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1.
Analyst ; 145(10): 3697-3704, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32297602

RESUMO

The cyclin-dependent kinase inhibitor p21 protein is a critical regulator that mediates various biological activities, such as cell cycle progression, apoptosis, and cellular senescence. As a DNA damage-inducing agent, doxorubicin could reactivate the transcriptional activity of p53 and modulate the p21 protein level. In this work, sensitive and selective monitoring of the intracellular p21 protein in doxorubicin-treated breast cancer cells was conducted using surface plasmon resonance (SPR). The fluidic channels were pre-immobilized with double stranded (ds) DNA/proliferating cell nuclear antigen (PCNA) for the capture of the p21 protein. The incorporation of the anti-p21 antibody-streptavidin conjugate pre-formed between streptavidin and biotinylated anti-p21 antibody that specifically recognizes the p21 protein leads to signal amplification. The detection limit of 0.85 pM for the p21 protein was lower than that using the commercial enzyme-linked immunosorbent assay (ELISA) kit. The treatment of MCF-7 breast cancer cells with wild-type p53 by various doses of doxorubicin leads to differences in the extent of DNA damage. Low-level DNA damage by low-dose doxorubicin up-regulates the p21 level, and p21 exerts its anti-apoptotic function, causing p53-dependent cell cycle arrest and DNA repair. However, massive DNA damage by high-dose doxorubicin represses the expression of the p21 protein through increased proteasome activity, leading to cell apoptosis. The proposed method is sensitive, selective and label-free, holding great promise for the assay of the DNA damage-induced intracellular p21 protein and understanding of p21 protein-mediated cell cycle arrest, DNA repair, and cell apoptosis.

2.
Colloids Surf B Biointerfaces ; 189: 110857, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32066087

RESUMO

Hydrophobic modification PEO-PPO copolymer BP123 was synthesized, with two aromatic rings in the centre linked to PEO-PPO blocks, and the identical PEO and PPO block numbers were possessed with commercial copolymer P123. The influence of three common pharmaceutical excipient salts sodium chloride (NaCl), sodium citrate (NaCA) and sodium benzoate (NaBZ) on self-assembly behaviors of BP123 and P123 was investigated via cloud point, surface tension, pyrene fluorescence and dynamic light scattering. Solubilization for hydrophobic drug simvastatin (SV) and in vitro drug release behavior were assessed accordingly. In the presence of NaCl or NaCA, cloud point and critical micellization concentration (CMC) decreased, micelles became more hydrophobic, micellar size and drug solubilization increased, drug release rate slowed, and the impact of NaCA was more significant than NaCl. Oppositely, cloud point and CMC increased with the addition of NaBZ. NaBZ could participate in the formation of micelles by hydrophobic aromatic ring, which greatly raised solubilization of SV. Moreover, a different performance occurred when NaBZ was added to BP123 or P123, due to the hydrophobic benzene rings in BP123, which prominently enhanced the interaction with hydrophobic drug, leading to obvious delay of drug release for BP123. This work is conducive to turning copolymer property in diverse pharmaceutical applications and in drug delivery systems as drug carriers.

3.
Biol Trace Elem Res ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31950399

RESUMO

The purpose of this study was to investigate the effect of iodine supplementation during pregnancy on thyroid function and also its effect on postpartum depression in an iodine-sufficient area. Healthy pregnant women were divided into three groups: group A (vitamin iodine-150) receiving vitamin containing 150 µg iodine, group B (vitamin iodine-0) receiving vitamin without iodine, and group C (no vitamin) receiving no vitamin. General information was collected by questionnaire and thyroid function was determined in the third trimester of pregnancy. Depression was assessed 1 month postpartum by the Edinburgh postnatal depression scale (EPDS). The results showed that there was no significant difference in thyroid-stimulating hormone (TSH) level among the three groups (P > 0.05). FT4 concentration was significantly lower in group A (n = 234: 10.68 pmol/L) than in group B (n = 220: 11.47 pmol/L) and group C (n = 195: 11.64 pmol/L) (P < 0.05), However, it was still within the normal range. EPDS scores obtained from group B (3.50) and group C (3.00) were similar but markedly lower than group A (5.00) (P < 0.05). Despite the difference in the EPDS score, the prevalence of postpartum depression was not significantly different among the three groups. In conclusion, 150 µg/day iodine supplementation for pregnant women in areas with adequate iodine had little effect on thyroid function in the third trimester, and serum FT4 level could not be increased. Iodine supplementation during pregnancy also had no significant effect on postpartum depression.

