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1.
Plant Mol Biol ; 102(4-5): 537-551, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31916084

RESUMO

KEY MESSAGE: Silencing of SlCAND1 expression resulted in dwarfish, loss of apical dominance, early flowering, suppression of seed germination, and abnormal root architecture in tomato Cullin-RING E3 ligases (CRLs)-dependent ubiquitin proteasome system mediates degradation of numerous proteins that controls a wide range of developmental and physiological processes in eukaryotes. Cullin-associated Nedd8-dissociated protein 1 (CAND1) acts as an exchange factor allowing substrate recognition part exchange and plays a vital role in reactivating CRLs. The present study reports on the identification of SlCAND1, the only one CAND gene in tomato. SlCAND1 expression is ubiquitous and positively regulated by multiple plant hormones. Silencing of SlCAND1 expression using RNAi strategy resulted in a pleiotropic and gibberellin/auxin-associated phenotypes, including dwarf plant with reduced internode length, loss of apical dominance, early flowering, low seed germination percentage, delayed seed germination speed, short primary root, and increased lateral root proliferation and elongation. Moreover, application of exogenous GA3 or IAA could partly rescue some SlCAND1-silenced phenotypes, and the expression levels of gibberellin/auxin-related genes were altered in SlCAND1-RNAi lines. These facts revealed that SlCAND1 is required for gibberellin/auxin-associated regulatory network in tomato. Although SlCAND1 is crucial for multiple developmental processes during vegetative growth stage, SlCAND1-RNAi lines didn't exhibit visible effect on fruit development and ripening. Meanwhile, we discussed that multiple physiological functions of SlCAND1 in tomato are different to previous report of its ortholog in Arabidopsis. Our study adds a new perspective on the functional roles of CAND1 in plants, and strongly supports the hypothesis that CAND1 and its regulated ubiquitin proteasome system are pivotal for plant vegetative growth but possibly have different roles in diverse plant species.

2.
Physiol Plant ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31985059

RESUMO

Leaf senescence is a highly-programmed developmental process during the plant life cycle. Cytokinin (CK) has been widely acknowledged as a negative regulator to delay leaf senescence. MiRNAs play key roles in a variety of developmental and physiological processes through negatively regulating their target gene expression. However, to date, the roles of microRNAs (miRNAs) in CK biosynthesis remain unclear, and the knowledge on miRNA regulation of leaf senescence is still very limited. Isopentenyltransferases (IPTs) catalyze the initial and rate-limiting step of CK biosynthesis in higher plants. Our previous work uncovered that silencing of SlIPT4 expression in tomato resulted in premature leaf senescence. Here, we identified a novel tomato miRNA, SlymiR208, which regulates the expression of SlIPT2 and SlIPT4 at the post-transcriptional level. SlymiR208 expression is ubiquitous in tomato and exhibits an opposite transition to its target transcripts in aged leaf. SlymiR208 overexpression in tomato sharply reduced the transcript levels of SlIPT2 and SlIPT4, and the concentrations of endogenous CKs in leaves. The early leaf senescence caused by SlymiR208 overexpression was consistent with the phenotype of SlIPT4-silenced lines. The data demonstrated that SlymiR208 is a positive regulator in leaf senescence through negatively regulating CK biosynthesis via targeting SlIPT2 and SlIPT4 in tomato. This study indicated that post-transcriptional regulation via miRNA is a control point of CK biosynthesis and added a new layer to the understanding of the regulation of CK biosynthesis in tomato and a new factual proof to support that miRNAs are involved in leaf senescence.

4.
Chem Biol Drug Des ; 94(4): 1824-1834, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31293023

RESUMO

Due to the potencies in the treatments of cancer, infectious diseases, and autoimmune diseases, the developments of human TLR8 (hTLR8) agonists and antagonists have attracted widespread attentions. The hTLR8 agonists and antagonists have similar structures but with completely opposite biological effects. Up to date, the subtle differences in the structures between the hTLR8 agonists and antagonists are still unknown. In this work, emerging chemical pattern (ECP) was successfully used to extract the key chemical patterns of the hTLR8 agonists and antagonists. By using CAEP classifier, an optimal ECP model with only 3 descriptors was established with the overall prediction accuracy larger than 90%. Further hierarchical cluster analysis and molecular docking showed that the H-bond and hydrophobic properties are the key features distinguishing the hTLR8 agonists from antagonists. Comparing with the antagonists, the agonists show stronger specific H-bond properties, while antagonists have stronger non-specific hydrophobic properties. The significant differences in the structural properties may be closely related to the activation/inhibition mechanism of hTLR8.

