Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 13 de 13
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Cells ; 8(10)2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31623153

RESUMO

BACKGROUND: Schistosomiasis is an immunopathogenic disease in which Th17 cells play vital roles. Hepatic granuloma formation and subsequent fibrosis are its main pathologic manifestations and the leading causes of hepatic cirrhosis, and effective therapeutic interventions are lacking. In this study, we explored the effects of fasudil, a selective RhoA-Rho-associated kinase (ROCK) inhibitor, on Th17 cells and the pathogenesis of schistosomiasis. METHODS: Mice were infected with Schistosoma japonicum and treated with fasudil. The worm burden, hepatic granuloma formation, and fibrosis were evaluated. The roles of fasudil on Th17, Treg, and hepatic stellate cells were analyzed. RESULTS: Fasudil therapy markedly reduced the granuloma size and collagen deposit in livers from mice infected with S. japonicum. However, fasudil therapy did not affect the worm burden in infected mice. The underlying cellular and molecular mechanisms were investigated. Fasudil suppressed the activation and induced the apoptosis of CD4+ T cells. Fasudil inhibited the differentiation and effector cytokine secretion of Th17 cells, whereas it upregulated Treg cells in vitro. It also restrained the in vivo interleukin (IL)-4 and IL-17 levels in infected mice. Fasudil directly induced the apoptosis of hepatic stellate cells and downregulated the expressions of hepatic fibrogenic genes, such as collagen type I (Col-I), Col-III, and transforming growth factor-1 (TGF-ß1). These effects may contribute to its anti-pathogenic roles in schistosomiasis. CONCLUSIONS: Fasudil inhibits hepatic granuloma formation and fibrosis with downregulation of Th17 cells. Fasudil might serve as a novel therapeutic agent for hepatic fibrosis due to schistosome infections and perhaps other disorders.

2.
ACS Appl Mater Interfaces ; 10(50): 43316-43322, 2018 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-30480425

RESUMO

Metal-organic frameworks (MOFs) with coordinatively unsaturated (open) metal sites have been intensively investigated in gas separations because their active sites can selectively interact with targeted molecules such as CO2. Although such MOFs have shown to exhibit exceptional CO2 uptake capacity at equilibrium, the dynamic separation behavior is often not satisfactory to be considered in practical applications. Herein, we report a facile and efficient self-sacrifice template strategy based on the nanoscale Kirkendall effect to form novel Co-MOF-74 hollow nanorods enabling adsorption/desorption of gas molecules in a facilitated manner. The time-dependent microscopic and diffraction examinations were performed to elucidate the formation mechanism of Co-MOF-74 hollow nanorods and to obtain insights into the factors critical to maintaining the rodlike morphology. Such nanostructured MOF exhibited much sharper CO2 molecular separation behavior than conventional MOF bulk crystals under a dynamic flow condition, because of its enhanced adsorption kinetics through the shortened diffusion distance. Such enhanced dynamic molecular separation behavior was further confirmed by chromatographic separations where a significant peak narrowing was demonstrated.

3.
ACS Appl Mater Interfaces ; 10(35): 29565-29573, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30091586

RESUMO

High-energy lithium/sulfur (Li/S) batteries still suffer from unsatisfactory cycle life and poor rate capability caused by the polysulfides shuttle and insulating nature of S cathodes. Here, we report our findings in the controlled synthesis of selenium (Se)-containing S-rich co-polymers of various compositions as novel cathode materials through a facile inverse vulcanization of S with selenium disulfide (SeS2) and 1,3-diisopropenylbenzene (DIB) as co-monomers. Nuclear magnetic resonance and X-ray photoelectron spectroscopy results show that divinyl functional groups of DIB were chemically cross-linked with S/SeS2 chain radicals through a ring-opening polymerization. The newly formed bonds of C-S, C-Se, and S-Se in novel S-SeS2-DIB co-polymers effectively alleviate the shuttle effects of polysulfides/polyselenides. Furthermore, various electrochemical techniques confirm the positive roles of Se-containing co-polymers in enhancing the electrode reaction kinetics and the formation of stable solid electrolyte interphase layer with low charge-transfer resistance, leading to improved high-rate performances. The as-synthesized co-polymer was then infiltrated into well-interconnected, porous nanocarbon networks (Ketjenblack EC600JD, KB600) to provide effective paths for the fast electron transport. Due to the synergistic combination of chemical and physical confinement of the reaction intermediates during cycling, good reversibility for 500 cycles with a low decay rate of 0.0549% per cycle was achieved at 1000 mA g-1. These encouraging results suggest that the combination of chemical incorporation of SeS2 into S-rich co-polymer and the physical confinement of carbon networks is a promising strategy for advancing Li/S batteries and their viability for practical applications.