4.
Pediatr Dermatol ; 37(1): 222-223, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31626359

RESUMO

Staphylococcal scalded skin syndrome causes widespread skin denudation primarily in infants < 1 year old. Selection of empiric therapy is complicated by rising rates of antibiotic resistance in community-acquired staphylococcal infections. Consistent with a previous study, this retrospective review found that SSSS-associated isolates were more likely to be clindamycin-resistant and less likely to be methicillin-resistant compared to overall staphylococcal infections. We favor cephalosporins and penicillinase-resistant penicillins (eg, oxacillin) for empiric management of SSSS, with consideration of adding MRSA coverage in communities with high MRSA prevalence or failure to improve following several days of treatment.

5.
6.
J Environ Sci (China) ; 88: 59-71, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31862080

RESUMO

The existence of electrolytes in aquatic environment on the photocatalytic performance and coagulation of nanodispersed TiO2 hydrosol and the corresponding photocatalytic alteration were investigated by studying cations (Na+, K+, Ca 2+, Mg2+, and Al3+). The photocatalysis reactions of nano TiO2 with different dosages of electrolytes were measured by monitoring the degradation of Rhodamine B (RhB) under ultraviolet A (UV-A) irradiation over time. The results showed that the photocatalytic performance of TiO2 was improved by the presence of Al3+, while the performance was impaired by the other tested cations. The negative influences of divalent ions on the photocatalytic performance of TiO2 were more significant than monovalent ions. The TiO2 sol dispersed stable at nano scale at low concentration of electrolyte (<0.01 mol/L) with slight change of pH, and coagulated into micro sizes at high concentration of electrolytes (>0.1 mol/L) with larger increase or decrease of pH. The positive effects of Al3+ on the photodegradation rate of RhB might relate to the strong hydrolytic action of Al3+ in aquatic solutions. The photocatalytic processes of TiO2 in the presence of all ions followed the Langmuir-Hinshelwood model, and the reaction kinetic constant was increased with the decrease of pH caused by different cations. These work suggested a new perspective about the relationship between coagulation and photocatalytic performance of TiO2 hydrosols in electrolyte with hydrolysable cations, which demonstrated that TiO2 hydrosols may be suitable as photocatalysts in aquatic environments.


Assuntos
Processos Fotoquímicos , Titânio , Raios Ultravioleta , Catálise , Cátions , Fotólise , Rodaminas/química
7.
Bioorg Med Chem Lett ; 30(3): 126885, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31862411

RESUMO

In order to explore novel Aurora kinase inhibitors, a series of novel 2,4-disubstituted pyrimidines were designed, synthesized and evaluated their in vitro anti-proliferative activities against a panel of cancerous cell lines (A549, HCT-116 and MCF-7). Among them, compound 12a showed the moderate to high anti-proliferative activities against A549 (IC50 = 12.05 ± 0.45 µM), HCT-116 (IC50 = 1.31 ± 0.41 µM) and MCF-7 (IC50 = 20.53 ± 6.13 µM) cells, as well as the Aurora A and Aurora B inhibitory activities with the IC50 values of 309 nM and 293 nM, respectively. Furthermore, compound 12a induced apoptosis by upregulated the pro-apoptotic proteins Bax and decreased the anti-apoptotic protein Bcl-xl in HCT-116 cells. Moreover, the molecular docking study showed that compound 12a had good binding modes with Aurora A and Aurora B and the bioinformatics prediction discovered that compound 12a exhibited good drug likeness using SwissADME. Taken together, these results indicated that 12a may be a potential anticancer compound that was worthy of further development as Aurora kinase inhibitor.

