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1.
Int J Mol Sci ; 20(18)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509978

RESUMO

Tumorous metastasis is a difficult challenge to resolve for researchers and for clinicians. Targeted delivery of antitumor drugs towards tumor cells' nuclei can be a practical approach to resolving this issue. This work describes an efficient nuclear-targeting delivery system prepared from trans-activating transcriptional activator (TAT) peptide-functionalized graphene nanocarriers. The TAT peptide, originally observed in a human immunodeficiency virus 1 (HIV-1), was incorporated with graphene via an edge-functionalized ball-milling method developed by the author's research group. High tumor-targeting capability of the resulting nanocarrier was realized by the strong affinity between TAT and the nuclei of cancer cells, along with the enhanced permeability and retention (EPR) effect of two-dimensional graphene nanosheets. Subsequently, a common antitumor drug, mitomycin C (MMC), was covalently linked to the TAT-functionalized graphene (TG) to form a nuclear-targeted nanodrug MMC-TG. The presence of nanomaterials inside the nuclei of ocular choroidal melanoma (OCM-1) cells was shown using transmission electron microscopy (TEM) and confocal laser scanning microscopy. In vitro results from a Transwell co-culture system showed that most of the MMC-TG nanodrugs were delivered in a targeted manner to the tumorous OCM-1 cells, while a very small amount of MMC-TG was delivered in a non-targeted manner to normal human retinal pigment epithelial (ARPE-19) cells. TEM results further confirmed that apoptosis of OCM-1 cells was started from the lysis of nuclear substances, followed by the disappearance of nuclear membrane and cytoplasm. This suggests that the as-synthesized MMC-TG is a promising nuclear-target nanodrugfor resolution of tumorous metastasis issues at the headstream.


Assuntos
Neoplasias da Coroide/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Grafite/química , Melanoma/tratamento farmacológico , Mitomicina/administração & dosagem , Peptídeos/química , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Linhagem Celular , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Núcleo Celular/ultraestrutura , Neoplasias da Coroide/metabolismo , Neoplasias da Coroide/patologia , Portadores de Fármacos/química , Humanos , Melanoma/metabolismo , Melanoma/patologia , Microscopia Eletrônica de Transmissão , Mitomicina/química , Nanoestruturas/administração & dosagem , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Produtos do Gene tat do Vírus da Imunodeficiência Humana/química
2.
R Soc Open Sci ; 6(7): 190504, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31417748

RESUMO

Biodegradable random copolymers were successfully synthesized by melt polycondensation of poly(butylene succinate) (PBS) and salicylic acid (SA). The obtained copolymers were characterized by proton nuclear magnetic resonance spectroscopy. The effect of different SA contents on the properties of copolymers was investigated by universal testing machine, thermogravimetric analyser, differential scanning calorimetry and X-ray diffraction analysis. The results showed that the copolymers with 0.5% SA contents exhibited excellent elastic modulus (1413.0 MPa) and tensile strength (192.8 MPa), and similar thermal decomposition temperature (≈320°C) compared with pure PBS. By molecular docking simulations, it was proved that the degradability of copolymers was more effective than that of pure PBS with a binding energy of -5.77 kcal mol-1. PBS copolymers with a small amount of SA were not only biodegradable but could stimulate the growth of green vegetables. So biodegradable copolymers can be used over a wide range as they are environmentally friendly.

3.
Int J Mol Sci ; 20(8)2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31022890

RESUMO

The regeneration of neurons is an important goal of neuroscience and clinical medicine. The electrical stimulation of cells is a promising technique to meet this goal. However, its efficiency highly depends on the electrochemical properties of the stimulation electrodes used. This work reports on the preparation and use of a highly electroactive and biocompatible nanoelectrode made from a novel polyaniline functionalized graphene composite. This nanocomposite was prepared using a facile and efficient polymerization-enhanced ball-milling method. It was used to stimulate the growth of PC12 cells under various electrical fields. The enhanced growth of axons and improved wound regeneration of PC12 cells were observed after this treatment, suggesting a promising strategy for neuro traumatology.