4.
PLoS One ; 13(5): e0196668, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29723230

RESUMO

BACKGROUND: China has a high rate of antibiotic use. The Chinese Ministry of Health (MOH) established the Center for Antibacterial Surveillance (CAS) to monitor the use of antibacterial agents in hospitals in 2005. The purpose of this study was to identify trends, pattern changes and regional differences in antibiotic consumption in 151 public general tertiary hospitals across China from 2011-2014. MATERIALS AND METHODS: Valid data for antibiotic use were collected quarterly, and the antibiotic consumption data were expressed as the defined daily dose (DDD) per 100 inpatient days (ID). We compared the patterns of antibiotic use in different classes and geographical clusters. RESULTS: Total antibiotic use significantly decreased (P = 0.018) from 75.86 DDD/100 ID in 2011 to 47.03 DDD/100 ID in 2014. The total consumption of flomoxef sodium and cefminox increased from 1.31 DDD/100 BD in 2011 to 8.6 DDD/100 BD in 2014. Cephalosporins were the most frequently used antibiotics in all regions. Third-generation cephalosporins accounted for more than 45% of the cephalosporins used. Carbapenem use substantially increased (P = 0.043). Penicillin combinations with inhibitors accounted for 50% of the penicillin used, and prescribed meropenem accounted for most of the carbapenems used in all regions in 2014. The subclasses in each antibiotic group were used differently between the seven regions, and the total hospital antibiotic use in 2014 differed significantly by region (P = 0.014). CONCLUSION: Although the volume and intensity of total antibiotic use decreased, the antibiotic use patterns were not optimal, and broad-spectrum antibiotics were still the main classes. The aggregate data obtained during the study period reveal similar antibiotic consumption patterns in different regions. These findings provide useful information for improving the rational use of antibiotics. More detailed data on antibiotics linked to inpatient diseases need to be collected in future studies.


Assuntos
Antibacterianos/uso terapêutico , Hospitais Gerais/estatística & dados numéricos , Hospitais Públicos/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Centros de Atenção Terciária/estatística & dados numéricos , Antibacterianos/economia , Gestão de Antimicrobianos , China , Uso de Medicamentos/tendências , Humanos , Motivação , Padrões de Prática Médica/economia
5.
6.
Biochim Biophys Acta Mol Basis Dis ; 1864(3): 934-941, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29305916

RESUMO

Asthma is a chronic airway inflammation in which Th2 and Th17 cells play critical roles in its pathogenesis. We have reported that atypical protein kinase (PKC) λ/ι is a new regulator for Th2 differentiation and function. However, the role of PKCλ/ι for Th17 cells remains elusive. In this study, we explored the effect of PKCλ/ι on Th17 cells in the context of ex vivo cell culture systems and an in vivo murine model of allergic airway inflammation with the use of activated T cell-specific conditional PKCλ/ι-deficient mice. Our findings indicate that PKCλ/ι regulates Th17 cells. The secretion of Th17 effector cytokines, including IL-17, IL-21 and IL-22, were inhibited from PKCλ/ι-deficient T cells under non-skewing or Th17-skewing culture conditions. Moreover, the impaired Th17 differentiation and function by the PKCλ/ι-deficiency was associated with the downregulation of Stat3 and Rorγt, key Th17 transcription factors. We developed a model of Th17 and neutrophil-involved allergic airway inflammation by intratracheal inoculation of house dust mites. PKCλ/ι-deficiency significantly inhibited airway inflammations. The infiltrating cells in the lungs and bronchoalveolar lavage fluids were significantly reduced in conditional PKCλ/ι-deficient mice. Th17 effector cytokines were reduced in the bronchoalveolar lavage fluids and lungs at protein and mRNA levels. Thus, PKCλ/ι emerges as a critical regulator of Th17 differentiation and allergic airway hyperresponsiveness.


