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1.
J Craniofac Surg ; 34(3): 1054-1057, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35119417

RESUMO

OBJECTIVE: To evaluate the feasibility of endoscope-assisted extracapsular resection of benign parotid tumors via temporal and retroauricular approach. MATERIALS AND METHODS: A total of 12 patients with parotid gland tumors had endoscope-assisted extracapsular resection performed via temporal and retroauricular approach (4 versus 8) between January 2018 and January 2019. RESULTS: All tumors were benign with a median diameter of 2.32 ± 0.49 cm. The mean length of the skin incision was 3.5 ±0.35 cm. The mean operating time 86.7 ± 10.8 minutes. The median blood loss was 30.4 ± 5.94 ml. The median volume of drainage was 27.1 ± 8.88 ml and the duration of drainage was 2 ± 0.71 days. The mean aesthetics scoring assigned by patients was 9.67 ± 0.51. Two patients had numbness of the earlobe and 1 patient developed a transient salivary sialocele. No facial nerve paresis was observed and no tumor recurrence occurred during the follow-up period. CONCLUSIONS: The minimally invasive endoscope-assisted extracapsular resection of benign parotid tumors provide both a safe and reliable technique for benign parotid tumors with excellent cosmetic results.


Assuntos
Pavilhão Auricular , Paralisia Facial , Neoplasias Parotídeas , Humanos , Neoplasias Parotídeas/cirurgia , Estética Dentária , Endoscopia/métodos , Pavilhão Auricular/cirurgia , Glândula Parótida/cirurgia , Complicações Pós-Operatórias
2.
Small ; 17(44): e2103406, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34561967

RESUMO

The controlled assembly of nanowires is one of the key challenges in the development of a range of functional 3D aerogels with unique physicochemical properties for practical applications. However, the deep understanding of the dynamic assemble process for fabricating nanowire aerogels remains elusive. Herein, a facile strategy is presented for the metallic ion-induced assembly of nanowires into macroscopic aerogels via a solution-based process. This method enables the interconnecting between polymer-decorated nanowires via metallic coordination, resulting in plenty of nanowire bundles with the same orientation. Besides, the coordinated binding strength of nanowires with different metallic ions is also discussed. The assembly mechanism that the metallic ions induced dynamic behavior of nanowires is revealed via molecular dynamics theoretical evaluation. These findings benefit for constructing nanowire-based aerogels with unique structural features and multi-function, which pave new opportunities for other material systems.


Assuntos
Nanofios , Íons , Simulação de Dinâmica Molecular , Polímeros
3.
Small ; 13(3)2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27775872

RESUMO

Inflammation has been reported as one significant hallmark of breast cancer in relation to tumor development, metastasis, and invasion. The bradykinin receptor 1 (B1R) is highly expressed on inflammatory breast tumor cells thus providing a promising targeting site for tumor recognition and sufficient receptor mediated endocytosis. In this study, the authors evaluate the targeting efficiency of l-form and d-form [des-Arg10 ]kallidin both in vitro and in vivo. To further improve the drug delivery efficiency, the authors establish a dandelion like nanoparticle by combining the polymeric drug conjugates and aptamer complex together. The doxorubicin conjugated polymer is complexed with adenosine-5'-triphosphate (ATP) sensitive hybridized aptamer in self-assembly process by intercalating into the double strand scaffolds. The acid labile conjugating bond and ATP sensitive aptamer endow the nanoparticle with dual responsiveness to intracellular milieu, thus triggering a quick drug release in tumor cells. Remarkable therapeutic effects and tuned in vivo pharmacokinetics profiles are shown by the aptamer complexed drug conjugates nanoparticle with B1R active targeting modification. Therefore the strategies of B1R targeting and ATP/pH dual-responsiveness nanoparticle help achieve enhanced drug accumulation within tumor cells and efficient chemotherapy for breast cancer.


Assuntos
Trifosfato de Adenosina/química , Sistemas de Liberação de Medicamentos , Calidina/análogos & derivados , Nanopartículas/química , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Liberação Controlada de Fármacos , Endocitose , Feminino , Concentração de Íons de Hidrogênio , Calidina/uso terapêutico , Masculino , Neoplasias Mamárias Animais/tratamento farmacológico , Neoplasias Mamárias Animais/patologia , Camundongos Nus , Nanopartículas/ultraestrutura , Polímeros/química , Ratos Sprague-Dawley , Distribuição Tecidual , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
4.
J Reconstr Microsurg ; 32(9): 661-669, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27351937

RESUMO

Background Function and aesthetics have a significant impact on the quality of life in patients undergoing mandibular reconstructive surgery, but achieving satisfactory results remain challenging. The aim of the study is to investigate the feasibility and accuracy of robot-assisted mandibular reconstruction with fibula flap in comparison to that with a computer-assisted navigation system and the freehand technique. Methods Experimental procedures (15 phantom studies and 6 animal experiments) were performed with a custom three-arm robotic system automatically, under the guidance of a computer-assisted navigation system, and by the freehand technique, respectively. The accuracy of the reconstruction was assessed by comparison between the preoperative and postoperative three-dimensional surface virtual models. Results All procedures were successfully performed. In the phantom study, the mean deviation of the fibula implant was 1.221, 1.581, and 2.313 mm, respectively, with the robotic system, the navigation system, and the freehand technique; in the animal experiment the corresponding figures were 1.7697, 1.7847, and 2.0815 mm, respectively. The mean deviation of the proximal mandibular ramus was 1.0420, 1.0532, 1.8800 mm with the robotic system, computer-assisted navigation system, and freehand technique, respectively, and the mean deviation of the distal mandibular segment was 1.1645, 2.7198, and 2.8445 mm, respectively. Conclusions The robotic system is feasible, efficient, and reliable for mandibular reconstruction. The accuracy of the fibula implant orientation with the robotic system was comparable to that with navigation system and superior to that with the freehand technique.


Assuntos
Simulação por Computador , Fíbula/transplante , Retalhos de Tecido Biológico/cirurgia , Mandíbula/cirurgia , Reconstrução Mandibular/métodos , Robótica , Cirurgia Assistida por Computador , Animais , Modelos Animais de Doenças , Estética , Retalhos de Tecido Biológico/irrigação sanguínea , Humanos , Mandíbula/patologia , Qualidade de Vida , Reprodutibilidade dos Testes , Ovinos , Tomografia Computadorizada por Raios X
5.
Plant Cell ; 23(5): 1971-84, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21610183

RESUMO

Osmotic stress activates the biosynthesis of abscisic acid (ABA). One major step in ABA biosynthesis is the carotenoid cleavage catalyzed by a 9-cis epoxycarotenoid dioxygenase (NCED). To understand the mechanism for osmotic stress activation of ABA biosynthesis, we screened for Arabidopsis thaliana mutants that failed to induce the NCED3 gene expression in response to osmotic stress treatments. The ced1 (for 9-cis epoxycarotenoid dioxygenase defective 1) mutant isolated in this study showed markedly reduced expression of NCED3 in response to osmotic stress (polyethylene glycol) treatments compared with the wild type. Other ABA biosynthesis genes are also greatly reduced in ced1 under osmotic stress. ced1 mutant plants are very sensitive to even mild osmotic stress. Map-based cloning revealed unexpectedly that CED1 encodes a putative α/ß hydrolase domain-containing protein and is allelic to the BODYGUARD gene that was recently shown to be essential for cuticle biogenesis. Further studies discovered that other cutin biosynthesis mutants are also impaired in osmotic stress induction of ABA biosynthesis genes and are sensitive to osmotic stress. Our work demonstrates that the cuticle functions not merely as a physical barrier to minimize water loss but also mediates osmotic stress signaling and tolerance by regulating ABA biosynthesis and signaling.


Assuntos
Ácido Abscísico/biossíntese , Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Dioxigenases/genética , Dioxigenases/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácido Abscísico/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Carotenoides/metabolismo , Regulação para Baixo , Regulação da Expressão Gênica de Plantas , Lipídeos de Membrana/metabolismo , Mutação , Osmose/efeitos dos fármacos , Permeabilidade , Fenótipo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Polietilenoglicóis/farmacologia , Plântula/genética , Plântula/metabolismo , Plântula/fisiologia , Transdução de Sinais , Estresse Fisiológico , Água/metabolismo
6.
Bioconjug Chem ; 24(1): 133-43, 2013 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-23241015

RESUMO

The application of tumor targeting ligands for the treatment of cancer holds the promise of enhanced efficacy and reduced toxicity. L-SP5 ((L)(SVSVGMKPSPRP)) is a peptide that recognizes tumor neovasculature but not normal blood vessels (Lee et al., Cancer Res.2007, 67, 10958-65). The current report presents the design and application of D-SP5 ((D)(PRPSPKMGVSVS)), a novel retro-inverso analogue of L-SP5. Peptides D-SP5 and parental L-SP5 are shown to compete for the same target sites of a yet unknown cellular target and possess a dual-targeting bioactivity for both activated endothelial cells (HUVEC) and several tumor cell lines. Cellular uptake experiments showed superior in vitro targeting abilities of D-SP5 compared with L-SP5, such as enhanced internalization into stimulated HUVEC or KB, U87, and SGC tumor cells. A radioligand receptor binding assay revealed a higher cell affinity of D-SP5 in all tested cell lines, with K(d) values for D-SP5 about 2-fold lower than for L-SP5. An up to 3-fold higher maximum binding capacity (B(max)) to cells of D-SP5 was noted. Fluorescein-labeled D-SP5 upon intravenous administration displayed strong association with tumor endothelium. D-SP5-conjugated PEG-DSPE micelles displayed enhanced tumor homing (evidenced by near-infrared in vivo imaging). When loaded with doxorubicin, D-SP5 micelles could markedly suppress tumor growth with higher efficacy than L-SP5 micelles both in vitro and in vivo in KB tumor xenografts. In summary, the data demonstrate that D-SP5 displays higher binding affinities toward tumor endothelium as well as tumor cells and enhanced tumor targeting capability in vitro and in vivo.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Neoplasias/irrigação sanguínea , Neoplasias/tratamento farmacológico , Peptídeos/química , Sequência de Aminoácidos , Animais , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapêutico , Portadores de Fármacos/metabolismo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/patologia , Peptídeos/metabolismo , Fosfatidiletanolaminas/química , Fosfatidiletanolaminas/metabolismo , Polietilenoglicóis/química , Polietilenoglicóis/metabolismo
7.
ACS Appl Bio Mater ; 6(11): 4703-4713, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37865928

RESUMO

The utilization of guided tissue regeneration membranes is a significant approach for enhancing bone tissue growth in areas with bone defects. Biodegradable magnesium alloys are increasingly being used as guided tissue regeneration membranes due to their outstanding osteogenic properties. However, the degradation rates of magnesium alloy bone implants documented in the literature tend to be rapid. Moreover, many studies focus only on the initial 3-month period post-implantation, limiting their applicability and impeding clinical adoption. Furthermore, scant attention has been given to the interplay between the degradation of magnesium alloy implants and the adjacent tissues. To address these gaps, this study employs a well-studied magnesium-aluminum (Mg-Al) alloy membrane with a slow degradation rate. This membrane is implanted into rat skull bone defects and monitored over an extended period of up to 48 weeks. Observations are conducted at various intervals (2, 4, 8, 12, 24, and 48 weeks) following the implantation. Assessment of degradation behavior and tissue regeneration response is carried out using histological sections, micro-CT scans, and scanning electron microscopy (SEM). The findings reveal that the magnesium alloy membranes demonstrate remarkable biocompatibility and osteogenic capability over the entire observation duration. Specifically, the Mg-Al alloy membranes sustain their structural integrity for 8 weeks. Notably, their osteogenic ability is further enhanced as a corrosion product layer forms during the later stages of implantation. Additionally, our in vitro experiments employing extracts from the magnesium alloy display a significant osteogenic effect, accompanied by a notable increase in the expression of osteogenic-related genes. Collectively, these results strongly indicate the substantial potential of Mg-Al alloy membranes in the context of guided tissue regeneration.


Assuntos
Ligas , Magnésio , Ratos , Animais , Ligas/farmacologia , Ligas/química , Magnésio/farmacologia , Magnésio/química , Alumínio/farmacologia , Regeneração Óssea , Osteogênese
8.
Bioinorg Chem Appl ; 2022: 4941635, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35371192

RESUMO

We explored the feasibility and efficacy of a degradable magnesium (Mg) alloy guided bone regeneration (GBR) in the treatment of bone defects after tooth extraction. A GBR membrane (MAR-Gide (MG)) was used to treat a mandibular second molar (M2M)-distal bone defect (DBD). In eight beagle dogs, bilateral mandibular second and fourth premolars were hemi-sected. The distal roots were removed to create a two-wall bony defect of dimension 5 mm × 5 mm × 5 mm to simulate M2M-DBD. Thirty-two bone defects were assigned randomly into four groups according to GBR membranes (MG and Bio-Gide (BG)) applied and the time of killing (3 months and 6 months after surgery). The osteogenesis of bone defects and MG degradation were analyzed using micro-CT, histology (staining, tartrate-resistant acid phosphatase), and inductively coupled plasma mass spectrometry. MG did not increase the prevalence of infection, wound dehiscence, or subcutaneous emphysema compared with those using BG. Trabecular volume/total volume at 3 months (63.71 ± 10.4% vs. 59.97 ± 8.94%) was significantly higher in the group MG than that in the group BG. Implanted MG was degraded completely within 3 months, and "island-shaped" new bone was found near MG degradation products. A significant difference was not found in vertical bone height or percent of new bone formation (45.44 ± 12.28% vs. 43.49 ± 7.12%) between the groups. The concentration of rare-earth elements in mandibular lymph nodes of the group MG was significantly higher than that of the group BG (P ≤ 0.017) but did not lead to histopathological changes. In summary, MG exhibited good biocompatibility and clinical applicability compared with BG in vivo. The osteogenic effect of MG could be enhanced by regulating the degradation rate of Mg-alloy.

9.
Plant J ; 63(1): 128-40, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20409003

RESUMO

Osmotic stress imposed by soil salinity and drought stress significantly affects plant growth and development, but osmotic stress sensing and tolerance mechanisms are not well understood. Forward genetic screens using a root-bending assay have previously identified salt overly sensitive (sos) mutants of Arabidopsis that fall into five loci, SOS1 to SOS5. These loci are required for the regulation of ion homeostasis or cell expansion under salt stress, but do not play a major role in plant tolerance to the osmotic stress component of soil salinity or drought. Here we report an additional sos mutant, sos6-1, which defines a locus essential for osmotic stress tolerance. sos6-1 plants are hypersensitive to salt stress and osmotic stress imposed by mannitol or polyethylene glycol in culture media or by water deficit in the soil. SOS6 encodes a cellulose synthase-like protein, AtCSLD5. Only modest differences in cell wall chemical composition could be detected, but we found that sos6-1 mutant plants accumulate high levels of reactive oxygen species (ROS) under osmotic stress and are hypersensitive to the oxidative stress reagent methyl viologen. The results suggest that SOS6/AtCSLD5 is not required for normal plant growth and development but has a critical role in osmotic stress tolerance and this function likely involves its regulation of ROS under stress.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Glucosiltransferases/metabolismo , Osmose , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Parede Celular/química , Mapeamento Cromossômico , Clonagem Molecular , DNA de Plantas/genética , Secas , Regulação da Expressão Gênica de Plantas , Teste de Complementação Genética , Glucosiltransferases/genética , Manitol/farmacologia , Análise de Sequência com Séries de Oligonucleotídeos , Estresse Oxidativo , Paraquat/farmacologia , Polietilenoglicóis/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Salinidade , Cloreto de Sódio/farmacologia , Estresse Fisiológico
10.
Biosci Biotechnol Biochem ; 75(3): 473-9, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21389628

RESUMO

An analytical methodology for the analysis of methamidophos in water and soil samples incorporating a molecularly imprinted solid-phase extraction process using methamidophos-imprinted polymer was developed. Binding study demonstrated that the polymer exhibited excellent affinity and high selectivity to the methamidophos. Evidence was also found by FT-IR analysis that hydrogen bonding between the CO(2)H in the polymer cavities and the NH(2) and P=O of the template was the origin of methamidophos recognition. The use of molecularly imprinted solid-phase extraction improved the accuracy and precision of the GC method and lowered the limit of detection. The recovery of methamidophos extracted from a 10.0 g soil sample at the 100 ng/g spike level was 95.4%. The limit of detection was 3.8 ng/g. The recovery of methamidophos extracted from 100 mL tap and river water at 1 ng/mL spike level was 96.1% and 95.8%, and the limits of detection were 10 and 13 ng/L respectively. These molecularly imprinted solid-phase extraction procedures enabled selective extraction of polar methamidophos successfully from water and soil samples, demonstrating the potential of molecularly imprinted solid-phase extraction for rapid, selective, and cost-effective sample pretreatment.


Assuntos
Impressão Molecular/métodos , Compostos Organotiofosforados/isolamento & purificação , Extração em Fase Sólida/métodos , Purificação da Água/métodos , Sítios de Ligação , Cromatografia Gasosa , Análise de Fourier , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Limite de Detecção , Compostos Organotiofosforados/análise , Polímeros/síntese química , Sensibilidade e Especificidade , Solo/química , Água/química , Poluentes Químicos da Água/análise
12.
Opt Express ; 18(17): 18106-12, 2010 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-20721198

RESUMO

By employing low molecular-weight polyvinyl alcohol (PVA) as binder, the spatial resolution of a red-sensitive PVA/acrylamide based photopolymer are improved from 1000 lines/mm to 3000 lines/mm. By increasing the ambient temperature during the holographic recording, the photosensitivity of photopolymer is also increased about 5 times. The optimized photopolymer system has high capacity such as high photosensitivity (8 mJ/cm(2)), high spatial resolution (over 3000 lines/mm) and high diffraction efficiency (over 94%). To our knowledge, its holographic recording performance is the best of ever reported PVA/acrylamide based photopolymer systems. It has good application prospects in real-time holographic interferometry, holographic storage and holographic display.


Assuntos
Acrilamida/química , Holografia/instrumentação , Interferometria/instrumentação , Óptica e Fotônica/instrumentação , Álcool de Polivinil/química , Sistemas Computacionais , Desenho de Equipamento , Peso Molecular , Refratometria
13.
Pharm Res ; 27(5): 933-42, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20221899

RESUMO

PURPOSE: A novel conjugate, Folate-PEG-CKK(2)-DTPA, was designed and prepared as a carrier for lymphatic metastasized tumor imaging diagnosis and targeting therapy. METHODS: Folate-PEG-CKK(2)-DTPA was synthesized and characterized by analysis High Performance Liquid Chromatography, Size Exclusive Chromatography and (1)H-NMR. (99m)Tc-labeled conjugation was prepared, and in vivo quantitative biodistribution and SPECT imaging were studied after subcutaneously injected into the rats and rabbits, respectively. Cell uptake study was carried in a KB cell line using fluorescent methods. In vivo and ex vivo fluorescent imaging study was carried in tumor-bearing nude mouse to evaluate its targeting ability. RESULTS: Folate-PEG-CKK(2)-DTPA was synthesized with high purity. Both in vivo biodistribution study and SPECT imaging study show the rapid direction and high distribution of the conjugation to the lymph nodes. The uptake of fluorescence-labeled Folate-PEG-CKK(2)-DTPA in human oral epidermis carcinoma cells was observed. In vivo and ex vivo fluorescent imaging study indicated it could accumulate in tumor region after vein tail injection in nude mouse. CONCLUSIONS: All these findings suggested Folate-PEG-CKK(2)-DTPA as a novel and dependable carrier for tumor diagnosis and therapy, especially for lymph-metastasized tumors.


Assuntos
Portadores de Fármacos/síntese química , Sistemas de Liberação de Medicamentos , Ácido Fólico/análogos & derivados , Ácido Fólico/química , Metástase Linfática , Oligopeptídeos/química , Ácido Pentético/análogos & derivados , Polietilenoglicóis/química , Compostos Radiofarmacêuticos/química , Pentetato de Tecnécio Tc 99m/química , Animais , Fluoresceína-5-Isotiocianato , Corantes Fluorescentes , Ácido Fólico/administração & dosagem , Ácido Fólico/síntese química , Humanos , Marcação por Isótopo , Células KB , Linfonodos/diagnóstico por imagem , Masculino , Camundongos , Transplante de Neoplasias , Ácido Pentético/administração & dosagem , Ácido Pentético/síntese química , Coelhos , Compostos Radiofarmacêuticos/administração & dosagem , Ratos , Ratos Wistar , Pentetato de Tecnécio Tc 99m/administração & dosagem , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único
14.
Clin Oral Investig ; 14(6): 629-36, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19826843

RESUMO

The purpose of the present study was to investigate systemic and local levels of platelet-activating factor (PAF), a potent proinflammatory mediator implicated in cardiovascular pathophysiology in adult nonsmoking patients with periodontitis with or without coronary heart disease (CHD). Eighty-seven volunteers, 25 periodontitis patients, 19 periodontitis with CHD patients, 19 CHD patients, and 24 healthy controls were included, and periodontal conditions were assessed. Gingival crevicular fluid (GCF) and venous blood were collected, and PAF levels were measured by enzyme-linked immunosorbent assay. PAF levels in serum (303.3 ± 204 pg/ml) and in GCF (26.3 ± 6 pg/µl) of the periodontitis group with CHD, the periodontitis group (serum, 302.4 ± 241 pg/ml and GCF, 26.3 ± 8 pg/µl) and the CHD group (serum, 284.7 ± 192 pg/ml and GCF, 20.8 ± 6 pg/µl) were significantly higher than the healthy control group (serum, 65.4 ± 35 pg/ml and GCF, 7.7 ± 3 pg/µl; p < 0.05). In summary, the present study could demonstrate that in patients with periodontitis, the inflammatory mediator PAF is released into serum at least in the same range as for patients with coronary heart disease. However, no additive effects were seen when both conditions were present.


Assuntos
Doença das Coronárias/sangue , Líquido do Sulco Gengival/química , Periodontite/sangue , Fator de Ativação de Plaquetas/análise , Adulto , Perda do Osso Alveolar/sangue , Perda do Osso Alveolar/metabolismo , Doença das Coronárias/complicações , Doença das Coronárias/metabolismo , Índice de Placa Dentária , Feminino , Hemorragia Gengival/sangue , Hemorragia Gengival/metabolismo , Humanos , Mediadores da Inflamação/análise , Mediadores da Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal/sangue , Perda da Inserção Periodontal/metabolismo , Bolsa Periodontal/sangue , Bolsa Periodontal/metabolismo , Periodontite/complicações , Periodontite/metabolismo , Sulfetos/análise , Adulto Jovem
15.
J Mater Chem B ; 8(6): 1290-1301, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31967176

RESUMO

Multidrug resistance (MDR) is one of the major obstacles for tumor therapy. Intake by receptor-mediated endocytosis enables molecules to bypass ABC transporter efflux, which is the primary mechanism of MDR. Here, we developed a novel pH/enzyme dual-responsive polypeptide prodrug to reverse multidrug resistance. This drug is composed of pH/MMP2-sensitive nanoparticles (MSNPs) self-assembled from mPEG-peptide-DOX. MSNPs can overcome sequential physiological barriers of multidrug resistance by prolonging the circulation time through PEGylation, enhancing tumor accumulation through passive targeting, increasing tumor penetration by enzyme-sensitive PEG deshielding, bypassing ABC transporter efflux by undergoing receptor-mediated endocytosis, and inducing sufficient DOX release from nanoparticles triggered by lysosomal pH. The reversal of MDR by MSNPs was evaluated in MCF-7/ADR cells and nude mice bearing tumors consisting of MCF-7/ADR cells. Both in vitro and in vivo studies showed that the MSNPs can effectively reverse MDR. Thus, MSNPs may constitute a potentially promising strategy for overcoming MDR in clinical applications.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Polietilenoglicóis/farmacologia , Pró-Fármacos/farmacologia , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Doxorrubicina/química , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Endocitose/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Células MCF-7 , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Metaloproteinase 2 da Matriz/química , Camundongos , Camundongos Nus , Estrutura Molecular , Nanopartículas/química , Tamanho da Partícula , Peptídeos/química , Peptídeos/farmacologia , Polietilenoglicóis/química , Pró-Fármacos/química , Ratos , Ratos Sprague-Dawley , Propriedades de Superfície
16.
Nanoscale ; 12(4): 2673-2685, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31942900

