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1.
J Colloid Interface Sci ; 672: 401-414, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38850865

RESUMO

Crafting an inorganic semiconductor heterojunction with defect engineering and morphology modulation is a strategic approach to produce clean energy by the highly efficient light-driven splitting of water. In this paper, a novel Z-scheme sulfur-vacancy containing Zn3In2S6 (Vs-Zn3In2S6) nanosheets/In2O3 hollow hexagonal prisms heterostructrue (Vs-ZIS6INO) was firstly constructed by an oil bath method, in which Vs-Zn3In2S6 nanosheets grew on the surfaces of In2O3 hollow hexagonal prisms to form a hollow core-shell structure. The obtained Vs-ZIS6INO heterostructrue exhibited much enhanced activity of the production of H2 and H2O2 by the light-driven water splitting. In particular, under visible light irradiation (λ > 420 nm), the rate of generation of H2 of Vs-ZIS6INO sample containing 30 wt% Vs-Zn3In2S6 (30Vs-ZIS6INO) could reach 3721 µmol g-1h-1, which was 87 and 6 times higher than those of Zn3In2S6 (43 µmol g-1h-1) and Vs-Zn3In2S6 (586 µmol g-1h-1), respectively. Meanwhile, 30Vs-ZIS6INO could exhibit the rate of H2O2 production of 483 µmol g-1h-1 through the dual pathways of indirect 2e- oxygen reduction (ORR) and water oxidation (WOR) without adding any sacrifice agents, far exceeding In2O3 (7 µmol g-1h-1) and Vs-Zn3In2S6 (58 µmol g-1h-1). The excellent photocatalytic activities of H2 and H2O2 generations of Vs-ZIS6INO sample might result from the synergistic effect of the sulfur vacancy, hollow core-shell structure, and Z-scheme heterostructure, which accelerated the electron delocalization, enhanced the absorption and conversion of solar energy, reduced the carrier diffusion distance, and ensured high REDOX ability. In addition, the possible photocatalytic mechanisms for the production of H2 and H2O2 were discussed in detail. This study provided a new idea and reference for constructing the novel and efficient inorganic semiconductor heterostructures by coordinating vacancy defect and morphology design to adequately utilize water splitting for the production of clean energy.

2.
Polymers (Basel) ; 16(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38543426

RESUMO

The polarization state of light waves significantly affects the quality of holographic recordings. This paper quantitatively analyzes the impact of different polarization states of signal and reference beams on the quality of holographic recordings in PQ/PMMA photopolymer systems during the holography process. By deriving the light field distribution of the interference between two light waves of different polarization states and introducing the interference fringe contrast and the modulation of the refractive index of the photopolymer, we established the relationship between the diffraction efficiency of PQ/PMMA photopolymer holographic gratings and the angle between polarization directions. Based on this relationship, simulations and experiments were conducted. The experimental results demonstrated that as the angle between the polarization directions increased, the diffraction efficiency of the material decreased, with the efficiency dropping to 24.69% of its original value when the angle increased from 0° to 50°. When the angle increased to 60°, the influence of polarization characteristics became gradually significant, and at 90°, it was entirely dominated by polarization characteristics. The photoinduced birefringence properties of the PQ/PMMA prepared in the measurement experiment were studied, and the polarization characteristics of the reconstructed light under polarization direction angles of 0°, 60°, and 90° were investigated. The results indicated that at a polarization direction angle of 60 degrees, the material exhibited a significant response to the polarization information of the signal light. Finally, holographic recordings of objects at different polarization direction angles were conducted, and the reconstructed images were used to visually reflect the impact of the polarization direction angle on the quality of holographic recordings.

