Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Nanotechnology ; 34(21)2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36753747

RESUMO

The development of high efficiency oxygen evolution electrocatalyst is of great significance for water splitting reaction. Herein, an efficient cone-structured NiFe-LDH/Nicone/Ti catalyst is fabricated by electrodeposition method towards enhanced oxygen evolution reaction (OER). The featured tip curvature of nanocone structure can accelerate the reaction kinetics of OER by offering a field-enhanced aggregation of local hydroxide ion reactant on the catalyst surface, and thus improves the performance of the NiFe catalyst. Accordingly, NiFe-LDH/Nicone/Ti requires only a low overpotential of 292 mV to achieve 50 mA cm-2, and with high stability under continuous high-current operations. In addition, the alkali-electrolyzer using NiFe-LDH/Nicone/Ti electrode exhibits good performance with a voltage of 1.73 V at 50 mA cm-2and displays excellent stability in long-term stability test. This cone-structured catalyst design with field-enhanced local hydroxide ion aggregation effect provides a promising method for the development of highly active OER electrocatalysts.

2.
Nanotechnology ; 33(15)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-34952529

RESUMO

Developing efficient and stable multifunctional electrocatalyst is very important for zinc-air batteries in practical. Herein, semiconductive spinel CuFe2O4supported Co-N co-doped carbon (Co-NC) and CoFe alloy nanoparticles were proposed. In this strategy, the three-dimensional ordered macroporous CuFe2O4support provides rich channels for mass transmission, revealling good corrosion-resistance and durability at the same time. ZIF-67 derived Co-NC decoration improves the conductivity of the catalyst. Further, the uniformly distributed Co-NC and CoFe nanoparticles (C/CF) dramatically promote the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) performance. Accordingly, C/CF@CuFe2O4catalyst shows remarkable bifunctional electrocatalytic activity, with an ORR half-wave potential of 0.86 V, and an OER over-potential of 0.46 V at 10 mA cm-2. The zinc-air battery using this catalyst exhibits a power density of 95.5 mW cm-2and a durable cyclability for over 170 h at a current density of 10 mA cm-2, which implies a great potential in practical application.

3.
J Virol ; 88(16): 9379-90, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24920808

RESUMO

UNLABELLED: Viruses take advantage of host posttranslational modifications for their own benefit. It was recently reported that influenza A virus proteins interact extensively with the host sumoylation system. Thereby, several viral proteins, including NS1 and M1, are sumoylated to facilitate viral replication. However, to what extent sumoylation is exploited by influenza A virus is not fully understood. In this study, we found that influenza A virus nucleoprotein (NP) is a bona fide target of sumoylation in both NP-transfected cells and virus-infected cells. We further found that NP is sumoylated at the two most N-terminal residues, lysines 4 and 7, and that sumoylation at lysine 7 of NP is highly conserved across different influenza A virus subtypes and strains, including the recently emerged human H7N9 virus. While NP stability and polymerase activity are little affected by sumoylation, the NP sumoylation-defective WSN-NPK4,7R virus exhibited early cytoplasmic localization of NP. The growth of the WSN-NPK4,7R virus was highly attenuated compared to that of the wild-type WSN virus, and the lysine residue at position 7 is indispensable for the virus's survival, as illustrated by the rapid emergence of revertant viruses. Thus, sumoylation of influenza A virus NP is essential for intracellular trafficking of NP and for virus growth, illustrating sumoylation as a crucial strategy extensively exploited by influenza A virus for survival in its host. IMPORTANCE: Host posttranslational modifications are heavily targeted by viruses for their own benefit. We and others previously reported that influenza A virus interacts extensively with the host sumoylation system. However, the functional outcomes of viral sumoylation are not fully understood. Here we found that influenza A virus nucleoprotein (NP), an essential component for virus replication, is a new target of SUMO. This is the first study to find that NP from different influenza A viruses, including recently emerged H7N9, is sumoylated at conserved lysine 7. Our data further illustrated that sumoylation of influenza A virus NP is essential for intracellular trafficking of NP and virus growth, indicating that influenza A virus relies deeply on sumoylation to survive in host cells. Strategies to downregulate viral sumoylation could thus be a potential antiviral treatment.