5.
Integr Biol (Camb) ; 2019 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-30855664

RESUMO

Binding/unbinding kinetics are key determinants of drug potencies. However, there are still a lot of challenges in predicting kinetic properties during early-stage drug development. In this work, position-restrained molecular dynamics simulations combined with energy decomposition were applied to extract protein-ligand interaction (PLI) fingerprints along the unbinding pathway of 20 p38 mitogen-activated protein kinase (p38 MAPK) Type II inhibitors. The results showed that the electrostatic and/or van der Waals interaction fingerprints at three key positions can be used for accurate prediction of the dissociation rate constants (koff) of p38 MAPK Type II inhibitors. The strategy proposed in this paper can provide not only an efficient method of predicting the dissociation rates of the p38 MAPK Type II inhibitors, but also the atom-level mechanism of enthalpy-driven unbinding process.

6.
Comput Struct Biotechnol J ; 17: 319-323, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30899446

RESUMO

P-glycoprotein (P-gp) is a multidrug transporter, which harnesses the chemical energy of ATP to power the efflux of diverse chemotherapeutics out of cells and thus contributes to the development of multidrug resistance (MDR) in cancer. It has been proved that the ligand-binding pocket of P-gp is located at the transmembrane domains (TMDs). However, the access of ligands into the binding pocket remains to be elucidated, which definitely hinder the development of P-gp inhibitors. Herein, the access pathways of a well-known substrate rhodamine-123 and a cyclopeptide inhibitor QZ-Leu were characterized by time-independent partial nudged elastic band (PNEB) simulations. The decreasing free energies along the PNEB-optimized access pathway indicated that TM4/6 cleft may be an energetically favorable entrance gate for ligand entry into the binding pocket of P-gp. The results can be reconciled with a range of experimental studies, further corroborating the reliability of the gate revealed by computational simulations. Our atomic level description of the ligand access pathway provides valuable insights into the gating mechanism for drug uptake and transport by P-gp and other multidrug transporters.

7.
Food Res Int ; 116: 767-777, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30717006

RESUMO

Volatiles of shell eggs were identified by SPME-GC-MS to characterize and discriminate white Leghorn (W), Hy-line brown (H) and Jing fen (J) hatching eggs with comparison, principal components (PC), partial least squares (PLS), random forest classification (RFC) and canonical discriminant (CD) analyses. DVB/CAR/PDMS fiber and extraction 60 min were suited to analyze the volatiles emitted from eggs. A total of 17 or 18 volatile compounds were identified in raw shell hatching eggs, namely, nonanal, decanal and 6-methly-5-hepten-2-one were the main volatile components with contributions that over 70%. The composition and/or profile of volatile compounds from W and H eggs were much more similar than J eggs. Hexanal, decanal, 6-methly-5-hepten-2-one, heptanal, etc. have greatly contributed to the distinction of W, H and J eggs in sparse (S)-PLS and orthogonal (O)-PLS models. The accuracy of RFC and CD model were 100%, 100% (initial) and 83.3% (cross-validation), respectively. Heptanal, 6-methly-5-hepten-2-one, octanal, etc. were contributed positively to the classification of W, H, J eggs in RFC, especially for heptanal.

8.
J Sci Food Agric ; 99(7): 3264-3275, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30549050

RESUMO

BACKGROUND: Early and non-destructive identification of fertile (F) eggs is a difficult task in the process of breeding laying hens. The odors emitted from unfertilized (UF), infertile (IF), and fertile (F) eggs were characterized by solid-phase microextraction / gas chromatograph-mass spectrometry (SPME/GC-MS) and electronic nose (E-nose) to determine their differences by principal component, partial least squares, and canonical discriminant analyses. RESULTS: A total of 14 volatiles were identified in unhatched shell white Leghorn eggs, such as nonanal, decanal, 6-methyl-5-hepten-2-one, and 6,10-dimethyl-5,9-undecadien-2-one. Cedrene and decanal contributed greatly to the classification of UF and fertilized (Fd)/IF eggs; cedrene, decanal, 1-octanol and hexanal contributed greatly to the distinction between UF and IF eggs; heptanal might be the potential marker to determine F/IF eggs. P40/1, P10/2, P10/1, TA/2, T40/2 and T30/1, P30/1, P40/2, PA/2, T40/2 mostly contributed to the distinction between UF and Fd eggs and between F and IF eggs, respectively. Canonical discriminant analysis presented superior differentiating efficiency for almost all groups, and the odor differences between UF and Fd eggs were significantly larger than the differences between F and IF eggs. CONCLUSION: Solid-phase microextraction / gas chromatograph-mass spectrometer combined with E-nose may have the potential to non-destructively distinguish UF, F, and IF eggs, which will provide a new perspective to understand the differences among them. © 2018 Society of Chemical Industry.


