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1.
BMC Health Serv Res ; 23(1): 953, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37674190

RESUMO

BACKGROUND: Long term care (LTC) services for functionally impaired senior citizens are crucial for addressing the challenges of aging. However, research on eligibility criteria and coverage of LTC in China is lacking. Our objective is to assess the current status of LTC and explore eligibility criteria and coverage for the elderly. METHODS: This is a cross-sectional study conducted in two first-tier cities in China. Residents aged 65 or over were recruited from a nursing home and four primary hospitals. Participants were divided into three groups (bedridden, domestic, and community), then six grades (grade one to six) according to the Longshi Scale, and their functional ability was assessed using the Modified Barthel Index. Information such as diseases, complications, and daily care needs were collected. Nursing staff were invited to indicate patients' needs for care. A one-way ANOVA test, Kruskal Wallis H test and Mann-Whitney U test were used to explore the differences of variables in three Longshi groups or Longshi grades. RESULTS: Among all 1157 participants, with an average age of 80.54, 69.3% were in the bedridden group. The most common diagnosis was stroke (71.4%), with the most prevalent complication being pulmonary infection (25.2%). In the nursing assessment, basic health care, disease care, activity care, complication prevention care and psychosocial care were summarized as the five main aspects of LTC for the elderly. Feeding, bathing, drinking, bowel management and bladder management were identified as the basic care which fulfills participants' basic physical needs in each Longshi group. Mouth care, artificial airway management, and body reposition, which can prevent immobility complications, were highly demanded by bedridden elderly. CONCLUSIONS: The elderly in grade one to three are the ones in need of LTC most. The content of LTC for elderly should include basic care which fulfills their basic physical needs and complication care which can prevent immobility complications. The evidence of this research may contribute to the design of LTC in China. TRIAL REGISTRATION: The study design was registered in the Chinese Clinical Trial Registry (ChiCTR-2000034067, Registered 22 Jun 2020, http://www.chictr.org.cn/showproj.aspx?proj=54770 ).


Assuntos
Assistência de Longa Duração , Casas de Saúde , Idoso , Humanos , Estudos Transversais , Cidades , China/epidemiologia
2.
Proc Natl Acad Sci U S A ; 116(13): 5872-5877, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30850523

RESUMO

Nanoscale multipoint structure-function analysis is essential for deciphering the complexity of multiscale biological and physical systems. Atomic force microscopy (AFM) allows nanoscale structure-function imaging in various operating environments and can be integrated seamlessly with disparate probe-based sensing and manipulation technologies. Conventional AFMs only permit sequential single-point analysis; widespread adoption of array AFMs for simultaneous multipoint study is challenging owing to the intrinsic limitations of existing technological approaches. Here, we describe a prototype dispersive optics-based array AFM capable of simultaneously monitoring multiple probe-sample interactions. A single supercontinuum laser beam is utilized to spatially and spectrally map multiple cantilevers, to isolate and record beam deflection from individual cantilevers using distinct wavelength selection. This design provides a remarkably simplified yet effective solution to overcome the optical cross-talk while maintaining subnanometer sensitivity and compatibility with probe-based sensors. We demonstrate the versatility and robustness of our system on parallel multiparametric imaging at multiscale levels ranging from surface morphology to hydrophobicity and electric potential mapping in both air and liquid, mechanical wave propagation in polymeric films, and the dynamics of living cells. This multiparametric, multiscale approach provides opportunities for studying the emergent properties of atomic-scale mechanical and physicochemical interactions in a wide range of physical and biological networks.