8.
Nat Commun ; 10(1): 4599, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601813

RESUMO

Host-guest interactions are of central importance in many biological and chemical processes. However, the investigation of the formation and decomplexation of host-guest systems at the single-molecule level has been a challenging task. Here we show that the single-molecule conductance of organoplatinum(II) metallocycle hosts can be enhanced by an order of magnitude by the incorporation of a C60 guest molecule. Mechanically stretching the metallocycle-C60 junction with a scanning tunneling microscopy break junction technique causes the release of the C60 guest from the metallocycle, and consequently the conductance switches back to the free-host level. Metallocycle hosts with different shapes and cavity sizes show different degrees of flexibility to accommodate the C60 guest in response to mechanical stretching. DFT calculations provide further insights into the electronic structures and charge transport properties of the molecular junctions based on metallocycles and the metallocycle-C60 complexes.


Assuntos
Fulerenos/química , Compostos Organoplatínicos/química , Teoria da Densidade Funcional , Eletrodos , Ouro , Espectroscopia de Ressonância Magnética , Microscopia de Força Atômica , Microscopia de Tunelamento , Espectrofotometria Ultravioleta
9.
Nat Commun ; 10(1): 2811, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31243280

RESUMO

How developmental programs reactivate in regeneration is a fundamental question in biology. We addressed this question through the study of Wound Induced Hair follicle Neogenesis (WIHN), an adult organogenesis model where stem cells regenerate de novo hair follicles following deep wounding. The exact mechanism is uncertain. Here we show that self-noncoding dsRNA activates the anti-viral receptor toll like receptor 3 (TLR3) to induce intrinsic retinoic acid (RA) synthesis in a pattern that predicts new hair follicle formation after wounding in mice. Additionally, in humans, rejuvenation lasers induce gene expression signatures for dsRNA and RA, with measurable increases in intrinsic RA synthesis. These results demonstrate a potent stimulus for RA synthesis by non-coding dsRNA, relevant to their broad functions in development and immunity.


Assuntos
Folículo Piloso/fisiologia , RNA de Cadeia Dupla/fisiologia , Regeneração/fisiologia , Receptor 3 Toll-Like/metabolismo , Tretinoína/metabolismo , Animais , Benzoatos/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Humanos , Interleucina-6/administração & dosagem , Interleucina-6/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Interferência de RNA , RNA Interferente Pequeno , Estilbenos/farmacologia , Cicatrização
10.
Proc Natl Acad Sci U S A ; 116(9): 3407-3412, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30737288

RESUMO

Electron transfer reactions can now be followed at the single-molecule level, but the connection between the microscopic and macroscopic data remains to be understood. By monitoring the conductance of a single molecule, we show that the individual electron transfer reaction events are stochastic and manifested as large conductance fluctuations. The fluctuation probability follows first-order kinetics with potential dependent rate constants described by the Butler-Volmer relation. Ensemble averaging of many individual reaction events leads to a deterministic dependence of the conductance on the external electrochemical potential that follows the Nernst equation. This study discloses a systematic transition from stochastic kinetics of individual reaction events to deterministic thermodynamics of ensemble averages and provides insights into electron transfer processes of small systems, consisting of a single molecule or a small number of molecules.

11.
Nat Mater ; 18(4): 357-363, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30742082

RESUMO

Quantum interference can profoundly affect charge transport in single molecules, but experiments can usually measure only the conductance at the Fermi energy. Because, in general, the most pronounced features of the quantum interference are not located at the Fermi energy, it is highly desirable to probe charge transport in a broader energy range. Here, by means of electrochemical gating, we measure the conductance and map the transmission functions of single molecules at and around the Fermi energy, and study signatures associated with constructive and destructive interference. With electrochemical gate control, we tune the quantum interference between the highest occupied molecular orbital and lowest unoccupied molecular orbital, and directly observe anti-resonance, a distinct feature of destructive interference. By tuning the molecule in and out of anti-resonance, we achieve continuous control of the conductance over two orders of magnitude with a subthreshold swing of ~17 mV dec-1, features relevant to high-speed and low-power electronics.

