESULTS: We observed statistically significant differences in EPHX1 c.337T>C polymorphisms between patients with CBZ-SJS/TEN and CBZ-tolerant controls in terms of allelic and genotypic frequencies (p = 0.011 and p = 0.007, respectively). The C allele and the C-G diplotype of EPHX1 may play important roles in increasing the risk of CBZ-SJS/TEN development (odds ratio [OR] 0.478, 95% confidence interval [CI] = 0.267-0.855, p = 0.011; OR = 0.213, 95% CI = 0.049-0.930, p = 0.025, respectively). We did not observe any significant associations between ABCB1, CYP3A4, EPHX1, FAS, SCN1A, MICA or BAG6 genes and CBZ dose or dose-adjusted concentration in CBZ-tolerant patients. SIGNIFICANCE: We found a significant association between EPHX1 c.337T>C polymorphisms and the development of CBZ-SJS/TEN in patients of Han ethnicity living in northeastern China. EPHX1 c.337T>C polymorphisms may contribute to the risk of severe CBZ-SJS/TEN by increasing the concentration of a CBZ metabolite, CBZ-10,11-epoxide, in patients with epilepsy.


Assuntos
Povo Asiático/genética , Carbamazepina/efeitos adversos , Epilepsia/genética , Epóxido Hidrolases/genética , Polimorfismo Genético/genética , Síndrome de Stevens-Johnson/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Adolescente , Adulto , Alelos , Anticonvulsivantes/efeitos adversos , Citocromo P-450 CYP3A/genética , Epilepsia/tratamento farmacológico , Feminino , Genótipo , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares/genética , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Fenótipo , Síndrome de Stevens-Johnson/diagnóstico , Adulto Jovem , Receptor fas/genética
11.
Hippocampus ; 24(4): 493-501, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24436084

RESUMO

Stress influences the development of depression, and depression is associated with structural and functional changes in the hippocampus. The current study sought to determine whether chronic corticosteroid (CORT) treatment influences serotonin transporter (5-HTT) protein expression and function in the CA1, CA3, and dentate gyrus (DG) subregions of the hippocampus. Male CD-1 mice were subcutaneously injected with CORT at a dose of 20 mg/kg once daily for 3 weeks. Behavioral state was assessed using sucrose preference, physical state of the coat, forced swimming test, and tail suspension test. We then determine 5-HTT protein expression and synaptosomal 5-HT uptake in the CA1, CA3 and DG subregions. CORT treatment induced anhedonia and behavioral despair, two core endophenotypes of clinical depression; 5-HTT protein expression levels and synaptosomal 5-HT uptake were both decreased in a subregion-specific manner, with the greatest decrease observed in the DG, a moderate decrease in the CA3, and the CA1 showed no apparent change. In addition, a reduction in tissue mass was detected in the DG following the CORT treatment. These data indicate that subregion-specific decreases in hippocampal 5-HTT protein expression and function are associated with endophenotypes of depression.


Assuntos
Transtorno Depressivo/metabolismo , Endofenótipos , Hipocampo/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Corticosteroides , Anedonia/fisiologia , Animais , Região CA1 Hipocampal/metabolismo , Região CA3 Hipocampal/metabolismo , Giro Denteado/metabolismo , Giro Denteado/patologia , Transtorno Depressivo/patologia , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos , Tamanho do Órgão , Distribuição Aleatória , Serotonina/metabolismo , Sinaptossomos/metabolismo
12.
Pharmacol Rep ; 65(5): 1256-62, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24399721

RESUMO

BACKGROUND: This study examined the significant association between carbamazepine (CBZ)-induced Stevens-Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) and HLA-B*15:02 in epilepsy patients of Han ethnicity living in northeastern China. METHODS: CBZ-SJS/TEN patients and CBZ-tolerant control patients were genotyped for HLA-B*15:02 by PCR amplification using sequence-specific primers. Patients then were evaluated for HLA genotypes using PCR with sequence-based typing. RESULTS: Eight of 35 CBZ-SJS/TEN patients carried HLA-B*15:02 (22.9%) versus 2 of 125 in CBZ-tolerant control patients (OR = 18.222, 95% CI = 3.662-90.662, p = 0.000). Our results suggest that HLA-B*15:02 is necessary but is not sufficient to produce SJS/TEN following CBZ treatment among Han individuals from northeastern China. Other HLA alleles, including A*33:03, B*58:01, C*03:02, DQB1*03:03, and DRB1*07:01 may be associated weakly with CBZ-SJS/TEN. CONCLUSIONS: Our results are not consistent with previous studies reporting a strong association between HLA-B*15:02 and CBZ-SJS/TEN among individuals from southern, southwestern, and central China. Other genes may be more tightly associated with CBZ-SJS/TEN. Screening for HLA-B*15:02 still may be recommended for patients in northeastern China before starting CBZ.