RESUMO

Legumain enzyme is a well-conserved lysosomal cysteine protease and is over-expressed in many tumor cells and tumor stromal cells and exhibits higher protease activity under acidic conditions, such as in lysosomes and endosomes. Legumain enzyme-triggered drug delivery systems have demonstrated potential therapeutic values in cancer targeted therapy. To realize a more efficient delivery of anticancer therapeutic agents, we herein report a legumain/pH dual-responsive drug delivery system for enhancing site-specific controlled release of antitumor drugs. The carrier (named "DS-NA") is a hybrid vector constituting PEG-b-PBLA polymers, pH-responsive OAPI polymers, and legumain-sensitive peptide-doxorubicin prodrug decorated fluorescent carbon dots (CDs-C9-AANL-DOX). In tumor cells, DS-NA could disassemble rapidly in acidic environments, and then release doxorubicin through legumain digestion. Except as a drug vector, the drug release process from DS-NA could also be dynamically monitored by CLSM as the DOX was released from the surface of CDs through the AANL peptide linker digested by legumain, then transferred into the cell nucleus and exerted cytotoxicity, while the CDs themselves remained in the cytoplasm. As a control, the CDs-C9-DOX, which did not contain the AANL peptide linker, also still resided in the cytoplasm. Furthermore, in vivo studies show that DS-NA had a stronger inhibitory effect on tumor tissue with attenuated side effects to normal tissues than control nanoparticles or free drugs, which may be due to comprehensive effects including pH/legumain dual-triggered drug release, long blood circulation periods, and EPR effects. Together, a combination strategy of acid sensitivity and legumain enzyme sensitivity used for site-specific controlled release of drugs provides a novel method for enhanced and precise antitumor chemotherapy.


Assuntos
Antineoplásicos/administração & dosagem , Cisteína Endopeptidases/química , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Pró-Fármacos/administração & dosagem , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Doxorrubicina/química , Liberação Controlada de Fármacos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia Eletrônica de Transmissão , Nanomedicina , Nanopartículas/química , Permeabilidade , Polímeros/química , Pró-Fármacos/química
17.
Chem Commun (Camb) ; (9): 1106-8, 2009 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-19225651

RESUMO

A facile biomimetic method is reported for the synthesis of novel BaCO(3) nanofibres with double-stranded and cylindrical helical morphologies via a phosphonated block co-polymer-controlled mineralization process.


Assuntos
Bário/química , Materiais Biomiméticos/química , Carbonatos/química , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Varredura , Polímeros/química , Difração de Raios X
18.
FASEB J ; 21(4): 1117-25, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17218540

RESUMO

The blood-brain barrier (BBB) poses great difficulties for gene delivery to the brain. To circumvent the BBB, we investigated a novel brain-targeting gene vector based on the nanoscopic high-branching dendrimer, polyamidoamine (PAMAM), in vitro and in vivo. Transferrin (Tf) was selected as a brain-targeting ligand conjugated to PAMAM via bifunctional polyethyleneglycol (PEG), yielding PAMAM-PEG-Tf. UV and nuclear magnetic resonance (NMR) spectroscopy were used to evaluate the synthesis of vectors. The characteristics and biodistribution of gene vectors were evaluated by fluorescent microscopy, flow cytometry, and a radiolabeling method. The transfection efficiency of vector/DNA complexes in brain capillary endothelial cells (BCECs) was evaluated by fluorescent microscopy and determination of luciferase activity. The potency of vector/DNA complexes was evaluated by using frozen sections and measuring tissue luciferase activity in Balb/c mice after i.v. administration. UV and NMR results demonstrated the successful synthesis of PAMAM-PEG-Tf. This vector showed a concentration-dependent manner in cellular uptake study and a 2.25-fold brain uptake compared with PAMAM and PAMAM-PEG in vivo. Transfection efficiency of PAMAM-PEG-Tf/DNA complex was much higher than PAMAM/DNA and PAMAM-PEG/DNA complexes in BCECs. Results of tissue expression experiments indicated the widespread expression of an exogenous gene in mouse brain after i.v. administration. With a PAMAM/DNA weight ratio of 10:1, the brain gene expression of the PAMAM-PEG-Tf/DNA complex was approximately 2-fold higher than that of the PAMAM/DNA and PAMAM-PEG/DNA complexes. These results suggested that PAMAM-PEG-Tf can be exploited as a potential nonviral gene vector targeting to brain via noninvasive administration.


