RESUMO
AIM: To investigate the associations between oral health and depression, anxiety and their comorbidity in the UK Biobank cohort. MATERIALS AND METHODS: Oral health problems were self-reported at baseline. Symptoms of depression and anxiety were assessed using the Mental Health Questionnaire (PHQ-4) in a cross-sectional study. In the cohort study, diagnoses of depression and anxiety disorders were based on hospital records. Logistic regression and Cox regression models were used to analyse the association between oral health and depression/anxiety. RESULTS: A total of 305,188 participants were included in the cross-sectional study, and multivariate analysis showed that periodontal disease was associated with depression and/or anxiety (odds ratio [OR]: 1.79, 95% confidence interval [CI]: 1.73-1.86). In the prospective cohort study involving 264,706 participants, periodontal disease was significantly associated with an increased risk of depression and/or anxiety (hazard ratio [HR]: 1.14, 95% CI: 1.10-1.19), depression (HR: 1.19, 95% CI: 1.13-1.25) and anxiety (HR: 1.13, 95% CI: 1.07-1.19). Periodontal disease was also significantly associated with comorbid depression and anxiety (HR: 1.27, 95% CI: 1.16-1.38). Multiple mediation analysis using baseline inflammatory factors showed that white blood cell count and C-reactive protein explained 3.07% and 3.15% of the association between periodontal disease and depression and anxiety, respectively. However, the results of longitudinal multiple mediation analysis of inflammatory factors at first follow-up (N = 10,673) were not significant. CONCLUSIONS: Periodontal disease was found to be consistently associated with an increased risk of depression, anxiety and their comorbidity.
Assuntos
Ansiedade , Depressão , Saúde Bucal , Humanos , Estudos Transversais , Estudos Prospectivos , Masculino , Feminino , Reino Unido/epidemiologia , Saúde Bucal/estatística & dados numéricos , Pessoa de Meia-Idade , Depressão/epidemiologia , Ansiedade/epidemiologia , Idoso , Bancos de Espécimes Biológicos , Doenças Periodontais/epidemiologia , Adulto , Comorbidade , Biobanco do Reino UnidoRESUMO
. A sandwich-type photoelectrochemical (PEC) immunosensor based on a ZnO/poly(5-formylindole) (P5FIn)/anthocyanin heterostructure was developed to achieve sensitive background-free detection of the tumor marker CYFRA21-1. ZnO with good photovoltaic properties is combined with narrow bandgap P5FIn to form a p-n type heterojunction. This structure reduces the electron-hole pair recombination, thereby enhancing the photocurrent response of the composite. Anthocyanidins are environmentally friendly natural compounds with excellent antioxidant, redox properties, and remarkable electrochemical activity. After sensitization by anthocyanins, the absorption and utilization of visible light in the composites are enhanced, further improving the PEC luminescence efficiency of the materials. Additionally, boron nitride quantum dots (BN QDs) are combined with Ab2 via polydopamine (PDA) as a secondary antibody marker, enhancing its sensitivity. The biosensor exhibited a linear detection range of 0.001-100 ng mL-1 with a limit of detection (LOD) of 0.00033 ng mL-1. Furthermore, this biosensor demonstrates excellent selectivity, reproducibility, and stability, as well as successful results in analyzing actual human serum samples. This approach provides a feasible method for tumor marker detection.
Assuntos
Antocianinas , Antígenos de Neoplasias , Técnicas Biossensoriais , Técnicas Eletroquímicas , Queratina-19 , Limite de Detecção , Óxido de Zinco , Humanos , Técnicas Biossensoriais/métodos , Queratina-19/sangue , Queratina-19/imunologia , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Óxido de Zinco/química , Antígenos de Neoplasias/sangue , Antígenos de Neoplasias/imunologia , Antocianinas/química , Pontos Quânticos/química , Anticorpos Imobilizados/imunologia , Biomarcadores Tumorais/sangue , Imunoensaio/métodos , Polímeros/química , Reprodutibilidade dos Testes , Indóis/química , Processos FotoquímicosRESUMO
As a safe, effective, economical, and convenient technique, tooth whitening is one of the most popular treatments for improving tooth discoloration. This review summarizes the theoretical and recent research developments in the classification and mechanisms of tooth discoloration, as well as the principles, agents, effects, and side effects of tooth whitening techniques. The aim is to provide a basis for the clinical treatment of tooth whitening techniques and to suggest possible new ideas for further research. The accepted mechanism of whitening is the redox reaction of oxides in the whitening reagent, and the whitening effect is remarkable. However, side effects such as tooth sensitivity and irritation of gum and other oral soft tissues can still occur. It is recommended that more monitoring be carried out in the clinic to monitor these side effects, and care should be taken to protect the soft tissues in the mouth during office whitening procedures. Furthermore, there is a need to develop new additives or natural whitening products to reduce the occurrence of side effects.