3.
Polymers (Basel) ; 15(22)2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-38006115

RESUMO

To enhance the holographic properties, one of the main methods is increasing the solubility of the photosensitizer and modifying the components to improve the modulation of the refractive index in the photopolymer. This study provides evidence, through the introduction of a mutual diffusion model, that the incorporation of SiO2 nanoparticles in photopolymers can effectively enhance the degree of refractive index modulation, consequently achieving the objective of improving the holographic performance of the materials. Different concentrations of SiO2 nanoparticles have been introduced into highly soluble photosensitizer Irgacure 784 (solubility up to 10wt%)-doped poly-methyl methacrylate (Irgacure 784/PMMA) photopolymers. Holographic measurement experiments have been performed on the prepared samples, and the experiments have demonstrated that the Irgacure 784/PMMA photopolymer doped with 1.0 × 10-3wt% SiO2 nanoparticles exhibits the highest diffraction efficiency (74.5%), representing an approximate 30% increase in diffraction efficiency as compared to an undoped photopolymer. Finally, we have successfully achieved the recording of real objects on SiO2/Irgacure 784/PMMA photopolymers, demonstrated by the SiO2/Irgacure 784/PMMA photopolymer material prepared in this study, which exhibits promising characteristics for holographic storage applications. The strategy of doping nanoparticles (Nps) in Irgacure 784/PMMA photopolymers has also provided a new approach for achieving high-capacity holographic storage in the future.

4.
J Immunol Res ; 2022: 1886083, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36199667

RESUMO

Objectives: Antisynthetase syndrome (ASS) and dermatomyositis (DM) are serious autoimmune diseases, with lungs being the most frequently involved organ and sometimes fatal. This study is aimed at clarifying the role of neutrophil-associated biological markers in suggesting ASS and DM-associated respiratory infections and interstitial lung diseases. Methods: We carried out a retrospective review of the medical records of 46 cases of ASS and DM diagnosed at the Second Hospital of Zhejiang University College of Medicine, between January 2017 and December 2020. Serum myeloperoxidase (MPO), neutrophil elastase (NE), α1 anti-trypsin (AAT), and interleukin-6 (IL-6) were also detected. Results: Gottron's sign is characteristic of dermatomyositis, while polyarthritis is more characteristic of ASS. Pulmonary function is worse in ASS than in DM patients. Patients with ASS and DM had abnormal lymphocyte and neutrophil counts compared to healthy subjects, but not in relation to lung function and rapid progression of interstitial lung disease (RP-ILD). Elevated serum NE, MPO, and IL-6 levels are suggestive of respiratory infections, whereas decreased circulating IL-6 is predictive of RP-ILD. Conclusion: Our study identified the neutrophil-associated biomarkers MPO, NE, and IL-6 as promising indicators with different suggestive roles in respiratory infections and interstitial lung diseases in patients with ASS and DM.


Assuntos
Dermatomiosite , Doenças Pulmonares Intersticiais , Infecções Respiratórias , Humanos , Biomarcadores , Dermatomiosite/complicações , Dermatomiosite/diagnóstico , Interleucina-6 , Elastase de Leucócito , Doenças Pulmonares Intersticiais/diagnóstico , Miosite , Neutrófilos , Peroxidase , Infecções Respiratórias/complicações , Estudos Retrospectivos
5.
World J Clin Cases ; 10(26): 9447-9453, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36159442

RESUMO

BACKGROUND: Ascites, pleural effusion and raised CA-125 in the absence of malignancy in systemic lupus erythematosus is known as Tjalma syndrome. CASE SUMMARY: We report a special case of a systemic lupus erythematosus patient presenting with Tjalma syndrome. She presented with ascites and elevated CA-125 in the absence of benign or malignant ovarian tumor and no pleural effusions, which is an unusual presentation for this rare condition. CONCLUSION: Tjalma syndrome can present with massive ascites alone without pleural or pericardial effusions.

