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1.
Stem Cells Int ; 2018: 5976519, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30356447

RESUMO

Objective: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in preterm neonates and has no effective treatment. This study aimed to investigate the therapeutic effects of neonatal mouse lung resident mesenchymal stem cells (L-MSCs) on the hyperoxia-induced lung injury. Methods: L-MSCs were separated and identified according to the MSC criterions. Hyperoxia-Induced Lung Injury (HILI) of neonatal KM mice was induced with hyperoxia (FiO2 = 60%) and investigated with pathological methods. Neonatal KM mice were divided into 3 groups (hyperoxia + L-MSC group, hyperoxia + PBS group, and air control group). Mice in the hyperoxia + L-MSC group were treated with L-MSCs at 3, 7, and 14 days after birth. After hyperoxia exposure for 21 days, the lung pathology, Radial Alveolar Count (RAC), CD31 expression, and vascular endothelial growth factor (VEGF) expression were investigated. Results: After hyperoxia exposure, the body weight, RAC, CD31 expression, and VEGF expression in the hyperoxia + L-MSC group were significantly better than those in the hyperoxia + PBS group but inferior to those in the air control group significantly. These indicate L-MSCs are partially protective on the lung injury of mice with hyperoxia-induced BPD. Conclusion: L-MSCs are helpful for the prevention and treatment of BPD, and endogenous L-MSCs may play a role in the postinjury repair of the lung.

2.
J Org Chem ; 83(19): 11905-11916, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30199250

RESUMO

With the aid of density functional theory (DFT) calculations, mechanistic investigations have been carried out for the nickel-catalyzed dehydrogenative cross-coupling reaction of benzaldehyde with benzyl alcohol in the presence of N-heterocyclic carbene (NHC) ligand. The overall Ni(0)/Ni(II) catalytic cycle consists of four basic steps: ligand exchange, oxidative addition, hydrogen transfer, and reductive elimination. Considerable interests are paid on detecting the transition state of the rate-determining step, with particular emphasis on the structural and electronic properties, together with clarifying the important roles of external oxidant and hydrogen acceptor. The hydrogen transfer process in the oxidative addition step is rate-determining in the whole catalytic cycle, which is accomplished by C-Ha (active Ha) activation without generating the high energy nickel hydride intermediate. Such process could be understood as the direct hydrogen transfer, instead of general concerted oxidative addition to low valent transition metal. The analysis of the bond distances, electron distributions, and orbital interactions highlights the direct hydrogen transfer mechanism. Furthermore, by exploring the influences from the electronic effect of different substrates on the reaction energy barriers, the  a,a,a-trifluoroacetophenone could accelerate the direct hydrogen transfer with low activate energy.

3.
BMC Med Genet ; 19(1): 167, 2018 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-30217188

RESUMO

BACKGROUND: L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria neurometabolic disease that is inherited as an autosomal recessive mode and have a variety of symptoms, such as psychomotor developmental retardation, epilepsy, cerebral symptoms as well as increased concentrations of 2-hydroxyglutarate (2-HG) in the plasma, urine and cerebrospinal fluid. The causative gene of L-2-HGA is L-2-hydroxyglutarate dehydrogenase gene (L2HGDH), which consists of 10 exons. CASE PRESENTATION: We presented a rare patient primary diagnosis of L-2-HGA based on the clinical symptoms, magnetic resonance imaging (MRI), and gas chromatography-mass spectrometry (GC-MS) results. Mutational analysis of the L2HGDH gene was performed on the L-2-HGA patient and his parents, which revealed two novel mutations in exon 3: a homozygous missense mutation (c.407 A > G, p.K136R) in both the maternal and paternal allele, and a heterozygous frameshift mutation [c.407 A > G, c.408 del G], (p.K136SfsX3) in the paternal allele. The mutation site p.K136R of the protein was located in the pocket of the FAD/NAD(P)-binding domain and predicted to be pathogenic. CONCLUSION: We predicted the homozygous missense mutation (c.407 A > G, p.K136R) was considered as the pathogenic mutation of the patient. The study highlights the power of pedigree analysis in order to interpret novel mutations.