Assuntos
Diferenciação Celular/genética , Inflamação , Isoenzimas/fisiologia , Proteína Quinase C/fisiologia , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória , Células Th17/fisiologia , Animais , Dermatophagoides pteronyssinus/imunologia , Embrião de Mamíferos , Feminino , Inflamação/genética , Inflamação/imunologia , Isoenzimas/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Gravidez , Proteína Quinase C/genética , Hipersensibilidade Respiratória/genética , Hipersensibilidade Respiratória/imunologia
7.
PLoS One ; 12(6): e0179565, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28614408

RESUMO

The "hygiene hypothesis" is a theory try to explain the dramatic increases in the prevalence of autoimmune and allergic diseases over the past two to three decades in developed countries. According to this theory, reduced exposure to parasites and microorganisms in childhood is the main cause for the increased incidences of both T helper 1 (Th1)-mediated autoimmunity and Th2-mediated allergy. In this study, we investigated the impact of Schistosoma japonicum infection on the allergic airway inflammation induced by repeated intracheal inoculations of house dust mites (HDM), which is a Th17 and neutrophils dominant murine asthma model, mimicking severe asthma. We found that S. japonicum infection downregulated airway hyperresponsiveness. The infiltrating cells, Th17 and Th2 effector cytokines in the bronchoalveolar lavage (BAL) fluids and lungs were significantly reduced in the infected mice. Our findings indicated that S. japonicum infection was able to effectively inhibit host's allergic airway inflammation, which may be related to the upregulated Treg cells upon infection. To our knowledge, it is the first study to reveal the impact of S. japonicum infection on house dust mite induced severe asthma. More in depth investigation is need to elucidate the underlying mechanisms.


Assuntos
Inflamação/imunologia , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/imunologia , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Animais , Asma/sangue , Asma/imunologia , Asma/parasitologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Regulação para Baixo/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Interações Hospedeiro-Parasita/imunologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Inflamação/sangue , Inflamação/parasitologia , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Neutrófilos/metabolismo , Pyroglyphidae/fisiologia , Hipersensibilidade Respiratória/sangue , Hipersensibilidade Respiratória/parasitologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Schistosoma japonicum/fisiologia , Esquistossomose Japônica/parasitologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Células Th2/imunologia , Células Th2/metabolismo
8.
Immunol Lett ; 187: 1-6, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28442365

RESUMO

BACKGROUND: Previous studies have suggested that B lymphocytes can be polyclonally activated by human cytomegalovirus (HCMV), and individuals infected by HCMV exhibit characteristic features of an autoimmunity disease. B cell-activating factor (BAFF) plays important roles in the survival and differentiation of B cells; however, few studies have examined the potential role of BAFF on B cells infected by HCMV. METHODS: HCMV virus strain (HCMV AD-169) was concentrated by normal methods and used to infect microbead-purified tonsil CD19+ B cells. Cells and supernatants were collected at the 1st, 3rd, 5th, and 7th day of co-culture, respectively. Cellular phenotypes, including expression of BAFF and its cognate receptors (BAFF-R, TACI, and BCMA) were detected by flow cytometry (FCM); cells apoptosis rates were also examined by FCM; and IgG titers in supernatants was detected by ELISA. In parallel, neutralizing anti-BAFF-R antibody was applied to observe the effect of BAFF/BAFF-R signaling on apoptosis and the IgG secretion ability of B cells stimulated by HCMV. RESULTS: LogTCID50 of 3rd and 4th generation of HCMV was -3.54 and -3.28, respectively. FCM results showed that the purity of CD19+ B cells was >98%. BAFF-R was highly expressed and upregulated on HCMV-infected B cells (93.5%-99.3%), compared with B cells prior to HCMV infection and uninfected group; while BAFF-R expression gradually decreased with time and to the lowest level at 5th day (81%) in the control medium-only group. In contrast, expression of TACI and BCMA gradually increased during culture in both HCMV-infected and medium-only control B cells. Furthermore, the apoptosis rate of HCMV-infected and medium-only control B cells did not vary significantly during culture, but IgG secretion ability of HCMV-infected B cells significantly increased over time while no changes were observed with the medium-only control. Importantly, the apoptosis rate of B cells significantly increased when BAFF/BAFF-R signal was blocked prior to HCMV infection (P<0.05), although no significant changes of IgG levels were observed (P>0.05). CONCLUSIONS: BAFF-R was consistently expressed on B cells infected by HCMV. Enhancement of BAFF/BAFF-R signaling decreased the apoptosis rate and extended the survival of B cells.