6.
Rheumatol Ther ; 9(5): 1421-1434, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36057763

RESUMO

INTRODUCTION: The aim of this study is to explore the efficacy and renal safety of febuxostat in gout and stage 2-4 chronic kidney disease (CKD) and factors that correlated with target serum urate (SU). METHODS: A single-center retrospective study including male patients with gout and CKD was conducted. SU, the rate of SU < 360 µmol/L (RAT), and renal safety were analyzed in subjects who received febuxostat over 44 weeks. Factors that correlated with target SU were also explored. RESULTS: Between January 2017 and March 2021, 102 patients (stage 2 CKD: n = 27; stage 3 CKD: n = 70; stage 4 CKD: n = 5) were enrolled. The SU level reduced significantly over 44 weeks (600.76 ± 95.42 versus 405.52 ± 111.93 µmol/L; P < 0.05), and RAT increased to 39.20%. The overall estimated glomerular filtration rate (eGFR) level improved over 44 weeks (52.05 ± 11.68 versus 55.46 ± 14.49 mL/min/1.73 cm2, P < 0.05). An obvious improvement of eGFR was observed in stage 3 CKD, in patients with ≤ 1 risk factor (hypertension, diabetic mellitus, hyperlipidemia, or usage of non-steroidal anti-inflammatory drugs), and in patients with terminal SU < 360 µmol/L (P < 0.05). Logistic regression analysis indicated that baseline SU level and body weight were correlated with RAT. Further analysis revealed that patients with SU < 600 µmol/L and body weight ≤ 70 kg reached higher RAT (56.7%). CONCLUSIONS: Febuxostat demonstrated efficacy and renal safety in patients with gout and CKD in clinical practice. Achieving the target SU could obviously improve renal function. Baseline SU level and body weight could affect the achievement of target SU.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(3): 704-710, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-35680793

RESUMO

OBJECTIVE: To construct cytarabine-resistant acute myeloid leukemia (AML) cell lines, and explore the correlation between Sirt1, PGC-1α expression levels and drug resistance. METHODS: Human acute promyelocytic leukemia Kasumi-1 cells were induced by the method of gradually increasing the concentration of Ara-C drug. The IC50 value of Kasumi-1 cells before and after drug addition was detected by CCK-8 method, so as to construct Ara-C resistant cell lines. The expression levels of Sirt1 and PGC-1α mRNA in Kasumi-1 drug-resistant cell lines and their parental cell lines were detected by real-time fluorescence quantitative PCR, and the expression levels of Sirt1 and PGC-1α protein in kasumi-1 drug-resistant cell lines and their parental cell lines were detected by Western blot. RESULTS: The constructed Kasumi-1 cell line had common morphological characteristics of drug-resistant cell lines under microscope, and the drug resistance index was greater than 5, indicating that Kasumi-1 drug-resistant cells had good drug resistance after the construction. The RT-qPCR and Western blot assays showed that the expression levels of Sirt1 and PGC-1α mRNA and protein in the drug-resistant cell lines were higher than those of the parental cell lines (P<0.001). CONCLUSION: AML cell lines resistant to Ara-C can be successfully induced by the method of gradually increasing the concentration, and the co-high expression of Sirt1 and PGC-1α may mediate the drug resistance of AML cells.


Assuntos
Leucemia Mieloide Aguda , Sirtuína 1 , Linhagem Celular , Citarabina/farmacologia , Resistência a Medicamentos , Humanos , Leucemia Mieloide Aguda/genética , RNA Mensageiro/genética
8.
Arch Microbiol ; 204(5): 263, 2022 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-35430693

RESUMO

In this study, a global proteomic change was characterized by iTRAQ analysis and bioinformatics analysis to study the influence by different pH conditions on proteins accumulation when Pseudomonas aeruginosa P6 degraded petroleum hydrocarbons. Compared with the condition of pH 7.2, 228 proteins in pH 5.0 and 93 proteins in pH 8.5 were identified as differentially accumulated proteins. The results further showed that in the condition of pH 5.0, fourteen chemotaxis-related proteins, two uptake-related proteins, two cytochromes, nineteen ABC transporters and five porins were downregulated, while two dioxygenases, five ß-oxidation-related proteins and one acyl-CoA metabolism-related protein were upregulated. In the condition of pH 8.5, one fimbrial protein, one aldehyde dehydrogenase, eight ABC transporters and six porins were downregulated, while five terminal oxidation-related proteins, one alcohol dehydrogenase, one ß-oxidation-related protein and one acyl-CoA metabolism-related protein were upregulated. The results indicated that in the condition of pH 5.0, chemotaxis and uptake of carbon, terminal oxidation of short-chain alkanes and transmembrane transport which are considered as key cellular processes in biodegradation of petroleum hydrocarbons in P.aeruginosa P6 may be disturbed. While in the condition of pH 8.5, the activity of transmembrane transport may decrease.


