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1.
Small ; : e2400421, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38431934

RESUMO

Integrating more than one type of metal into a nanoparticle that has a well-defined morphology and composition expands the functionalities of nanocatalysts. For a metal core/porous multimetallic shell nanoparticle, the availability of catalytically active surface sites and molecular mass transport can be enhanced, and the multielemental synergy can facilitate intraparticle charge transport. In this work, a reliable and robust synthesis of such a functional tetrametallic nanoparticle type is presented, where a micro- and mesoporous PdPtIr shell is grown on Au nanorods. The effect of critical synthesis parameters, namely temperature and the addition of HCl are investigated on the hydrodynamic size of the micellar pore template as well as on the stability of the metal chloride complexes and various elemental analysis techniques prove composition of the porous multimetallic shell. Due to the synergistic properties, the tetrametallic nanorods possess extensive negative surface charge making them a promising catalyst in reduction reactions. Dye degradation as well as the conversion of p-nitrophenol to p-aminophenol is catalyzed by the supportless nanorods without light illumination. By depositing the particles onto conductive substrates, the nanostructured electrodes show promising electrocatalytic activity in ethanol oxidation reaction. The nanocatalyst presents excellent morphological stability during all the catalytic test reactions.

2.
Faraday Discuss ; 249(0): 50-68, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-37799072

RESUMO

Vibrational spectroscopy is a powerful approach to visualising interfacial phenomena. However, extracting structural and dynamical information from vibrational spectra is a challenge that requires first-principles simulations, including non-Condon and quantum nuclear effects. We address this challenge by developing a machine-learning enhanced first-principles framework to speed up predictive modelling of infrared, Raman, and sum-frequency generation spectra. Our approach uses machine learning potentials that encode quantum nuclear effects to generate quantum trajectories using simple molecular dynamics efficiently. In addition, we reformulate bulk and interfacial selection rules to express them unambiguously in terms of the derivatives of polarisation and polarisabilities of the whole system and predict these derivatives efficiently using fully-differentiable machine learning models of dielectric response tensors. We demonstrate our framework's performance by predicting the IR, Raman, and sum-frequency generation spectra of liquid water, ice and the water-air interface by achieving near quantitative agreement with experiments at nearly the same computational efficiency as pure classical methods. Finally, to aid the experimental discovery of new phases of nanoconfined water, we predict the temperature-dependent vibrational spectra of monolayer water across the solid-hexatic-liquid phases transition.

3.
Phys Rev Lett ; 131(2): 028001, 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37505943

RESUMO

Density-based representations of atomic environments that are invariant under Euclidean symmetries have become a widely used tool in the machine learning of interatomic potentials, broader data-driven atomistic modeling, and the visualization and analysis of material datasets. The standard mechanism used to incorporate chemical element information is to create separate densities for each element and form tensor products between them. This leads to a steep scaling in the size of the representation as the number of elements increases. Graph neural networks, which do not explicitly use density representations, escape this scaling by mapping the chemical element information into a fixed dimensional space in a learnable way. By exploiting symmetry, we recast this approach as tensor factorization of the standard neighbour-density-based descriptors and, using a new notation, identify connections to existing compression algorithms. In doing so, we form compact tensor-reduced representation of the local atomic environment whose size does not depend on the number of chemical elements, is systematically convergable, and therefore remains applicable to a wide range of data analysis and regression tasks.

4.
J Chem Phys ; 159(4)2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37522405

RESUMO

The MACE architecture represents the state of the art in the field of machine learning force fields for a variety of in-domain, extrapolation, and low-data regime tasks. In this paper, we further evaluate MACE by fitting models for published benchmark datasets. We show that MACE generally outperforms alternatives for a wide range of systems, from amorphous carbon, universal materials modeling, and general small molecule organic chemistry to large molecules and liquid water. We demonstrate the capabilities of the model on tasks ranging from constrained geometry optimization to molecular dynamics simulations and find excellent performance across all tested domains. We show that MACE is very data efficient and can reproduce experimental molecular vibrational spectra when trained on as few as 50 randomly selected reference configurations. We further demonstrate that the strictly local atom-centered model is sufficient for such tasks even in the case of large molecules and weakly interacting molecular assemblies.