Assuntos
Microscopia de Força Atômica/métodos , Animais , Camundongos , Miócitos Cardíacos/ultraestrutura , Nanotecnologia/métodos , Imagem Óptica/métodos , Polímeros/química , Relação Estrutura-Atividade , Propriedades de Superfície
3.
Am J Orthod Dentofacial Orthop ; 154(2): 249-259, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30075927

RESUMO

INTRODUCTION: The aims of this study were to investigate the expression of proteins of elastic fibers and collagen type I in the supra-alveolar structure of orthodontically rotated teeth in rats and to elucidate whether circumferential supracrestal fiberotomy diminishes relapse. METHODS: The rats' maxillary left first molars were rotated by couple of force. Specimens were divided into groups according to different orthodontic procedures. A1-3 and B1-3 were blank control groups and operation control groups. Group C underwent rotation only, and group D was treated with rotation and retention. Groups E and F were treated with rotation, retention, and release of retention; additionally, circumferential supracrestal fiberotomy was performed in group F before the release of retention. The animals were killed, and the jaws were processed for histologic evaluation using the immunohistochemical method to evaluate the protein expressions of elastin, fibrillin-1, fibrillin-2, and collagen type I in supra-alveolar structures (around and below the gingival sulcus) between the maxillary left first and second molars. The degree and percentage of relapse were measured by a series of impressions. RESULTS: The degree and percentage of relapse in group F were much lower than those in group E (P <0.05). Collagen type I was increased in group C (P <0.05) and at normal levels in groups D, E, and F. Elastin below the gingival sulcus and fibrillin-1 showed the same patterns of expression and were consistently elevated in groups C, D, E, and F (P <0.05). No positive staining for elastin was found around the gingival sulcus in any specimen. The difference in the expression of fibrillin-2 between the experimental groups (C, D, E, and F) and their matching control groups was not statistically significant (P >0.05). CONCLUSIONS: Circumferential supracrestal fiberotomy can alleviate the relapse of rotated teeth. Collagen fibers of supra-alveolar structures might contribute to relapse in a short time, whereas elastic fibers may be the reason that rotated teeth relapse to their original positions after retention.


Assuntos
Colágeno Tipo I/biossíntese , Tecido Elástico/metabolismo , Biossíntese de Proteínas , Técnicas de Movimentação Dentária , Animais , Masculino , Ratos , Ratos Sprague-Dawley
4.
Am J Orthod Dentofacial Orthop ; 152(5): 654-662, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29103443

RESUMO

INTRODUCTION: The purpose of this study was to investigate the mechanical loading-induced changes in protein and mRNA expressions of interleukin-6 (IL-6) and its key signaling factors glycoprotein 130 (gp130), signal transducer and activator of transcription 3 (STAT3), and the Src homology phosphotyrosine phosphatase (SHP2) at the tension and compression sides of the teeth in mouse models. METHODS: A total of 55 C57B/6 mice (10 weeks old) were divided into 3 groups. Orthodontic force was applied in group A (experimental group, n = 30); the tooth movement device was placed without activation in group B (sham control group, n = 15), and group C (blank control group, n = 10). Tooth movement was induced by a nickel-titanium coil spring inserted between the maxillary left incisor and the first molar with a force of approximately 4 g. The animals were killed 12 days after the interventions; protein and mRNA expressions of IL-6, gp130, STAT3, and SHP2 in the periodontal tissues were observed with immunohistochemistry and in-situ hybridization, respectively. RESULTS: In contrast with the control groups, we observed enhanced expressions of IL-6, gp130, STAT3, and SHP2 protein and mRNA at the mesial and distal sides of the teeth with application of orthodontic forces in the experimental group. In contrast with the distal side, we observed enhanced expression of gp130 protein and mRNA at the mesial side in the experimental group. CONCLUSIONS: We observed enhanced expression of IL-6 and its key signaling factors gp130, STAT3, and SHP2 protein and mRNA at the tension and compression sides of the teeth with application of orthodontic forces. The mechanical loading applied for orthodontic tooth movement might induce changes in protein localization and mRNA expression patterns of IL-6 and its key signaling factors gp130, STAT3, and SHP2 at the tension and compression sides of the periodontal ligaments of the teeth in mouse models. The result might demonstrate the special role of IL-6 and its key signaling factors in the alveolar bone-modeling process.