Assuntos
Clareadores Dentários , Clareamento Dental , Clareamento Dental/métodos , Humanos , Descoloração de Dente/induzido quimicamenteRESUMO
Putatively, tooth agenesis was attributed to the initiation failure of tooth germs, though little is known about the histological and molecular alterations. To address if constitutively active FGF signaling is associated with tooth agenesis, we activated Fgf8 in dental mesenchyme with Osr-cre knock-in allele in mice (Osr2-creKI; Rosa26R-Fgf8) and found incisor agenesis and molar microdontia. The cell survival assay showed tremendous apoptosis in both the Osr2-creKI; Rosa26R-Fgf8 incisor epithelium and mesenchyme, which initiated incisor regression from cap stage. In situ hybridization displayed vanished Shh transcription, and immunostaining exhibited reduced Runx2 expression and enlarged mesenchymal Lef1 domain in Osr2-creKI; Rosa26R-Fgf8 incisors, both of which were suggested to enhance apoptosis. In contrast, Osr2-creKI; Rosa26R-Fgf8 molar germs displayed mildly suppressed Shh transcription, and the increased expression of Ectodin, Runx2 and Lef1. Although mildly smaller than WT controls prenatally, the Osr2-creKI; Rosa26R-Fgf8 molar germs produced a miniature tooth with impaired mineralization after a 6-week sub-renal culture. Intriguingly, the implanted Osr2-creKI; Rosa26R-Fgf8 molar germs exhibited delayed odontoblast differentiation and accelerated ameloblast maturation. Collectively, the ectopically activated Fgf8 in dental mesenchyme caused incisor agenesis by triggering incisor regression and postnatal molar microdontia. Our findings reported tooth agenesis resulting from the regression from the early bell stage and implicated a correlation between tooth agenesis and microdontia.
Assuntos
Fator 8 de Crescimento de Fibroblasto , Incisivo , Mesoderma , Dente Molar , Animais , Fator 8 de Crescimento de Fibroblasto/genética , Fator 8 de Crescimento de Fibroblasto/metabolismo , Camundongos , Incisivo/anormalidades , Incisivo/metabolismo , Mesoderma/metabolismo , Mesoderma/patologia , Dente Molar/anormalidades , Dente Molar/metabolismo , Anodontia/genética , Anodontia/metabolismo , Anodontia/patologia , Apoptose , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide/genética , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Transdução de Sinais , Regulação da Expressão Gênica no Desenvolvimento , Odontogênese/genética , Camundongos TransgênicosRESUMO
Although traditional nanomedicines have enhanced the therapeutic efficacy and improved the survival quality of cancer patients, random drug release and drug resistance are deep-rooted problems hindering their clinical application. A precise nanoplatform combing chemotherapy and photodynamic therapy (PDT) is developing as a new therapeutic strategy to overcome the above challenges. Herein, a novel supramolecular nanomedicine is ingeniously constructed for in situ self-boosting cancer photochemotherapy. Hydrophilic polyethylene glycol (PEG) chains or ß-cyclodextrin (ß-CD) hosts are first conjugated onto tetraphenyl porphyrin (TCPP) to improve the solubility of TCPP and decrease their π-π stacking interactions, guaranteeing a high-efficiency PDT. Then, two camptothecin (CPT) molecules are linked together via a reactive oxygen species (ROS)-responsive thioketal bond, which averts the premature burst release of CPT and realizes in situ drug release at the tumor site where PDT is performed, resulting in an enhanced chemotherapy. Benefiting from the collaboration of host-guest complexation between ß-CD and CPT, multiple intermolecular hydrogen bonds of ß-CD, π-π stacking interactions among CPT and TCPP as well as PEG shell protection, a prolonged blood circulation time, and a selective tumor accumulation are acquired, which facilitate the synergistic photochemotherapy and bring a pre-eminent antitumor response with a low systemic toxicity.
Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Nanomedicina Teranóstica , Fotoquimioterapia/métodos , Neoplasias/tratamento farmacológico , Nanomedicina , Polietilenoglicóis/química , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes , Nanopartículas/químicaRESUMO
Cultivated jute, which comprises the two species Corchorus capsularis and C. olitorius, is the second most important natural fibre source after cotton. Here we describe chromosome-level assemblies of the genomes of both cultivated species. The C. capsularis and C. olitorius assemblies are each comprised of seven pseudo-chromosomes, with the C. capsularis assembly consisting of 336 Mb with 25,874 genes and the C. olitorius assembly containing 361 Mb with 28 479 genes. Although the two Corchorus genomes exhibit collinearity, the genome of C. olitorius contains 25 Mb of additional sequences than that of C. capsularis with 13 putative inversions, which might give a hint to the difference of phenotypic variants between the two cultivated jute species. Analysis of gene expression in isolated fibre tissues reveals candidate genes involved in fibre development. Our analysis of the population structures of 242 cultivars from C. capsularis and 57 cultivars from C. olitorius by whole-genome resequencing resulted in post-domestication bottlenecks occurred ~2000 years ago in these species. We identified hundreds of putative significant marker-trait associations (MTAs) controlling fibre fineness, cellulose content and lignin content of fibre by integrating data from genome-wide association studies (GWAS) with data from analyses of selective sweeps due to natural and artificial selection in these two jute species. Among them, we further validated that CcCOBRA1 and CcC4H1 regulate fibre quality in transgenic plants via improving the biosynthesis of the secondary cell wall. Our results yielded important new resources for functional genomics research and genetic improvement in jute and allied fibre crops.
Assuntos
Corchorus , Corchorus/genética , Estudo de Associação Genômica Ampla , Genômica , Lignina , Análise de Sequência de DNARESUMO
BACKGROUND AND OBJECTIVES: To date, few studies have comprehensively explored the associations between milk and dairy product intake and dental caries. Therefore, this study aimed to simultaneously assess the associations between whole milk, low-fat milk, skim milk, yogurt, milk desserts, cheese, creams, and total fluid milk intake and the risk of dental caries in children and adolescents. METHODS AND STUDY DESIGN: Data were from the National Health and Nutrition Examination Survey (NHANES) 2011-2016. Two 24-hour dietary recall interviews measured dietary milk and dairy product intake. Primary teeth caries was diagnosed by the dfs (decayed or filled primary tooth surfaces) index, and permanent teeth caries was diagnosed by the DMFS (decayed, missing, or filled permanent tooth surfaces) index. We used logistic regression to explore the associations between milk and dairy product intake and the risk of dental caries. RESULTS: A total of 6885 individuals aged 2-17 years were included in this study. In the fully adjusted model, the odds ratios (95% confidence intervals) of dental caries were 0.66 (0.47-0.93) for intake ≥123 g/day of yogurt and 0.82 (0.69-0.98) for intake <22.6 g/day of cheese, as compared with non-consumers. CONCLUSIONS: Our study indicates that high yogurt and low cheese intake were associated with a decreased risk of dental caries among American children and adolescents. These findings may be applied to update and supplement the evidence that informs public health policies on milk and dairy products and the prevention of dental caries.
Assuntos
Queijo , Cárie Dentária , Adolescente , Animais , Criança , Laticínios , Cárie Dentária/epidemiologia , Humanos , Leite , Inquéritos Nutricionais , IogurteRESUMO
BACKGROUND: The performance of drug-coated balloons (DCBs) in femoropopliteal interventions has been proven through randomized trials in short lesions and lesions with relatively low proportion of occlusions. There is limited evidence of DCBs in long or occlusive lesions. This study is to investigate the efficacy of the paclitaxel-coated balloon for treatment of long and occlusive femoropopliteal arterial lesions. METHODS: A single-arm trial including 44 femoropopliteal lesions (chronic total occlusion (CTO) plus > 10 cm) treated with DCBs was performed to collect data of average 1-year follow-up. Endpoints contain primary patency, target lesion revascularization (TLR), amelioration of the Rutherford classification, change of ankle brachial index (ABI) and major adverse events. RESULTS: Technical success is 97.7% while device success is 100%. Mean lesion length was 186 ± 86.3 cm. Stent implantation was performed in 13.6%. Cumulative probability of primary patency was 78.8% ± 6.8% at 1 year while that of freedom from TLR was 91.4% ± 4.9%. Rutherford classification improved from average 3.3 ± 1.0 to 2.1 ± 1.4 (p < 0.001) at follow-up with a 72.7% amelioration rate. Ankle-branchial index changed from 0.33 ± 0.40 to 0.67 ± 0.37 (p = 0.002). No major adverse event was observed. CONCLUSION: These results suggest that it is safe and effective to treat long and totally occlusive femoropopliteal artery disease with DCBs. Further studies are demanded to confirm these results.