12.
J Invest Dermatol ; 139(1): 91-99, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30120933

RESUMO

How cell and tissue identity persist despite constant cell turnover is an important biologic question with cell therapy implications. Although many mechanisms exist, we investigated the controls for site-specific gene expression in skin, given its diverse structures and functions. For example, the transcriptome of in vivo palmoplantar (i.e., volar) epidermis is globally unique, including Keratin 9 (KRT9). Although volar fibroblasts have the capacity to induce KRT9 in nonvolar keratinocytes, we show here that volar keratinocytes continue to express KRT9 in in vitro solo cultures. Despite this, KRT9 expression is lost with volar keratinocyte passaging, despite stable hypomethylation of its promoter. Coincident with KRT9 loss is a gain of the primitive keratin 7 and a signature of dsRNA sensing, including the double-stranded RNA (dsRNA) receptor DExD/H-Box Helicase 58 (DDX58/RIG-I). Exogenous dsRNA inhibits KRT9 expression in early passage volar keratinocytes or in vivo footpads of wild-type mice. Loss of DDX58 in passaged volar keratinocytes rescues KRT9 and inhibits KRT7 expression. Additionally, DDX58-null mice are resistant to the ability of dsRNA to inhibit KRT9 expression. These results show that the sensing of dsRNA is critical for loss of cell-specific gene expression; our results have important implications for how dsRNA sensing is important outside of immune pathways.


Assuntos
Regulação da Expressão Gênica , Queratina-9/genética , Queratinócitos/metabolismo , RNA de Cadeia Dupla/genética , RNA/genética , Animais , Células Cultivadas , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Queratina-9/biossíntese , Queratinócitos/citologia , Camundongos , RNA de Cadeia Dupla/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
13.
J Am Chem Soc ; 140(51): 18074-18081, 2018 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-30500187

RESUMO

Providing a mechanically stable and electronically efficient coupling between a molecule and an electrode is critical to the study of charge transfer and conductance of the molecule. A common method is to link the molecule to Au electrodes via a linker (e.g., thiol terminal of the molecule). Here we study the mechanical stability and electronic coupling of a S-Au bond in single-molecule junctions over a broad range of electrode potentials. Our results show that the mechanical and electromechanical properties of molecule-electrode contact undergo a systematic change with the potential involving Au oxidation at positive potentials and S protonation at negative potentials. The study establishes the potential range for a stable S-Au bond and determines the potential dependence of the mechanical and electromechanical properties of the molecule-electrode contact, which is crucial to the interpretation of potential-dependent charge transfer in electrochemistry and electrochemical gating of charge transport in molecular electronics.

14.
Mikrochim Acta ; 185(12): 549, 2018 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-30426239

RESUMO

A sensitive method is described for detection of the apoE 4 gene detection which is important for early diagnosis of Alzheimer's disease. It is based on signal amplification by using ferrocene (Fc) capped gold nanoparticles modified with streptavidin. The immobilized oligonucleotide probe captures complementary apoE 4 gene. This is followed by the specific recognition of the GCGC sequences which are hydrolyzed by the restriction enzyme HhaI. Cleavage only occurs at the complementary apoE 4 duplex, while mismatches prevent enzymatic cleavage. Thus, the apoE 4 sequence can be discriminated against other apoE sequences. Benefitting from amplified signal by Fc-capped nanoparticle/streptavidin and the recognition of HhaI, the detection limit is as low as 0.1 pM of the ApoE 4 gene. Four genomic DNA samples extracted from blood were analyzed for the presence of the apoE 4 gene. The approach presented here will provide viable proof-of-principle for an enzyme-assisted electrochemical assay for the apoE 4 gene in genomic DNAs. Graphical abstract Schematic presentation of amplified voltammetric detection of Alzheimer's Disease-related apoE 4 gene from unamplified genomic DNA extracts via ferrocene capped gold nanoparticle/streptavidin.