Assuntos
Subtipo H7N9 do Vírus da Influenza A/metabolismo , Vírus da Influenza A/metabolismo , Transporte Proteico/genética , Proteínas de Ligação a RNA/metabolismo , Sumoilação/genética , Proteínas do Core Viral/metabolismo , Proteínas Virais/metabolismo , Animais , Linhagem Celular , Linhagem Celular Tumoral , Cães , Células HEK293 , Interações Hospedeiro-Patógeno/genética , Humanos , Subtipo H7N9 do Vírus da Influenza A/genética , Vírus da Influenza A/genética , Lisina/genética , Lisina/metabolismo , Células Madin Darby de Rim Canino , Proteínas do Nucleocapsídeo , Proteínas de Ligação a RNA/genética , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Proteínas do Core Viral/genética , Proteínas Virais/genética , Replicação Viral/genética
4.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 32(2): 489-92, 2015 Apr.
Artigo em Zh | MEDLINE | ID: mdl-26211278

RESUMO

Cobalt or chromium alloys are the most common clinical materials of prosthesis and there have been some investigators at home and abroad have done related researches about the genotoxic effects of cobalt and chromium ions and nanoparticles. People have certain understanding about the mechanism of production of ions as well as their influence on cells. However, chromium or cobalt nanoparticles genotoxicity related research is still in its preliminary stage. In each stage, the mechanisms, from creating of the particles, through entering cells, until finally causing genotoxic, are still contained many problems to be solved. This article reviews the research progress in mechanisms of production and genotoxic effects of cobalt, chromium ions and nanoparticles.


Assuntos
Cromo/toxicidade , Cobalto/toxicidade , Dano ao DNA , Nanopartículas/toxicidade , Próteses e Implantes , Humanos , Íons
5.
J Biol Chem ; 288(49): 35093-103, 2013 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-24129573

RESUMO

Although lysine methylation is classically known to regulate histone function, its role in modulating antiviral restriction factor activity remains uncharacterized. Interferon-induced transmembrane protein 3 (IFITM3) was found monomethylated on its lysine 88 residue (IFITM3-K88me1) to reduce its antiviral activity, mediated by the lysine methyltransferase SET7. Vesicular stomatitis virus and influenza A virus infection increased IFITM3-K88me1 levels by promoting the interaction between IFITM3 and SET7, suggesting that this pathway could be hijacked to support infection; conversely, IFN-α reduced IFITM3-K88me1 levels. These findings may have important implications in the design of therapeutics targeting protein methylation against infectious diseases.


Assuntos
Histona-Lisina N-Metiltransferase/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular , Chlorocebus aethiops , Técnicas de Silenciamento de Genes , Células HEK293 , Histona-Lisina N-Metiltransferase/antagonistas & inibidores , Histona-Lisina N-Metiltransferase/genética , Humanos , Vírus da Influenza A/imunologia , Vírus da Influenza A/patogenicidade , Interferon Tipo I/metabolismo , Lisina/química , Proteínas de Membrana/genética , Metilação , Dados de Sequência Molecular , Processamento de Proteína Pós-Traducional , Proteínas de Ligação a RNA/genética , Transdução de Sinais , Células Vero , Vesiculovirus/imunologia , Vesiculovirus/patogenicidade , Viroses/imunologia , Viroses/metabolismo , Viroses/prevenção & controle
6.
Macromol Biosci ; : e2400027, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38462911

RESUMO

Addressing complex tissue infections remains a challenging task because of the lack of effective means, and the limitations of traditional bioantimicrobial materials in single-application scenarios hinder their utility for complex infection sites. Hence, the development of a bioantimicrobial material with broad applicability and potent bactericidal activity is necessary to treat such infections. In this study, a layered lithium magnesium silicate nanoclay (LMS) is used to construct a nanobactericidal platform. This platform exhibits a sandwich-like structure, which is achieved through copper ion modification using a dopamine-mediated metallophenolic network. Moreover, the nanoclay is encapsulated within gelatin methacryloyl (GelMA) hydrogel microspheres for the treatment of complex tissue infections. The results demonstrate that the sandwich-like micro- and nanobactericidal hydrogel microspheres effectively eradicated Staphylococcus aureus (S. aureus) while exhibiting excellent biocompatibility with bone marrow-derived mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs). Furthermore, the hydrogel microspheres upregulated the expression levels of osteogenic differentiation and angiogenesis-related genes in these cells. In vivo experiments validated the efficacy of sandwich-like micro- and nanobactericidal hydrogel microspheres when injected into deep infected tissues, effectively eliminating bacteria and promoting robust vascular regeneration and tissue repair. Therefore, these innovative sandwich-like micro- and nanobacteriostatic hydrogel microspheres show great potential for treating complex tissue infections.