5.
Biol Cell ; 113(7): 311-328, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33666950

RESUMO

BACKGROUND INFORMATION: Comprehensive libraries of plasmids for SARS-CoV-2 proteins with various tags (e.g., Strep, HA, Turbo) are now available. They enable the identification of numerous potential protein-protein interactions between the SARS-CoV-2 virus and host proteins. RESULTS: We present here a large library of SARS CoV-2 protein constructs fused with green and red fluorescent proteins and their initial characterisation in various human cell lines including lung epithelial cell models (A549, BEAS-2B), as well as in budding yeast. The localisation of a few SARS-CoV-2 proteins matches their proposed interactions with host proteins. These include the localisation of Nsp13 to the centrosome, Orf3a to late endosomes and Orf9b to mitochondria. CONCLUSIONS AND SIGNIFICANCE: This library should facilitate further cellular investigations, notably by imaging techniques.


Assuntos
COVID-19/virologia , Biblioteca de Peptídeos , SARS-CoV-2/metabolismo , Proteínas Virais/metabolismo , Células A549 , Linhagem Celular , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Microscopia de Fluorescência , Domínios e Motivos de Interação entre Proteínas , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , SARS-CoV-2/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Imagem com Lapso de Tempo , Proteínas Virais/genética , Proteína Vermelha Fluorescente
6.
Int J Mol Sci ; 23(2)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35055024

RESUMO

As an emerging new class, metal nanoparticles and especially silver nanoparticles hold great potential in the field of cancer biology. Due to cancer-specific targeting, the consequently attenuated side-effects and the massive anti-cancer features render nanoparticle therapeutics desirable platforms for clinically relevant drug development. In this review, we highlight those characteristics of silver nanoparticle-based therapeutic concepts that are unique, exploitable, and achievable, as well as those that represent the critical hurdle in their advancement to clinical utilization. The collection of findings presented here will describe the features that distinguish silver nanoparticles from other anti-cancer agents and display the realistic opportunities and implications in oncotherapeutic innovations to find out whether cancer therapy by silver nanoparticles is fiction or reality.


Assuntos
Antineoplásicos/administração & dosagem , Nanopartículas Metálicas , Nanomedicina , Neoplasias/tratamento farmacológico , Prata , Animais , Antineoplásicos/uso terapêutico , Técnicas de Química Sintética , Estudos Clínicos como Assunto , Terapia Combinada , Gerenciamento Clínico , Portadores de Fármacos/química , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Desenvolvimento de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Humanos , Nanopartículas Metálicas/química , Nanomedicina/métodos , Nanotecnologia , Prata/química , Resultado do Tratamento
7.
J Biol Chem ; 295(13): 4277-4288, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32075908

RESUMO

ORPphilins are bioactive natural products that strongly and selectively inhibit the growth of some cancer cell lines and are proposed to target intracellular lipid-transfer proteins of the oxysterol-binding protein (OSBP) family. These conserved proteins exchange key lipids, such as cholesterol and phosphatidylinositol 4-phosphate (PI(4)P), between organelle membranes. Among ORPphilins, molecules of the schweinfurthin family interfere with intracellular lipid distribution and metabolism, but their functioning at the molecular level is poorly understood. We report here that cell line sensitivity to schweinfurthin G (SWG) is inversely proportional to cellular OSBP levels. By taking advantage of the intrinsic fluorescence of SWG, we followed its fate in cell cultures and show that its incorporation at the trans-Golgi network depends on cellular abundance of OSBP. Using in vitro membrane reconstitution systems and cellular imaging approaches, we also report that SWG inhibits specifically the lipid transfer activity of OSBP. As a consequence, post-Golgi trafficking, membrane cholesterol levels, and PI(4)P turnover were affected. Finally, using intermolecular FRET analysis, we demonstrate that SWG directly binds to the lipid-binding cavity of OSBP. Collectively these results describe SWG as a specific and intrinsically fluorescent pharmacological tool for dissecting OSBP properties at the cellular and molecular levels. Our findings indicate that SWG binds OSBP with nanomolar affinity, that this binding is sensitive to the membrane environment, and that SWG inhibits the OSBP-catalyzed lipid exchange cycle.