Assuntos
Interleucina-6/genética , RNA Mensageiro/biossíntese , Técnicas de Movimentação Dentária , Animais , Receptor gp130 de Citocina/biossíntese , Receptor gp130 de Citocina/genética , Interleucina-6/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Biossíntese de Proteínas , Proteína Tirosina Fosfatase não Receptora Tipo 11/biossíntese , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Fator de Transcrição STAT3/biossíntese , Fator de Transcrição STAT3/genética
5.
Mol Pharm ; 12(11): 4124-36, 2015 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-26393405

RESUMO

Galectin-3 is overexpressed by numerous carcinomas and is a potential target for active tumor treatments. On the other hand, galectin-3 also plays a key role in cancer progression and prevents cells from undergoing apoptosis, thereby offsetting the benefits of active targeting drugs. However, the relative contribution of the protective antiapoptotic effects of galectin-3 and the proapoptotic effects of galectin-3-targeted therapies has remained yet unrevealed. Here, we show that a galectin-3-binding peptide G3-C12 could reverse galectin-3 from foe to friend for active targeting delivery system. Results showed G3-C12 modified N-(2-hydroxypropyl)methacrylamide copolymer doxorubicin conjugates (G3-C12-HPMA-Dox) could internalize into galectin-3 overexpressed PC-3 cells via a highly specific ligand-receptor pathway (2.2 times higher cellular internalization than HPMA-Dox). The internalized Dox stimulated the translocation of galectin-3 to the mitochondria to prevent from apoptosis. In turn, this caused G3-C12-HPMA-Dox to concentrate into the mitochondria after binding to galectin-3 intracellularly. Initially, mitochondrial galectin-3 weakened Dox-induced mitochondrial damage; however, as time progressed, G3-C12 active-mediation allowed increasing amounts of Dox to be delivered to the mitochondria, which eventually induced higher level of apoptosis than nontargeted copolymers. In addition, G3-C12 downregulates galectin-3 expression, 0.43 times lower than control cells, which could possibly be responsible for the suppressed cell migration. Thus, G3-C12 peptide exerts sequential targeting to both cell membrane and mitochondria via regulating galectin-3, and eventually reverses and overcomes the protective effects of galectin-3; therefore, it could be a promising agent for the treatment of galectin-3-overexpressing cancers.


Assuntos
Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Galectina 3/antagonistas & inibidores , Fragmentos de Peptídeos/farmacologia , Polímeros/química , Neoplasias da Próstata/tratamento farmacológico , Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Proliferação de Células/efeitos dos fármacos , Endocitose/efeitos dos fármacos , Imunofluorescência , Galectina 3/metabolismo , Humanos , Masculino , Mitocôndrias/efeitos dos fármacos , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Espécies Reativas de Oxigênio/metabolismo , Células Tumorais Cultivadas , Cicatrização/efeitos dos fármacos
6.
Mol Pharm ; 11(10): 3251-60, 2014 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-24955652