Assuntos
Ovos/análise , Nariz Eletrônico , Cromatografia Gasosa-Espectrometria de Massas/métodos , Odorantes/análise , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/isolamento & purificação , Animais , Galinhas , Análise Discriminante , Feminino , Fertilização , Masculino , Análise de Componente Principal , Microextração em Fase Sólida
9.
J Chem Inf Model ; 59(1): 159-169, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30422654

RESUMO

Recent research has increasingly suggested that the crucial factors affecting drug potencies are related not only to the thermodynamic properties but also to the kinetic properties. Therefore, in silico prediction of ligand-binding kinetic properties, especially the dissociation rate constant ( koff), has aroused more and more attention. However, there are still a lot of challenges that need to be addressed. In this paper, steered molecular dynamics (SMD) combined with residue-based energy decomposition was employed to predict the dissociation rate constants of 37 HIV-1 protease inhibitors (HIV-1 PIs). For the first time, a predictive model of the dissociation rate constant was established by using the interaction-energy fingerprints sampled along the ligand dissociation pathway. On the basis of the key fingerprints extracted it can be inferred that the dissociation rates of 37 HIV-1 PIs are basically determined in the first half of the dissociation processes and that the H-bond interactions with active-site Asp25 and van der Waals interactions with flap-region Ile47 and Ile50 have important influences on the dissociation processes. In general, the strategy established in this paper can provide an efficient way for the prediction of dissociation rate constants as well as the unbinding mechanism research.


Assuntos
Inibidores da Protease de HIV/química , Simulação de Dinâmica Molecular , Domínio Catalítico , Protease de HIV/metabolismo , Inibidores da Protease de HIV/farmacologia , Ligações de Hidrogênio , Cinética , Termodinâmica
10.
Medchemcomm ; 9(11): 1961-1971, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30568763

RESUMO

Toll-like receptors (TLRs) are important pattern recognition receptors to human innate immunity, which can recognize pathogen-associated molecular patterns and initiate innate immune responses. As the receptor of single stranded RNA (ssRNA), toll-like receptor 8 (TLR8) has potential in the treatment of tumors, microbial infection, and inflammatory diseases. Herein, an emerging chemical pattern (ECP) method was utilized to predict the key chemical patterns of TLR8 agonists. Based on the ECPs discovered, a robust and predictive ECP model was derived with prediction accuracies of 83.3%, 81.0%, and 80.0% for 132 training samples, 79 validation samples, and 75 test samples, respectively. When the ECP model was applied with a molecular docking method, the hit rate of TLR8 agonists was greatly enhanced. The results of ECP-based hierarchical cluster analysis and Connolly surface analysis of the TLR8 receptor showed that the H-bonding, hydrophilic and hydrophobic potentials as well as the unbalanced degree of property distributions are very important for distinguishing the TLR8 agonists from non-agonists.

11.
Biomed Res Int ; 2017: 7348919, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28316988

RESUMO

Omega-3 fatty acids have proven to be very essential for human health due to their multiple health benefits. These essential fatty acids (EFAs) need to be uptaken through diet because they are unable to be produced by the human body. These are important for skin and hair growth as well as for proper visual, neural, and reproductive functions of the body. These fatty acids are proven to be extremely vital for normal tissue development during pregnancy and infancy. Omega-3 fatty acids can be obtained mainly from two dietary sources: marine and plant oils. Eicosapentaenoic acid (EPA; C20:5 n-3) and docosahexaenoic acid (DHA; C22:6 n-3) are the primary marine-derived omega-3 fatty acids. Marine fishes are high in omega-3 fatty acids, yet high consumption of those fishes will cause a shortage of fish stocks existing naturally in the oceans. An alternative source to achieve the recommended daily intake of EFAs is the demand of today. In this review article, an attempt has, therefore, been made to discuss the importance of omega-3 fatty acids and the recent developments in order to produce these fatty acids by the genetic modifications of the plants.