Assuntos
Transporte Biológico/efeitos dos fármacos , Lipídeos/genética , Receptores de Esteroides/metabolismo , Estilbenos/metabolismo , Proteínas de Transporte/química , Proteínas de Transporte/genética , Retículo Endoplasmático/química , Retículo Endoplasmático/genética , Fluorescência , Humanos , Lipídeos/química , Ligação Proteica/genética , Transporte Proteico/genética , Receptores de Esteroides/química , Estilbenos/química , Rede trans-Golgi/química , Rede trans-Golgi/genética
8.
J Am Chem Soc ; 142(38): 16364-16381, 2020 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-32902274

RESUMO

The development of force-responsive molecules called mechanophores is a central component of the field of polymer mechanochemistry. Mechanophores enable the design and fabrication of polymers for a variety of applications ranging from sensing to molecular release and self-healing materials. Nevertheless, an insufficient understanding of structure-activity relationships limits experimental development, and thus computation is necessary to guide the structural design of mechanophores. The constrained geometries simulate external force (CoGEF) method is a highly accessible and straightforward computational technique that simulates the effect of mechanical force on a molecule and enables the prediction of mechanochemical reactivity. Here, we use the CoGEF method to systematically evaluate every covalent mechanophore reported to date and compare the predicted mechanochemical reactivity to experimental results. Molecules that are mechanochemically inactive are also studied as negative controls. In general, mechanochemical reactions predicted with the CoGEF method at the common B3LYP/6-31G* level of density functional theory are in excellent agreement with reactivity determined experimentally. Moreover, bond rupture forces obtained from CoGEF calculations are compared to experimentally measured forces and demonstrated to be reliable indicators of mechanochemical activity. This investigation validates the CoGEF method as a powerful tool for predicting mechanochemical reactivity, enabling its widespread adoption to support the developing field of polymer mechanochemistry. Secondarily, this study provides a contemporary catalog of over 100 mechanophores developed to date.

9.
J Nanobiotechnology ; 18(1): 18, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964403

RESUMO

BACKGROUND: Although accumulating evidence suggests that the crosstalk between malignant cells and cancer-associated fibroblasts (CAFs) actively contributes to tumour growth and metastatic dissemination, therapeutic strategies targeting tumour stroma are still not common in the clinical practice. Metal-based nanomaterials have been shown to exert excellent cytotoxic and anti-cancerous activities, however, their effects on the reactive stroma have never been investigated in details. Thus, using feasible in vitro and in vivo systems to model tumour microenvironment, we tested whether the presence of gold, silver or gold-core silver-shell nanoparticles exerts anti-tumour and metastasis suppressing activities by influencing the tumour-supporting activity of stromal fibroblasts. RESULTS: We found that the presence of gold-core silver-shell hybrid nanomaterials in the tumour microenvironment attenuated the tumour cell-promoting behaviour of CAFs, and this phenomenon led to a prominent attenuation of metastatic dissemination in vivo as well. Mechanistically, transcriptome analysis on tumour-promoting CAFs revealed that silver-based nanomaterials trigger expressional changes in genes related to cancer invasion and tumour metastasis. CONCLUSIONS: Here we report that metal nanoparticles can influence the cancer-promoting activity of tumour stroma by affecting the gene expressional and secretory profiles of stromal fibroblasts and thereby altering their intrinsic crosstalk with malignant cells. This potential of metal nanomaterials should be exploited in multimodal treatment approaches and translated into improved therapeutic outcomes.