7.
Technol Health Care ; 31(6): 2165-2192, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37302054

RESUMO

BACKGROUND: The emergency rescue ability of firefighters is particularly important in the event of major disasters or accidents. Therefore, an assessment of the firefighter-training effectiveness is necessary. OBJECTIVE: This paper aims to achieve a scientific and effective assessment of the firefighter-training effectiveness in China. An assessment method based on human factor parameters and machine learning was proposed. METHOD: The model is constructed by collecting the corresponding human factor parameters such as electrocardiographic signals, electroencephalographic signals, surface electromyographic signals, and photoplethysmographic signals through wireless sensors and using them as constraint indicators. For the problems of weak human factor parameters and high noise proportion, an improved flexible analytic wavelet transform algorithm is used to denoise and extract the corresponding feature values. To overcome the limitations of traditional assessment methods, improved machine learning algorithms are used to comprehensively assess the training effectiveness of firefighters and provide targeted training suggestions. RESULTS: The effectiveness of this study's evaluation method is verified by comparing it with the expert scoring method and considering firefighters from a special fire station in Xhongmen, Daxing District, Beijing, as an example. CONCLUSION: This study can effectively guide the scientific training of firefighters and the method is more objective and accurate than the traditional method.


Assuntos
Bombeiros , Humanos , China , Eletrocardiografia , Aprendizado de Máquina , Fotopletismografia
8.
J Virol ; 85(2): 1086-98, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21047957

RESUMO

Nonstructural protein 1 (NS1) is one of the major factors resulting in the efficient infection rate and high level of virulence of influenza A virus. Although consisting of only approximately 230 amino acids, NS1 has the ability to interfere with several systems of the host viral defense. In the present study, we demonstrate that NS1 of the highly pathogenic avian influenza A/Duck/Hubei/L-1/2004 (H5N1) virus interacts with human Ubc9, which is the E2 conjugating enzyme for sumoylation, and we show that SUMO1 is conjugated to H5N1 NS1 in both transfected and infected cells. Furthermore, two lysine residues in the C terminus of NS1 were identified as SUMO1 acceptor sites. When the SUMO1 acceptor sites were removed by mutation, NS1 underwent rapid degradation. Studies of different influenza A virus strains of human and avian origin showed that the majority of viruses possess an NS1 protein that is modified by SUMO1, except for the recently emerged swine-origin influenza A virus (S-OIV) (H1N1). Interestingly, growth of a sumoylation-deficient WSN virus mutant was retarded compared to that of wild-type virus. Together, these results indicate that sumoylation enhances NS1 stability and thus promotes rapid growth of influenza A virus.


Assuntos
Interações Hospedeiro-Patógeno , Virus da Influenza A Subtipo H5N1/patogenicidade , Proteína SUMO-1/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , Proteínas não Estruturais Virais/metabolismo , Animais , Linhagem Celular , Cães , Humanos , Imuno-Histoquímica , Vírus da Influenza A Subtipo H1N1/genética , Lisina/genética , Lisina/metabolismo , Microscopia Confocal , Mutagênese Sítio-Dirigida , Ligação Proteica , Sumoilação , Técnicas do Sistema de Duplo-Híbrido , Proteínas não Estruturais Virais/genética , Virulência
9.
Adv Sci (Weinh) ; 9(4): e2104237, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34850599