Assuntos
Anticonvulsivantes/efeitos adversos , Povo Asiático/genética , Carbamazepina/efeitos adversos , Antígeno HLA-B15/genética , Síndrome de Stevens-Johnson/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , China/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Reação em Cadeia da Polimerase , Fatores de Risco , Análise de Sequência de DNA , Síndrome de Stevens-Johnson/etnologia , Síndrome de Stevens-Johnson/imunologia , Adulto Jovem
13.
Pharmacol Rep ; 63(3): 815-25, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21857093

RESUMO

The aim of this study was to retrospectively evaluate the effect of polymorphisms in the CYP3A4, CYP3A5 and ABCB1 genes on the dose-adjusted concentration and dose requirement of cyclosporine A(CsA) in Chinese recipients during the early period after bone marrow or hematopoietic stem cell transplantation. Ninety-one bone marrow transplant recipients were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay or by direct sequencing for the C1236T, G2677T/A and C3435T polymorphisms in CYP3A4*18B, CYP3A5*3, and ABCB1, respectively. The concentration at zero before administration (C0) and concentration at 2 h after administration (C2) of whole blood CsA were measured by fluorescence polarization immunoassay. Dose-adjusted C0 and C2 were determined and compared among groups with different genotypes. Compared with CYP3A5*3/*3 individuals, CYP3A5*1/*1 subjects have a significantly lower dose-adjusted C0 and C2 at days 1-10 and a higher dose requirement for CsA at days 16-30 (p < 0.05). In addition, homozygotes for the ABCB1 3435T mutant have a significantly higher dose-adjusted C0 and C2 and a lower dose requirement compared with wildtype (p < 0.05). Similar results were also derived for carriers of the T-G-C haplotype in CYP3A5 producers compared with non-carriers (p < 0.05 and p < 0.01, respectively). In summary, the ABCB1 3435T SNP, T-G-C haplotype in CYP3A5 producers, and CYP3A5*3 SNP are all associated with differences in CsA pharmacokinetics and dose requirements during the first month after bone marrow or hematopoietic stem cell transplantation. Genetic testing can therefore help to determine initial dosage and individualize immunosuppressive therapy.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Ciclosporina/farmacocinética , Citocromo P-450 CYP3A/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Adolescente , Adulto , Transplante de Medula Óssea/métodos , Criança , Pré-Escolar , China , Ciclosporina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Imunoensaio de Fluorescência por Polarização , Genótipo , Haplótipos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Masculino , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Adulto Jovem
14.
Eur J Clin Pharmacol ; 67(9): 885-7, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21424386

RESUMO

PURPOSE: The purpose of this study is to examine the association of HLA-B*1502 allele with CBZ-induced SJS/TEN in the mainland Han Chinese population. METHODS: HLA-B*1502 genotyping with sequence-specific primer polymerase chain reaction (PCR-SSP) and PCR-sequencing based typing (PCR-SBT) was performed on 17 CBZ-induced SJS/TEN patients, 21 CBZ-tolerant controls, and 185 healthy controls recruited during 2008-2010. RESULTS: HLA-B*1502 allele was present in 94.1% (16/17) of CBZ-SJS/TEN patients, 9.5% (2/21) of CBZ-tolerant patients, and 9.2% (17/185) of healthy controls. The risk of CBZ-induced SJS/TEN was significantly higher (P < 0.01) in the patients with HLA-B*1502. One CBZ-induced SJS patient tested negative for HLA-B*1502, and the test result showed HLA-B*3503/B*4601. CONCLUSIONS: We found a strong association between HLA-B*1502 and CBZ-induced SJS/TEN in the Han Chinese population from central and northern China. Combined with previous studies of the southern Han Chinese subpopulation, our results suggest that HLA-B*1502 is strongly associated with CBZ-induced SJS/TEN in the whole Han Chinese population.


