Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Fitoterapia ; 154: 105029, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34506872

RESUMO

Four new chalchonoid trimers, named cochinchinenins N-Q (1-4), along with a pair of known enantiomers (5-6), were isolated from the total phenolic extract of Chinese dragon's blood (the red resin of Dracaena cochinchinensis). The planar structures of 1-4 were elucidated by extensive spectroscopic analysis including HRESIMS and 1D/2D NMR. The absolute configurations of new compounds were established by ECD data. Compound 1 exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC50 value of 11.5 ± 1.7 µM.


Assuntos
Chalconas/farmacologia , Dracaena/química , Microglia/efeitos dos fármacos , Extratos Vegetais/química , Animais , Linhagem Celular , Chalconas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Camundongos , Óxido Nítrico , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Resinas Vegetais/química
2.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4131-4138, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467724

RESUMO

Eleven condensed tannins were isolated from the roots of Indigofera stachyodes by various column chromatography techniques including silica gel, octadecyl silica(ODS), Sephadex LH-20, and semi-preparative high performance liquid chromatography(HPLC). These compounds were identified on the basis of physicochemical properties, nuclear magnetic resonance(NMR) and mass spectrometry(MS) data as stachyotannin A(1), epicatechin-(2ß→O→7,4ß→8)-epiafzelechin-(4ß→8)-catechin(2), cinnamtannin D1(3), cinnamtannin B1(4), epicatechin-(2ß→O→7,4ß→8)-epiafzelechin-(4α→8)-epicatechin(5), gambiriin C(6), proanthocyanidin A1(7), proanthocyanidin A2(8), aesculitannin B(9), proanthocyanidin A4(10), and procyanidin B5(11). Compound 1 is a new compound. Compounds 2-11 were isolated from Indigofera for the first time. Furthermore, compounds 1, 2, and 4-11 showed inhibitory effects on thrombin-induced ATP release in platelets.


Assuntos
Indigofera , Proantocianidinas , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Extratos Vegetais
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1357-1362, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798426

RESUMO

OBJECTIVE: To explore the method for inducing the differentiation of bone marrow cells into megakaryocytes in vitro so as to use for evaluating the activity of traditional Chinese medicines. METHODS: The bone marrow cells were separated from femurs and tibias of mice. The experiments were divided into 4 groups: control (no adding cytokines), TPO (adding 50 ng/ml TPO), TPO+SCF (50 ng/ml+50 ng/ml) and TPO+SCF+IL-6+IL-9 (50 ng/ml+50 ng/ml+20 ng/ml+20 ng/ml). The bone marrow cells in 4 groups were cultured in vitro for 6 d. Then the cell growth status was observed by the inverted microscopy, and the cell count was detected by using the automatic cell counter. The ratio and absolute count of megakaryocytes were detected by flow cytometry. RESULTS: Compared with control, three induction methods could stimulate the differentiation of bone marrow cells into megakaryocytes in vitro. TPO could slightly enhance the differentiation of bone marrow cells into megakaryocytes. Both the combination of TPO and SCF, and the combination of TPO, SCF, IL-6 and IL-9 could intensively stimulate proliferation of bone morrow cells and promote the differentiation of bone marrow cells into megakaryocytes. The addition of IL-6 and IL-9 could decrease the proliferation of non-megakaryocytes, but promote the differentiation of bone marrow cells into megakaryocytes. CONCLUSION: The optimized differentiation of bone marrow cells into megakaryocytes has been completed by co-induction regimen of TPO, SCF, IL-6 and IL-9, which can be used to screen and evaluate traditional Chinese medicines promoting formation of platelets.


Assuntos
Interleucina-3 , Megacariócitos , Animais , Células da Medula Óssea , Contagem de Células , Diferenciação Celular , Divisão Celular , Células Cultivadas , Camundongos , Fator de Células-Tronco , Trombopoetina
4.
Nat Prod Res ; : 1-8, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32840396

RESUMO

Two new diterpenoids, penicichrysogene A (1) and penicichrysogene B (2), were isolated from the solid substrate fermentation cultures of Penicillium chrysogenum MT-12, an endophytic fungus isolated from the medicinal plant of Huperzia serrata. Their structures were elucidated on the basis of extensive spectroscopic and spectrometric data (1D and 2D NMR, UV, IR, and HRESIMS). The absolute configurations of 1 and 2 were assigned on the basis of experimental and calculated electronic circular dichroism spectra. Compound 1 exhibited inhibitory activity on ATP release of thrombin-activated platelets with IC50 = 42.7 ± 3.5 µM.

5.
Pharmacogenomics J ; 20(2): 169-178, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31796890

RESUMO

Many medical centers in the United States have implemented pharmacogenomics (PGx) programs to integrate PGx into clinical practice. The roles of pharmacists in optimizing medication use based on genetic testing results are emergently evolving. A literature search was conducted to assess pharmacists' roles in pharmacogenetics/pharmacogenomics or precision/personalized medicine programs. Fifteen PGx pharmacy practice models implemented in eleven hospitals and one community pharmacy in the U.S. were selected for evaluation. Pharmacists perform results interpretation, genotype-guided medication selection and adjustment, medication acquisition, adverse reactions monitoring, and patient education. Institutions that are interested in implementing a PGx program should plan the strategies to overcome the challenges, such as educational knowledge gaps, informatics, and reimbursement issues. Strong institutional support, well-defined goals, standardized procedures, and strategies to educate clinicians and patients are the prerequisites to comprehensively deliver genomic data for individualized drug therapy.


Assuntos
Serviços Comunitários de Farmácia/organização & administração , Conduta do Tratamento Medicamentoso/organização & administração , Farmacêuticos/organização & administração , Farmacogenética/métodos , Medicina de Precisão/métodos , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Educação de Pacientes como Assunto , Papel Profissional , Estados Unidos
6.
Nat Prod Res ; 33(3): 347-353, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29557177

RESUMO

Two new polyketides, penicilloxalones A (1) and B (2), together with 13 known compounds (3-15), were isolated from the ethyl acetate extract of the solid substrate fermentation cultures of the fungus Penicillium oxalicum MHZ153. The structures of the isolates were determined by spectroscopic analysis and comparison of their spectroscopic and physicochemical data with the literature values. Compounds 7 and 11 showed inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC50 values of 0.9 ± 0.2 µM and 87.9 ± 0.7 µM, respectively.


Assuntos
Penicillium/química , Policetídeos/isolamento & purificação , Animais , Linhagem Celular , Fermentação , Concentração Inibidora 50 , Lipopolissacarídeos , Camundongos , Microglia/efeitos dos fármacos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Policetídeos/química , Policetídeos/farmacologia
7.
Phytochemistry ; 158: 46-55, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30453219

RESUMO

Fifteen previously undescribed 2-(2-phenylethyl)chromone dimers, along with two known analogues were isolated from Chinese agarwood (Aquilaria sinensis) by a LC-MS-guided fractionation procedure. Their structures were elucidated on the basis of spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS). The isolated compounds exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC50 values in the range 0.6-37.1 µM.


Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Cromonas/química , Thymelaeaceae/química , Animais , Anti-Inflamatórios não Esteroides/isolamento & purificação , Cromatografia Líquida , Cromonas/isolamento & purificação , Dimerização , Avaliação Pré-Clínica de Medicamentos/métodos , Concentração Inibidora 50 , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Plantas Medicinais/química , Células RAW 264.7 , Espectrometria de Massas por Ionização por Electrospray
8.
Materials (Basel) ; 11(8)2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-30126127

RESUMO

Copper powder has broad applications in the powder metallurgy, heat exchanger, and electronic industries due to its intrinsically high electrical and thermal conductivities. However, the ease of formation of surface oxide or patina layer raises difficulty of storage and handling of copper powder, particularly in the case of Cu microparticles. Here, we developed a thermal chemical vapor deposition chemical vapor deposition (CVD) process for large-scale synthesis of graphene coatings on Cu microparticles, which importantly can remain monodisperse without aggregation after graphene growth at high temperature by using removal spacers. Compared to other protective coating methods, the intrinsic electrical and thermal properties of Cu powder would not be degraded by uniform growth of low defect few-layer graphene on each particle surface. As a result, when the anticorrosion performance test was carried out by immersing the samples in Cu etchant, the corrosion rate of graphene/Cu microparticles was significantly improved (ca three times slower) compared to that of pristine Cu powder, also showing a comparable anticorrosion ability to commercial CuZn30 alloy.

9.
Fitoterapia ; 127: 123-128, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29447980

RESUMO

Five new megastigmane glycosides, urenalobasides A-E (1-5), together with 11 known ones (6-16) were isolated from Urena lobata. Their structures were determined by extensive spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism method. Compounds 1 and 2 are two unusual megastigmanes structurally containing a 6/5 fused ring system. Compound 3 exhibits inhibition of nitric oxide production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells with IC50 value of 53.7 ±â€¯1.0 µM (positive control, dexamethasone, IC50 = 16.6 ±â€¯0.8 µM).


Assuntos
Cicloexanonas/isolamento & purificação , Glucosídeos/isolamento & purificação , Glicosídeos/isolamento & purificação , Malvaceae/química , Norisoprenoides/isolamento & purificação , Animais , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Células RAW 264.7
10.
J Nat Prod ; 81(3): 543-553, 2018 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-29227647

RESUMO

Sixteen new 2-(2-phenylethyl)chromone dimers, including four pairs of enantiomers (1a/1b, 3a/3b, 6a/6b, and 8a/8b), along with eight optically pure analogues (2, 4, 5, 7, and 9-12) were isolated from the resinous wood of Aquilaria sinensis. Their structures were determined by extensive spectroscopic analysis (1D and 2D NMR, UV, IR, and HRMS) and experimental and computed ECD data. Compounds 1-10 feature an unusual 3,4-dihydro-2 H-pyran ring linkage connecting two 2-(2-phenylethyl)chromone monomeric units, while compounds 11 and 12 possess an unprecedented 6,7-dihydro-5 H-1,4-dioxepine moiety in their structures. A putative biosynthetic pathway of the representative structures via a diepoxy derivative of a chromone with a nonoxygenated A-ring is also proposed. Compounds 1a/1b, 2, 3a/3b, 5, 7, 8a/8b, and 10-12 exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC50 values in the range 7.0-12.0 µM.


Assuntos
Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Thymelaeaceae/química , Madeira/química , Animais , Linhagem Celular , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7 , Resinas Vegetais/química , Resinas Vegetais/farmacologia
11.
ACS Appl Mater Interfaces ; 9(39): 34078-34084, 2017 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-28895720

RESUMO

Dense Pb(Zr0.52Ti0.42Sn0.02Nb0.04)O3 high-performance piezoceramics were prepared by spark plasma sintering. Phase structure, domain structure, and temperature-dependent electrical properties were systematically investigated. The spark-plasma-sintered ceramics possess a pure perovskite structure with rhombohedral-tetragonal (R-T) phase boundaries and a high Curie temperature of 347 °C. Reliable performance against temperature was observed. First, high strain behavior with a normalized strain d33* of 640 and 710 pm/V occurred at 25 and 150 °C, respectively, varying less than 11%. Besides, a large remnant polarization Pr of 36.9 µC/cm2 is observed at room temperature and varies less than 18% within the temperature range of 25-150 °C. In addition, an enhanced piezoelectric coefficient d33 of ∼460 pm/V was attained at a high temperature of 150 °C, manifesting a 40% enhancement with respect to the d33 value (330 pm/V) obtained at room temperature.

12.
Fitoterapia ; 123: 35-43, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28958955

RESUMO

Twelve new polyketides, penicichrysogenins A-L (1-10, 11a, and 11b) along with five known compounds (12a, 12b, and 13-15) were isolated from the solid substrate fermentation cultures of a Huperzia serrata endophytic fungus Penicillium chrysogenum MT-12. The structures of the new compounds were established using extensive spectroscopic (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism (ECD) methods. Compounds 11a/11b and 12a/12b were two pairs of enantiomers successfully separated by chiral HPLC resolution. Compounds 4, 5, 8, 9, 11a/11b, and 12a/12b exhibited inhibition of nitric oxide production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells with IC50 values in the range of 17.5-98.4µM.


Assuntos
Huperzia/microbiologia , Óxido Nítrico/metabolismo , Penicillium chrysogenum/química , Policetídeos/química , Animais , Camundongos , Estrutura Molecular , Policetídeos/isolamento & purificação , Células RAW 264.7
13.
Eur J Pharmacol ; 814: 283-293, 2017 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-28865677

RESUMO

Berkeleyacetal C (BAC), a meroterpenoid compound, was isolated from the fungus Penicillium purpurogenum MHZ 111 and showed favorable activity of inhibiting nitrogen oxide (NO) production of macrophages stimulated by lipopolysaccharide (LPS) in our preliminary screening. In order to develop novel therapeutic drug for acute and chronic inflammatory diseases, the anti-inflammatory activity and underlying mechanisms of BAC were investigated in macrophages and neutrophils. The results showed that BAC significantly inhibited the expression of inducible nitric oxide synthase (iNOS) and the following NO production by macrophages. The expression and secretion of key pro-inflammatory factors and chemokines, including tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6), interleukin-1ß (IL-1ß), macrophage inflammatory protein-1α (MIP-1α), and monocyte chemotactic protein-1 (MCP-1) were also intensively suppressed by BAC. Furthermore, BAC also markedly inhibited activation of neutrophils and reactive oxygen species production. In mechanism study, BAC selectively suppressed phosphorylation of nuclear factor-κB (NF-κB), extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), and interferon regulatory transcription factor 3 (IRF3) during the activation of NF-κB, mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 1 and 3 (STAT1/3), and IRF3 signaling pathways induced by LPS. In summary, BAC exerts strong anti-inflammatory effects by inhibiting NF-κB, ERK1/2 and IRF3 signaling pathways and thereby shows great potential to be developed into therapeutic agent for inflammatory disorders.


Assuntos
Anti-Inflamatórios/farmacologia , Fator Regulador 3 de Interferon/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Penicillium/química , Terpenos/farmacologia , Animais , Anti-Inflamatórios/química , Quimiocinas/metabolismo , Relação Dose-Resposta a Droga , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Células RAW 264.7 , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Terpenos/química
14.
Front Pharmacol ; 8: 281, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28588487

RESUMO

Multiple sclerosis is a chronic inflammatory autoimmune disease of the central nervous system characterized by demyelinating plaques and axonal loss. Inhibition on over activation of innate and adaptive immunity provides a rationale strategy for treatment of multiple sclerosis. In the present study, we investigated the inhibitory effects of GYF-21, an epoxide 2-(2-phenethyl)-chromone derivative isolated from Chinese agarwood, on innate and adaptive immunity for revealing its potential to treat multiple sclerosis. The results showed that GYF-21 markedly inhibited the activation of microglia, and dendritic cells as well as neutrophils, all of which play important roles in innate immunity. Furthermore, GYF-21 significantly suppressed adaptive immunity via inhibiting the differentiation of naive CD4+ T cells into T helper 1 (Th1) and T helper 17 (Th17) cells, and suppressing the activation, proliferation, and IFN-γ secretion of CD8+ T cells. The mechanism study showed that GYF-21 evidently inhibited the activation of STAT1/3 and NF-κB signaling pathways in microglia. In conclusion, we demonstrated that GYF-21 can significantly inhibit innate and adaptive immunity via suppressing STAT1/3 and NF-κB signaling pathways, and has potential to be developed into therapeutic drug for multiple sclerosis.

15.
Fitoterapia ; 118: 49-55, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28237880

RESUMO

Five new 2-(2-phenylethyl)chromone derivatives (1-5), along with eleven known compounds (6-16) were isolated from Chinese agarwood. Their structures were elucidated by spectroscopic data (NMR, UV, IR, and MS) analyses and comparison of their spectroscopic and physical data with the literature values. The absolute configurations of 2-4 were determined by electronic circular dichroism (ECD) calculations. Compounds 2-4, 11, 12, and 15 exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells with IC50 values in the range 1.6-7.3µM.


Assuntos
Anti-Inflamatórios/química , Flavonoides/química , Thymelaeaceae/química , Animais , Anti-Inflamatórios/isolamento & purificação , Flavonoides/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Células RAW 264.7 , Madeira/química
16.
Nat Prod Res ; 31(5): 562-567, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27399340

RESUMO

A new dihydroisocoumarin (1) and a new coumarin (2), along with eight known metabolites (3-10), were isolated from the solid substrate fermentation cultures of the fungus Penicillium purpurogenum MHZ 111. Their structures were elucidated by extensive spectroscopic analysis and comparison of their spectroscopic and physicochemical data with the literature values. Compounds 2 and 8 showed inhibition of nitric oxide production in lipopolysaccharide-activated BV-2 microglial cells with IC50 values of 26.5 and 52.7 µM, respectively.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Penicillium/metabolismo , Anti-Inflamatórios/farmacologia , Fermentação , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese
17.
Nat Prod Res ; 31(8): 918-924, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27830592

RESUMO

Two new furofuran lignan glucosides, cannabilignin (1) and isocannabilignin (2), together with four known compounds (3-6), were isolated from the leaves of Vitex negundo var. cannabifolia. The structures of the isolates were elucidated by analysis of spectroscopic data. Compound 3 exhibited weak inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC50 value of 69.1 ± 5.8 µM.


Assuntos
Glucosídeos/farmacologia , Lignanas/química , Vitex/química , Animais , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos/métodos , Glucosídeos/química , Glucosídeos/isolamento & purificação , Concentração Inibidora 50 , Lignanas/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Estrutura Molecular , Óxido Nítrico/biossíntese , Folhas de Planta/química
18.
Nat Prod Res ; 31(8): 870-877, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27784175

RESUMO

Three new dimeric furanocoumarins, dahuribiethrins H-J (1-3), and a new ester coumarin, dahurinol A (4), were isolated from the roots of Angelica dahurica. Their structures were elucidated on the basis of extensive spectroscopic data including UV, IR, HRESIMS, 1D and 2D NMR. Compounds 2 and 3 exhibited inhibition of nitric oxide production in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells with IC50 values of 8.7 ± 0.6 and 27.3 ± 0.9 µM, respectively.


Assuntos
Angelica/química , Furocumarinas/química , Furocumarinas/farmacologia , Animais , Avaliação Pré-Clínica de Medicamentos/métodos , Furocumarinas/isolamento & purificação , Concentração Inibidora 50 , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Raízes de Plantas/química , Plantas Medicinais/química , Células RAW 264.7/efeitos dos fármacos
19.
Fitoterapia ; 115: 135-141, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27769819

RESUMO

Eight new flavonoid dimers, named cochinchinenins I-M (1-5), including three pairs of enantiomers (1a/1b-3a/3b) and two optically pure flavonoid dimers (4-5), along with a known analogue (6), were isolated from total phenolic extract of the red resin of Dracaena cochinchinensis (Chinese dragon's blood). The planar structures of 1-5 were elucidated by extensive spectroscopic analysis including HRESIMS and 1D/2D NMR. Their absolute configurations were determined on the basis of experimental and calculated electronic circular dichroism (ECD) data. Compounds 4 and 5 exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells with IC50 value of 4.9±0.4 and 5.4±0.6µM, respectively.


Assuntos
Dracaena/química , Flavonoides/química , Extratos Vegetais/química , Resinas Vegetais/química , Animais , Linhagem Celular , Coix/química , Flavonoides/isolamento & purificação , Camundongos , Microglia/efeitos dos fármacos , Estrutura Molecular , Óxido Nítrico/metabolismo
20.
Eur J Hum Genet ; 25(1): 137-146, 2016 01.
Artigo em Inglês | MEDLINE | ID: mdl-27552965

RESUMO

Genome-wide association studies (GWASs) have been successful in discovering SNP trait associations for many quantitative traits and common diseases. Typically, the effect sizes of SNP alleles are very small and this requires large genome-wide association meta-analyses (GWAMAs) to maximize statistical power. A trend towards ever-larger GWAMA is likely to continue, yet dealing with summary statistics from hundreds of cohorts increases logistical and quality control problems, including unknown sample overlap, and these can lead to both false positive and false negative findings. In this study, we propose four metrics and visualization tools for GWAMA, using summary statistics from cohort-level GWASs. We propose methods to examine the concordance between demographic information, and summary statistics and methods to investigate sample overlap. (I) We use the population genetics Fst statistic to verify the genetic origin of each cohort and their geographic location, and demonstrate using GWAMA data from the GIANT Consortium that geographic locations of cohorts can be recovered and outlier cohorts can be detected. (II) We conduct principal component analysis based on reported allele frequencies, and are able to recover the ancestral information for each cohort. (III) We propose a new statistic that uses the reported allelic effect sizes and their standard errors to identify significant sample overlap or heterogeneity between pairs of cohorts. (IV) To quantify unknown sample overlap across all pairs of cohorts, we propose a method that uses randomly generated genetic predictors that does not require the sharing of individual-level genotype data and does not breach individual privacy.


Assuntos
Estudo de Associação Genômica Ampla/estatística & dados numéricos , Metanálise como Assunto , Locos de Características Quantitativas/genética , Alelos , Estudos de Coortes , Heterogeneidade Genética , Genótipo , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único , Software
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...