RESUMO

Prostate carcinoma is the second leading cause of cancer-related deaths. Increased expression of membrane-bound galectin-3 by prostate carcinoma cell has been found to correlate with more poorly differentiated and increased metastatic potential. In the present study, different amount of galectin-3-binding peptide, G3-C12 (the sequence ANTPCGPYTHDCPVKR), was attached to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers as targeting moiety. The results of qPCR and competitive binding test indicated that the expression level of galectin-3 in two metastatic prostate carcinoma cell lines (PC-3 and DU145 cells) could be significantly suppressed by the addition of G3-C12-modified HPMA copolymers (PG1 and PG2), demonstrating the high affinity of PG1 and PG2 to galectin-3. Due to the multivalent effects of moieties, the uptake of copolymers was remarkably enhanced with the increasing amount of conjugated G3-C12 peptide. A higher internalization of PG1 and PG2 occurred in PC-3 cells via caveolin- and clathrin-mediated endocytosis, whereas a clathrin-mediated uptake process was involved in DU145 cells. The in vivo biodistribution and pharmacokinetics of nonmodified ((131)I-pHPMA) and G3-C12-modified ((131)I-PG1 and (131)I-PG2) copolymers were estimated on a well-established mice model bearing PC-3 xenografts by (131)I-SPECT-imaging. Higher tumor accumulation of (131)I-PG1 (1.60 ± 0.08% ID/g, p < 0.05) and (131)I-PG2 (1.54 ± 0.06% ID/g, p < 0.05) was observed compared with (131)I-pHPMA (1.19 ± 0.04% ID/g) at 2 h post-intravenous injection. Although the amount of conjugated G3-C12 peptide performed a remarkable in vitro effect on the affinity and internalization of HPMA copolymers to the galectin-3 overexpressed prostate carcinoma cells, the molecular weight and ligand modification all play important roles on their in vivo tumor accumulation.


Assuntos
Acrilamidas/química , Peptídeos/química , Polímeros/química , Neoplasias da Próstata/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C
7.
Int J Biol Macromol ; 269(Pt 2): 131970, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38697413

RESUMO

This study investigated the properties of chitosan/zein/tea polyphenols (C/Z/T) films and analyzed the release kinetics of tea polyphenols (TP) in various food simulants to enhance the sustainability and functionality of food packaging. The results revealed that TP addition enhanced the hydrophilicity, opacity and mechanical properties of film, and improved the compatibility between film matrix. 1.5 % TP film showed the lowest lightness (76.4) and the highest chroma (29.1), while 2 % TP film had the highest hue angle (1.5). However, the excessive TP (above 1 % concentration) led to a decrease in compatibility and mechanical properties of film. The TP concentration (2 %) resulted in the highest swelling degree in aqueous (750.6 %), alcoholic (451.1 %), and fatty (6.4 %) food simulants. The cumulative release of TP decreased to 16.32 %, 47.13 %, and 5.87 % with the increase of TP load in the aqueous, alcoholic, and fatty food simulants, respectively. The Peleg model best described TP release kinetics. The 2 % TP-loaded film showed the highest DPPH (97.13 %) and ABTS (97.86 %) free radical scavenging activity. The results showed TP release influenced by many factors and obeyed Fick's law of diffusion. This study offered valuable insights and theoretical support for the practical application of active films.


Assuntos
Quitosana , Embalagem de Alimentos , Polifenóis , Chá , Zeína , Quitosana/química , Polifenóis/química , Chá/química , Cinética , Zeína/química , Preparações de Ação Retardada , Antioxidantes/química , Fenômenos Químicos , Interações Hidrofóbicas e Hidrofílicas , Polímeros/química
8.
Front Immunol ; 15: 1407035, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979420

RESUMO

Introduction: The Hand, Foot and Mouth Disease (HFMD), caused by enterovirus 71 infection, is a global public health emergency. Severe HFMD poses a significant threat to the life and well-being of children. Numerous studies have indicated that the occurrence of severe HFMD is associated with cytokine storm. However, the precise molecular mechanism underlying cytokine storm development remains elusive, and there are currently no safe and effective treatments available for severe HFMD in children. Methods: In this study, we established a mouse model of severe HFMD to investigate the molecular mechanisms driving cytokine storm. We specifically analyzed metabolic disturbances, focusing on arginine/ornithine metabolism, and assessed the potential therapeutic effects of spermine, an ornithine metabolite. Results: Our results identified disturbances in arginine/ornithine metabolism as a pivotal factor driving cytokine storm onset in severe HFMD cases. Additionally, we discovered that spermine effectively mitigated the inflammatory injury phenotype observed in mice with severe HFMD. Discussion: In conclusion, our findings provide novel insights into the molecular mechanisms underlying severe HFMD from a metabolic perspective while offering a promising new strategy for its safe and effective treatment.