RESUMO

Rational design of metal oxide supported non-precious metals is essential for the development of stable and high-efficiency oxygen reduction reaction (ORR) electrocatalysts. Here, an efficient ORR catalyst consisting of binary Fe/Co nanoclusters supported by defective tungsten oxide and embedded N-doped carbon layer (NC) with a 3D ordered macroporous architecture (3DOM Fe/Co@NC-WO2- x ) is developed. The oxygen deficient 3DOM WO2- x not only serves as a porous and stable support, but also enhances the conductivity and ensures good dispersion of the binary Fe/Co nanocluster, benefiting its ORR catalytic activity. Theoretical calculation shows that there exists a synergistic effect of electron transfer from Fe to Co in the supported binary Fe/Co cluster, promoting the ORR reaction energetics. Accordingly, the 3DOM Fe/Co@NC-WO2- x catalyst exhibits excellent ORR activity in alkaline medium with a half wave potential (E1/2 ) of 0.87 V higher than that of Pt/C (0.85 V). The zinc-air batteries assembled by 3DOM Fe/Co@NC-WO2- x cathode deliver a higher power density and specific capacity than that of Pt/C. A new strategy of combining synergistic binary-metal nanoclusters and conductive metal oxide support design is provided here to develop efficient and durable ORR electrocatalyst.

10.
Mol Ther Nucleic Acids ; 27: 1103-1115, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35228903

RESUMO

Despite the existence of a prophylactic vaccine against hepatitis B virus (HBV), chronic hepatitis B virus (CHB) infection remains the leading cause of cirrhosis and liver cancer in developing countries. Because HBV persistence is associated with insufficient host immune responses to the infection, development of an immunomodulator as a component of therapeutic vaccination may become an important strategy for treatment CHB. In the present study, we aimed to design a novel immunomodulator with the capacity to subvert immune tolerance to HBV. We developed a lymphoid organ-targeting immunomodulator by conjugating a naturally occurring, lipophilic molecule, α-tocopherol, to a potent CpG oligonucleotide adjuvant pharmacophore. This approach resulted in preferential trafficking of the α-tocopherol-conjugated oligonucleotide to lymphoid organs where it was internalized by antigen-presenting cells (APCs). Moreover, we show that conjugation of the oligonucleotides to α-tocopherol results in micelle-like structure formation, which improved cellular internalization and enhanced immunomodulatory properties of the conjugates. In a mouse model of chronic HBV infection, targeting CpG oligonucleotide to lymphoid organs induced strong cellular and humoral immune responses that resulted in sustained control of the virus. Given the potency and tolerability of an α-tocopherol-conjugated CpG oligonucleotide, this modality could potentially be broadly applied for therapeutic vaccine development.

11.
Antiviral Res ; 196: 105196, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34718044

RESUMO

JNJ-64794964 (JNJ-4964/AL-034/TQ-A3334), an oral toll-like receptor 7 agonist, is being investigated for the treatment of chronic hepatitis B (CHB), a condition with a high unmet medical need. The anti-hepatitis B (HBV) activity of JNJ-4964 was assessed preclinically in an adeno-associated virus vector expressing HBV (AAV/HBV) mouse model. Mice were treated orally with 2, 6 or 20 mg/kg of JNJ-4964 once-per-week for 12 weeks and then followed up for 4 weeks. At 6 mg/kg, a partial decrease in plasma HBV-DNA and plasma hepatitis B surface antigen (HBsAg) was observed, and anti-HBs antibodies and HBsAg-specific T cells were observed in 1/8 animals. At 20 mg/kg, plasma HBV-DNA and HBsAg levels were undetectable for all animals 3 weeks after start of treatment, with no rebound observed 4 weeks after JNJ-4964 treatment was stopped. High anti-HBs antibody levels were observed until 4 weeks after JNJ-4964 treatment was stopped. In parallel, HBsAg-specific immunoglobulin G-producing B cells and interferon-γ-producing CD4+ T cells were detected in the spleen. In 2/4 animals, liver HBV-DNA and HBV-RNA levels and liver hepatitis B core antigen expression dropped 4 weeks after JNJ-4964 treatment-stop. In these animals, HBsAg-specific CD8+ T cells were detectable. Throughout the study, normal levels of alanine aminotransferase were observed, with no hepatocyte cell death (end of treatment and 4 weeks later) and minimal infiltrations of B and T cells into the liver, suggesting induction of cytokine-mediated, non-cytolytic mechanisms.