Assuntos
Petróleo , Pseudomonas aeruginosa , Transportadores de Cassetes de Ligação de ATP/metabolismo , Biodegradação Ambiental , Coenzima A/metabolismo , Hidrocarbonetos/metabolismo , Concentração de Íons de Hidrogênio , Petróleo/metabolismo , Porinas , Proteômica/métodos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo
9.
Mol Genet Genomics ; 297(2): 287-301, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35187584

RESUMO

Gossypium provides the foremost natural fiber for supporting the rapid development of the textile industry. Quantitative trait locus (QTL) mapping of fiber yield and quality traits is, thus, of great significance for providing a foundation for the genetic improvement of key target traits in cotton production. In this study, a superior chromosome segment substitution line (CSSL), MBI8255, with high yield and premium fiber quality characteristics was cultivated from the BC5F3:5 lineage derived from G. barbadense Hai1 and G. hirsutum CCRI36, and was chosen to construct a segregation population containing 123 F2 individuals with CCRI36. A total of 71 polymorphic SSR (simple sequence repeat) markers were identified based on a previous high-density linkage map, and 17 QTLs distributed on five chromosomes were detected, of which 10 QTLs for cotton yield explained 0.26-15.41% of phenotypic variations, while 7 QTLs for fiber quality explained 0.84-9.38% of phenotypic variations, separately containing four and one stable QTLs detected from over two environments. Among three identified QTL clusters, only the Chr19 QTL cluster harbored two stable and one unstable QTL for three different traits, and hence this significant region, which included 1546 genes, was subjected to functional enrichment and transcriptome expression analyses, ultimately screening eight candidate genes relevant to fiber development. This study not only provides useful information for the further fine-mapping and functional verification of candidate genes, but also offers a solid foundation for revealing the molecular mechanisms of fiber formation.


Assuntos
Fibra de Algodão , Gossypium , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Gossypium/genética , Humanos , Fenótipo , Locos de Características Quantitativas/genética
10.
Front Public Health ; 10: 1028989, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36600937

RESUMO

Community-acquired pneumonia is a public health problem in all countries in the world, with a broad range of causative agents and Chlamydia psittaci infection tends to be overlooked. Pulmonary migratory infiltrates are commonly seen in eosinophilic pneumonia, cryptogenic organizing pneumonia, etc. However, the association of Chlamydia psittaci and pulmonary migratory infiltrates has been seldom described in literatures before. We reviewed a 64-year-old man referred to our hospital for treatment against Chlamydia psittaci pneumonia which was diagnosed by metagenomics next generation sequencing (mNGS). During the treatment period, chest imaging showed migratory infiltrates, which has been rarely described before.


Assuntos
Chlamydophila psittaci , Pneumonia , Psitacose , Humanos , Masculino , Pessoa de Meia-Idade , Sequenciamento de Nucleotídeos em Larga Escala , Pulmão , Psitacose/diagnóstico
11.
Arch Microbiol ; 203(5): 2463-2473, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33677632

RESUMO

Petroleum hydrocarbon contaminants, which are among the most serious pollutants in the petroleum industry, can be degraded sufficiently by Pseudomonas aeruginosa. However, temperature-induced stress will severely inhibit this biodegradation. In this study, the proteome of P. aeruginosa P6 at 25 °C, 43 °C and 37 °C was used to examine the impact of temperature on the molecular mechanism of biodegradation of petroleum hydrocarbon by P. aeruginosa P6. Differentially expressed proteins were identified by iTRAQ technology, and the functions of these proteins were identified by bioinformatic analysis. The impact of 25 °C and 43 °C on cellular processes has also been discussed. The results showed that the expression of proteins in chemotaxis toward petroleum hydrocarbons, terminal oxidation of aromatic rings in petroleum hydrocarbons and trans-membrane transport of fatty acids and nutriments were clearly inhibited under 25 °C condition. The expression of proteins in chemotaxis, emulsification, adhesion and terminal oxidation of petroleum hydrocarbons; catalysis of fatty alcohols and fatty aldehydes; trans-membrane transport of nutriments and ß-oxidation were clearly inhibited under 43 °C condition.