Assuntos
Arginina , Citocinas , Modelos Animais de Doenças , Doença de Mão, Pé e Boca , Ornitina , Animais , Doença de Mão, Pé e Boca/imunologia , Camundongos , Arginina/metabolismo , Humanos , Citocinas/metabolismo , Espermina/metabolismo , Feminino , Enterovirus Humano A/imunologia , Masculino , Camundongos Endogâmicos C57BL , Índice de Gravidade de Doença
9.
Talanta ; 274: 126005, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38599116

RESUMO

In preparing monoclonal antibodies by hybridoma cell technology, the quality of B lymphocytes used for cell fusion directly affects the sensitivity of monoclonal antibodies. To obtain B-lymphocytes producing high-quality specific antibodies for cell fusion during the immunization phase of the antigen, we prepared a TH2-Cell stimulatory delivery system as a novel adjuvant. Astragalus polysaccharide has a good ability to enhance antigenic immune response, and it was encapsulated in biocompatible materials PLGA as an immunostimulatory factor to form the delivery system (APS-PLGA). The preparation conditions of APSP were optimized using RSM to attain the highest utilization of APS. Immunization against ZEN-BSA antigen using APSP as an adjuvant to obtain B lymphocytes producing ZEN-specific antibodies for cell fusion. As results present, APSP could induce a stronger TH2 immune response through differentiating CD4 T cells and promoting IL-4 and IL-6 cytokines. Moreover, it could slow down the release efficiency of ZEN-BSA and enhance the targeting of ZEN-BSA to lymph nodes in vivo experiments. Ultimately, the sensitivity of mouse serum ZEN-specific antibodies was enhanced upon completion of immunization, indicating a significant upregulation of high-quality B lymphocyte expression. In the preparation of monoclonal antibodies, the proportion of positive wells for the first screening was 60%, and the inhibition rates of the antibodies were all similar (>50%). Then we obtained the ZEN monoclonal antibody with IC50 of 0.049 ng/mL, which was more sensitive than most antibodies prepared under conventional adjuvants. Finally, a TRFIAS strip assay was preliminarily established with a LOD value of 0.246 ng/mL.


Assuntos
Adjuvantes Imunológicos , Anticorpos Monoclonais , Linfócitos B , Camundongos Endogâmicos BALB C , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Animais , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Linfócitos B/imunologia , Linfócitos B/efeitos dos fármacos , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/química , Nanopartículas/química , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Camundongos , Feminino , Ativação Linfocitária/efeitos dos fármacos , Imunização
10.
Gut Pathog ; 13(1): 69, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809671

RESUMO

BACKGROUND: The increase of inflammation-inducing enterobacteria was recently observed in severe hand, foot, and mouth disease (HFMD) caused by Enterovirus A71 (EV-A71). This study aimed to verify the occurrence of bacterial translocation (BT) and further explore the contributory role of BT to severity of EV-A71-mediated HFMD cases. METHODS: Serum specimens from 65 mild and 65 severe EV-A71-associated HFMD cases and 65 healthy children were collected. EV-A71 VP1 in serum, inflammatory mediators including C-reactive protein, IL-1ß, IL-6, interferon-γ and tumor necrosis factor-α, BT related biomarkers including Claudin-3, intestinal fatty acid binding protein, lipopolysaccharide (LPS), soluble CD14 (sCD14) and endotoxin core antibody were measured by ELISA. Bacterial DNA (BactDNA) fragments were quantified by quantified PCR (qPCR). Rhabdomyosarcoma (RD) or SH-SY5Y cells, infected with LPS-pre-incubated EV-A71 or transfected with plasmid containing viral 2Apro or mRNA containing viral internal ribosomal entry site (IRES), were post-treated with or without LPS in vitro. EV-A71 RNA and viral or cellular proteins were determined by qPCR and western blot, respectively. RESULTS: Compared to mild HFMD patients, remarkably higher inflammatory mediators as well as BT-related biomarkers except BactDNA were observed in severe HFMD cases (all P < 0.05). In severe HFMD group, circulating concentrations of LPS and sCD14 showed statistical correlations with inflammation indices (all P < 0.05), serum levels of EV-A71 VP1 were found to be positively correlated with serum LPS (r = 0.341, P = 0.005) and serum sCD14 (r = 0.458, P < 0.001). In vitro, EV-A71 attachment and internalization were only slightly promoted by LPS pre-incubation; however, EV-A71 proliferation and viral 2Apro-mediated IRES activity were significantly accelerated by LPS post-treatment. CONCLUSIONS: Our results collectively indicate that gut-derived translocating LPS contributes to the severity of EV-A71-induced HFMD by driving inflammatory response and viral proliferation via viral 2Apro-mediated IRES.