Assuntos
Antivirais/uso terapêutico , Citocinas/sangue , Drogas em Investigação/uso terapêutico , Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Receptor 7 Toll-Like/agonistas , Animais , Antivirais/farmacologia , Citocinas/imunologia , Avaliação Pré-Clínica de Medicamentos , Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
12.
Mol Med Rep ; 16(5): 7591-7596, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28944833

RESUMO

The aim of the present study was to investigate the effects of cobalt nanoparticles (CoNPs) on the proliferation and differentiation of human osteoblasts in vitro, and to investigate the molecular mechanisms via which CoNPs affect proliferation and differentiation of osteoblasts. The MG­63 human osteoblast cell line was treated with different concentrations of CoNPs for 12 to 48 h in vitro. At each time point, cell morphology was observed and an MTT assay was performed to assess cell viability. Alkaline phosphatase (ALP), osteocalcin (BGLAP), collagen I (COL I), osteoprotegerin (OPG) and receptor activator of nuclear factor κ­B ligand mRNA expression levels, and ALP, BGLAP and COL protein expression levels, were assessed by reverse transcription­quantitative polymerase chain reaction and western blotting, respectively. The viability of MG­63 cells decreased significantly after treatment with CoNPs. As CoNP concentration increased, a higher growth inhibition and cell death was observed. Compared with CoNPs, treatment with the same concentration of Co2+ may have a greater inhibitory effect on the growth of MG­63 cells. CoNPs affected the mRNAs expression levels of ALP, BGLAP, COL I and OPG in MG­63 cells, and reduced the protein expression levels of ALP, BGLAP and COL I. In conclusion, the present study demonstrated that CoNPs induce cytotoxic effects on MG­63 cells by markedly reducing cell viability and inducing cell death at high concentrations. In addition, CoNPs may inhibit the function and differentiation of osteoblasts by affecting the mRNA and protein expression levels of associated genes. The results of the present study indicate that CoNPs may serve an important role in the aseptic loosening mechanism following total joint replacement surgery, particularly in situations where metal on metal prostheses are used. Further study into inhibiting this effect is required.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Cobalto/química , Nanopartículas Metálicas/toxicidade , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Humanos , Nanopartículas Metálicas/química , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogênese/efeitos dos fármacos , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismo , RNA Mensageiro/metabolismo
13.
Int Immunopharmacol ; 34: 101-106, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26938675

RESUMO

Osteosarcoma is one of the most common childhood cancers with high numbers of cancer-related deaths. Progress in conventional therapies is showing limited improvement. An adaptive T cell-based immunotherapy represents a promising new therapeutic option, but to improve its efficacy, regulatory mechanisms in osteosarcoma need further elucidation. Here, to evaluate the regulatory effect of tumor microenvironment of T cells in osteosarcoma, we examined the peripheral blood (PB) and tumor infiltrating (TI) T cells, and their correlations with PB and tumor immune characteristics. We found that TI T cells contained significantly higher levels of TIM-3(+)PD-1(-) and TIM-3(+)PD-1(+) cells than their PB counterparts. Similar to that in chronic HIV and HCV infections, these TIM-3(+)PD-1(-) and TIM-3(+)PD-1(+) T cells presented reduced proliferation and proinflammatory cytokine secretion in response to stimulation. Presence of M2-type (CD163(+)) macrophages exacerbated T cell immunosuppression, since frequencies of CD163(+) tumor-associated macrophages were directly correlated with the frequencies of suppressed TIM-3(+)PD-1(+) T cells. Moreover, depletion of CD163(+) macrophages significantly improved T cell proliferation and proinflammatory cytokine production. Overall, our data presented an intratumoral T cell-specific immunosuppression that was amplified by M2-type tumor-associated macrophages.


Assuntos
Imunoterapia Adotiva/métodos , Linfócitos do Interstício Tumoral/imunologia , Macrófagos/imunologia , Osteossarcoma/imunologia , Linfócitos T/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Diferenciação Celular , Células Cultivadas , Citocinas/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Terapia de Imunossupressão , Linfócitos do Interstício Tumoral/transplante , Osteossarcoma/terapia , Receptor de Morte Celular Programada 1/metabolismo , Receptores de Superfície Celular/metabolismo , Evasão Tumoral , Microambiente Tumoral
14.
Orthop Surg ; 7(2): 168-73, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26033999