Assuntos
Anticonvulsivantes/efeitos adversos , Carbamazepina/efeitos adversos , Antígeno HLA-B15/genética , Síndrome de Stevens-Johnson/genética , Adulto , Alelos , Anticonvulsivantes/uso terapêutico , Carbamazepina/uso terapêutico , China/epidemiologia , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Síndrome de Stevens-Johnson/induzido quimicamente , Síndrome de Stevens-Johnson/etnologia , Síndrome de Stevens-Johnson/etiologia
15.
J Zhejiang Univ Sci B ; 12(1): 40-6, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21194185

RESUMO

OBJECTIVE: This study was carried out to test the effects of methotrexate (MTX) and black seed oil (BSO) on pristane-induced arthritis (PIA) in rats. METHODS: Inbred dark agouti (DA) rats were induced by a single subcutaneous injection of pristane, and then treated with MTX or BSO. Arthritis severity was evaluated macroscopically and microscopically. Plasma nitric oxide (NO) concentration was determined by the Griess method and cytokine mRNA expression in the spleen was detected by the real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The clinical arthritis severity was decreased after MTX treatment, while the BSO groups did not show significant changes compared with the disease group. The plasma NO level of the MTX group was significantly decreased compared with the disease group, but the BSO groups showed no difference from the disease group in plasma NO levels. The interferon-γ (IFN-γ) and interleukin-17A (IL-17A) mRNA expressions in the spleens were significantly decreased in the MTX group, but only showed a declining trend in the BSO groups compared with the disease group. Neither MTX nor BSO had an effect on the mRNA expressions of IL-4, transforming growth factor ß (TGF-ß), and tumor necrosis factor-α (TNF-α) in the spleen. CONCLUSIONS: MTX, but not BSO, can reduce the arthritis severity and decrease the mRNA expressions of IFN-γ and IL-17A in pristane-induced arthritis of rats.


Assuntos
Artrite Experimental/tratamento farmacológico , Interferon gama/genética , Interleucina-17/genética , Metotrexato/farmacologia , Animais , Antirreumáticos/farmacologia , Artrite Experimental/genética , Artrite Experimental/imunologia , Artrite Experimental/patologia , Sequência de Bases , Feminino , Expressão Gênica/efeitos dos fármacos , Articulações/patologia , Masculino , Óxido Nítrico/sangue , Óleos de Plantas/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos , Baço/imunologia , Terpenos/toxicidade
16.
Pharmacol Rep ; 61(5): 843-50, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19904007

RESUMO

The aim of this study was to evaluate the effects of ABCB1 gene polymorphisms on azithromycin pharmacokinetics in Chinese Han ethnic subjects. In total, 20 healthy volunteers with various ABCB1 genotypes (6 with 2677GG/3435CC, 8 with 2677GT/3435CT, 6 with 2677TT/3435TT) were enrolled. Each was given a single oral dose of 500 mg azithromycin. Plasma concentration was measured for up to 96 h by LC/MS/MS. As shown, C(max) was significantly lower among individuals with 2677TT/3435TT genotype (468.0 +/- 173.4 ng x h/ml) than those with 2677GG/3435CC (911.2 +/- 396.4 ng x h/ml, p = 0.013). However, the t(max) value was higher among subjects with 2677TT/3435TT (2.0 +/- 0.5 h) than those with 2677GT/3435CT (1.6 +/- 0.3 h) or 2677GG/3435CC (1.4 +/- 0.4 h) genotypes (p = 0.068 and p = 0.026, respectively). Furthermore, the AUC(last) tended to be higher among subjects with 2677GG/3435CC than those with 2677GT/3435CT or 2677TT/3435TT genotypes (5000.2 +/- 1610.0 vs. 4558.0 +/- 805.0 vs. 4131.0 +/- 995.1 ng/ml). Our results showed for the first time that azithromycin pharmacokinetics may be influenced by particular polymorphisms of the ABCB1 gene. Individualized dosage regimen design incorporating such information may improve the efficacy of the drug while reducing adverse reactions.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Antibacterianos/farmacocinética , Azitromicina/farmacocinética , Polimorfismo de Nucleotídeo Único , Subfamília B de Transportador de Cassetes de Ligação de ATP , Área Sob a Curva , Povo Asiático , China , Cromatografia Líquida , Genótipo , Humanos , Masculino , Espectrometria de Massas em Tandem
17.
Br J Clin Pharmacol ; 68(3): 395-401, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19740397