11.
Nanoscale ; 9(4): 1547-1558, 2017 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-28067924

RESUMO

Co-delivery of multiple agents via nanocarriers is of great interest in cancer therapy, but subcellular delivery to the corresponding site of action remains challenging. Here we report a smart nanovehicle which enables two different site-oriented payloads to reach their targeted organelles based on stimulus-responsive release and nucleus-targeted modification. First, all trans retinoic acid (RA) conjugated camptothecin (RA-CPT) was loaded in a polyhedral oligomericsilsesquioxane (POSS)-based core; docetaxel (DTX) was grafted on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers. The POSS core grafted with semitelechelic HPMA copolymers then self-assembled into micelles. Once internalized into the cell, the two drugs were unleashed environment-responsively, and nuclear targeted RA remarkably facilitated the nuclear transport of CPT. Compared with single drug-loaded micelles, the dual drug-loaded platform showed superior synergic cytotoxicity, which was further strengthened by the involvement of RA. The ability to induce DNA damage and apoptosis was also enhanced by nucleus-targeted modification. Finally, dual drug-loaded micelles exhibited much better in vivo tumor inhibition (87.1%) and less systemic toxicity than the combination of single drug-loaded systems or the dual drug-loaded micelles without RA. Therefore, our study provides a novel "one platform, two targets" strategy in combinatory anti-cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Micelas , Neoplasias/tratamento farmacológico , Acrilamidas , Animais , Apoptose , Camptotecina/administração & dosagem , Linhagem Celular Tumoral , Dano ao DNA , Docetaxel , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Compostos de Organossilício , Polímeros , Taxoides/administração & dosagem , Tretinoína , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Photomed Laser Surg ; 35(1): 3-11, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27564090

RESUMO

OBJECTIVE AND BACKGROUND: Low-level laser therapy (LLLT) has been used to reduce the relapse of orthodontically rotated teeth. However, controversial conclusions have been drawn by different authors. This review aimed to evaluate the efficacy of LLLT on relapse of corrected tooth rotations systematically by overall search of available studies and scientific assessment. METHODS: A comprehensive electronic search was performed through PubMed, MEDLINE, EMBASE, Web of Science, CENTRAL, PRL, and WHO ICTRP up to November 2015 with no language limitation. This systematic review was carried out according to Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Risk of bias assessment was undertaken according to Cochrane Handbook for Systematic Reviews of Interventions. Two review authors conducted the work of search, selection, and quality assessment independently in duplicate. RESULTS: Out of 112 studies, two animal experiments and one human study were included. Degree and percentage of relapse of rotated teeth were compared between control and LLLT group. CONCLUSIONS: According to the results of our systematic review, the effect of LLLT on relapse of corrected tooth rotations is related to energy density. Namely, low energy density seems to promote relapse, while high energy density might alleviate the relapse. Since available investigations are limited, more well-designed randomized controlled trials involving humans are needed to get more clinically significant conclusions.