Assuntos
Angioplastia com Balão/instrumentação , Fármacos Cardiovasculares/administração & dosagem , Materiais Revestidos Biocompatíveis , Artéria Femoral , Paclitaxel/administração & dosagem , Doença Arterial Periférica/terapia , Artéria Poplítea , Idoso , Idoso de 80 Anos ou mais , Angioplastia com Balão/efeitos adversos , Pequim , Constrição Patológica , Feminino , Artéria Femoral/diagnóstico por imagem , Artéria Femoral/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
Neutrophils can responsively release reactive oxygen species (ROS) to actively combat infections by exogenous stimulus and cascade enzyme catalyzed bio-oxidation. A supramolecular nanogel is now used as an artificial neutrophil by enzymatic interfacial self-assembly of peptides (Fmoc-Tyr(H2 PO3 )-OH) with magnetic nanoparticles (MNPs) and electrostatic loading of chloroperoxidase (CPO). The MNPs within the nanogel can elevate H2 O2 levels in cancer cells under programmed alternating magnetic field (AMF) similar to the neutrophil activator, and the loaded CPO within protective peptides nanolayer converts the H2 O2 into singlet oxygen (1 O2 ) in a sustained manner for neutrophil-inspired tumor therapy. As a proof of concept study, both the H2 O2 and 1 O2 in cancer cells increase stepwise under a programmed alternating magnetic field. An active enzyme dynamic therapy by magnetically stimulated oxygen stress and sustained enzyme bio-oxidation is thus shown with studies on both cells and animals.
Assuntos
Cloreto Peroxidase/metabolismo , Nanopartículas de Magnetita/química , Nanogéis/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cloreto Peroxidase/química , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Campos Magnéticos , Camundongos , Nanogéis/uso terapêutico , Nanogéis/toxicidade , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neoplasias/patologia , Neutrófilos/química , Neutrófilos/imunologia , Tamanho da Partícula , Peptídeos/química , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo , Eletricidade Estática , Taxa de Sobrevida , Transplante HeterólogoRESUMO
Design and construction of multifunctional theranostic nanoplatforms are still desired for cancer-effective treatment. Herein, a kind of polypyrrole (PPy)-based multifunctional nanocomposite was designed and successfully constructed for dual-model imaging and enhanced synergistic phototherapy against cancer cells. Through graphene oxide (GO) sheet coating, PPy nanoparticles (NPs) were effectively combined with polyethylene glycol chains, Au NPs, and IR820 molecules. The obtained PGPAI NPs showed promising ability for photoacoustic/computed tomography imaging. Under near-infrared light irradiation, the PPy core and IR820 molecule effectively generated heat and reactive oxygen species (ROS), respectively. Furthermore, the loaded Au NPs owning catalase-like activity produced oxygen by decomposing H2O2 (up-regulated in tumor region), enhancing the oxygen-dependent photodynamic therapy efficacy. The formed PGPAI NPs were also proved to own desirable photothermal conversion efficiency, photothermal stability, colloidal stability, cytocompatibility, and cellular internalization behaviors. Furthermore, cell assay demonstrated that PGPAI NPs displayed enhanced synergistic phototherapy efficacy against cancer cells. These developed multifunctional nanoplatforms are promising for effective cancer theranostic applications.