RESUMO

AIMS: To assess the association between polymorphisms of the ABCB1 gene and the pharmacokinetics of verapamil among healthy Chinese Han ethnic subjects. METHODS: Based on polymorphisms of the ABCB1 gene at positions 2677 and 3435, 24 healthy male participants were divided into three groups: 2677GG/3435CC (n = 6), 2677GT/3435CT (n = 12) and 2677TT/3435TT (n = 6). Each subject had received a single oral dose of verapamil (80 mg) under fasting conditions. Multiple blood samples were collected over 24 h, and plasma concentrations of verapamil were determined by HPLC. Pharmacokinetic characteristics were compared between the different genotypic groups. RESULTS: The pharmacokinetics parameters of verapamil differed significantly among the three genotypic groups. AUC(last) was significantly lower among individuals with the 2677TT/3435TT (159.5 +/- 79.0 ng ml(-1) h) and 2677GT/3435CT (189.3 +/- 73.1 ng ml(-1) h) genotypes than those with the 2677GG/3435CC genotype (303.1 +/- 83.7 ng ml(-1) h) (P= 0.004 and P= 0.008, respectively). However, the CL/F value was higher among subjects with the 2677TT/3435TT (523.0 +/- 173.7 l h(-1)) genotype than those with the 2677GT/3435CT (452.2 +/- 188.6 l h(-1)) or 2677GG/3435CC (265.4 +/- 72.8 l h(-1)) genotypes. A significant difference was also found between the latter two groups (P= 0.034). In addition, the C(max) tended to be higher among subjects with the 2677GG/3435CC genotype than those with the 2677GT/3435CT or 2677TT/3435TT genotypes (42.2 +/- 3.9 vs 32.2 +/- 16.2 vs 38.1 +/- 13.7 ng ml(-1)). CONCLUSIONS: Our study showed for the first time that verapamil pharmacokinetics may be influenced by particular genetic polymorphisms of the ABCB1 gene among healthy Chinese Han ethnic subjects. An individualized dosage regimen design incorporating such information may improve the efficacy of the drug whilst reducing adverse reactions.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Povo Asiático/genética , Bloqueadores dos Canais de Cálcio/farmacocinética , Polimorfismo de Nucleotídeo Único/genética , Verapamil/farmacocinética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Administração Oral , Adulto , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Genótipo , Meia-Vida , Humanos , Masculino , Fenótipo , Adulto Jovem
18.
Zhongguo Zhen Jiu ; 29(2): 147-50, 2009 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-19391541

RESUMO

Professor He Pu-ren, the founder of Santong method of acupuncture and moxibustion, is a well known acupuncturist at home and abroad. His main contributions include combined martial arts and Chinese medicine, showing obvious therapeutic effect; taking part in establishment of The Department of Acupuncture, Beijing Chinese Medicine Hospital; creating Santong method of acupuncture and moxibustion; advocating fire needle therapy; writing medical books and teaching students; advocating the culture of acupuncture; making the metal model of acupuncture and moxibustion, and others. His achievements have become an important part of acupuncture and moxibustion science.


Assuntos
Terapia por Acupuntura/métodos , Moxibustão/métodos , Terapia por Acupuntura/história , China , História do Século XX , História do Século XXI , Humanos , Moxibustão/história
19.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 8): o2050, 2009 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-21583712

RESUMO

In the title Schiff base compound, C(14)H(11)N(3)O(5), the dihedral angle between the two benzene rings is 1.6 (1)°. The mol-ecule displays an E configuration about the C=N bond. An intra-molecular O-H⋯O hydrogen bond is observed. In the crystal, mol-ecules are linked into layers parallel to (101) by O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds. One of the hydroxyl groups is disordered over two positions, with occupancies of 0.643 (5) and 0.357 (5).

20.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 5): o1153, 2009 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-21583956

RESUMO

In the chiral title compound, C(38)H(28)O(4)P(2), the intra-molecular P⋯P separation is 3.671 (2) Šand the dihedral angle between the two benzene rings in the biphenyl unit is 77.9 (2)°.

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