Assuntos
Terapia com Luz de Baixa Intensidade , Animais , Humanos , Recidiva , Rotação , Doenças Dentárias/terapia
13.
ACS Appl Mater Interfaces ; 8(21): 13251-61, 2016 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-27167898

RESUMO

To further fine tune drug release and enhance therapeutic effects of polyhedral oligomericsilsesquioxane (POSS)-based nanomedicine, a starlike organic-inorganic conjugate was synthesized by grafting semitelechelic N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers to a POSS rigid core through reductively degradable disulfide bonds. The hydrophobic docetaxel (DTX) was attached to the grafts by pH-sensitive hydrazone bonds and also encapsulated into the POSS core (SP-DTX). Thus, the final amphiphilic star-shaped conjugates could self-assemble into nanoparticles and exhibited conspicuous drug-loading capacity (20.1 wt %) based on the covalently conjugated accompanied by physically encapsulated DTX. The stimuli-responsive DTX release under acidic lysosomal and reducing cytoplasmic environments was verified, leading to enhanced cytotoxicity against PC-3 human prostate carcinoma cells. To evaluate the in vivo therapeutic effects of the DTX-loaded nanovehicles objectively, a stroma-rich, prostate xenograft tumor model was generated. SP-DTX displayed uniform tumor distribution and suppressed tumor growth to a more pronounced level (tumor inhibition of 78.9%) than nonredox-sensitive SP-DTX-A (67.4%), SP-DTX-C contained DTX only in the core (65.5%) or linear P-DTX (60.7%) through enhanced depletion of cancer-associated fibroblasts and induction of apoptosis. The hybrid POSS-based polymeric nanoparticles offer an efficient approach to transport hydrophobic drugs for cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Portadores de Fármacos/síntese química , Nanopartículas/química , Polímeros/química , Antineoplásicos/química , Linhagem Celular Tumoral , Portadores de Fármacos/química , Humanos , Masculino , Nanopartículas/administração & dosagem , Taxoides/química , Taxoides/farmacologia
14.
Biomaterials ; 35(19): 5171-87, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24702960

RESUMO

Although folate exhibits many advantages over other targeting ligands, it has one major defect: poor water solubility. Once it was conjugated to hydrophilic drug carrier such as N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer, the hydrophobic folate may be buried inside the random polymer coil and not exposed to be accessible to its receptor on the cell surface, thus losing its active targeting ability. To address this folate dilemma, the positive charge was introduced in the present study. The obtained cationic folate-functionalized HPMA copolymers exhibited a synergistic enhancing effect on cellular uptake by folate receptor (FR) positive Hela cells via electrostatic absorptive endocytosis and folate receptor-mediated endocytosis, with the involvement of multiple internalization pathways including clathrin-mediated endocytosis, caveolae-mediated endocytosis, macropinocytosis and energy-dependent endocytosis. As demonstrated in binding efficiency study, the FR antibody bound to 71.2% of tested cells in the competition with neutral folate modified HPMA copolymers, while the FR antibody-bounded cells decreased to only 34.0% in competition with cationic folate modified HPMA copolymers, indicating that the positively charge could probably amplify the binding efficiency of folate to its receptor due to close proximity of the conjugates to the cell surface by the electronic adhesion. In addition, the cell uptake study on FR negative A549 cells also confirmed the specific role of folate as targeting ligand. Then, to avoid non-specific binding by positive charge in the circulation, the charge shielding/deshielding approach was further employed. With selective hydrolysis of the charge shielding groups 2,3-dimethylmaleic anhydride (DMA) at tumor extracellular pH 6.8, the conjugates underwent a quick charge-reversible process with more than 80% DMA cleavage within 2 h and endocytosed into the endo/lysosomes much more rapidly than at physiological pH 7.4. And then the drug release was triggered by the cleavage of hydrazone spacer at another level of pH 5 in endo/lysosomal compartment. Furthermore, the anticancer activity results showed that Dox-loaded, charge-switchable, folate modified HPMA copolymer conjugates could indeed lead to enhanced cytotoxicity, stronger apoptosis and greater tumor spheroid inhibition towards Hela cells, indicating the great potential feasibility of this multiple responsive drug delivery system.


Assuntos
Doxorrubicina/química , Doxorrubicina/farmacologia , Metacrilatos/química , Polímeros/química , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Células HeLa , Humanos , Anidridos Maleicos/química , Ratos , Ratos Sprague-Dawley
15.
Arch Oral Biol ; 58(4): 362-9, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23092608

RESUMO

OBJECTIVE: The purpose of this study was to investigate the effect of enamel matrix derivative on remineralisation of initial enamel carious lesions in vitro. DESIGN: Initial enamel carious lesions were created in bovine enamel blocks in vitro. The lesions were subjected to a pH-cycling regime of 24days. Each daily cycle included 4×3-min applications with one of four treatments: 1g/L NaF aqueous solution (positive control), 6% propylene glycol alginate (PGA) or distilled and deionised water (DDW) (both negative controls), and a gel of enamel matrix derivative and PGA (EMDgel). Samples were subjected to surface microhardness (SMH) testing, polarised light microscopy (PLM) and transverse microradiography (TMR) to measure SMH, mineral loss, lesion depth and mineral content of the surface layer and lesion body before and after pH-cycling. RESULTS: NaF samples showed the highest SMH recovery of all the groups (P<0.05). EMDgel samples showed significantly higher SMH recovery than did PGA ones (P<0.05). NaF samples showed significantly less mineral loss and shallower lesions than all other groups (P<0.05). The DDW and EMDgel samples showed significantly less mineral loss and shallower lesions than PGA samples. Mineral deposition predominated much more at the surface layer in the EMDgel group than in the PGA group (P<0.05). CONCLUSIONS: EMD, the active ingredient of EMDgel, may play an essential role in promoting remineralisation of initial enamel carious lesions. However, EMDgel as a whole did not cause detectable remineralisation of such lesions in vitro.


Assuntos
Alginatos/farmacologia , Cariostáticos/farmacologia , Cárie Dentária/terapia , Proteínas do Esmalte Dentário/farmacologia , Esmalte Dentário/efeitos dos fármacos , Fluoreto de Sódio/farmacologia , Remineralização Dentária/métodos , Análise de Variância , Animais , Bovinos , Esmalte Dentário/química , Esmalte Dentário/patologia , Concentração de Íons de Hidrogênio , Microrradiografia
16.
ACS Nano ; 7(6): 4911-8, 2013 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-23683028

RESUMO

We herein report a new class of photonic crystals with hierarchical structures, which are of color tunability over pH. The materials were fabricated through the deposition of polymethylacrylic acid (PMAA) onto a Morpho butterfly wing template by using a surface bonding and polymerization route. The amine groups of chitosan in Morpho butterfly wings provide reaction sites for the MAA monomer, resulting in hydrogen bonding between the template and MAA. Subsequent polymerization results in PMAA layers coating homogenously on the hierarchical photonic structures of the biotemplate. The pH-induced color change was detected by reflectance spectra as well as optical observation. A distinct U transition with pH was observed, demonstrating PMAA content-dependent properties. The appearance of the unique U transition results from electrostatic interaction between the -NH3(+) of chitosan and the -COO(-) groups of PMAA formed, leading to a special blue-shifted point at the pH value of the U transition, and the ionization of the two functional groups in the alkali and acid environment separately, resulting in a red shift. This work sets up a strategy for the design and fabrication of tunable photonic crystals with hierarchical structures, which provides a route for combining functional polymers with biotemplates for wide potential use in many fields.


Assuntos
Biomimética/métodos , Nanoestruturas/química , Nanotecnologia/métodos , Fótons , Animais , Borboletas/anatomia & histologia , Concentração de Íons de Hidrogênio , Fenômenos Ópticos , Polimerização , Ácidos Polimetacrílicos/química , Propriedades de Superfície , Asas de Animais
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