Assuntos
Oxirredutases do Álcool/genética , Encefalopatias Metabólicas Congênitas/genética , Mutação da Fase de Leitura , Mutação de Sentido Incorreto , Oxirredutases do Álcool/química , Oxirredutases do Álcool/metabolismo , Sequência de Bases , Encefalopatias Metabólicas Congênitas/diagnóstico por imagem , Encefalopatias Metabólicas Congênitas/etnologia , Encefalopatias Metabólicas Congênitas/patologia , Análise Mutacional de DNA , Éxons , Feminino , Flavina-Adenina Dinucleotídeo/química , Flavina-Adenina Dinucleotídeo/metabolismo , Expressão Gênica , Genes Recessivos , Heterozigoto , Homozigoto , Humanos , Lactente , Imagem por Ressonância Magnética , Masculino , Modelos Moleculares , NADP/química , NADP/metabolismo , Linhagem , Domínios e Motivos de Interação entre Proteínas , Estrutura Secundária de Proteína
5.
Sci Rep ; 6: 29088, 2016 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-27353517

RESUMO

Neonatal hypotonia is extremely challenging to diagnose because numerous disorders present similar clinical manifestations. Two panels for diagnosing neonatal hypotonia were developed, which enriches 35 genes corresponding to 61 neonatal hypotonia-related disorders. A cohort of 214 neonates with hypotonia was recruited from 2012 to 2014 in China for this study. Of these subjects, twenty-eight neonates with hypotonia were eliminated according to exclusion criteria and 97 were confirmed using traditional detection methods. The clinical diagnoses of the remaining 89 neonates with hypotonia were approached by targeted next-generation sequencing (NGS). Among the 89 tested neonates, 25 potentially pathogenic variants in nine genes (RYR1, MECP2, MUT, CDKL5, MPZ, PMM2, MTM1, LAMA2 and DMPK) were identified in 22 patients. Six of these pathogenic variants were novel. Of the 186 neonates with hypotonia, we identified the genetic causes for 117 neonates by the traditional detection methods and targeted NGS, achieving a high solving rate of 62.9%. In addition, we found seven neonates with RETT syndrome carrying five mutations, thus expanding the mutation profiles in Chinese neonates with hypotonia. Our study highlights the utility of comprehensive molecular genetic testing, which provides the advantage of speed and diagnostic specificity without invasive procedures.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Hipotonia Muscular/diagnóstico , Doenças Neuromusculares/diagnóstico , Síndrome de Rett/diagnóstico , China , Feminino , Predisposição Genética para Doença , Testes Genéticos , Humanos , Recém-Nascido , Masculino , Hipotonia Muscular/genética , Hipotonia Muscular/patologia , Mutação , Doenças Neuromusculares/genética , Doenças Neuromusculares/patologia , Patologia Molecular/métodos , Síndrome de Rett/genética , Síndrome de Rett/patologia
6.
Medicine (Baltimore) ; 95(17): e3564, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27124067

RESUMO

To compare differences in metabolites between newborns with intrauterine growth restriction (IUGR) and those who are appropriate for gestational age (AGA) in order to understand the changes in metabolites of newborns with IUGR and to explore the possible metabolic mechanism of tissue and organ damages in patients with IUGR, with the ultimate goal of providing the basis for clinical intervention.A total of 60 newborns with IUGR and 60 AGA newborns who were hospitalized in the neonatal intensive care unit of our hospital between January 2011 and December 2015 and who underwent metabolic disease screening were enrolled in this study. The differences in 21 amino acids and 55 carnitines in peripheral blood, as well as changes in the ratios of free carnitine and acylcarnitine to total carnitine, were compared.Metabolites, particularly alanine, homocysteine, leucine, methionine, ornithine, serine, tyrosine, isovaleryl carnitine, and eicosenoyl carnitine, differed according to newborns' birth weight (<3rd percentile, 3rd-5th percentiles, 5th-10th percentiles, and 10th-90th percentiles), with those with lower birth weight showing the greater difference (P < 0.05). Metabolites also differed by gestational age, and the differences observed were mainly as follows: preterm and full-term newborns showed differences in metabolites, mainly in alanine, proline, cerotoyl carnitine, and tetradecanedioyl carnitine (P < 0.05); preterm and full-term AGA newborns showed differences in metabolites, mainly in alanine, glutamine, homocysteine, pipecolic acid, proline, heptanoyl carnitine, and sebacoyl carnitine (P < 0.05); and preterm and full-term newborns with IUGR showed differences in metabolites, mainly in arginine, glutamic acid, homocysteine, histidine, leucine, isoleucine, ornithine, serine, threonine, tryptophan, valine, heptanoyl carnitine, decanoyl carnitine, linoleyl carnitine, methylmalonyl carnitine, glutarylcarnitine, sebacoyl carnitine, hydroxyacetyl carnitine, and hydroxyhexadecancenyl carnitine (P < 0.05). Among newborns with IUGR, metabolites differed among males and females, mainly in aspartic acid, glutamic acid, and hexacosenoic acid (P < 0.05). Birth weight had no significant effects on free carnitine concentration or on the ratios of free carnitine and acylcarnitine to total carnitine (P < 0.05).IUGR infants exhibit significant abnormalities in amino acid and acylcarnitine metabolism, especially those with birth weight below the third percentile. With increasing birth weight, amino acids and acylcarnitines showed compensatory increases or reductions, and when birth weight reached the 10th percentile, the newborns with IUGR resembled the AGA newborns.


Assuntos
Retardo do Crescimento Fetal/fisiopatologia , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/fisiopatologia , Metabolômica/métodos , Aminoácidos/sangue , Carnitina/análogos & derivados , Carnitina/sangue , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Triagem Neonatal , Valores de Referência , Pesquisa
7.
Chemosphere ; 150: 329-340, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26921586

RESUMO

Singlet and triplet potential energy surfaces for the atmospheric ozonation of trans-2-chlorovnyldichloroarsine (lewisite) are investigated theoretically. Optimizations of the reactants, products, intermediates and transition states are carried out at the BHandHLYP/6-311+G(d,p) level. Single point energy calculations are performed at the CCSD(T)/6-311+G(d,p) level based on the optimized structures. The detailed mechanism is presented and discussed. Various possible H (or Cl)-abstraction and C (or As)-addition/elimination pathways are considered. The results show that the As-addition/elimination is more energetically favorable than the other mechanisms. Rice-Ramsperger-Kassel-Marcus (RRKM) theory is used to compute the rate constants over the possible atmospheric temperature range of 200-3000 K and the pressure range of 10(-8)-10(9) Torr. The calculated rate constant is in good agreement with the available experimental data. The total rate coefficient shows positive temperature dependence and pressure independence. The modified three-parameter Arrhenius expressions for the total rate coefficient and individual rate coefficients are represented. Calculation results show that major product is CHClCHAs(OOO)Cl2 (s-IM3) at the temperature below 600 K and O2 + CHClCHAsOCl2 (s-P9) play an important role at the temperature between 600 and 3000 K. Time-dependent DFT (TD-DFT) calculations indicate that CHCl(OOO)CHAsCl2 (s-IM3) and CHOAsCl2 (s-P5) can take photolysis easily in the sunlight. Due to the absence of spectral information for arsenide, computational vibrational spectra of the important intermediates and products are also analyzed to provide valuable evidence for subsequent experimental identification.


Assuntos
Poluentes Atmosféricos/análise , Arsenicais/análise , Substâncias para a Guerra Química/análise , Modelos Teóricos , Ozônio/química , Poluentes Atmosféricos/química , Poluentes Atmosféricos/efeitos da radiação , Arsenicais/química , Arsenicais/efeitos da radiação , Substâncias para a Guerra Química/química , Substâncias para a Guerra Química/efeitos da radiação , Cinética , Fotólise , Pressão , Temperatura Ambiente
8.
J Mol Graph Model ; 59: 31-9, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25899446

RESUMO

The heterocyclic urea of deazapterin (DeAPa) and its protomeric conformers (b, c) with different substituents are selected as the building block for a series of dimers in different configurations. The stabilities of all dimers in various conditions have been investigated by density functional theory. Homodimer of b has more stability than other dimers. Topological analyses certify the coexistence of intermolecular with intramolecular H-bonds. Investigations into frequency demonstrate that all H-bonds show an evident red shift in their stretching vibrational frequencies. Electron donating substituents can provide favorable free energies of the dimer. Solvent effect computations suggest that the dimerization can be favored in weakly polar solvents, such as toluene and chloroform. UV-visible spectra exhibit obvious difference of maximum absorption wavelengths between monomers and dimers, thus may have potential applications for identifying intermolecular H-bonds and calculating association constant of DeAP equilibrium systems in experiments.


Assuntos
Hidrogênio/química , Polímeros/química , Simulação por Computador , Dimerização , Elétrons , Ligações de Hidrogênio , Modelos Moleculares , Teoria Quântica , Solventes/química , Vibração
9.
J Comput Chem ; 35(22): 1646-56, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24995629

RESUMO

The reaction of propargyl alcohol with hydroxyl radical has been studied extensively at CCSD(T)/aug-cc-pVTZ//MP2/cc-pVTZ level. This is the first time to gain a conclusive insight into the reaction mechanism and kinetics for this important reaction in detail. Two reaction mechanisms were revealed, namely addition/elimination and hydrogen abstraction mechanism. The reaction mechanism confirms that OH addition to C≡C triple bond forms the chemically activated adducts, IM1 (·CHCOHCH2OH) and IM2 (CHOH·CCH2OH), and the hydrogen abstraction pathways (-CH2OH bonded to the carbon atom and alcohol hydrogen) may occur via low barriers. Harmonic model of Rice-Ramsperger-Kassel-Marcus theory and variational transition state theory are used to calculate the overall and individual rate constants over a wide range of temperatures and pressures. The calculated rate constants are in good agreement with the experimental data. At atmospheric pressure with Ar as bath gas, IM1 (·CHCOHCH2OH) and IM2 (CHOH·CCH2OH) formed by collisional stabilization are dominant in the low temperature range. The production of CHCCHOH + H2O via hydrogen abstraction becomes dominate at higher temperature. The fraction of IM3 (CH2COHCH2·O) is very significant over the moderate temperature range.


Assuntos
Alquinos/química , Gases/química , Radical Hidroxila/química , Modelos Químicos , Propanóis/química
10.
J Mol Model ; 20(7): 2335, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25007917

RESUMO

The trans-2-chlorovinyldichloroarsine (Lewisite) was produced and handled during WWI and WWII as chemical warfare agents. It was very difficult to explore its chemical characterization by experiments ways. The quantum chemical calculations proved to be a precise and harmless method for the toxicological system. In this paper, the gas phase reaction mechanisms of OH radical with trans-2-chlorovinyldichloroarsine (lewisite) were studied by second-order Møller-Plesset perturbation theory (MP2) method. The geometries of reactants, products, complexes, and transition states were optimized at the MP2/6-311++G(d,p) level. To gain more accurate mechanistic knowledge, the single-point energies were calculated using G3 and CCSD(T) method. This reaction exhibited three mechanisms, namely, direct hydrogen abstraction, direct chlorine abstraction, and addition/elimination. Multichannel Rice-Ramsperger-Kassel-Marcus theory and transition-state theory have been carried out for overall and individual rate constants over a wide range of temperatures and pressures. The computational results indicated that addition/elimination reaction is more favorable than direct hydrogen abstraction and direct chlorine abstraction. The major products for the total reaction are AsCl2 and CHClCH2O generated via C(2)-addition/elimination.

11.
J Chem Phys ; 140(8): 084309, 2014 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-24588171

RESUMO

The reaction of allyl chloride with the hydroxyl radical has been investigated on a sound theoretical basis. This is the first time to gain a conclusive insight into the reaction mechanism and kinetics for important pathways in detail. The reaction mechanism confirms that OH addition to the C=C double bond forms the chemically activated adducts, IM1 (CH2CHOHCH2Cl) and IM2 (CH2OHCHCH2Cl) via low barriers, and direct H-abstraction paths may also occur. Variational transition state model and multichannel RRKM theory are employed to calculate the temperature-, pressure-dependent rate constants. The calculated rate constants are in good agreement with the experimental data. At 100 Torr with He as bath gas, IM6 formed by collisional stabilization is the major products in the temperature range 200-600 K; the production of CH2CHCHCl via hydrogen abstractions becomes dominant at high temperatures (600-3000 K).


Assuntos
Compostos Alílicos/química , Gases/química , Radical Hidroxila/química , Teoria Quântica , Pressão , Temperatura Ambiente
12.
Cell Biol Int ; 36(6): 589-94, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22339670

RESUMO

BPD (bronchopulmonary dysplasia) is predominantly characterized by persistent abnormalities in lung structure and arrested lung development, but therapy can be palliative. While promising, the use of BMSC (bone marrow-derived mesenchymal stem cell) in the treatment of lung diseases remains controversial. We have assessed the therapeutic effects of BMSC in vitro and in vivo. In vitro co-culturing with injured lung tissue increased the migration-potential of BMSC; and SP-C (surfactant protein-C), a specific marker of AEC2 (type II alveolar epithelial cells), was expressed. Following intraperitoneal injection of BMSC into experimental BPD mice on post-natal day 7, it was found that BMSC can home to the injured lung, express SP-C, improve pulmonary architecture, attenuate pulmonary fibrosis and increase the survival rate of BPD mice. This work supports the notion that BMSC are of therapeutic benefit through the production of soluble factors at bioactive levels that regulate the pathogenesis of inflammation and fibrosis following hyperoxia.


Assuntos
Células da Medula Óssea/fisiologia , Displasia Broncopulmonar/prevenção & controle , Hiperóxia/complicações , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Animais , Animais Recém-Nascidos , Células da Medula Óssea/metabolismo , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/patologia , Diferenciação Celular , Movimento Celular , Forma Celular , Células Cultivadas , Técnicas de Cocultura , Modelos Animais de Doenças , Feminino , Fibrose , Humanos , Recém-Nascido , Injeções Intraperitoneais , Pulmão/patologia , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Pneumonia/etiologia , Pneumonia/prevenção & controle
13.
Mol Syst Biol ; 7: 536, 2011 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-21988832

RESUMO

Proteome-scale protein interaction maps are available for many organisms, ranging from bacteria, yeast, worms and flies to humans. These maps provide substantial new insights into systems biology, disease research and drug discovery. However, only a small fraction of the total number of human protein-protein interactions has been identified. In this study, we map the interactions of an unbiased selection of 5026 human liver expression proteins by yeast two-hybrid technology and establish a human liver protein interaction network (HLPN) composed of 3484 interactions among 2582 proteins. The data set has a validation rate of over 72% as determined by three independent biochemical or cellular assays. The network includes metabolic enzymes and liver-specific, liver-phenotype and liver-disease proteins that are individually critical for the maintenance of liver functions. The liver enriched proteins had significantly different topological properties and increased our understanding of the functional relationships among proteins in a liver-specific manner. Our data represent the first comprehensive description of a HLPN, which could be a valuable tool for understanding the functioning of the protein interaction network of the human liver.


Assuntos
Fígado , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteoma/metabolismo , Proteômica/métodos , Saccharomyces cerevisiae/metabolismo , Biologia de Sistemas , Bases de Dados de Proteínas , Inativação Gênica/efeitos dos fármacos , Genes Reporter , Células HEK293 , Humanos , Imunoprecipitação , Fígado/metabolismo , Luciferases/análise , Fases de Leitura Aberta , Plasmídeos , Proteínas/genética , Proteínas/metabolismo , Proteoma/genética , RNA Interferente Pequeno/farmacologia , Saccharomyces cerevisiae/genética , Transfecção , Técnicas do Sistema de Duplo-Híbrido
14.
Nucleic Acids Res ; 38(19): 6544-54, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20542919

RESUMO

HDM2 is a p53-specific E3 ubiquitin ligase. Its overexpression leads to excessive inactivation of tumor protein p53, diminishing its tumor suppressor function. HDM2 also affects the cell cycle, apoptosis and tumorigenesis through interacting with other molecules, including several ribosomal proteins. To identify novel HDM2 regulators, we performed a yeast two-hybrid screening using HDM2 as bait. Among the candidates, ribosomal protein L26 (RPL26) was characterized as a novel HDM2-interactor. The interaction between HDM2 and RPL26 was further validated by in vivo and in vitro assays. RPL26 modulates the HDM2-p53 interaction by forming a ternary complex among RPL26, HDM2 and p53, which stabilize p53 through inhibiting the ubiquitin ligase activity of HDM2. The ribosomal stress caused by a low dose of Act D enhances RPL26-HDM2 interaction and activates p53. Overexpression of RPL26 results in activating of p53, inhibits cell proliferation and induces a p53-dependent cell cycle arrest. These results provide a novel regulatory mechanism of RPL26 to activate p53 by inhibiting HDM2.


Assuntos
Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Proteínas Ribossômicas/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Ciclo Celular , Proliferação de Células , Células Cultivadas , Dactinomicina/farmacologia , Humanos , Camundongos , Domínios e Motivos de Interação entre Proteínas , Proteínas Proto-Oncogênicas c-mdm2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-mdm2/química , Proteínas Ribossômicas/química , Ubiquitinação
15.
Mol Biol Cell ; 21(14): 2500-13, 2010 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-20484576

RESUMO

TANK/I-TRAF is a TRAF-binding protein that negatively regulates NF-kappaB activation. The underlying mechanism of this activity remains unclear. Here we show that TANK directly interacts with PLK1, a conserved cell cycle-regulated kinase. PLK1 inhibits NF-kappaB transcriptional activation induced by TNF-alpha, IL-1beta, or several activators, but not by nuclear transcription factor p65. PLK1 expression reduces the DNA-binding activity of NF-kappaB induced by TNF-alpha. Moreover, endogenous activation of PLK1 reduces the TNF-induced phosphorylation of endogenous IkappaBalpha. PLK1 is bound to NEMO (IKKgamma) through TANK to form a ternary complex in vivo. We describe a new regulatory mechanism for PLK1: PLK1 negatively regulates TNF-induced IKK activation by inhibiting the ubiquitination of NEMO. These findings reveal that the scaffold protein TANK recruits PLK1 to negatively regulate NF-kappaB activation and provide direct evidence that PLK1 is required for the repression function of TANK.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Ciclo Celular/metabolismo , NF-kappa B/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Ativação Transcricional/genética , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Citoplasma/efeitos dos fármacos , Citoplasma/enzimologia , Ativação Enzimática/efeitos dos fármacos , Humanos , Quinase I-kappa B/metabolismo , Proteínas I-kappa B/metabolismo , Mutação/genética , Inibidor de NF-kappaB alfa , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Mapeamento de Interação de Proteínas , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Técnicas do Sistema de Duplo-Híbrido , Ubiquitinação/efeitos dos fármacos
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