RESUMO

OBJECTIVE: To explore the toxicity and biological activity of cobalt nanoparticles on the osteoclasts. Analyze the relationship between cobalt nanoparticles and osteolysis. METHODS: Monocyte-macrophages (RAW 264.7) was cultured in vitro, osteoclast-like cells were induced by lipopolysaccharides (LPS). After RAW 264.7 was induced for 24 h, Methyl Thiazolium Tetrazolium (MTT) biological toxicity test of osteoclast-like cell was preceded using Cobalt nanoparticles (set 4 concentrations: 10, 20, 50, 100 µM) and cobalt chloride (set 4 concentrations: 10, 20, 50, 100 µM) at 2, 4, 8, 24 and 48 h respectively. The relative expression of mRNA of CA II and Cat K after RAW 264.7 induction was determined by Q-PCR. RESULTS: mRNA relative expression of CA II, Cat K were reduced at multiple concentrations both cobalt nanoparticles and cobalt chloride, and was time and concentration dependent, cobalt nanoparticles are more significant than cobalt chloride group. But when the cobalt nanoparticles concentration is in 10-50 µM, the mRNA relative expression of CA II, Cat K increased. CONCLUSION: Cobalt nanoparticles have biological toxicity. At multiple concentrations, the differentiation and proliferation of osteoclasts was inhibited, but when the concentration of cobalt nanoparticles is in 10-50 µM, it has been strengthened.


Assuntos
Cobalto/toxicidade , Monócitos/efeitos dos fármacos , Nanopartículas/toxicidade , Osteoclastos/efeitos dos fármacos , Osteólise/induzido quimicamente , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cobalto/metabolismo , Relação Dose-Resposta a Droga , Humanos , Monócitos/metabolismo , Nanopartículas/metabolismo , Osteoclastos/metabolismo , Osteólise/metabolismo
15.
Oncol Rep ; 34(2): 877-83, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26062455

RESUMO

Accumulating evidence has shown that miR-196a plays an important role in tumorigenesis and tumor progression in various types of cancer. miRNA profiling studies have suggested that miR-196a is highly overexpressed in breast cancer. However, the functional mechanism of miR-196a in breast cancer remains unclear. In the present study, we first showed that the expression of miR-196a was significantly upregulated in human breast cancer samples and breast cancer cell lines. Using a loss-of-function approach, we showed that the downregulation of miR-196a inhibited the proliferation of breast cancer cells in vitro and in vivo. Ubiquitin-conjugating enzyme E2C (UBE2C) gene as a cellular proto-oncogene, which was overexpressed and positively correlated with miR-196a expression in breast cancer tissues, was identified as a direct target of miR-196a. Moreover, in order to investigate whether miR-196a regulated cell growth in breast cancer cells by targeting UBE2C, rescue studies were performed in breast cancer cells. The restoration of UBE2C by transfecting UBE2C cDNA in anti-miR-196a-transfected breast cancer cells rescued the suppression of cell proliferation. In conclusion, the present study showed that miR-196a promoted cell proliferation by targeting UBE2C in breast cancer. Thus, miR-196a may be a potential oncogene in breast cancer and a promising therapeutic target in breast cancer treatment.


Assuntos
Neoplasias da Mama/genética , Carcinogênese , MicroRNAs/genética , Enzimas de Conjugação de Ubiquitina/genética , Adulto , Idoso , Animais , Neoplasias da Mama/patologia , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Camundongos , MicroRNAs/biossíntese , Pessoa de Meia-Idade , Processamento de Proteína Pós-Traducional/genética , Proto-Oncogene Mas , Enzimas de Conjugação de Ubiquitina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Vaccine ; 33(2): 374-81, 2015 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-25448099

RESUMO

A cell culture-based vaccine production system is preferred for the large-scale production of influenza vaccines and has advantages for generating vaccines against highly pathogenic influenza A viruses. Vero cells have been widely used in human vaccine manufacturing, and the safety of these cells has been well demonstrated. However, the most commonly used influenza-vaccine donor virus, A/Puerto Rico/8/1934 (PR8) virus, does not grow efficiently in Vero cells. Therefore, we adapted the PR8 virus to Vero cells by continuous passaging, and a high-growth strain was obtained after 20 passages. Sequence analysis and virological assays of the adapted strain revealed that mutations in four viral internal genes (NP, PB1, PA and NS1) were sufficient for adaptation. The recombinant virus harboring these mutations (PR8-4mut) displayed accelerated viral transport into the nucleus and increased RNP activity. Importantly, the PR8-4mut could serve as a backbone donor virus to support the growth of the H7N1, H9N2 and H5N1 avian viruses and the H1N1 and H3N2 human viruses in Vero cells without changing its pathogenicity in either chicken embryos or mice. Thus, our work describes the generation of a Vero-adapted, high-yield PR8-4mut virus that may serve as a promising candidate for an influenza-vaccine donor virus.