Assuntos
Nanocompostos/química , Imagem Óptica , Fototerapia , Polímeros/química , Pirróis/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Humanos , Camundongos , Tamanho da Partícula , Polímeros/farmacologia , Pirróis/farmacologia , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Propriedades de SuperfícieRESUMO
Functionalized nanomaterials with near-infrared (NIR) responsive capacity are quite promising for theranostic treatment of tumors, but formation of NIR responsive nanomaterials with enhanced theranostic ability and excellent biocompatibility is still very challenging. Herein, PEGylated indocyanine green (ICG)-loaded polypyrrole nanoparticles (PPI NPs) were designed and successfully formed through selecting polydopamine as the linkage between each component, demonstrating enhanced NIR responsive theranostic ability against tumor. By combining in vitro cell study with in vivo assay, the formed PPI NPs were proven to be fantastically biocompatible while effectively internalization in HeLa cells and retention in HeLa tumor were demonstrated by in vitro flow cytometry/confocal measurement and in vivo photoacoustic imaging assay. With the guidance of photoacoustic imaging, successful photothermal ablation of tumor was achieved by treatment with PPI NPs plus laser, which was much more effective than the group treated with NPs free of ICG. The combined enhanced photoacoustic and photothermal effect is mainly ascribed to the functionalized polypyrrole nanoparticles, which could accumulate in the tumor site more effectively with a relatively longer retention time taking advantage of the nanomaterial-induced endothelial leakiness phenomenon. All these results demonstrating that this designed PPI NPs possessing enhanced NIR responsive property hold great promise for tumor NIR theranostic applications.
Assuntos
Hipertermia Induzida/métodos , Nanopartículas/química , Neoplasias Experimentais/terapia , Técnicas Fotoacústicas/métodos , Fototerapia/métodos , Animais , Células HeLa , Humanos , Verde de Indocianina/química , Indóis/química , Raios Infravermelhos/uso terapêutico , Camundongos , Camundongos Nus , Nanopartículas/efeitos adversos , Nanopartículas/uso terapêutico , Neoplasias Experimentais/diagnóstico por imagem , Polietilenoglicóis/química , Polímeros/química , Pirróis/químicaRESUMO
The purpose of this study was to research a novel combination of Plasdone-S630 and HPMCAS-HF as hot-melt carrier used in ziprasidone hydrochloride for enhanced oral bioavailability and dismissed food effect. Ziprasidone hydrochloride solid dispersion (ZH-SD) was prepared by hot-melt extrusion technique, and its optimized formulation was selected by the central composite design (CCD), which was characterized for powder X-ray diffraction (PXRD), fourier transform infrared spectroscopy (FTIR), in vitro dissolution study, and stability study. Finally, the in vivo study in fasted/fed state was carried out in beagle dogs. Based on PXRD analysis, HME technique successfully dispersed ziprasidone with a low crystallinity hydrochloride form in the polymers. According to the analysis of FTIR, hydrogen bonds were formed between drug and polymers during the process of HME. Without any noticeable bulk, crystalline could be found from the micrograph of ZH-SD when analyzed the result of scanning electron microscope (SEM). Pharmacokinetics studies indicated that the bioavailability of ZH-SD formulation had no significant difference in fasted and fed state, and the Cmax and AUC of ZH-SD were two fold higher than Zeldox® in fasted state. This result indicated that ziprasidone has achieved a desired oral bioavailability in fasted state and no food effect.
Assuntos
Jejum , Metilcelulose/análogos & derivados , Piperazinas/síntese química , Povidona/síntese química , Tiazóis/síntese química , Administração Oral , Animais , Disponibilidade Biológica , Cães , Combinação de Medicamentos , Jejum/metabolismo , Metilcelulose/administração & dosagem , Metilcelulose/síntese química , Metilcelulose/metabolismo , Excipientes Farmacêuticos/administração & dosagem , Excipientes Farmacêuticos/metabolismo , Piperazinas/administração & dosagem , Piperazinas/farmacocinética , Povidona/administração & dosagem , Povidona/metabolismo , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Tiazóis/administração & dosagem , Tiazóis/farmacocinética , Difração de Raios X/métodosRESUMO
Despite significant advances in therapy, the 5-year survival rates for patients with advanced stage oral cancers still remains poor as an appropriate treatment has not been found yet, due to side effects of chemo/radiotherapy. Verbascoside (VB), a major bioactive constituent of the Tsoong herb, displays pharmacological properties by exhibiting anti-oxidative, anti-inflammatory and anti-cancer activities. However, the underlining function and mechanism of VB in human oral squamous cell carcinoma (OSCC) remains unclear. In this study, we show that VB significantly decreased the viability and metastasis of HN4 and HN6 tumor cells, while promoting apoptosis. A xenograft OSCC mouse model further showed that intraperitoneal injection of VB strongly inhibited growth and lung metastasis of implanted tumor cells. Immunoblot analysis confirmed that VB effectively suppressed nuclear factor (NF)-κB activation and downstream Bcl-2/Bcl-XL expression, resulting in increased OSCC cell apoptosis. In addition, VB suppressed mRNA and protein expression of matrix metalloproteinase-9 via suppression of NF-κB activation, thereby inhibiting tumor cell metastasis. Inspiringly, compared to cisplatin-treated group, VB is a biocompatible agent without signficant side effects in vivo. Collectively, our results demonstrate that VB effectively inhibits OSCC tumor cell growth and metastasis via suppression of IκB kinase complex (IKK)/NF-κB-related signaling activation, suggesting that VB has potential use as a potent anticancer agent in OSCC therapeutic strategies.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/patologia , Glucosídeos/farmacologia , Neoplasias Bucais/patologia , Fenóis/farmacologia , Animais , Materiais Biocompatíveis , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Quinase I-kappa B/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Bucais/metabolismo , NF-kappa B/metabolismo , Invasividade Neoplásica/prevenção & controle , Metástase Neoplásica , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína X Associada a bcl-2/metabolismoRESUMO
Although demanding, the development of multifunctional theranostic nanoplatforms is attracting considerable worldwide interest. Herein, a theranostic nanoplatform with multifunctions based on polydopamine (PDA) nanoparticles (NPs) was developed, owning dual-imaging and dual-therapy functions for cancer theranostic applications. PDA NPs were generated using a facile polymerization method under alkaline conditions, followed by poly(ethylene glycol) (PEG) modification. Then, the obtained NPs were loaded with IR820 and Fe3+ ions to produce the final PEGylated PDA/IR820/Fe3+ (PPIF) NPs. The PPIF NPs thus generated displayed increasingly brighter photoacoustic and magnetic resonance signals with increasing NP concentration and were demonstrated to be cytocompatible and effectively taken up and internalized into HeLa cells. Under near-infrared light irradiation, PPIF NPs can produce heat and reactive oxygen species for photothermal/photodynamic combined cancer therapy. In this study, the versatility of PDA NPs was demonstrated to be promising as a multifunctional nanoplatform for potential cancer theranostic applications.
Assuntos
Antineoplásicos/farmacologia , Verde de Indocianina/análogos & derivados , Ferro/química , Nanopartículas/química , Radiossensibilizantes/farmacologia , Nanomedicina Teranóstica/métodos , Animais , Antineoplásicos/efeitos da radiação , Células HeLa , Calefação , Humanos , Verde de Indocianina/farmacologia , Verde de Indocianina/efeitos da radiação , Indóis/síntese química , Indóis/química , Indóis/toxicidade , Raios Infravermelhos , Camundongos , Nanopartículas/toxicidade , Tamanho da Partícula , Técnicas Fotoacústicas/métodos , Polietilenoglicóis/química , Polietilenoglicóis/toxicidade , Polímeros/síntese química , Polímeros/química , Polímeros/toxicidade , Radiossensibilizantes/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismoRESUMO
Toll-like receptors (TLRs) act as molecular sentinels, detecting invading viral pathogens and triggering host innate immune responses, including autophagy. However, many viruses have evolved a series of strategies to manipulate autophagy for their own benefit. Enterovirus 71 (EV71) and coxsackievirus A16 (CA16), as the primary agents causing hand, foot and mouth disease (HFMD), can induce autophagy leading to their replication. Therefore, the objective of this study was to investigate whether enhanced viral replication caused by autophagy in EV71 and CA16 infections was associated with a TLR-related signaling pathway. Our results demonstrate that complete autophagy and incomplete autophagy were observed in human bronchial epithelial (16HBE) cells infected with EV71 and CA16. Moreover, suppression of autophagy by the pharmacological modulator 3-MA significantly and clearly decreased the survival rates and viral replication of EV71 and CA16 in 16HBE cells. Inhibition of autophagy also enhanced the expression of molecules related to the TLR7-dependent type I interferon (IFN-I) production pathway, such as TLR7, MyD88, IRF7 and IFN-α/ß. Finally, immunofluorescence staining demonstrated that TLR7 endosome marker M6PR levels were clearly reduced in EV71- and CA16-infected cells, while they were markedly elevated in infected cells treated with 3-MA. These findings suggest that increased EV71 and CA16 replication meditated by autophagy in 16HBE cells might promote degradation of the endosome, leading to suppression of the TLR7-mediated IFN-I signaling pathway.
Assuntos
Autofagia , Enterovirus Humano A/fisiologia , Enterovirus/fisiologia , Interferon Tipo I/metabolismo , Receptor 7 Toll-Like/metabolismo , Replicação Viral/fisiologia , Animais , Linhagem Celular , Chlorocebus aethiops , Humanos , Interferon-alfa/genética , Interferon-alfa/metabolismo , Interferon beta/genética , Interferon beta/metabolismo , Plasmídeos , Transdução de Sinais/fisiologia , Células VeroRESUMO
The biodegradation rates of carbon nanotube (CNT)/ polymer nanocomposites (PNCs) containing poly-ε-caprolactone (PCL) were investigated using Pseudomonas aeruginosa, a microorganism commonly found in the environment. CNT/PCL nanocomposite mass loss profiles revealed that the rate of PCL matrix biodegradation decreased systematically as the CNT loading increased from 0.1 to 10% w/w. Addition of even a low CNT loading (<1% w/w) caused the CNT/PCL biodegradation rate constant to decrease by more than 50%. Similar trends in biodegradation rate were observed for both pristine and oxidized multiwall CNTs embedded in PCL. During PCL matrix biodegradation, CNT accumulation was observed at the surface of CNT/PCL nanocomposites and single particle inductively coupled-mass spectrometry experiments revealed no measurable CNT release to the culture fluid. Experimental data indicated that biodegradation proceeded as a result of biofilm formation on the CNT/PCL nanocomposites and decreased as a function of CNT loading due to the cytotoxicity of CNTs toward P. aeruginosa and the physical barrier presented by the surface-accumulated CNTs to the underlying PCL substrate. As the CNT loading in the CNT/PCL nanocomposites increased, the microbial proliferation of planktonic cells in the surrounding media also decreased as did the biodegradation rate of PCL samples present in the same reactors. Results from this study demonstrate that the inclusion of CNTs into polymer matrices could increase the environmental persistence of polymers in lakes, landfills, and surface waters.
Assuntos
Nanocompostos , Nanotubos de Carbono , Biodegradação Ambiental , Polímeros , Pseudomonas aeruginosaRESUMO
Voltage-gated sodium (Na(v)) channels are essential for the rapid depolarization of nerve and muscle, and are important drug targets. Determination of the structures of Na(v) channels will shed light on ion channel mechanisms and facilitate potential clinical applications. A family of bacterial Na(v) channels, exemplified by the Na(+)-selective channel of bacteria (NaChBac), provides a useful model system for structure-function analysis. Here we report the crystal structure of Na(v)Rh, a NaChBac orthologue from the marine alphaproteobacterium HIMB114 (Rickettsiales sp. HIMB114; denoted Rh), at 3.05 Å resolution. The channel comprises an asymmetric tetramer. The carbonyl oxygen atoms of Thr 178 and Leu 179 constitute an inner site within the selectivity filter where a hydrated Ca(2+) resides in the crystal structure. The outer mouth of the Na(+) selectivity filter, defined by Ser 181 and Glu 183, is closed, as is the activation gate at the intracellular side of the pore. The voltage sensors adopt a depolarized conformation in which all the gating charges are exposed to the extracellular environment. We propose that Na(v)Rh is in an 'inactivated' conformation. Comparison of Na(v)Rh with Na(v)Ab reveals considerable conformational rearrangements that may underlie the electromechanical coupling mechanism of voltage-gated channels.
Assuntos
Alphaproteobacteria/química , Proteínas de Bactérias/química , Ativação do Canal Iônico , Canais de Sódio/química , Sequência de Aminoácidos , Proteínas de Bactérias/metabolismo , Cristalização , Cristalografia por Raios X , Células HEK293 , Humanos , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , Canais de Sódio/metabolismo , Relação Estrutura-AtividadeRESUMO
Degradation rate is an important index for evaluating biomaterials. The authors' aim was to determine whether the degradation rate of biomaterials is different in distinct tissues and to clarify the underlying mechanism of degradation. The collagen-chitosan (CG-CS) composite scaffolds were prepared using freeze-drying technology. The porosity, water absorption and swelling ratio of the scaffolds were tested in vitro. The scaffolds were implanted into the subcutis, spinal cord and brain tissues of SD rats, the rate of degradation was assessed by continuous monitoring of weight loss, the pathological changes of target areas were observed by histological staining, and matrix metalloproteinase 9 (MMP-9) and lysozyme were detected at the rapid stage of degradation of the scaffolds. Physical and chemical property testing confirmed that CG-CS composite scaffold components can meet the biological requirements of in vivo transplantation. The in vivo experimental results showed that the scaffolds were completely absorbed in the subcutis at 12 days, the scaffolds in the spinal cord and brain groups exhibited progressive mass loss starting from the 3rd week, and a substantial fraction of the scaffold was degraded at 12 weeks. HE staining found that compared with the spinal cord and brain groups, macrophages and capillaries appeared earlier in the subcutis group, and the number was significantly higher (P < 0.05). Western blot analysis showed that the MMP-9 and lysozyme levels in the subcutis were higher than those in the spinal cord and brain (P < 0.05). The results of in vivo experiments demonstrated that the CG-CS scaffold has good biocompatibility and biodegradability, while the rate of degradation was significantly different between the three tissues at the same time point. Macrophage behavior and vascularization in different parts of the body may result in control over the balance of degradation and reconstruction.
Assuntos
Encéfalo/metabolismo , Quitosana/química , Colágeno/química , Medula Espinal/metabolismo , Alicerces Teciduais/química , Animais , Materiais Biocompatíveis , Microscopia Eletrônica de Varredura , Ratos , Ratos Sprague-Dawley , Engenharia Tecidual/métodosRESUMO
This study explored a bidirectional impact on the recognition accuracy of various facial expressions deriving from both the observer and sender in a sample of Chinese participants. A facial manipulation task was used to examine the ability of an observer's facial feedback to modulate the recognition of various facial expressions. Furthermore, the effect of a sender's facial expression with an open or closed mouth on recognition accuracy was investigated. The results showed that only recognition accuracy of a sad facial expression was influenced simultaneously by bidirectional sources from a sender and observer. Moreover, the impact of the unidirectional cue of a sender's facial feature (i.e., mouth openness) on happy and neutral faces was found to influence the recognition accuracy of these faces, but not the observer's bodily state. These findings indicate that the bidirectional impact derived from an observer and sender on facial expression recognition accuracy differs for emotional and neutral expressions.
Assuntos
Emoções/fisiologia , Expressão Facial , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: Enterovirus 71 (EV71) is a major cause of hand, foot, and mouth disease in children and may be fatal. A vaccine against EV71 is needed. METHODS: We conducted a randomized, double-blind, placebo-controlled phase 3 trial involving healthy children 6 to 71 months of age in Guangxi Zhuang Autonomous Region, China. Two doses of an inactivated EV71 vaccine or placebo were administered intramuscularly, with a 4-week interval between doses, and children were monitored for up to 11 months. The primary end point was protection against hand, foot, and mouth disease caused by EV71. RESULTS: A total of 12,000 children were randomly assigned to receive vaccine or placebo. Serum neutralizing antibodies were assessed in 549 children who received the vaccine. The seroconversion rate was 100% 4 weeks after the two vaccinations, with a geometric mean titer of 170.6. Over the course of two epidemic seasons, the vaccine efficacy was 97.4% (95% confidence interval [CI], 92.9 to 99.0) according to the intention-to-treat analysis and 97.3% (95% CI, 92.6 to 99.0) according to the per-protocol analysis. Adverse events, such as fever (which occurred in 41.6% of the participants who received vaccine vs. 35.2% of those who received placebo), were significantly more common in the week after vaccination among children who received the vaccine than among those who received placebo. CONCLUSIONS: The inactivated EV71 vaccine elicited EV71-specific immune responses and protection against EV71-associated hand, foot, and mouth disease. (Funded by the National Basic Research Program and others; ClinicalTrials.gov number, NCT01569581.).