Assuntos
Ácidos Graxos Ômega-3/química , Plantas Geneticamente Modificadas/química , Animais , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/química , Ácido Eicosapentaenoico/química , Ácidos Graxos Insaturados/química , Feminino , Peixes , Humanos , Lipídeos/química , Microalgas , Óleos Vegetais/química , Gravidez
12.
Integr Biol (Camb) ; 8(11): 1158-1169, 2016 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-27731447

RESUMO

ATP-binding cassette (ABC) exporters mediate vital transport of a variety of molecules across the lipid bilayer in all organisms. To explore the allosteric effect of ATP binding at the asymmetric ATPase sites, molecular dynamics simulations were performed on the nucleotide-binding domains (NBDs) of a heterodimeric exporter TM287/288 in 4 different ATP-bound states. The results showed that ATP bound at the degenerate site can maintain a semi-open conformation of NBD1-NBD2, which may be defective in ATP hydrolysis. By contrast, when bound at the consensus site, ATP can induce an intra-domain rotation of the α-helical subdomain towards the RecA-like subdomain of NBD2 at the degenerate site. The rotation of the α-helical subdomain rearranged the hydrogen bond networks at the NBD1-NBD2 interface, induced a significant conformational change in the D-loop at the degenerate site and inter- and intra-domain communications at both sites, and eventually elicited dimerization of NBD1-NBD2. These findings indicate that the asymmetric ATPase sites of the heterodimeric exporter are structurally and functionally distinct.


Assuntos
Transportadores de Cassetes de Ligação de ATP/química , Transportadores de Cassetes de Ligação de ATP/ultraestrutura , Adenosina Trifosfatases/química , Adenosina Trifosfatases/ultraestrutura , Trifosfato de Adenosina/química , Simulação de Dinâmica Molecular , Regulação Alostérica , Dimerização , Modelos Químicos , Ligação Proteica , Conformação Proteica , Domínios Proteicos
13.
J Chem Inf Model ; 56(10): 2061-2068, 2016 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-27624663

RESUMO

Accumulated evidence suggests that the in vivo biological potency of a ligand is more strongly correlated with the binding/unbinding kinetics than the equilibrium thermodynamics of the protein-ligand interaction (PLI). However, the existing experimental and computational techniques are largely insufficient and limited in large-scale measurements or accurate predictions of the kinetic properties of PLI. In this work, elaborate efforts have been made to develop interconsistent, reasonable, and predictive models of the association rate constant (kon), dissociation rate constant (koff), and equilibrium dissociation constant (KD) of a series of HIV protease inhibitors with different structural skeletons. The results showed that nine Volsurf descriptors derived from water (OH2) and hydrophobic (DRY) probes are key molecular determinants for the kinetic and thermodynamic properties of HIV-1 protease inhibitors. To the best of our knowledge, this is the first time that interconsistent and reasonable models with strong prediction power have been established for both the kinetic and thermodynamic properties of HIV protease inhibitors.


Assuntos
Inibidores da Protease de HIV/química , Inibidores da Protease de HIV/farmacologia , Protease de HIV/metabolismo , HIV-1/enzimologia , Desenho de Drogas , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Humanos , Cinética , Modelos Moleculares , Termodinâmica
14.
Sensors (Basel) ; 16(9)2016 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-27626418

RESUMO

The detection of university online learners' reading ability is generally problematic and time-consuming. Thus the eye-tracking sensors have been employed in this study, to record temporal and spatial human eye movements. Learners' pupils, blinks, fixation, saccade, and regression are recognized as primary indicators for detecting reading abilities. A computational model is established according to the empirical eye-tracking data, and applying the multi-feature regularization machine learning mechanism based on a Low-rank Constraint. The model presents good generalization ability with an error of only 4.9% when randomly running 100 times. It has obvious advantages in saving time and improving precision, with only 20 min of testing required for prediction of an individual learner's reading ability.