Assuntos
Vírus da Influenza A/crescimento & desenvolvimento , Vírus da Influenza A/imunologia , Vírus Reordenados/genética , Inoculações Seriadas , Células Vero/virologia , Cultura de Vírus , Adaptação Fisiológica , Animais , Embrião de Galinha , Galinhas/virologia , Chlorocebus aethiops , Genes Virais , Humanos , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/crescimento & desenvolvimento , Virus da Influenza A Subtipo H5N1/genética , Virus da Influenza A Subtipo H5N1/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H7N1/genética , Vírus da Influenza A Subtipo H7N1/crescimento & desenvolvimento , Vírus da Influenza A Subtipo H9N2/genética , Vírus da Influenza A Subtipo H9N2/crescimento & desenvolvimento , Vírus da Influenza A/genética , Vírus da Influenza A/isolamento & purificação , Vacinas contra Influenza/análise , Camundongos , Mutação , Vírus Reordenados/crescimento & desenvolvimento , Ribonucleoproteínas/metabolismo , Análise de Sequência , Proteínas Virais/metabolismo
17.
Virology ; 482: 32-40, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25817403

RESUMO

Vaccination is the most effective way to prevent and control infection by influenza viruses, and a cell-culture-based vaccine production system is preferred as the future choice for the large-scale production of influenza vaccines. As one of the WHO-recommended cell lines for producing influenza vaccines, Vero cells do not efficiently support the growth of the current influenza A virus vaccine donor strain, the A/Puerto Rico/8/1934 (PR8) virus. In this study, a single mutation of K86R in the NS2 protein can sufficiently render the high-yielding property to the PR8 virus in Vero cells. Further analysis showed that the later steps in the virus replication cycle were accelerated by NS2(K86R) mutation, which may relate to an enhanced interaction between NS2(K86R) and the components of host factor F1Fo-ATPase, FoB and F1ß. Because the NS2(K86R) mutation does not increase PR8 virulence in either mice or embryonated eggs, the PR8-NS2(K86R) virus could serve as a promising vaccine donor strain in Vero cells.


Assuntos
Vírus da Influenza A/crescimento & desenvolvimento , Mutação de Sentido Incorreto , Proteínas não Estruturais Virais/genética , Substituição de Aminoácidos , Animais , Embrião de Galinha , Chlorocebus aethiops , Feminino , Camundongos Endogâmicos BALB C , Células Vero , Virulência
18.
Exp Ther Med ; 5(6): 1697-1700, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23837057

RESUMO

Heparanase (HPSE) is a type of endoglycosidase that decomposes the heparan sulfate (HS) lateral chains of heparan sulfate proteoglycans (HSPGs), releases related growth factors and participates in angiogenesis and bone formation. HPSE is expressed in osteoblasts and is involved in fracture healing. However, the role of HPSE in osteogenic differentiation requires in-depth investigation. To investigate the expression of HPSE in the osteogenic differentiation of rat marrow stromal cells (MSCs), the protein and mRNA expression levels of HPSE on days 0, 1, 3, 7, 10, 14 and 21 of osteogenic differentiation of MSCs in 2- and 10-month-old rats were detected using western blotting and reverse transcription-polymerase chain reaction (RT-PCR), respectively. From the third day of osteogenic differentiation onwards, all HPSE protein and mRNA expression levels in 2-month-old rats were significantly increased compared with basal levels (days 0 and 1; P<0.05). The protein and mRNA expression levels reached a peak on days 10 and 14, respectively, followed by a gradual decline. The same pattern was observed in 10-month-old rats; however, when compared with with basal levels, the differences were not statistically significant (P>0.05). The protein and mRNA levels of HPSE in the 2-month-old rats were significantly higher compared with the respective levels in the 10-month-old rats (P<0.05). HPSE is involved in the osteogenic differentiation of rat MSCs. The protein and mRNA expression levels of HPSE in aged rats are weaker compared with those in young rats, which may be related to the declined osteogenic differentiation ability.