Assuntos
Compostos de Anilina/química , Proliferação de Células , Estimulação Elétrica/instrumentação , Grafite/química , Nanocompostos/química , Neurônios/citologia , Animais , Microeletrodos , Regeneração Nervosa , Células PC12 , Polimerização , Ratos
4.
Adv Healthc Mater ; 7(16): e1800377, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29957869

RESUMO

The synthesis of transferrin (Tf)-modified pegylated graphene (PG) and its application as a highly efficient drug delivery carrier for therapy of Ocular Choroidal Melanoma-1 (OCM-1) cells is presented. For the first reported time, nanoscaled PG is prepared using an environmentally friendly ball-milling technique. The unique 2D nanostructure obtained using this PG synthesis approach offers considerable advantages in terms of drug loading and delivery, as well as the conjugation of Tf to PG providing a more targeted delivery vehicle. A highly efficient targeted pathway toward OCM-1 cells triggered by an affinity between Tf and Tf receptors expressed on the surface of OCM-1 cells is reported first here. PG-Tf is observed to easily anchor anticancer drugs such as doxorubicin via π-π stacking. This work performs a Transwell two cells coculture experiment, a 3D in vitro tumor model, and an in vivo mouse model with OCM-1 tumors to demonstrate the composite's therapeutic superiority over conventional systems for the targeted delivery and controlled release of antitumor drugs.


Assuntos
Neoplasias da Coroide/tratamento farmacológico , Grafite/química , Melanoma/tratamento farmacológico , Transferrina/química , Transferrina/uso terapêutico , Animais , Linhagem Celular , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Humanos , Camundongos
5.
J Biomed Nanotechnol ; 14(8): 1420-1429, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29903057

RESUMO

An efficient and targeted treatment for tumor cells is demonstrated. This targeting is based upon the strong affinity between hydroxyl-functional groups on graphene and acidic tumors. The hydroxylated graphene (GOH) with a unique 2D architecture further improve the targeting capacity of the system via an enhanced permeability and retention (EPR) process. Polyethylene glycol (PEG) was employed for better biocompatibility and the antitumor drug doxorubicin (DOX) was then incorporated. These additions created a biocompatible system with a superior pH-dependent drug release property. Its proficiency was due to its ability to pass through cell membranes via a process of endocytosis and exocytosis. The results from a Transwell co-culture system discovered that the PEG-GOH-DOX system had a large impact on tumor cell viability (less than 10% survived after treatment) and little influence on normal cells (more than 80% survived). An in vitro 3D tumor model study demonstrated that the size of the PEG-GOH-DOX treated tumor was 50% less than that of the pristine DOX treated tumor. In vivo data indicated that the PEG-GOH-DOX system was able to inhibit the size of tumors by a factor of 6.5 when compared to the untreated tumors.


Assuntos
Grafite/química , Antineoplásicos , Linhagem Celular Tumoral , Sobrevivência Celular , Doxorrubicina , Sistemas de Liberação de Medicamentos , Humanos , Polietilenoglicóis
6.
ACS Chem Neurosci ; 9(7): 1616-1624, 2018 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-29708326

RESUMO

Ethanol is a principle ingredient of alcoholic beverages with potential neurotoxicity and genotoxicity, and the ethanol-associated oxidative DNA damage in the central nervous system is well documented. Natural source compounds may offer new options to protect the brain against ethanol-induced genotoxicity. Veratrum maackii Regel is a toxic rangeland plant linked to teratogenicity which is also used in traditional Chinese medicine as "Lilu" and is reported to contain a family of compounds called stilbenes that can have positive biological activity. In this study, nine stilbenes were isolated from the aerial parts of V. maackii Regel, and their structures were identified as cis-mulberroside A (1), resveratrol-4,3'- O-ß-d-diglucopyranoside (2), mulberroside A (3), gentifolin K (4), resveratrol-3,5- O-ß-d-diglucopyranoside (5), oxyresveratrol- 4'- O-ß-d-glucopyranoside (6), oxyresveratrol-3- O-ß-d-glucopyranoside (7), oxyresveratrol (8), and resveratrol (9) using ESI-MS and NMR techniques. The total concentration of extracted compounds 2-9 was 2.04 mg/g, suggesting that V. maackii Regel is a novel viable source of these compounds. In an in vivo comet assay, compounds 1-9 were observed to decrease DNA damage in mouse cerebellum and cerebral cortex caused by acute ethanol administration. Histological observation also revealed decreased brain injury in mice administered with compounds 1-9 after acute ethanol administration. The protective effects of compound 6 were associated with increasing T-SOD and GSH-PX activities and a decrease in NO and MDA concentrations. These findings suggest that these compounds are potent inhibitors of ethanol-induced brain injury possibly via the inhibition of oxidative stress and may be valuable leads for future therapeutic development.