Assuntos
Movimentos Oculares/fisiologia , Internet , Aprendizagem , Leitura , Adolescente , Algoritmos , Fixação Ocular/fisiologia , Humanos , Modelos Teóricos , Movimentos Sacádicos/fisiologia , Adulto Jovem
15.
Mol Biosyst ; 12(5): 1667-75, 2016 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-27008437

RESUMO

Different QSAR models of 40 natural compounds as neuraminidase inhibitors (NIs) are developed to comprehend chemical-biological interactions and predict activities against neuraminidase (NA) from Clostridium perfringens. Based on the constitutional, topological and conformational descriptors, R(2) and Q(2) values of the obtained SRA model are 0.931 and 0.856. The R(2) and Q(2) values of the constructed HQSAR and almond models are 0.903 and 0.767, 0.904 and 0.511, respectively. Based on the pharmacophore alignment, R(2) and Q(2) values of the optimal CoMSIA model are 0.936 and 0.654. Moreover, Rtest(2) and Qext(2) of values of SRA, HQSAR, almond and CoMSIA models are 0.611 and 0.565, 0.753 and 0.750, 0.612 and 0.582, 0.582 and 0.571, respectively. So, QSAR models have good predictive capability. They can be further used to evaluate and screen new compounds. Moreover, hydrogen bonds and electrostatic factors have high contributions to activities. To understand molecular interactions between natural compounds and NA from Clostridium perfringens, molecular docking is investigated. The docking results elucidate that Arg266, Asp291, Asp328, Tyr485, Glu493, Arg555, Arg615 and Tyr655 are especially the key residues in the active site of 2bf6. Hydrogen bonds and electrostatics are key factors, which impact the interactions between NIs and NA. So, the influential factors of interactions between NIs and NA in the docking results are in agreement with the QSAR results.


Assuntos
Inibidores Enzimáticos/química , Modelos Moleculares , Neuraminidase/química , Algoritmos , Sítios de Ligação , Domínio Catalítico , Inibidores Enzimáticos/farmacologia , Ligações de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Neuraminidase/antagonistas & inibidores , Ligação Proteica , Relação Quantitativa Estrutura-Atividade , Reprodutibilidade dos Testes
16.
Int J Pharm ; 502(1-2): 61-9, 2016 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-26899974

RESUMO

P-glycoprotein (P-gp), an ATP-binding cassette (ABC) multidrug transporter, can actively transport a broad spectrum of chemically diverse substrates out of cells and is heavily involved in multidrug resistance (MDR) in tumors. So far, the multiple specific binding sites remain a major obstacle in developing an efficient prediction method for P-gp substrates. Herein, emerging chemical pattern (ECP) combined by hierarchical cluster analysis was utilized to predict P-gp substrates as well as their potential binding sites. An optimal ECP model using only 3 descriptors was established with prediction accuracies of 0.80, 0.81 and 0.74 for 803 training samples, 120 test samples, and 179 independent validation samples, respectively. Hierarchical cluster analysis (HCA) of the ECPs of P-gp substrates derived 2 distinct ECP groups (ECPGs). Interestingly, HCA of the P-gp substrates based on ECP similarities also showed 2 distinct classes, which happened to be dominated by the 2 ECPGs, respectively. In the light of available experimental proofs and molecular docking results, the 2 distinct ECPGs were proved to be closely related to the binding profiles of R- and H-site substrates, respectively. The present study demonstrates, for the first time, a successful ECP model, which can not only accurately predict P-gp substrates, but also identify their potential substrate-binding sites.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Modelos Moleculares , Sítios de Ligação , Análise por Conglomerados , Preparações Farmacêuticas/metabolismo
17.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(4): 981-5, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30048093

RESUMO

The freshness of egg is an important index to reflect the internal quality. In order to achieve non-destructive detection of freshness, micro fiber spectrometer was used to sample 550~950 nm transmittance spectra of eggs which performed quantitative analysis with haugh unit of eggs. Different pretreatment was combined with partial least squares regression(PLS) and support vector regression(SVR) respectively to find that first derivative combined with SVR predicted better than others through comparison, and it was better to model by SVR than by PLS. In order to improve efficiency and decrease adverse effects of useless information for modeling, the linear dimensionality reduction with principal component analysis (PCA) and the nonlinear dimensionality reduction with locally linear embedding(LLE) were used for the data of first derivative respectively. It indicated that LLE was better than PCA after comparison, and the correlation coefficient of calibration and prediction were 92.2%, 91.1%, and the root mean square error were 7.21, 8.80. The root mean square error of cross validation decreased 0.79.The experimental result illustrated that the nonlinear model of LLE combined with SVR improved predictive performance of egg freshness. It is feasible for the detection of visible/near-infrared spectrum of egg freshness to apply this method.

18.
Sci Rep ; 5: 14633, 2015 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-26419945

RESUMO

Ginkgo biloba leaf extract has been shown to increase the incidence in liver tumors in mice in a 2-year bioassay conducted by the National Toxicology Program. In this study, the DNA damaging effects of Ginkgo biloba leaf extract and many of its constituents were evaluated in human hepatic HepG2 cells and the underlying mechanism was determined. A molecular docking study revealed that quercetin, a flavonoid constituent of Ginkgo biloba, showed a higher potential to interact with topoisomerase II (Topo II) than did the other Ginkgo biloba constituents; this in silico prediction was confirmed by using a biochemical assay to study Topo II enzyme inhibition. Moreover, as measured by the Comet assay and the induction of γ-H2A.X, quercetin, followed by keampferol and isorhamnetin, appeared to be the most potent DNA damage inducer in HepG2 cells. In Topo II knockdown cells, DNA damage triggered by Ginkgo biloba leaf extract or quercetin was dramatically decreased, indicating that DNA damage is directly associated with Topo II. DNA damage was also observed when cells were treated with commercially available Ginkgo biloba extract product. Our findings suggest that Ginkgo biloba leaf extract- and quercetin-induced in vitro genotoxicity may be the result of Topo II inhibition.


Assuntos
Dano ao DNA/efeitos dos fármacos , DNA Topoisomerases Tipo II/metabolismo , Ginkgo biloba/química , Hepatócitos/efeitos dos fármacos , Hepatócitos/fisiologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , DNA Topoisomerases Tipo II/química , DNA Topoisomerases Tipo II/genética , Ativação Enzimática/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Inativação Gênica , Células Hep G2 , Humanos , Modelos Moleculares , Conformação Molecular , Mutagênicos/química , Mutagênicos/farmacologia , Mutagênicos/toxicidade , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Quercetina/farmacologia , Quercetina/toxicidade , Inibidores da Topoisomerase II/química , Inibidores da Topoisomerase II/farmacologia , Inibidores da Topoisomerase II/toxicidade
19.
Biomark Med ; 9(11): 1079-93, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26501190

RESUMO

AIM: To establish a database for the associations between idiosyncratic drug reactions (IDRs) and human leukocyte antigens (HLAs) and to systematically assess the characteristics of the drug-HLA associations. MATERIALS & METHODS: Electronic databases were searched to extensively identify drug-HLA association studies from 1966 to present. RESULTS: A drug-HLA-IDR database, HLADR, was created. The drug-HLA relationship network clearly reflected an ethnicity dependency of the associations. The positive predictive values and the negative predictive values demonstrated that other potential factors may also regulate the occurrence of HLA-specific IDRs. CONCLUSIONS: Constructing studies with samples from homogeneous ethnic groups and identifying cofactors that affect negative predictive values and positive predictive values will become necessary to enhance the predictability of HLA biomarkers for future research on IDRs.


Assuntos
Biologia Computacional/métodos , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Antígenos HLA/genética , Alelos , Biomarcadores/metabolismo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etnologia , Humanos
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(4): 919-23, 2015 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-26197575

RESUMO

Due to the harmfulness of melamine to human, the quantitative detection of melamine in egg is very necessary. In the present study, the surface enhanced Raman spectra technology combined with chemometric analysis method was used to conduct melamine quantitative detection in egg white. Firstly, the melamine egg sample could be got by the method of artificial feeding hens usingdifferent feeding formulation. Then the surface enhanced Raman spectra of egg white was determined using portable Raman spectroscopy (Opto Trace RamTracer-200) and Raman enhancement reagents, and the melamine content within the white eggs was measured with gas chromatography mass spectrometry technology. The software of Raman Analyzer was used for baseline correction of Raman spectra. The correlation coefficient method was used to choose 320 spectral variables from the surface enhanced Raman spectroscopy as input variables to establish partial least squares quantitative calibration model . And the peaks-decomposition method was used to establish peaks-decomposition quantitative calibration model. Both models selected 90 and 44 samples respectively as calibration sets and validation sets during model establishment, and both models achieved good prediction effect. The determination coefficient between predicted values of partial least squares quantitative calibration model and measured values of gas chromatography mass spectrometry was 0.856, and root mean square error of prediction was 1.547. The determination coefficient was 0.947 and RMSEP was 0.893 for the peaks-decomposition quantitative calibration model. This study demonstrated that the method can effectively quantitatively detect melamine in eggs. Testing a sample only takes 15 minutes, which can provide a new way for the melamine egg detection.


Assuntos
Clara de Ovo/análise , Contaminação de Alimentos/análise , Análise Espectral Raman , Triazinas/análise , Cromatografia Gasosa-Espectrometria de Massas , Análise dos Mínimos Quadrados , Modelos Teóricos
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