Assuntos
Poluentes Ambientais/metabolismo , Hidrocarbonetos/metabolismo , Petróleo/metabolismo , Proteoma/metabolismo , Pseudomonas aeruginosa/metabolismo , Proteínas de Bactérias/metabolismo , Biodegradação Ambiental , Oxirredução , Estresse Fisiológico , Temperatura
13.
Curr Microbiol ; 76(11): 1270-1277, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31401778

RESUMO

In this study, iTRAQ analysis and bioinformatics analysis were used to reveal the changes in key proteins induced by different concentrations of petroleum hydrocarbons during the biodegradation of petroleum hydrocarbons in Pseudomonas aeruginosa P6. Sixty-three proteins were identified as differentially expressed proteins, and all of them were strongly associated with the cellular processes related to the biodegradation of petroleum hydrocarbons. The results further showed that among the differentially expressed proteins, 3 chemotaxis-related proteins, 10 terminal oxidation of short-chain alkane-related proteins, and 13 transmembrane transport-related proteins were down regulated, while 1 uptake of petroleum hydrocarbon-related protein, 3 terminal oxidation of long-chain alkane-related proteins, 4 dehydrogenation-related proteins, 12 ß-oxidation-related proteins, and 2 metabolisms of acyl-CoA-related proteins were up regulated. These results indicated that during the biodegradation of petroleum hydrocarbons in P. aeruginosa P6, the activity of chemotaxis, the terminal oxidation of short-chain alkanes, and transmembrane transport decreased, while the activity of the uptake of petroleum hydrocarbons, the terminal oxidation of long-chain alkanes, dehydrogenation, ß-oxidation, and the metabolism of acyl-CoA increased under the 20,000 mg/L petroleum hydrocarbon condition compared with the 500 mg/L petroleum hydrocarbon condition. The findings revealed changes in the key proteins and the corresponding cellular process of the biodegradation of petroleum hydrocarbons in P. aeruginosa P6 under high and low concentrations of petroleum hydrocarbons and provided references for future studies.


Assuntos
Proteínas de Bactérias/genética , Hidrocarbonetos/metabolismo , Petróleo/metabolismo , Pseudomonas aeruginosa/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Biodegradação Ambiental , Hidrocarbonetos/análise , Oxirredução , Petróleo/análise , Proteômica , Pseudomonas aeruginosa/química , Pseudomonas aeruginosa/genética
14.
Curr Microbiol ; 74(10): 1178-1184, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28698911

RESUMO

In this work, proteomic analysis was used to identify the up-regulated key proteins of Pseudomonas aeruginosa (P6), a bacteria used in petroleum degradation, responsible for its high efficiency in degrading crude oil. Seventeen proteins were identified as up-regulated proteins by proteomic analysis and classified by bioinformatics analysis. The results indicated that most of the up-regulated proteins were responsible for P. aeruginosa (P6) survival under harsh environmental conditions and utilization crude oil as carbon source in a better way. The physiological processes, chemotaxis to carbon sources, terminal oxidation of carbons, carbon source uptake and nutrients transport, were associated with the up-regulated proteins in the study. The findings revealed the most influential proteins and set a clear direction for future research.


Assuntos
Biodegradação Ambiental , Petróleo/metabolismo , Proteoma , Proteômica , Pseudomonas aeruginosa/metabolismo , Biologia Computacional/métodos , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Proteômica/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
15.
Stem Cells Dev ; 25(8): 648-59, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26906411