Assuntos
Depressores do Sistema Nervoso Central/efeitos adversos , Dano ao DNA/efeitos dos fármacos , Etanol/efeitos adversos , Substâncias Protetoras/farmacologia , Estilbenos/farmacologia , Veratrum , Transtornos Relacionados ao Uso de Álcool/tratamento farmacológico , Transtornos Relacionados ao Uso de Álcool/metabolismo , Transtornos Relacionados ao Uso de Álcool/patologia , Animais , Cerebelo/efeitos dos fármacos , Cerebelo/metabolismo , Cerebelo/patologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Masculino , Camundongos , Estrutura Molecular , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fototerapia , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Distribuição Aleatória , Estilbenos/química , Estilbenos/isolamento & purificação
7.
Sci China Life Sci ; 61(4): 476-482, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29675550

RESUMO

Surface plasmon resonance (SPR) nanosensors based on metallic nanohole arrays have been widely reported to detect binding interactions in biological specimens. A simple and effective method for constructing nanoscale arrays is essential for the development of SPR nanosensors. In this work, we report a one-step method to fabricate nanohole arrays by thermal nanoimprinting in the matrix of IPS (Intermediate Polymer Stamp). No additional etching process or supporting substrate is required. The preparation process is simple, time-saving and compatible for roll-to-roll process, potentially allowing mass production. Moreover, the nanohole arrays were integrated into detection platform as SPR sensors to investigate different types of biological binding interactions. The results demonstrate that our one-step method can be used to efficiently fabricate large-area and uniform nanohole arrays for biochemical sensing.


Assuntos
Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Ouro/química , Nanoestruturas/química , Nanotecnologia/instrumentação , Ressonância de Plasmônio de Superfície , Modelos Químicos , Nanoestruturas/ultraestrutura , Ligação Proteica
8.
Sensors (Basel) ; 17(7)2017 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-28703749

RESUMO

Various whole cell-based biosensors have been reported in the literature for the last 20 years and these reports have shown great potential for their use in the areas of pollution detection in environmental and in biomedical diagnostics. Unlike other reviews of this growing field, this mini-review argues that: (1) the selection of reporter genes and their regulatory proteins are directly linked to the performance of celllular biosensors; (2) broad enhancements in microelectronics and information technologies have also led to improvements in the performance of these sensors; (3) their future potential is most apparent in their use in the areas of medical diagnostics and in environmental monitoring; and (4) currently the most promising work is focused on the better integration of cellular sensors with nano and micro scaled integrated chips. With better integration it may become practical to see these cells used as (5) real-time portable devices for diagnostics at the bedside and for remote environmental toxin detection and this in situ application will make the technology commonplace and thus as unremarkable as other ubiquitous technologies.


Assuntos
Técnicas Biossensoriais , Monitoramento Ambiental , Genes Reporter , Humanos
9.
Case Rep Med ; 2016: 9675171, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27895669

RESUMO

We describe a 59-year-old female who presented with ischaemic digits, preceded by a 6-month history of Raynaud's phenomenon affecting her fingers and toes. There were no clinical or laboratory features of primary vasculitis or connective tissue disease, Doppler imaging was normal, and bloods were unremarkable aside from a platelet count of 786 × 109/L (150-400) and white cells of 16 × 109/L (4-11). In view of the thrombocytosis a JAK2 mutation assay was requested which confirmed a JAK2 V617F mutation, suggesting essential thrombocytosis (ET) as the cause. She received treatment with hydroxycarbamide which normalised her platelet count and led to a complete resolution of her Raynaud's symptoms. Raynaud's phenomenon is a rare manifestation of ET. Myeloproliferative disorders such as ET should be considered in the differential diagnosis of Raynaud's phenomenon and vasculitis.