Assuntos
Doença de Alzheimer/genética , Apolipoproteína E4/genética , Técnicas Biossensoriais/métodos , DNA/genética , Compostos Ferrosos/química , Ouro/química , Nanopartículas Metálicas/química , Metalocenos/química , Doença de Alzheimer/sangue , DNA/sangue , DNA/isolamento & purificação , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção
15.
ACS Sens ; 3(11): 2402-2407, 2018 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-30350593

RESUMO

Identification of gene variation is of great importance for attaining information related to disease susceptibility. A highly sensitive and specific surface plasmon resonance (SPR) method for quantification of the apoE gene and genotype discrimination was demonstrated. The complementary sequences with the specific recognition sites of GCGC bases upon hybridization to the preimmobilized biotinylated probes could be cleaved by the restriction enzyme HhaI, while the existence of the single-base mismatch (GTGC) prevented the cleavage reaction. In both cases, the incorporation of streptavidin increased the sensitivity of the SPR assay, and the detection levels of 10 fM and 50 fM for the complementary and single-base mismatched sequences were attained, respectively. The sensing protocol is simple, label-free, and quantitative, thus avoiding the complicated polymerase chain reaction (PCR) amplification procedures. The proposed method serves as a viable means for facile and sensitive analyses of apoE genes in four unamplified genomic DNA extracts.


Assuntos
Apolipoproteínas E/genética , DNA/análise , Técnicas de Genotipagem/métodos , Alelos , Pareamento Incorreto de Bases , DNA/química , DNA/genética , Sondas de DNA/genética , Desoxirribonucleases de Sítio Específico do Tipo II/química , Humanos , Hibridização de Ácido Nucleico , Estudo de Prova de Conceito , Ressonância de Plasmônio de Superfície/métodos
16.
Opt Express ; 26(18): 23854-23867, 2018 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-30184881

RESUMO

Both plasmon-phonon-polariton (SPP-PHP) modes and phonon-polariton (PHP) modes supported in graphene-coated hexagon boron nitride (h-BN) single nanowire are presented. The field distributions of the lowest 5 order modes of SPP-PHP modes supported in graphene-coated hexagon boron nitride nanowire pairs (SPP-PHP-GHNP) and the lowest 5 order modes of PHP modes supported in graphene-coated hexagon boron nitride nanowire pairs (GHNP) are also demonstrated and analyzed, respectively. The results of numerical calculation show that SPP-PHP-GHNP mode 0 owns the strongest confinement and lowest loss among the lowest 5 order modes of SPP-PHP-GHNP. Furthermore, the field enhancement of SPP-PHP-GHNP mode 0 can reach over 105 by controlling the geometry parameters of GHNP. Meanwhile, the influence of tuning the Fermi level of graphene on the field enhancement is also presented in the paper. The proposed structure may improve the development of graphene-h-BN-based optoelectronic devices.

17.
Analyst ; 143(9): 2029-2034, 2018 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-29637949

RESUMO

Murine double minute 2 (MDM2) is an oncoprotein mediating the degradation of the tumor suppressor p53 protein. The physiological levels of MDM2 protein are closely related to malignant transformation and tumor growth. In this work, the simultaneous and label-free determination of free and p53-bound MDM2 proteins from sarcoma tissue extracts was conducted using a dual-channel surface plasmon resonance (SPR) instrument. Free MDM2 protein was measured in one fluidic channel covered with the consensus double-stranded (ds)-DNA/p53 conjugate, while MDM2 bound to p53 was captured by the consensus ds-DNA immobilized onto the other channel. To achieve higher sensitivity and to confirm specificity, an MDM2-specific monoclonal antibody (2A10) was used to recognize both the free and p53-bound MDM2 proteins. The resultant method afforded a detection limit of 0.55 pM of MDM2. The amenability of the method to the analysis of free and p53-bound MDM2 proteins was demonstrated for normal and sarcoma tissue extracts from three patients. Our data reveal that both free and total MDM2 (free and bound forms combined) proteins from sarcoma tissue extracts are of much higher concentrations than those from normal tissue extracts and the p53-bound MDM2 protein only constitutes a small fraction of the total MDM2 concentration. In comparison with enzyme-linked immunosorbent assay (ELISA), the proposed method possesses higher sensitivity, is more cost-effective, and is capable of determining free and p53-bound MDM2 proteins in clinical samples.


Assuntos
Proteínas Proto-Oncogênicas c-mdm2/análise , Sarcoma/metabolismo , Ressonância de Plasmônio de Superfície , Proteína Supressora de Tumor p53/análise , Humanos
18.
Opt Express ; 25(20): 23989-24000, 2017 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-29041347

RESUMO

Due to the characteristic of surface plasmon polaritons (SPP) excitation, radial polarized beams and circular polarized beams are widely used for plasmonic lens and plasmonic near field focusing. In this paper, a plasmonic lens based on in-plane total internal reflection (TIR) scheme is proposed and numerically demonstrated to achieve the simultaneous nanofocusing of azimuthal and radial polarized beams. By means of the in-plane TIR mechanism, the operation bandwidth of lens ranges from visible light to mid-infrared. The proposed structure has been utilized in the design of a plasmonic liquid refractive index sensor and is expected to find potential applications in near-field optical energy focusing, near-field imaging and sensing.

19.
Anal Chem ; 89(20): 10834-10840, 2017 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-28956430

RESUMO

MicroRNAs (miRNAs) serve as diagnostic and prognostic biomarkers for a wide variety of cancers. Via the novel conjugates of gold nanoparticle-coated magnetic microbeads (AuNP-MMBs) and the diblock oligonucleotide (ODN)-modified AuNPs, multiplexed electrochemical assay of miRNAs was performed. The hybridization to target miRNAs leads to the conformational change of the hairpin-structured ODN probes, and the attachment of the diblock ODN-modified AuNPs was achieved. By examining the oxidation peak currents of methylene blue (MB) and ferrocene (Fc) moieties residing on the diblock ODNs, simultaneous quantification of miRNA-182 and miRNA-381 was conducted. The detection signals were significantly enhanced due to the numerous MB and Fc tags on the AuNPs. The proposed assay was highly selective for discriminating miRNAs with similar sequences, and detection limits of 0.20 fM and 0.12 fM for miRNA-182 and miRNA-381, respectively, were achieved. The feasibility of the method for sensitive determination of miRNA-182 and miRNA-381 from serum samples of glioma patients at different stages was demonstrated. The sensing protocol thus holds great potential for early diagnosis and treatment of cancer patients.


Assuntos
Técnicas Eletroquímicas/métodos , Ouro/química , Nanopartículas Metálicas/química , MicroRNAs/sangue , Oligonucleotídeos/química , Biomarcadores Tumorais/sangue , Técnicas Biossensoriais , Compostos Ferrosos/química , Glioma/diagnóstico , Glioma/patologia , Humanos , Limite de Detecção , Magnetismo , Metalocenos/química , Azul de Metileno/química , Estadiamento de Neoplasias , Hibridização de Ácido Nucleico , Oxirredução
20.
ACS Omega ; 2(8): 4188-4195, 2017 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-30023716

RESUMO

The aggregation or misfolding of amyloid-ß (Aß) is a major pathological hallmark of Alzheimer's disease (AD). The regulation of Aß aggregation is thought to be an effective strategy for AD treatment. The capability of a water-soluble porphyrin, 5,10,15,20-tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP), to inhibit Aß aggregation and to lower Aß-induced toxicity was demonstrated. As evidenced by surface plasmon resonance and circular dichroism, TMPyP can not only disrupt Aß aggregation but also disassemble the preformed Aß aggregates. The atomic force microscopy imaging proves that TMPyP inhibits the formation of both oligomers and fibrils. Molecular dynamic simulations provide an insight into the interaction between TMPyP and Aß at the molecular level. The half-maximal inhibitory concentrations of TMPyP acting on the oligomers and fibrils were determined to be 0.6 and 0.43 µM, respectively. As a member of porphyrin family, TMPyP is of rather low cytotoxicity, and the cytotoxicity of the Aß aggregates was also relieved upon coincubation with TMPyP. The excellent performance of TMPyP thus makes it a potential drug candidate for AD therapy.

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