RESUMO

The innate immunity of embryonic stem cells (ESCs) has recently emerged as an important issue in ESC biology and in ESC-based regenerative medicine. We have recently reported that mouse ESCs (mESCs) do not have a functional type I interferon (IFN)-based antiviral innate immunity. They are deficient in expressing IFN in response to viral infection and have limited ability to respond to IFN. Using fibroblasts (FBs) as a cell model, the current study investigated the development of antiviral mechanisms during in vitro differentiation of mESCs. We demonstrate that mESC-differentiated FBs (mESC-FBs) share extensive similarities with naturally differentiated FBs in morphology, marker expression, and growth pattern, but their development of antiviral mechanisms lags behind. Nonetheless, the antiviral mechanisms are inducible during mESC differentiation as demonstrated by the transition of nuclear factor kappa B (NFκB), a key transcription factor for IFN expression, from its inactive state in mESCs to its active state in mESC-FBs and by increased responses of mESC-FBs to viral stimuli and IFN during their continued in vitro propagation. Together with our previously published study, the current data provide important insights into molecular basis for the deficiency of IFN expression in mESCs and the development of antiviral innate immunity during mESC differentiation.


Assuntos
Diferenciação Celular , Imunidade Inata , Células-Tronco Embrionárias Murinas/imunologia , Animais , Linhagem Celular , Vírus Chikungunya/imunologia , Chlorocebus aethiops , Técnicas de Cocultura , Interferon Tipo I/metabolismo , Vírus La Crosse/imunologia , Camundongos , Células-Tronco Embrionárias Murinas/fisiologia , Células-Tronco Embrionárias Murinas/virologia , NF-kappa B/metabolismo , Medicina Regenerativa , Células Vero
16.
J Biol Chem ; 289(36): 25186-98, 2014 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-24966329

RESUMO

We have recently reported that mouse embryonic stem cells (mESCs) are deficient in expressing type I interferons (IFNs) in response to viral infection and synthetic viral RNA analogs (Wang, R., Wang, J., Paul, A. M., Acharya, D., Bai, F., Huang, F., and Guo, Y. L. (2013) J. Biol. Chem. 288, 15926-15936). Here, we report that mESCs are able to respond to type I IFNs, express IFN-stimulated genes, and mediate the antiviral effect of type I IFNs against La Crosse virus and chikungunya virus. The major signaling components in the IFN pathway are expressed in mESCs. Therefore, the basic molecular mechanisms that mediate the effects of type I IFNs are functional in mESCs; however, these mechanisms may not yet be fully developed as mESCs express lower levels of IFN-stimulated genes and display weaker antiviral activity in response to type I IFNs when compared with fibroblasts. Further analysis demonstrated that type I IFNs do not affect the stem cell state of mESCs. We conclude that mESCs are deficient in type I IFN expression, but they can respond to and mediate the cellular effects of type I IFNs. These findings represent unique and uncharacterized properties of mESCs and are important for understanding innate immunity development and ESC physiology.


Assuntos
Antivirais/imunologia , Células-Tronco Embrionárias/imunologia , Fibroblastos/imunologia , Interferon Tipo I/imunologia , Animais , Antivirais/metabolismo , Antivirais/farmacologia , Western Blotting , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Células Cultivadas , Vírus Chikungunya/imunologia , Vírus Chikungunya/fisiologia , Chlorocebus aethiops , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Células-Tronco Embrionárias/metabolismo , Células-Tronco Embrionárias/virologia , Fibroblastos/metabolismo , Fibroblastos/virologia , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/genética , Imunidade Inata/imunologia , Interferon Tipo I/metabolismo , Interferon Tipo I/farmacologia , Vírus La Crosse/imunologia , Vírus La Crosse/fisiologia , Camundongos , Microscopia Confocal , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/imunologia , Receptor de Interferon alfa e beta/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ubiquitinas/genética , Ubiquitinas/imunologia , Ubiquitinas/metabolismo , Células Vero
17.
Stem Cells Dev ; 23(6): 594-604, 2014 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-24219369

RESUMO

We have recently reported that mouse embryonic stem cells (mESCs) are deficient in expressing type I interferons (IFN) when exposed to viral infection and double-stranded RNA. In this study, we extended our investigation and demonstrated that single-stranded RNA and protein-encoding mRNA can induce strong IFN expression and cytotoxicity in fibroblasts and epithelial cells, but none of the effects associated with these antiviral responses were observed in mESCs. Our results provided additional data to support the conclusion that mESCs are intrinsically deficient in antiviral responses. While our findings represent a novel feature of mESCs that in itself is important for understanding innate immunity development, we exploited this property to develop a novel mRNA-mediated gene expression cell model. Direct introduction of synthetic mRNA to express desired genes has been shown as an effective alternative to DNA/viral vector-based gene expression. However, a major biological challenge is that a synthetic mRNA is detected as a viral RNA analog by the host cell, resulting in a series of adverse effects associated with antiviral responses. We demonstrate that the lack of antiviral responses in mESCs effectively avoids this problem. mESCs can tolerate repeated transfection and effectively express proteins from their synthetic mRNA with expected biological functions, as demonstrated by the expression of green fluorescent protein and the transcription factor Etv2. Therefore, mRNA-based gene expression could be developed into a novel ESC differentiation strategy that avoids safety concerns associated with viral/DNA-based vectors in regenerative medicine.


Assuntos
Antivirais/farmacologia , Diferenciação Celular/genética , Células-Tronco Embrionárias/citologia , Expressão Gênica/efeitos dos fármacos , RNA Mensageiro/genética , Animais , Células-Tronco Embrionárias/efeitos dos fármacos , Camundongos , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo
18.
J Biol Chem ; 288(22): 15926-36, 2013 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-23580653

RESUMO

Embryonic stem cells (ESCs) are considered to be a promising cell source for regenerative medicine because of their unlimited capacity for self-renewal and differentiation. However, little is known about the innate immunity in ESCs and ESC-derived cells. We investigated the responses of mouse (m)ESCs to three types of live viruses as follows: La Crosse virus, West Nile virus, and Sendai virus. Our results demonstrated mESCs were susceptible to viral infection, but they were unable to express type I interferons (IFNα and IFNß, IFNα/ß), which differ from fibroblasts (10T1/2 cells) that robustly express IFNα/ß upon viral infections. The failure of mESCs to express IFNα/ß was further demonstrated by treatment with polyIC, a synthetic viral dsRNA analog that strongly induced IFNα/ß in 10T1/2 cells. Although polyIC transiently inhibited the transcription of pluripotency markers, the stem cell morphology was not significantly affected. However, polyIC can induce dsRNA-activated protein kinase in mESCs, and this activation resulted in a strong inhibition of cell proliferation. We conclude that the cytosolic receptor dsRNA-activated protein kinase is functional, but the mechanisms that mediate type I IFN expression are deficient in mESCs. This conclusion is further supported by the findings that the major viral RNA receptors are either expressed at very low levels (TLR3 and MDA5) or may not be active (retinoic acid-inducible gene I) in mESCs.


Assuntos
Células-Tronco Embrionárias/metabolismo , Interferon-alfa/biossíntese , Interferon beta/biossíntese , Células-Tronco Pluripotentes/metabolismo , Infecções por Vírus de RNA/metabolismo , Vírus de RNA/metabolismo , RNA de Cadeia Dupla/metabolismo , RNA Viral/metabolismo , Animais , Antígenos de Diferenciação/biossíntese , Antígenos de Diferenciação/imunologia , RNA Helicases DEAD-box/biossíntese , RNA Helicases DEAD-box/imunologia , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/imunologia , Células-Tronco Embrionárias/virologia , Humanos , Indutores de Interferon/farmacologia , Helicase IFIH1 Induzida por Interferon , Interferon-alfa/imunologia , Interferon beta/imunologia , Camundongos , Células-Tronco Pluripotentes/imunologia , Células-Tronco Pluripotentes/virologia , Poli I-C/farmacologia , Infecções por Vírus de RNA/imunologia , Vírus de RNA/imunologia , RNA de Cadeia Dupla/imunologia , RNA de Cadeia Dupla/farmacologia , RNA Viral/imunologia , RNA Viral/farmacologia , Receptor 3 Toll-Like/biossíntese , Receptor 3 Toll-Like/imunologia , Transcrição Gênica/efeitos dos fármacos
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