Assuntos
Antineoplásicos/química , Fibroblastos Associados a Câncer/efeitos dos fármacos , Nanopartículas Metálicas/química , Metástase Neoplásica/tratamento farmacológico , Ligas/química , Animais , Antineoplásicos/uso terapêutico , Fibroblastos Associados a Câncer/patologia , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Progressão da Doença , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Feminino , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Ouro/química , Humanos , Nanopartículas Metálicas/uso terapêutico , Camundongos Endogâmicos BALB C , Metástase Neoplásica/patologia , Transplante de Neoplasias , Prata/química , Microambiente Tumoral/efeitos dos fármacos
10.
J Nanobiotechnology ; 17(1): 9, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30670028

RESUMO

BACKGROUND: Development of multidrug resistance (MDR) is a major burden of successful chemotherapy, therefore, novel approaches to defeat MDR are imperative. Although the remarkable anti-cancer propensity of silver nanoparticles (AgNP) has been demonstrated and their potential application in MDR cancer has been proposed, the nanoparticle size-dependent cellular events directing P-glycoprotein (Pgp) expression and activity in MDR cancer have never been addressed. Hence, in the present study we examined AgNP size-dependent cellular features in multidrug resistant breast cancer cells. RESULTS: In this study we report that 75 nm AgNPs inhibited significantly Pgp efflux activity in drug-resistant breast cancer cells and potentiated the apoptotic effect of doxorubicin, which features were not observed upon 5 nm AgNP treatment. Although both sized AgNPs induced significant ROS production and mitochondrial damage, 5 nm AgNPs were more potent than 75 nm AgNPs in this respect, therefore, these effects can not to be accounted for the reduced transport activity of ATP-driven pumps observed after 75 nm AgNP treatments. Instead we found that 75 nm AgNPs depleted endoplasmic reticulum (ER) calcium stores, caused notable ER stress and decreased plasma membrane positioning of Pgp. CONCLUSION: Our study suggests that AgNPs are potent inhibitors of Pgp function and are promising agents for sensitizing multidrug resistant breast cancers to anticancer drugs. This potency is determined by their size, since 75 nm AgNPs are more efficient than smaller counterparts. This is a highly relevant finding as it renders AgNPs attractive candidates in rational design of therapeutically useful agents for tumor targeting. In the present study we provide evidence that exploitation of ER stress can be a propitious target in defeating multidrug resistance in cancers.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Neoplasias da Mama/tratamento farmacológico , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Nanopartículas Metálicas , Prata , Antineoplásicos/uso terapêutico , Retículo Endoplasmático/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Tamanho da Partícula , Prata/farmacologia
11.
Ideggyogy Sz ; 70(3-4): 127-135, 2017 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-29870617

RESUMO

BACKGROUND AND PURPOSE: Particles of titanium dioxide (TiO2) with typical size below 100 nm have gained a broad range of application by now, partly involving direct human exposure. Their known properties - high specific surface, mobility within the organism, induction of oxidative stress, release of inflammation mediators etc. - raise the possibility of nervous system damage but the available data regarding this are scarce and contradictory. Based on that, and the experiences with other metal oxide nanoparticles, the aim of the present study was to investigate certain general end nervous system toxic effects of TiO2 nanoparticles applied in the airways of rats. METHODS: Young adult Wistar rats (5 groups of 10 rats each) received, daily for 28 days, intratracheal instillations of titanium dioxide nanoparticles of ca. 10 nm diameter, suspended in 1% hydroxyethyl cellulose dissolved in phosphate-buffered saline, in the doses of 1, 3, and 10 mg/kg b. w. Vehicle controls received the suspension medium and there was also an untreated control group. During treatment, the rats' body weight was measured, and their clinical state observed, daily. After the 28 days, spontaneous cortical activity, sensory evoked potentials and tail nerve action potential was recorded in urethane anesthesia, then the rats were dissected and tissue samples were taken for Ti level determination and biochemical measurements of some oxidative stress indicators. RESULTS: The two higher doses reduced the rate of body weight gain significantly. Sensory evoked potentials and tail nerve action potential were significantly slowed, but the change in the spectrum of spontaneous cortical activity was not significant. Correlation of moderate strength was found between certain evoked potential parameters and brain Ti level and oxidative stress data. CONCLUSION: Our results underlined the possible neurotoxicity of TiO2 NPs but also the need for further investigations.


Assuntos
Encéfalo/efeitos dos fármacos , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Titânio/toxicidade , Animais , Eletroencefalografia , Estresse Oxidativo , Ratos , Ratos Wistar , Aumento de Peso/efeitos dos fármacos
12.
J Mol Cell Cardiol ; 99: 138-150, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27515282

RESUMO

AIMS: Exogenously administered biglycan (core protein with high-molecular weight glycosaminoglycan chains) has been shown to protect neonatal cardiomyocytes against simulated ischemia/reperfusion injury (SI/R), however, the mechanism of action is not clear. In this study we aimed to investigate, which structural component of biglycan is responsible for its cardiocytoprotective effect and to further explore the molecular mechanisms involved in the cytoprotection. METHODS AND RESULTS: A pilot study was conducted to demonstrate that both native (glycanated) and deglycanated biglycan can attenuate cell death induced by SI/R in a dose-dependent manner in primary neonatal cardiomyocytes isolated from Wistar rats. In separate experiments, we have shown that similarly to glycanated biglycan, recombinant human biglycan core protein (rhBGNc) protects cardiomyocytes against SI/R injury. In contrast, the glycosaminoglycan component dermatan sulfate had no significant effect on cell viability, while chondroitin sulfate further enhanced cell death induced by SI/R. Treatment of cardiomyocytes with rhBGNc reverses the effect of SI/R upon markers of necrosis, apoptosis, mitochondrial membrane potential, and autophagy. We have also shown that pharmacological blockade of Toll-like receptor 4 (TLR4) signaling or its downstream mediators (IRAK1/4, ERK, JNK and p38 MAP kinases) abolished the cytoprotective effect of rhBGNc against SI/R injury. Pretreatment of cardiomyocytes with rhBGNc for 20h resulted in increased Akt phosphorylation and NO production without having significant effect on phosphorylation of ERK1/2, STAT3, and on the production of superoxide. Treatment over 10min and 1h with rhBGNc increased ERK1 phosphorylation, while the SI/R-induced increase in superoxide production was attenuated by rhBGNc. Blockade of NO synthesis also prevented the cardiocytoprotective effect of rhBGNc. CONCLUSIONS: The core protein of exogenous biglycan protects myocardial cells from SI/R injury via TLR4-mediated mechanisms involving activation of ERK, JNK and p38 MAP kinases and increased NO production. The cytoprotective effect of rhBGNc is due to modulation of SI/R-induced changes in necrosis, apoptosis and autophagy.


Assuntos
Biglicano/metabolismo , Miócitos Cardíacos/metabolismo , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo , Animais , Apoptose , Autofagia , Biglicano/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Glicosilação , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Modelos Biológicos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Necrose/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Projetos Piloto , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Dev Biol ; 404(1): 80-7, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-25959239

RESUMO

The molting during Drosophila development is tightly regulated by the ecdysone hormone. Several steps of the ecdysone biosynthesis have been already identified but the regulation of the entire process has not been clarified yet. We have previously reported that dATAC histone acetyltransferase complex is necessary for the steroid hormone biosynthesis process. To reveal possible mechanisms controlled by dATAC we made assumptions that either dATAC may influence directly the transcription of Halloween genes involved in steroid hormone biosynthesis or it may exert an indirect effect on it by acetylating the Ftz-F1 transcription factor which regulates the transcription of steroid converting genes. Here we show that the lack of dATAC complex results in increased mRNA level and decreased protein level of Ftz-F1. In this context, decreased mRNA and increased protein levels of Ftz-F1 were detected upon treatment of Drosophila S2 cells with histone deacetylase inhibitor trichostatin A. We showed that Ftz-F1, the transcriptional activator of Halloween genes, is acetylated in S2 cells. In addition, we found that ecdysone biosynthetic Halloween genes are transcribed in S2 cells and their expression can be influenced by deacetylase inhibitors. Furthermore, we could detect H4K5 acetylation at the regulatory regions of disembodied and shade Halloween genes, while H3K9 acetylation is absent on these genes. Based on our findings we conclude that the dATAC HAT complex might play a dual regulatory role in Drosophila steroid hormone biosynthesis through the acetylation of Ftz-F1 protein and the regulation of the H4K5 acetylation at the promoters of Halloween genes.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Ecdisona/biossíntese , Histona Acetiltransferases/metabolismo , Histonas/metabolismo , Fatores de Transcrição/metabolismo , Acetilação , Animais , Citocromos/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo
14.
Brain Behav Immun ; 56: 96-104, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26891860

RESUMO

Interleukin-1ß is one of the main mediators in the cross-talk between the immune system and the central nervous system. Higher interleukin-1ß levels are found in mood spectrum disorders, and the stress-induced expression rate of the interleukin-1ß gene (IL1B) is altered by polymorphisms in the region. Therefore we examined the effects of rs16944 and rs1143643 single nucleotide polymorphisms (SNPs) within the IL1B gene on depressive and anxiety symptoms, as measured by the Brief Symptom Inventory, in a Hungarian population sample of 1053 persons. Distal and proximal environmental stress factors were also included in our analysis, namely childhood adversity and recent negative life-events. We found that rs16944 minor (A) allele specifically interacted with childhood adversity increasing depressive and anxiety symptoms, while rs1143643's minor (A) allele showed protective effect against depressive symptoms after recent life stress. The genetic main effects of the two SNPs were not significant in the main analysis, but the interaction effects remained significant after correction for multiple testing. In addition, the effect of rs16944 A allele was reversed in a subsample with low-exposure to life stress, suggesting a protective effect against depressive symptoms, in the post hoc analysis. In summary, both of the two IL1B SNPs showed specific environmental stressor-dependent effects on mood disorder symptoms. We also demonstrated that the presence of exposure to childhood adversity changed the direction of the rs16944 effect on depression phenotype. Therefore our results suggest that it is advisable to include environmental factors in genetic association studies when examining the effect of the IL1B gene.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância/estatística & dados numéricos , Transtornos de Ansiedade , Transtorno Depressivo , Interação Gene-Ambiente , Interleucina-1beta/genética , Estresse Psicológico , Adolescente , Adulto , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/genética , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/etiologia , Transtorno Depressivo/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estresse Psicológico/epidemiologia , Adulto Jovem
15.
J Neural Transm (Vienna) ; 123(5): 541-8, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26821321

RESUMO

Interleukin-6 (IL-6) has emerged as a potent biomarker for depression as its elevated plasma levels in patients with clinical depression have been confirmed by meta-analyses. Increased plasma IL-6 concentration was associated with various psychological stress factors and physical disorders accompanied by pain. Another modulator of the IL-6 level is rs1800795, a promoter polymorphism in the IL-6 gene which is able to influence its expression rate. Therefore, we examined in a Hungarian population sample of 1053 volunteers with European origins if rs1800795 polymorphism can affect depression symptoms measured by Zung Self-rating Depression Scale (ZSDS), and Brief Symptom Inventory (BSI). We also investigated the interactions of the polymorphism with reported painful physical conditions and Recent Negative Life Events (RLE) measured by the List of Life Threatening Experiences. Rs1800795 significantly interacted with both RLE and painful condition on depressive symptoms measured by ZSDS and BSI using different heritability models, while no main effects of the polymorphism were identified. After correction for multiple testing only the rs1800795 × RLE interaction effect (recessive model) remained significant on the BSI score, while both RLE and painful conditions significantly interacted on the ZSDS. In conclusion, the functional IL-6 rs1800795 polymorphism in interaction with various stress factors increases the risk of depression and has a greater impact on symptoms measured by the ZSDS. Thus, IL-6 and other cytokines may be more relevant in the development of somatic symptoms compared to affective signs of depression, delineating a specific genotype-phenotype relationship in this heterogeneous disorder.


Assuntos
Transtorno Depressivo/etiologia , Interleucina-6/genética , Dor/complicações , Dor/genética , Polimorfismo de Nucleotídeo Único/genética , Estresse Psicológico/complicações , Estresse Psicológico/genética , Adolescente , Adulto , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Regiões Promotoras Genéticas/genética , Escalas de Graduação Psiquiátrica , Adulto Jovem
16.
Nanomedicine ; 12(3): 601-610, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26656631

RESUMO

The emergence of multidrug resistant (MDR) cancer phenotypes dramatically attenuates the efficiency of antineoplastic drug treatments often leading to the failure of chemotherapy. Therefore there is an urgent need to engineer new therapeutically useful agents and propose innovative approaches able to defeat resistant cancer cells. Although the remarkable anti-cancer features of silver nanoparticles (AgNPs) have already been delineated their impact on MDR cancer has never been investigated. Herein, we report that AgNPs have notable anti-proliferative effect and induce apoptosis mediated cell death both in drug sensitive and in MDR cancer cells. Furthermore we show evidence that AgNPs exert an inhibitory action on the efflux activity of MDR cancer cells which feature could be exploited to enhance drug accumulation. We verified synergistic interactions of AgNPs with six different antineoplastic agents on drug resistant cells which emphasizes the excellent potential of AgNPs as combinational partners in the chemotherapy of MDR cancer. FROM THE CLINICAL EDITOR: The treatment of cancer often fails due to the development of multidrug resistant (MDR) cancer cells. Hence, novel approaches are being investigated to combat drug resistant cancer cells. One particular method studied here uses silver nanoparticles (AgNPs). The authors showed that AgNPs had anti-proliferative effect and ?exerted an inhibitory action on ABC transporter. The findings could suggest the possible use of AgNPs in combination with other chemotherapeutic agents in the clinical setting.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Antibacterianos/farmacologia , Antineoplásicos/farmacocinética , Nanopartículas Metálicas , Neoplasias/tratamento farmacológico , Prata/farmacologia , Antibacterianos/química , Antineoplásicos/química , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Sinergismo Farmacológico , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Neoplasias/metabolismo , Prata/química
17.
J Basic Microbiol ; 56(5): 557-65, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26972521

RESUMO

One-dimensional titanate nanotubes (TiONTs) were subjected to systematic ion exchange to determine the impact of these modifications on biological activities. Ion exchanged TiONTs (with Ag, Mg, Bi, Sb, Ca, K, Sr, Fe, and Cu ions) were successfully synthesized and the presence of the substituted ions was verified by energy dispersive X-ray spectroscopy (EDS). A complex screening was carried out to reveal differences in toxicity to human cells, as well as in antibacterial, antifungal, and antiviral activities between the various modified nanotubes. Our results demonstrated that Ag ion exchanged TiONTs exerted potent antibacterial and antifungal effects against all examined microbial species but were ineffective on viruses. Surprisingly, the antibacterial activity of Cu/TiONTs was restricted to Micrococcus luteus. Most ion exchanged TiONTs did not show antimicrobial activity against the tested bacterial and fungal species. Incorporation of various ions into nanotube architectures lead to mild, moderate, or even to a massive loss of human cell viability; therefore, this type of biological effect exerted by TiONTs can be greatly modulated by ion exchange. These findings further emphasize the contribution of ion exchange in determining not only the physical and chemical characteristics but also the bioactivity of TiONT against different types of living cells.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Nanopartículas Metálicas , Nanotubos/toxicidade , Titânio/farmacologia , Bacillus subtilis/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Células HeLa , Humanos , Troca Iônica , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Espectrometria por Raios X , Titânio/toxicidade
18.
Orv Hetil ; 157(24): 938-45, 2016 Jun 12.
Artigo em Húngaro | MEDLINE | ID: mdl-27263433

RESUMO

INTRODUCTION: Renal transplantation provides longer life expectancy in patients with renal failure. Nonetheless, this improved life expectancy is still shorter than that for the general population. The main couse of death in renal transplant patients is cardiovascular disease, and chronic allograft nephropathy is the most significant cause of graft loss. Genetic polymorphisms of the renin angiotensin system have been implicated in both chronic allograft nephropathy and fatal cardiovascular diseases. AIM: The long term goal of the authors was to improve the survival of renal transplanted patients. The authors aimed to identify novel biomarkers which correlate with the survival of the transplant organ and the recipient with a special attention to elements of the renin-angiotensin system. METHOD: A retrospective clinical trial was performed involving 72 renal transplanted patients. Angiotensin-converting enzyme I/D genotypes and activity, kidney function and morphological properties of the heart were determined. RESULTS: A significant positive correlation was found between the DD genotype of the angiotensin-converting enzíme gene, and the DD genotype predicted severe left ventricular hypertrophy. CONCLUSIONS: These findings suggest that the I/D genotypes of the angiotensin-converting enzyme gene predict not only the expected survival of the transplanted organ, but also that of the patient. Patients with the DD genotype are more susceptible for transplant failure. These patients should be identified and a special attention should be made on their pharmacological treatment (renin-angiotensin system inhibition), and their complience should also be maintained.


Assuntos
Doenças Cardiovasculares/enzimologia , Doenças Cardiovasculares/epidemiologia , Sobrevivência de Enxerto , Falência Renal Crônica/cirurgia , Transplante de Rim , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Adulto , Idoso , Doença Crônica , Feminino , Rejeição de Enxerto , Humanos , Hipertrofia Ventricular Esquerda/epidemiologia , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
19.
Orv Hetil ; 157(24): 956-63, 2016 Jun 12.
Artigo em Húngaro | MEDLINE | ID: mdl-27430050

RESUMO

INTRODUCTION: Development of atherosclerosis is accelerated in kidney transplant patients. Impaired metabolic pathways have complex effect on the arterial wall which can be measured by non-invasive techniques. Only few data are available on the change of stiffness parameters in the postoperative course. Therefore, in this study the authors analysed the stiffness parameters of kidney transplant recipients during the perioperative period. AIM: Non-invasive clinical trial of the arterial functional parameters in the early postoperative period. METHOD: Seventeen successful primary kidney transplant patients with uneventful postoperative period (8 females, 9 males; age, 46.16 ± 12.19 years) were involved in this short-term prospective longitudinal study. The authors analysed correlations between non-in vasively assessed stiffness parameters (pulse wave velocity PWV, augmentation index - AIx). Stiffness parameters were measured with a TensioMed Arteriograph. These parameters were assessed before the transplantation, as well as 24 hours, 1 and 2 weeks after surgery under standard conditions. RESULTS: It was found that PWV (p = 0.0075) and AIx (p = 0.013) improved significantly. There was no significant change in case of PP and the other monitored parameters. Serum creatinine decreased (p = 0.0008) and glomerular filtration rate increased significantly (p = 0.0005). CONCLUSIONS: Along with the available data in the literature, the findings suggest that kidney transplantation has a positive effect on the arterial function. Improvement can be detected non-invasively with Arteriograph in the early postoperative period.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Transplante de Rim , Rigidez Vascular , Adulto , Idoso , Pressão Sanguínea , Doenças Cardiovasculares/fisiopatologia , Seleção do Doador , Feminino , Taxa de Filtração Glomerular , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Análise de Onda de Pulso , Fatores de Risco
20.
Orv Hetil ; 157(24): 946-55, 2016 Jun 12.
Artigo em Húngaro | MEDLINE | ID: mdl-27263434

RESUMO

INTRODUCTION: To ease organ shortage many transplant centres developed different donor scoring systems, however, a general consensus among clinicians on the use of these systems does not still exist. AIM: The aim of the authors was to analyse the effect of expanded criteria donor, deceased donor score and kidney donor risk index on postoperative kidney function and graft survival. METHOD: Analysis of the characteristics of 138 kidney transplantations and 205 donors in a retrospective study of a five-year period. RESULTS: There was a trend towards rejecting donors in higher risk groups; 22.7% of standard criteria donors belonged to the high risk group of deceased donor score. Graft function was worse in high risk patients. High risk donors can be divided due to the use of deceased donor score. Patients with the highest risk had worse graft function and survival. CONCLUSIONS: With the use of these scoring systems grafts with favourable outcome can be selected more precisely.


Assuntos
Cadáver , Seleção do Doador/normas , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/estatística & dados numéricos , Transplante de Rim/normas , Doadores de Tecidos/estatística & dados numéricos , Adulto , Idoso , Seleção do Doador/tendências , Feminino , Sobrevivência de Enxerto , Humanos , Hungria/epidemiologia , Doadores Vivos/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
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