Assuntos
Materiais Biocompatíveis/química , Encéfalo/metabolismo , Técnicas de Transferência de Genes , Terapia Genética/instrumentação , Vetores Genéticos , Poliaminas/farmacologia , Polietilenoglicóis/metabolismo , Transferrina/farmacologia , Animais , Barreira Hematoencefálica , Cátions , Linhagem Celular , Dendrímeros , Terapia Genética/métodos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
19.
Int J Pharm ; 340(1-2): 207-15, 2007 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-17499948

RESUMO

Surface engineering of nanoparticles with lectins opened a novel pathway to improve the brain uptake of agents loaded by biodegradable PEG-PLA nanoparticles following intranasal administration. Ulex europeus agglutinin I (UEA I), specifically binding to l-fucose, which is largely located in the olfactory epithelium, was selected as a promising targeting ligand and conjugated onto the PEG-PLA nanoparticles surface with an optimized protocol relying on maleimide-mediated covalent binding technique. The in vivo results in rats suggested that UEA I modification at the nanoparticles surface facilitated the absorption of a fluorescent marker--6-coumarin associated with the nanoparticles into the brain following intranasal administration with significant increase in the area under the concentration-time curve (about 1.7 times) in different brain tissues compared with that of coumarin incorporated in the unmodified ones. UEA I-conjugation also elevated the brain-targeting efficiency of nanoparticles. Inhibition experiment of specific sugar suggested that the interactions between the nasal mucosa and the lectinised nanoparticles were due to the immobilization of carbohydrate-binding pockets on the surface of the nanoparticles. Distribution profiles of UEA I-modified nanoparticles indicated their higher affinity to the olfactory mucosa than to the respiratory one. Therefore, the UEA I-modified nanoparticles might serve as potential carriers for brain drug delivery, especially for mental therapeutics with multiple biological effects.


Assuntos
Encéfalo/metabolismo , Cumarínicos/farmacocinética , Portadores de Fármacos , Corantes Fluorescentes/farmacocinética , Lactatos/química , Nanopartículas , Mucosa Nasal/metabolismo , Lectinas de Plantas/química , Polietilenoglicóis/química , Administração Intranasal , Animais , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Cumarínicos/administração & dosagem , Cumarínicos/química , Reagentes de Ligações Cruzadas/química , Composição de Medicamentos , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/química , Fucose/metabolismo , Imidoésteres/química , Maleimidas/química , Ratos , Ratos Sprague-Dawley , Solubilidade , Espectrometria de Fluorescência , Compostos de Sulfidrila/química
20.
Mol Med Rep ; 16(5): 7459-7467, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28944821

RESUMO

Periodontitis is a chronic oral inflammatory disease caused by microorganisms. Human ß­defensin­3 (HBD­3) is an endogenous antimicrobial peptide that inhibits a broad spectrum of microorganisms. Cell sheet technology has been widely applied in tissue and organ reconstructions. In the current study, it was aimed to investigate the anti­inflammatory effect of periodontal tissue engineered by HBD­3 gene­modified periodontal ligament cell (PDLC) sheets, and to identify a suitable method of promoting the regeneration of periodontal tissues. Western blot analysis and antimicrobial tests were used to confirm the expression of HBD­3. The effect of the cell sheets on anti­inflammatory activity and bone remodeling in a dog model of periodontitis was demonstrated by immunohistochemistry. The results demonstrated that the transfected PDLCs stably expressed HBD­3. Periodontal pathogens were susceptible to the antimicrobial activity of the cell sheets. In addition, the cell sheets relieved the bone resorption caused by inflammation in the in vivo model. HBD­3 may potentially be applied in the treatment of periodontitis and may function as osteogenic promoter via its anti­inflammatory effect.


Assuntos
Ligamento Periodontal/transplante , Periodontite/terapia , beta-Defensinas/metabolismo , Animais , Candida albicans/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Cães , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Inflamação/patologia , Interleucina-1beta/metabolismo , Testes de Sensibilidade Microbiana , Ligamento Periodontal/citologia , Ligamento Periodontal/metabolismo , Periodonto/patologia , Periodonto/fisiologia , Porphyromonas gingivalis/efeitos dos fármacos , Regeneração , Streptococcus mutans/efeitos dos fármacos , Transfecção , beta-Defensinas/análise , beta-Defensinas/genética , beta-Defensinas/farmacologia
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