10.
Neurocrit Care ; 23(2): 145-8, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26195086

RESUMO

Part of the responsibility of a professional society is to establish the expectations for appropriate behavior for its members. Some codes are so essential to a society that the code itself becomes the central document defining the organization and its tenets, as we see with the Hippocratic Oath. In that tradition, we have revised the code of professional conduct for the Neurocritical Care Society into its current version, which emphasizes guidelines for personal behavior, relationships with fellow members, relationships with patients, and our interactions with society as a whole. This will be a living document and updated as the needs of our society change in time.Available online: http://www.neurocriticalcare.org/about-us/bylaws-procedures-and-code-professional-conduct (1) Code of professional conduct (this document) (2) Leadership code of conduct (3) Disciplinary policy.


Assuntos
Códigos de Ética , Cuidados Críticos/ética , Ética Médica , Neurologia/ética , Sociedades Médicas/ética , Humanos
11.
BMJ Case Rep ; 20132013 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-24177456

RESUMO

This is a case of a 65-year-old man with seropositive erosive rheumatoid arthritis (RA), well controlled on methotrexate, sulfasalazine, low-dose prednisolone and monthly infusions of tocilizumab. He presented with a 3-week history of pain and swelling in his left knee, gradually increasing in severity with an inability to bear weight. He was systemically well with normal vital signs. Examination confirmed an effusion and aspiration was turbid in appearance. C reactive protein (CRP) was normal. He was treated empirically with antibiotics. Synovial fluid and blood cultures confirmed Staphylococcus aureus infection. He completed a 6 weeks course of antibiotics with complete resolution of symptoms. Throughout the treatment his CRP remained normal which is likely to have been the result of prior treatment with tocilizumab.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Infecciosa/sangue , Artrite Reumatoide/tratamento farmacológico , Proteína C-Reativa/metabolismo , Infecções Estafilocócicas/sangue , Idoso , Antibacterianos/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/etiologia , Artrite Reumatoide/sangue , Biomarcadores/análise , Biomarcadores/metabolismo , Humanos , Articulação do Joelho , Masculino , Metotrexato/administração & dosagem , Prednisolona/administração & dosagem , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/etiologia , Sulfassalazina/administração & dosagem , Resultado do Tratamento
12.
Int J Cancer ; 98(4): 561-6, 2002 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-11920616

RESUMO

A number of experimental antibody mediated cancer therapies aim to redirect cytotoxic T cells (CTLs) of non-tumour specificity to cancer cells. It has been previously demonstrated that cancer cells targeted with recombinant HLA-class I/viral peptide complexes via antibody delivery systems can be killed by virus specific CTLs. This novel therapeutic system has been developed with a simple pre-clinical model using the recombinant anti-CD20 B9E9 scFvSA fusion protein to target HLA-A2/peptide complexes to CD20 +ve Daudi lymphoma cells. In vitro data confirmed that, although binding of the B9E9 scFvSA fusion protein alone to Daudi cells had no effect on their growth, effective CTL mediated killing of Daudi cells could be achieved by targeting with B9E9 sfvScSA and recombinant HLA-A2/MI complexes at dilutions as low as 100 pg/ml. In contrast the free HLA-A2/MI complexes only significantly inhibited CTL activity at concentrations in excess of 100 ng/ml. The in vivo tumour protection assays in SCID mice demonstrated that only 1 of the 4 mice that received anti-HLA-A2/M1 CTLs and Daudi cells targeted with the B9E9 scFvSA fusion protein and HLA-A2/M1 complexes developed a tumour. In contrast in the control mice that received CTL and native Daudi cells all 4 developed tumours, as did all 4 that received targeted Daudi cells but no CTLs. Similar results were obtained in a parallel experiment using Daudi cells targeted with B9E9 scFvSA and HLA-A2/BMLF1 complexes and a CTL line to HLA-A2/BMLF1. The demonstration of in vivo activity for targeted HLA class I/peptide complexes combined with anti-viral T cells, supports the further clinical development of the system where it may be combined with autologous CTLs produced by vaccination or ex vivo expansion.


Assuntos
Anticorpos/imunologia , Antígenos HLA/imunologia , Neoplasias Experimentais/imunologia , Linfócitos T Citotóxicos/imunologia , Animais , Anticorpos/farmacologia , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Citometria de Fluxo , Humanos , Masculino , Camundongos , Camundongos SCID , Transplante de Neoplasias , Neoplasias Experimentais/patologia , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Células Tumorais Cultivadas/efeitos dos fármacos , Vírus/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
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