19.
Zhongguo Gu Shang ; 24(7): 597-9, 2011 Jul.
Artigo em Zh | MEDLINE | ID: mdl-21870404

RESUMO

OBJECTIVE: To evaluate the clinical effects of surgical treatment for open dislocation of talus. METHODS: From June 2001 to July 2008,the complete data of 11 patients with open dislocations of talus were retrospectively analyzed, including 8 males and 3 females with an average age of 39.5 years (ranged 19 to 52). According to Gustilo typing, type I was in 2 cases, type II in 6 cases, type III A in 2 cases, type III B in 1 case. Five cases were tibial astragaloid joint dislocation in which 3 cases associated with subtalar joint dislocation, 4 cases were subtalar joint dislocation and 2 cases were total dislocation of talus. Among them, 8 dislocations associated with talus fractures. All patients were treated with debridement, open reduction, internal fixation with K-wires or screws and external fixation with plaster or external fixator within 8 hours after injury. External fixations were removed at 6 weeks after operation. Partial weight bearing was permitted only when X-rays indicated bony healing. Clinical effects were evaluated according to AOFAS system and X-ray films during follow-up. RESULTS: The mean time of follow-up was 13.8 months(ranged 10 to 15 months). Eight patients with fractures obtained bone healing in 4-7 months with an average of 4.3 months. No infection of wound or deep tissue was found. At final follow-up, talus necrosis was in 2 cases and traumatic arthritis was in 2 cases. The AOFAS score was 71.3 +/- 8.6, among the total, the pain, function, alignment was respectively (32.4 +/- 7.1), (31.0 +/- 15.7), (7.6 +/- 2.3) scores. CONCLUSION: Complete debridement may avoid infection in treating open dislocation of talus, early reduction and fixation is a key point during treatment.


Assuntos
Luxações Articulares/cirurgia , Tálus/lesões , Adulto , Feminino , Seguimentos , Humanos , Luxações Articulares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Tálus/cirurgia , Tomografia Computadorizada por Raios X , Adulto Jovem
20.
Orthop Surg ; 3(4): 242-6, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22021140

RESUMO

OBJECTIVE: To investigate the effect of timing of surgery on clinical results and perioperative complications in pediatric patients with Gartland III type supracondylar humeral fractures without neurovascular compromise. METHODS: Eighty-six consecutive children treated surgically at our hospital from April 2005 to June 2007 for displaced supracondylar humeral fractures were reviewed. All these patients were treated by the same group of doctors. The children were divided into two groups: early if treated within 12 hours after injury and delayed if treated later than that. Perioperative complications and clinical results, especially for open surgery, were compared between the two groups. RESULTS: Forty pediatric patients underwent surgery in the early group and 46 in the delayed group. There were no significant differences between the two groups in perioperative complications such as pin tract infection, iatrogenic nerve injury, compartment syndrome and conversion to open surgery. For open surgery, both the clinical results and perioperative complications were not affected by delaying for more than 12 hours after injury. However, blood loss and operation time were greater in the early than in the delayed group, possibly due to relatively more edema. CONCLUSION: Delay in surgery, regardless of whether it is closed or open, for more than 12 hours after injury does not influence the perioperative complications and clinical results for displaced supracondylar humeral fractures in children. However early open reduction and pinning may increase intra-operative blood loss and take longer.


Assuntos
Lesões no Cotovelo , Fixação Interna de Fraturas/métodos , Fraturas do Úmero/cirurgia , Fraturas Intra-Articulares/cirurgia , Complicações Pós-Operatórias/epidemiologia , Distribuição por Idade , Criança , Pré-Escolar , Feminino , Seguimentos , Consolidação da Fratura/fisiologia , Humanos , Fraturas do Úmero/diagnóstico por imagem , Incidência , Escala de Gravidade do Ferimento , Fraturas Intra-Articulares/diagnóstico por imagem , Masculino , Complicações Pós-Operatórias/diagnóstico por imagem , Radiografia , Medição de Risco , Distribuição por Sexo , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA