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1.
Phys Chem Chem Phys ; 22(8): 4490-4500, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32067002

RESUMO

Once introduced into the human body, nanoparticles often interact with blood proteins, which in turn undergo structural changes upon adsorption. Although protein corona formation is a widely studied phenomenon, the structure of proteins adsorbed on nanoparticles is far less understood. We propose a model to describe the interaction between human serum albumin (HSA) and nanoparticles (NPs) with arbitrary coatings. Our model takes into account the competition between protonated and unprotonated polymer ends and the curvature of the NPs. To this end, we explored the effects of surface ligands (citrate, PEG-OMe, PEG-NH2, PEG-COOH, and glycan) on gold nanoparticles (AuNPs) and the pH of the medium on structural changes in the most abundant protein in blood plasma (HSA), as well as the impact of such changes on cytotoxicity and cellular uptake. We observed a counterintuitive effect on the ζ-potential upon binding of negatively charged HSA, while circular dichroism spectroscopy at various pH values showed an unexpected pattern in the reduction of α-helix content, as a function of surface chemistry and curvature. Our model qualitatively reproduces the decrease in α-helix content, thereby offering a rationale based on particle curvature. The simulations quantitatively reproduce the charge inversion measured experimentally through the ζ-potential of the AuNPs in the presence of HSA. Finally, we found that AuNPs with adsorbed HSA display lower toxicity and slower cell uptake rates, compared to functionalized systems in the absence of protein. Our study allows examining and explaining the conformational dynamics of blood proteins triggered by NPs and corona formation, thereby opening new avenues toward designing safer NPs for drug delivery and nanomedical applications.


Assuntos
Ouro/química , Ouro/metabolismo , Nanopartículas Metálicas/química , Albumina Sérica Humana/química , Humanos , Ligações de Hidrogênio , Concentração de Íons de Hidrogênio , Ligação Proteica , Estrutura Terciária de Proteína , Albumina Sérica Humana/metabolismo , Eletricidade Estática , Propriedades de Superfície
2.
Toxicol Lett ; 321: 1-11, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31846690

RESUMO

Upon entering the body, nerve agents can bind active amino acid residues to form phosphonylated adducts. Tabun derivatives (O-alkyl-N,N-dialkyl phosphoroamidocyanidates) have strikingly different structural features from other G-series nerve agents, such as sarin and soman. Here, we investigate the binding mechanism for the phosphonylated adducts of nerve agents of tabun derivatives. Binding sites for three tabun derivatives, O-ethyl-N,N- dimethyl phosphoramidocyanidate (GA), O-ethyl-N,N-ethyl(methyl) phosphoramidocyanidate, and O-ethyl-N,N-diethylphosphoramidocyanidate were studied. Quadrupole-orbitrap mass spectrometry (Q-Orbitrap-MS) coupled to proteomics was used to screen adducts between tabun derivatives and albumin, immunoglobulin, and hemoglobin. The results reveal that all three tabun derivatives exhibit robust selectivity to lysine residues, rather than other amino acid residue types. A set of 10 lysine residues on human serum albumin are labeled by tabun derivatives in vitro, with K525 (K*QTALVELVK) and K199 (LK*CASLQK) peptides displaying the most reactivity. Tabun derivatives formed stable adducts on K525 and K414 (K*VPQVSTPTLVEVSR) for at least 7 days and on K351 (LAK*TYETTLEK) for at least 5 days in a rabbit model. Three of these peptides-K525, K414, and K351-have the highest homology with human serum albumin of all 5 lysine residues that bound to examined rabbit blood proteins in vivo. Molecular simulation of the tabun-albumin interaction using structural analysis and molecular docking provided theoretical evidence supporting lysine residue reactivity to phosphonylation by tabun derivatives. K525 has the lowest free binding energy and the strongest hydrogen bonding to human albumin. In summary, these findings identify unique binding properties for tabun derivatives to blood proteins.


Assuntos
Substâncias para a Guerra Química/metabolismo , Organofosfatos/metabolismo , Albumina Sérica Humana/metabolismo , Animais , Sítios de Ligação , Substâncias para a Guerra Química/química , Feminino , Hemoglobinas/metabolismo , Humanos , Ligações de Hidrogênio , Imunoglobulina G/metabolismo , Lisina , Masculino , Espectrometria de Massas , Simulação de Dinâmica Molecular , Organofosfatos/química , Ligação Proteica , Conformação Proteica , Coelhos , Albumina Sérica Humana/química , Relação Estrutura-Atividade
3.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117452, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31408792

RESUMO

Nucleoside drugs are known for their remarkable anticancer and antiviral properties. The development of nucleoside drugs has attracted much attention and generated a great deal of research interest. ß-L-cytidine and ß-D-cytidine are a pair of cytosine nucleoside enantiomers. In this work, the interactions between cytosine nucleoside enantiomers and human serum albumin were studied by ultraviolet-visible spectra, fluorescence spectrum and circular dichroism spectrum under simulated human physiological environment. The data of fluorescence spectra were corrected for the inner-filter effect to improve accuracy. Stern-Volmer quenching constants and binding constants in addition to thermodynamic parameters have been analyzed, which established that complexes formation have taken place via static quenching mechanism, and that hydrophobic force involved in these interactions. CD spectrum revealed that on addition of cytosine nucleoside enantiomers, the α-helix% of HSA increased slightly. What's more, molecular modeling method indicated that cytosine nucleoside enantiomers prefer binding at the IIIA site of HSA.


Assuntos
Citidina/química , Citidina/metabolismo , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Ligação Proteica , Espectrometria de Fluorescência , Estereoisomerismo
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117463, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31421349

RESUMO

Real-time process quality control of ramulus cinnamomi (cassia twig) is still a challenge in pharmaceutical industry. Rapid critical quality attribute (CQA) determination of ramulus cinnamomi is essential for quality control. Microscale thermophoresis (MST) was used to investigate the CQA of ramulus cinnamomi by the interaction with biomacromolecule. There was a good affinity between cinnamaldehyde and human serum albumin (HSA) with Ka as 2.1722×103mol/L. It was an excellent combination of similarity to ibuprofen with same binding force as discovered as hydrogen bond and van der Waals force. Furthermore, regarding cinnamaldehyde as CQA, on-line near-infrared was used to monitor pilot extraction process of ramulus cinnamomi combined with high performance liquid chromatography (HPLC). Quantitative model was established with Rpre2 as 0.9798 and RMSECV as 0.0993, suggesting the NIR model was so robust and accurate for pilot process quality control. This method provided a perfect guideline for rapid CQA determination and real-time process quality control of Chinese materia medica (CMM) based on a vital CQA.


Assuntos
Acroleína/análogos & derivados , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Acroleína/análise , Acroleína/química , Acroleína/metabolismo , Acroleína/normas , Humanos , Lauraceae , Limite de Detecção , Modelos Lineares , Materia Medica/normas , Ligação Proteica , Controle de Qualidade , Reprodutibilidade dos Testes , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Temperatura Ambiente
5.
Food Chem ; 307: 125514, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31639576

RESUMO

The thermodynamics and kinetics of binding between human serum albumin (HSA) and resveratrol (RES) or its analog (RESAn1) were investigated by surface plasmon resonance (SPR). The binding constant and the kinetic constants of association and dissociation indicated that RESAn1 has higher affinity toward HSA than does RES. The formation of these complexes was entropically driven ( [Formula: see text] , [Formula: see text]  KJ mol-1). However, for both polyphenols, the activation energy (Eact) of association (a) of free molecules was higher than that for dissociation (d) of the stable complex ( [Formula: see text]  KJ mol-1), and the rate of association was faster than that of dissociation since the activation Gibbs free energy (ΔG‡) was lower for the former (ΔGaHSA-RES‡â‰…54.73,ΔGdHSA-RES‡â‰…73.83,ΔGaHSA-RESAn1‡â‰…54.14,ΔGdHSA-RESAn1‡â‰…73.97 KJ mol-1). This study showed that small differences in the structure of polyphenols such as RES and RESAn1 influenced the thermodynamics and kinetics of the complex formation with HSA.


Assuntos
Fenóis/química , Resveratrol/metabolismo , Albumina Sérica Humana/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Proteínas Imobilizadas/química , Proteínas Imobilizadas/metabolismo , Cinética , Ligação Proteica , Resveratrol/química , Albumina Sérica Humana/química , Ressonância de Plasmônio de Superfície , Temperatura Ambiente , Termodinâmica
6.
Int J Nanomedicine ; 14: 9113-9125, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819422

RESUMO

Background: Prednisolone (PD) is extremely effective for treating rheumatoid arthritis (RA). However, it distributes nonspecifically throughout the body and its use is associated with serious side effects, which promoted us to compound it into a phytomedicine for greater efficacy and safety. Methods: We combined PD with curcumin (CU), an effective monomer from traditional Chinese medicine, and human serum albumin (HSA) in a nanoparticulate system (N-PD/CU) to compensate for the poor bioavailability of PD and CU. N-PD/CU was prepared by high-pressure homogenization, and its characteristics were evaluated in vitro. Next, we investigated its toxicity and mechanism of anti-inflammatory to macrophages. Finally, its pharmacokinetics, biodistribution and therapeutic efficacy were assessed in rats with adjuvant-induced arthritis (AIA). Results: N-PD/CU showed a narrow size distribution around 150.4 ± 2.4 nm, a polydispersity index of 0.22 ± 0.02 and drug loading efficiency (DLE) of 88.75 ± 1.82% for PD and 85.79 ± 1.43% for CU. N-PD/CU showed sustained release of both drugs in vitro. N-PD/CU had no toxicity to macrophages in vitro on concentrations between 0.1 and 1.2 µmol/mL. In activated macrophages, N-PD decreased levels of pro-inflammatory cytokines, while N-CU increased levels of anti-inflammatory IL-10, and N-PD/CU exhibited best therapeutic effect in vitro, suggesting co-delivery of PD and CU may synergistically control the course of RA. In AIA rats, N-PD/CU accumulated in inflamed joints through the effect of extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (ELVIS effect) in inflammatory lesion and showed higher therapeutic efficacy than single-loaded nanoparticles, either free drug on its own, or a simple mixture of the two drugs. Conclusion: This codelivery system based on HSA is a promising platform for combination chemotherapy in RA.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Curcumina/administração & dosagem , Curcumina/uso terapêutico , Sistemas de Liberação de Medicamentos , Nanopartículas/administração & dosagem , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Albumina Sérica Humana/metabolismo , Animais , Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/patologia , Disponibilidade Biológica , Citocinas/metabolismo , Liberação Controlada de Fármacos , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Nanopartículas/ultraestrutura , Tamanho da Partícula , Células RAW 264.7 , Ratos Sprague-Dawley , Distribuição Tecidual
7.
Medicine (Baltimore) ; 98(50): e18366, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852142

RESUMO

We aimed to compare the impact on survival among albumin-bilirubin (ALBI) grade, modified ALBI (mALBI) and our proposed combined ALBI grade and Mac-2 binding protein glycosylation isomer (M2BPGi) or FIB4 index grading system in chronic hepatitis C (CHC) related compensated liver cirrhosis (n = 165, 93 men and 72 women, median age = 67 years). Patients with ALBI grade 1, 2, and 3 were allocated a score of 1, 2, and 3 points, respectively. Patients with mALBI grade 1, 2A, and 2B were allocated a score of 1, 2, and 3 points, respectively. Patients with a high or low M2BPGi were allocated a score of 1 and 0 point. Patients with a high or low FIB4 index were allocated a score of 1 and 0 point. Sum of the point of ALBI (1, 2, or 3) and M2BPGi (0 or 1) or FIB4 index (0 or 1) was defined as ALBI-M2BPGi grade or ALBI-FIB4 grade. Prognostic accuracy was compared using the Akaike information criterion (AIC) value and time dependent receiver operating characteristics (ROC) curve analysis. The median follow-up duration was 5.422 years. AIC value for survival by ALBI-M2BPGi grade was the lowest among 4 prognostic models (AIC: 205.731 in ALBI grade, 200.913 in mALBI grade, 189.816 in ALBI-M2BPGi grade, and 204.671 in ALBI-FIB4 grade). All area under the ROC curves of ALBI-M2BPGi grade in each time point were higher than those of ALBI grade, mALBI grade, and ALBI-FIB4 grade. In conclusion, our proposed ALBI-M2BPGi grading system seems to be helpful for estimating prognosis in patients with CHC related compensated LC.


Assuntos
Bilirrubina/genética , Cirrose Hepática/genética , Albumina Sérica Humana/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/sangue , Antígenos de Neoplasias/genética , Bilirrubina/sangue , Bilirrubina/metabolismo , Feminino , Marcadores Genéticos , Humanos , Cirrose Hepática/mortalidade , Masculino , Glicoproteínas de Membrana/sangue , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Estudos Retrospectivos , Albumina Sérica Humana/metabolismo
9.
Chem Commun (Camb) ; 55(97): 14574-14577, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31663530

RESUMO

Non-specific binding of a fluorescent probe to human serum albumin is problematic because it induces signal interference when the probe detects the target biomarker in human serum. To eliminate this problem, we used intrinsically problematic non-specific fluorescence in designing a fluorescent probe for butyrylcholinesterase activity in serum. The probe containing a fluorophore with specific binding affinity for albumin could sensitively detect butyrylcholinesterase activity in serum with high selectivity to acetylcholinesterase and screen the efficiency of butyrylcholinesterase inhibitors.


Assuntos
Butirilcolinesterase/sangue , Fluorescência , Corantes Fluorescentes/análise , Corantes Fluorescentes/química , Albumina Sérica Humana/química , Sítios de Ligação , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Corantes Fluorescentes/metabolismo , Galantamina/química , Galantamina/farmacologia , Humanos , Estrutura Molecular , Albumina Sérica Humana/metabolismo , Espectrometria de Fluorescência , Tacrina/química , Tacrina/farmacologia
10.
Nat Commun ; 10(1): 4520, 2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31586045

RESUMO

Control over the protein corona of nanomaterials allows them to function better. Here, by taking graphene/gold as examples, we comprehensively assessed the association of surface properties with the protein corona. As revealed by in vitro measurements and computations, the interaction between graphene/gold and HSA/IgE was inversely correlated with the hydroxyl group availability, whereas the interaction between that and ApoE was comparatively less relevant. Molecular simulations revealed that the number and the distribution of surface hydroxyl groups could regulate the manner in which nanomaterials interact with proteins. Moreover, we validated that ApoE pre-adsorption before injection enhances the blood circulation of nanomaterials relative to their pristine and IgE-coated counterparts. This benefit can be attributed to the invulnerability of the complementary system provided by ApoE, whose encasement does not increase cytotoxicity. Overall, this study offers a robust yet simple way to create protein corona enriched in dysopsonins to realize better delivery efficacy.


Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Coroa de Proteína/metabolismo , Adsorção , Animais , Apolipoproteínas E/química , Apolipoproteínas E/metabolismo , Linhagem Celular Tumoral/transplante , Modelos Animais de Doenças , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Feminino , Ouro/química , Grafite/química , Humanos , Imunoglobulina E/química , Imunoglobulina E/metabolismo , Injeções Intravenosas , Camundongos , Simulação de Dinâmica Molecular , Nanopartículas/metabolismo , Neoplasias/tratamento farmacológico , Proteínas Opsonizantes/química , Ligação Proteica , Coroa de Proteína/química , Estrutura Secundária de Proteína , Células RAW 264.7 , Albumina Sérica Humana/metabolismo , Propriedades de Superfície
11.
Rev Cardiovasc Med ; 20(3): 161-169, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601090

RESUMO

Transcatheter aortic valve replacement is becoming a more common therapeutic option for the treatment of aortic stenosis in patients at high risk for invasive surgery, but detecting which patients will benefit clinically can be challenging. Hypoalbuminemia is a useful prognostic marker for chronic inflammation in this population. We carried out a systematic review and meta-analysis of studies evaluating the prognostic value of serum albumin level in patients undergoing transcatheter aortic valve replacement. A literature search of PubMed, Embase, ScienceDirect, Web of Science, SciELO, BIOSIS, Wanfang, and CNKI databases was conducted. Articles published between January 2000 and December 2017 reporting on the prognostic value of low levels of serum albumin in patients undergoing transcatheter aortic valve replacement were analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. 11 studies including 6456 patients met inclusion criteria for meta-analysis. A lower serum albumin level was associated with a lower survival rate at follow-up in patients who underwent transcatheter aortic valve replacement. A sub-group analysis of eight studies reporting adjusted hazard ratios indicated that low serum albumin was independently correlated with increased post-operative mortality. The hazard ratio of mortality risk associated with each 1 g/dL increment in serum albumin level was 0.46, suggesting a potential dose-response relationship between increased serum albumin level and increased survival rate in patients undergoing transcatheter aortic valve replacement. This meta-analysis provides strong evidence for the utility of serum albumin as a prognostic marker in aortic stenosis patients undergoing transcatheter aortic valve replacement, with low serum albumin levels (2.5-3.5 g/dL) suggesting poor prognosis.


Assuntos
Estenose da Valva Aórtica/cirurgia , Hipoalbuminemia/sangue , Albumina Sérica Humana/metabolismo , Substituição da Valva Aórtica Transcateter , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/sangue , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/mortalidade , Biomarcadores/sangue , Feminino , Nível de Saúde , Humanos , Hipoalbuminemia/diagnóstico , Hipoalbuminemia/mortalidade , Masculino , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/mortalidade , Resultado do Tratamento
12.
Biochimie ; 167: 187-197, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31562898

RESUMO

Rad51 is a key protein in DNA repair by homologous recombination and an important target for development of drugs in cancer therapy. 4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) has been used in clinic during the past 30 years as an inhibitor of anion transporters and channels. Recently DIDS has been demonstrated to affect Rad51-mediated homologous pairing and strand exchange, key processes in homologous recombination. Consequently, DIDS has been considered as a potential revertant of radio- and chemo-resistance of cancer cells, the major causes of therapy failure. Here, we have investigated the behavior of DIDS towards serum albumins. The effects of environmental factors, primarily, solvent polarity, on DIDS stability were evaluated, and the mechanisms of interaction of DIDS with human or bovine serum albumin were analyzed using isothermal calorimetry, circular dichroism and fluorescence spectroscopies. DIDS interaction with both serum albumins have been demonstrated, and the interaction characteristics have been determined. By comparing these characteristics for several DIDS derivatives, we have identified the DIDS moiety essential for the interaction. Furthermore, site competition data indicate that human albumin has two DIDS-binding sites: a high-affinity site in the IIIA subdomain and a low-affinity one in the IB subdomain. Molecular docking has revealed the key molecular moieties of DIDS responsible for its interactions in each site and shown that the IB site can bind two ligands. These findings show that binding of DIDS to serum albumin may change the balance between the free and bound DIDS forms, thereby affecting its bioavailability and efficacy against Rad51.


Assuntos
Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/análogos & derivados , Ácido 4,4'-Di-Isotiocianoestilbeno-2,2'-Dissulfônico/farmacologia , Soroalbumina Bovina/metabolismo , Albumina Sérica Humana/metabolismo , Animais , Sítios de Ligação , Bovinos , Humanos , Ligantes , Simulação de Acoplamento Molecular , Ligação Proteica , Rad51 Recombinase/metabolismo
13.
Oncol Rep ; 42(5): 2057-2064, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31545443

RESUMO

The interaction between tumor necrosis factor receptor superfamily, member 4 (OX40) on T cells and the OX40 ligand (OX40L) on antigen­presenting cells (APCs) is a pivotal step for T­cell activation and the promotion of antitumor immunity. However, it is hypothesized that soluble OX40 (sOX40) in blood suppresses T­cell activation by blocking the OX40/OX40L interaction. In the present study, the association between blood sOX40 levels and the clinical characteristics of advanced colorectal cancer (CRC) patients was investigated. Blood was collected from 22 patients with advanced CRC. Blood sOX40 levels were determined by enzyme­linked immunosorbent assay (ELISA). Messenger RNA (mRNA) expression encoding OX40 or cytokines was analyzed by quantitative RT­PCR. Blood sOX40 levels were positively correlated with the blood levels of carbohydrate antigen (CA) 19­9, carcinoembryonic antigen (CEA), C­reactive protein (CRP) and soluble programmed cell death ligand­1 (PD­L1) in patients but negatively correlated with the blood levels of albumin. Blood sOX40 levels were not correlated with the mRNA expression of interferon (IFN)­gamma, interleukin (IL)­6, IL­10 and IL­4 in the peripheral blood mononuclear cells (PBMCs) of the patients and were not correlated with the frequency of programmed cell death­1 (PD­1) expressing CD4+, CD8+ and CD56+ cells. Notably, according to both univariate and multivariate analyses, high blood sOX40 levels were significantly correlated with a reduced survival time in patients. Although activated Jurkat cells (a human T cell line) exhibited an upregulation of sOX40 production and OX40 mRNA expression, the OX40 mRNA expression of the PBMCs of patients was not correlated with blood sOX40 levels. High blood levels of sOX40 were correlated with a reduced survival time in patients with advanced CRC, possibly associated with the suppression of antitumor immunity by sOX40.


Assuntos
Neoplasias Colorretais/mortalidade , Receptores OX40/sangue , Receptores OX40/genética , Regulação para Cima , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Glicosídicos Associados a Tumores/sangue , Proteína C-Reativa/metabolismo , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/imunologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células Jurkat , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organotiofosforados/sangue , Albumina Sérica Humana/metabolismo , Análise de Sobrevida
14.
Molecules ; 24(17)2019 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-31480459

RESUMO

Theaflavin is a kind of multi-pharmacological and health beneficial black tea factor. The aim of this study is to investigate the mechanisms by which theaflavin interacts with glycosylated and non-glycosylated serum albumins and compares their binding properties. Fluorescence and ultraviolet spectra indicated that theaflavin interacted with native and glycated human serum albumin through a static quenching mechanism and had a higher degree of quenching of human serum albumin. The thermodynamic parameters revealed that the combinations of theaflavin with native and glycated human serum albumin were a spontaneous endothermic reaction, and the hydrophobic force was a major driving force in the interaction process. Zeta potential, particle size, synchronous fluorescence, three-dimensional fluorescence spectroscopy and circular dichroism further clarified the effect of theaflavin on the conformation of human serum albumin structure were more pronounced. In addition, site competition experiments and molecular docking technique confirmed that the binding sites of theaflavin on both native and glycated human serum albumin were bound at site II. This study had investigated the effects of glycation on the binding of HSA with polyphenols and the potential nutriology significance of these effects.


Assuntos
Biflavonoides/metabolismo , Catequina/metabolismo , Albumina Sérica Humana/metabolismo , Aminoácidos/metabolismo , Biflavonoides/química , Sítios de Ligação , Catequina/química , Dicroísmo Circular , Glicosilação , Humanos , Cinética , Simulação de Acoplamento Molecular , Tamanho da Partícula , Albumina Sérica Humana/química , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Eletricidade Estática , Termodinâmica
15.
Molecules ; 24(17)2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31480789

RESUMO

Studies of interactions between pesticides and target mammalian proteins are important steps toward understanding the pesticide's toxicity. Using calorimetric and spectroscopic methods, the interaction between triazole fungicide tebuconazole and human serum albumin has been investigated. The spectroscopic techniques showed that fluorescence quenching of human serum albumin by tebuconazole was the result of the formation of tebuconazole/human serum albumin complex with the static type as the dominant mechanism. The association constant was found to be 8.51 × 103 L/mol. The thermodynamic parameters were obtained as ΔH = -56.964 kJ/mol, ΔS = -115.98 J/mol·K. The main active interactions forming the tebuconazole/human serum albumin complex were identified as the interplay between hydrogen bonds and/or van der Waals forces, based on thermodynamic experiments. These binding modes were corroborated well by the predictions of molecular modeling. Hydrogen bonding of tebuconazole with Arg222, Ala215 and Ala291 of human serum albumin played a relevant role in binding. The conformation changes in secondary structure were characterized by circular dichroism and 3D fluorescence spectra.


Assuntos
Fungicidas Industriais/farmacologia , Albumina Sérica Humana/química , Triazóis/farmacologia , Varredura Diferencial de Calorimetria , Humanos , Ibuprofeno/farmacologia , Cetoprofeno/farmacologia , Simulação de Acoplamento Molecular , Ligação Proteica , Albumina Sérica Humana/metabolismo , Espectrometria de Fluorescência , Termodinâmica , Triazóis/química
16.
Acta Diabetol ; 56(12): 1323-1331, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31494747

RESUMO

AIMS: Nephropathic patients show higher levels of advanced glycation end products (AGEs) and oxidized human serum albumin (HSAox) compared to healthy subjects. These two classes of compounds are formed as the result of oxidative insults; for this reason, they can be useful oxidative stress biomarkers. The present study examines the variation of AGEs and HSAox in hemodialysis (HD) patients before and after dialysis session, evaluating the impact of different dialytic techniques and filters on their removal. METHODS: A total of 50 healthy subjects (control group) and 130 HD patients were enrolled in the study. Hemodialysis patients were subdivided based on dialytic techniques: 109 in diffusive technique and 22 in convective technique. We monitored HSAox, AGEs and other laboratory parameters at early morning in healthy subjects and in HD patients before and after the dialysis procedures. RESULTS: The level of HSAox decreases after a single dialytic session (from 58.5 ± 8.8% to 41.5 ± 11.1%), but the concentration of total AGEs increases regardless of adopted dialytic techniques (from 6.8 ± 5.2 µg/ml to 9.2 ± 4.4 µg/ml). In our study, levels of HSAox and total AGEs are similar in diabetic and non-diabetic HD patients. The increase in total AGEs after dialysis was only observed using polysulfone filters but was absent with polymethacrylate filters. CONCLUSIONS: HSAox is a simple and immediate method to verify the beneficial effect of a single dialysis session on the redox imbalance, always present in HD patients. Total AGEs assayed by ELISA procedure seem to be a less reliable biomarker in this population.


Assuntos
Biomarcadores , Produtos Finais de Glicação Avançada/sangue , Diálise Renal , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Albumina Sérica Humana/metabolismo , Biomarcadores/análise , Biomarcadores/sangue , Estudos de Casos e Controles , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/terapia , Feminino , Produtos Finais de Glicação Avançada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução , Estresse Oxidativo/fisiologia , Polímeros/química , Ácidos Polimetacrílicos/química , Prognóstico , Diálise Renal/métodos , Diálise Renal/estatística & dados numéricos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/epidemiologia , Albumina Sérica Humana/análise , Sulfonas/química , Resultado do Tratamento
17.
Molecules ; 24(16)2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31394747

RESUMO

The steady rise in the cancer burden and grim statistics set a vital need for new therapeutic solutions. Given their high efficiency, metallodrugs are quite appealing in cancer chemotherapy. This work examined the anticancer activity of an anti-trypanosomal ruthenium-based compound bearing the 5-nitrofuryl pharmacophore, [RuII(dmso)2(5-nitro-2-furaldehyde semicarbazone)] (abbreviated as RuNTF; dmso is the dimethyl sulfoxide ligand). The cytotoxicity of RuNTF was evaluated in vitro against ovarian adenocarcinoma, hormone-dependent breast adenocarcinoma, prostate carcinoma (grade IV) and V79 lung fibroblasts human cells. The activity of RuNTF was similar to the benchmark metallodrug cisplatin for the breast line and inactive against the prostate line and lung fibroblasts. Given the known role of serum protein binding in drug bioavailability and the distribution via blood plasma, this study assessed the interaction of RuNTF with human serum albumin (HSA) by circular dichroism (CD) and fluorescence spectroscopy. The fluorescence emission quenching from the HSA-Trp214 residue and the lifetime data upon RuNTF binding evidenced the formation of a 1:1 {RuNTF-albumin} adduct with log Ksv = (4.58 ± 0.01) and log KB = (4.55 ± 0.01). This is supported by CD data with an induced CD broad band observed at ~450 nm even after short incubation times. Importantly, the binding to either HSA or human apo-transferrin is beneficial to the cytotoxicity of the complex towards human cancer cells by enhancing the cytotoxic activity of RuNTF.


Assuntos
Proteínas Sanguíneas/química , Complexos de Coordenação/química , Rutênio/química , Semicarbazonas/química , Algoritmos , Antineoplásicos/química , Antineoplásicos/farmacologia , Proteínas Sanguíneas/metabolismo , Dicroísmo Circular , Interações de Medicamentos , Humanos , Modelos Moleculares , Modelos Teóricos , Estrutura Molecular , Ligação Proteica , Rutênio/metabolismo , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo
18.
Dalton Trans ; 48(41): 15646-15656, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31465061

RESUMO

Two optically pure chiral binuclear copper(ii) complexes [Cu2(µ-Cl)2L2]·CH2Cl2 (1) and Cu2L4 (2) based on the natural product rosin derivative N-(5-dehydroabietyl-1,3,4-thiadiazole)-2-substituted pyridinecarboxamide (HL) were prepared, fully characterized and their biological activities were evaluated. The circular dichroism (CD), fluorescence spectroscopy, and DNA melting studies indicate that 1 and 2 interact with calf thymus DNA (CT DNA) via intercalation. It can be concluded that 1 and 2 have a strong affinity to bovine serum albumin (BSA) based on the fluorescence and CD spectral evidence. The MTT assay illustrates that the selective cytotoxic activity of 1 is better than that of HL, 2, cisplatin and oxaliplatin. The exposure of 1 to MCF-7 cells resulted in cell cycle arrest in the G1 phase, apoptosis, mitochondrial dysfunction and an elevated ROS level. The western blot analysis results indicate that 1 might induce apoptosis through intrinsic and extrinsic pathways, autophagy and DNA damage in MCF-7 cells. Furthermore, the down-regulated VEGFR2, MMP-2 and MMP-9 expression levels indicate that 1 should have the ability to resist metastasis and angiogenesis. Thus, based on the above described results 1 has high potential value for anticancer applications.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/química , Resinas Vegetais/química , Animais , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Bovinos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Complexos de Coordenação/metabolismo , DNA/metabolismo , Eletroquímica , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Modelos Moleculares , Conformação Molecular , Espécies Reativas de Oxigênio/metabolismo , Soroalbumina Bovina/metabolismo , Albumina Sérica Humana/metabolismo
19.
J Agric Food Chem ; 67(37): 10470-10480, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31469565

RESUMO

Foodborne nanoparticles (FNPs) produced by roasting have attracted the attention of people, owing to their safety risk to body health. Herein, we reported the formation, physicochemical properties, elemental composition, biodistribution, and binding with human serum albumin (HSA) of FNPs extracted from roast squid. The results showed that the FNP size gradually decreased from 4.1 to 2.3 nm as the roasting temperature changed from 190 to 250 °C. The main component elements of FNPs are carbon, oxygen, and nitrogen, and the carbon and nitrogen contents of FNPs increased with the roasting temperature rising. The surface of FNPs contained hydroxyl, amino, and carboxyl functional groups. The FNPs can emit fluorescence in ultraviolet light and show excitation-dependent emission behavior. Furthermore, it was found that the FNPs derived from roast squid could be accumulated in the stomach, intestine, and brain of BALB/c mice after oral feeding. Static fluorescence quenching of HSA was found by the Stern-Volmer equation and ultraviolet-visible spectrum analysis after interaction with the FNPs. After the addition of FNPs, the α-helix content of HSA decreased and the morphological height of HSA increased, which indicated that the FNPs could cause structural changes in HSA. The atomic force microscopy characterization showed the formation of nanocorona between FNPs and HSA.


Assuntos
Decapodiformes/química , Nanopartículas/química , Nanopartículas/metabolismo , Albumina Sérica Humana/química , Animais , Culinária , Decapodiformes/metabolismo , Fluorescência , Temperatura Alta , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Força Atômica , Tamanho da Partícula , Ligação Proteica , Conformação Proteica , Albumina Sérica Humana/metabolismo , Distribuição Tecidual
20.
Bioanalysis ; 11(13): 1255-1274, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31298568

RESUMO

Aim: To develop a method for enantioseparation of several chiral derivatives of xanthones (CDXs) by LC using a human serum albumin-chiral stationary phase (HSA-CSP) and screening CDX-HSA affinity. Additionally, recognition mechanisms were investigated. Materials & methods: The influence of organic modifier, buffer type, pH and ionic strength of mobile phase, and temperature were explored. The affinity was determined by measuring the retention times and further calculation of bound percentage. Chiral recognition mechanisms were investigated by docking. Results: Enantioselectivity and resolution values ranged from 1.40 to 9.16 and 1.51 to 4.97. Bound percentages ranged from 79.02 to 99.99%. Conclusion: LC systematic study and binding affinity of CDXs on HSA-CSP are presented here for the first time, expanding the applications of HSA-CSP for this class of compounds.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Albumina Sérica Humana/metabolismo , Xantonas/metabolismo , Sítios de Ligação , Humanos , Concentração de Íons de Hidrogênio , Simulação de Acoplamento Molecular , Concentração Osmolar , Ligação Proteica , Estrutura Terciária de Proteína , Albumina Sérica Humana/química , Estereoisomerismo , Temperatura Ambiente , Xantonas/química
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