Assuntos
Fator Ativador de Células B/imunologia , Receptor do Fator Ativador de Células B/imunologia , Linfócitos B/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Transdução de Sinais/imunologia , Anticorpos Antivirais/imunologia , Apoptose/imunologia , Linfócitos B/patologia , Linfócitos B/virologia , Sobrevivência Celular/imunologia , Infecções por Citomegalovirus/patologia , Humanos , Imunoglobulina G/imunologia
9.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 32(11): 1475-1480, 2016 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-27774938

RESUMO

Objective To explore the effects of miR-338-5p on the nuclear factor κB1 (NF-κB1) expression and the IgG-producing ability of B cells. Methods Dual-luciferase reporter assay was used to test the target gene of miR-338-5p. The purified CD20+ B cells were transfected with miR-338-5p agomiR, miR-338-5p antagomiR, NF-κB1 siRNA (siNF-κB1) and their corresponding negative control reagents, and then cultured with anti-IgM antibody and/or recombinant human B cell activating factor (rhBAFF). Real-time RCR and Western boltting were applied to determine the mRNA and protein levels of NF-κB1. IgG level in the supernatant was detected by ELISA. Results Compared with the control group, the hRluc/hLuc relative luciferase activity was significantly elevated in miR-338-5p mimic and NF-κB1-3'-UTR reporter co-transfected group. In the co-culture system with anti-IgM antibody and rhBAFF, the NF-κB1 mRNA, p105, p50 and IgG levels in B cells transfected with miR-338-5p agomiR were significantly increased, while the NF-κB1 mRNA and IgG levels in B cells transfected with miR-338-5p antagomiR were significantly decreased. The effect of siNF-κB1 on B cells was opposite to that of miR-338-5p agomiR. Correlation analysis suggested that NF-κB1 mRNA level was significantly positively correlated with IgG concentration. Conclusion miR-338-5p regulates the biological functions of B cells by positively regulating NF-κB1 expression and indirectly regulating BAFF signal.


Assuntos
Linfócitos B/metabolismo , MicroRNAs/metabolismo , Subunidade p50 de NF-kappa B/metabolismo , Fator Ativador de Células B/genética , Fator Ativador de Células B/metabolismo , Western Blotting , Células HEK293 , Humanos , Imunoglobulina G/genética , Imunoglobulina G/metabolismo , MicroRNAs/genética , Subunidade p50 de NF-kappa B/genética , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Transfecção
10.
Sci Rep ; 5: 18215, 2015 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-26655928

RESUMO

Previously, we characterized the biological properties of Akbu-LAAO, a novel L-amino acid oxidase from Agkistrodon blomhoffii ussurensis snake venom (SV). Current work investigated its in vitro anti-tumor activity and underlying mechanism on HepG2 cells. Akbu-LAAO inhibited HepG2 growth time and dose-dependently with an IC50 of ~38.82 µg/mL. It could induce the apoptosis of HepG2 cells. Akbu-LAAO exhibited cytotoxicity by inhibiting growth and inducing apoptosis of HepG2 as it showed no effect on its cell cycle. The inhibition of Akbu-LAAO to HepG2 growth partially relied on enzymatic-released H2O2 as catalase only partially antagonized this effect. cDNA microarray results indicated TGF-ß signaling pathway was linked to the cytotoxicity of Akbu-LAAO on HepG2. TGF-ß pathway related molecules CYR61, p53, GDF15, TOB1, BTG2, BMP2, BMP6, SMAD9, JUN, JUNB, LOX, CCND1, CDK6, GADD45A, CDKN1A were deregulated in HepG2 following Akbu-LAAO stimulation. The presence of catalase only slightly restored the mRNA changes induced by Akbu-LAAO for differentially expressed genes. Meanwhile, LDN-193189, a TGF-ß pathway inhibitor reduced Akbu-LAAO cytotoxicity on HepG2. Collectively, we reported, for the first time, SV-LAAO showed anti-tumor cell activity via TGF-ß pathway. It provides new insight of SV-LAAO exhibiting anti-tumor effect via a novel signaling pathway.


Assuntos
Antineoplásicos/farmacologia , Peróxido de Hidrogênio/metabolismo , L-Aminoácido Oxidase/farmacologia , Transdução de Sinais/efeitos dos fármacos , Venenos de Serpentes/química , Fator de Crescimento Transformador beta/metabolismo , Apoptose/efeitos dos fármacos , Catalase/metabolismo , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Humanos
11.
ACS Appl Mater Interfaces ; 7(43): 24103-9, 2015 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-26473579

RESUMO

In this article, we reported the stacked structure zinc-indium-tin oxide (ZITO) thin-film transistors (TFTs) with graphene nanosheets (GNSs) prepared by solution process. GNSs were used as bridge layer between dual-ZITO layers. The transmission of stacked ZITO/GNSs/ZITO films are more than 80% in the visible region and the resistivity of ZITO films with GNSs bridge layer decreased from 502.9 to 13.4 Ω cm. The solution-processed TFT devices with GNSs bridge layer exhibited a desirable characteristic with a subthreshold slope of 0.25 V/dec and current on-off ratio of 1 × 10(7), and the saturation filed effect mobility is improved to 45.9 cm(2)V(-1)s(-1), which exceeds the mobility values of the pristine ZITO TFTs by one order. These results demonstrate the solution-processed ZITO/GNSs/ZITO TFTs maybe make a further step to achieve high-performance TFTs and show the potential for next-generation applications.

12.
Microbiol Immunol ; 58(8): 439-48, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24931438

RESUMO

The objective of the present study was to explore the correlation between the BAFF signal and HCMV-TLR activation in RTx recipients complicated by HCMV. Peripheral blood (anticoagulated by EDTA-Na2 ) and urine of 113 RTx recipients were collected; healthy volunteers were controlled. Urine HCMV-DNA was detected by real-time PCR. Recipients were classified into a positive group (>10,000 copies/mL urine) and a negative group (<10,000 copies/mL urine). ELISA results showed that sBAFF, sera anti-HCMV pp65 immunoglobulin (Ig)G antibody, and total IgG all significantly increased in recipients with positive HCMV-DNA (>10,000 copies/mL urine) (P < 0.05) compared with negative recipients (<10,000 copies/mL urine). In the positive group, HCMV-DNA copies and total IgG positively correlated with sBAFF (r = 0.988 and 0.625, respectively) (P < 0.05). Luminex assay results suggested that the incidence of anti-HLA I and II and MICA antibody obviously increased in positive recipients. The expression level of BAFF and BAFF-R increased in positive recipients. A total of 88 particular genes-involved in TLR signaling pathways, NF-κB signaling pathways, and cytokine-cytokine receptor signaling pathways-were detected in real-time PCR chip assay. A total of 46 genes were differentially expressed greater than two-fold, and the expression characteristic of BAFF-R was concordant with FACS results. Our findings are that activation of HCMV would induce or enhance the activation of BAFF code in RTx recipients, which may independently or cooperatively participate in renal allograft injury and decrease the long-term outcome of renal allografts.


Assuntos
Fator Ativador de Células B/metabolismo , Infecções por Citomegalovirus/virologia , Citomegalovirus/fisiologia , Transplante de Rim/efeitos adversos , Adolescente , Adulto , Idoso , Fator Ativador de Células B/genética , Receptor do Fator Ativador de Células B/genética , Receptor do Fator Ativador de Células B/metabolismo , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/genética , Infecções por Citomegalovirus/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Transplantados , Adulto Jovem
13.
J Biomed Mater Res A ; 102(1): 76-83, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23606462

RESUMO

To overcome release of silk sericin (SS) from semi-interpenetrating polymer network (semi-IPN) SS/poly(N-isopropylacrylamide) (PNIPAm) hydrogels, natural biocompatible genipin (GNP) was adopted as cross-linking agent of SS. The GNP/SS/PNIPAm hydrogels with various GNP contents were prepared by radical polymerization. Depending on GNP content, the resultant hydrogels present white, yellow, or dark blue. Required time of color change for GNP/SS mixture solution shortened with increasing GNP ratio. The GNP/SS/PNIPAm hydrogels present good oscillatory shrinking-swelling behavior between 20 and 37°C. The behaviors of L929 cell proliferation, desorption, and transshipment on the surface of hydrogels and tissue culture polystyrene were investigated by 3-(4,5-dimethy thioazol-2-yl)-2,5-di-phenytetrazoliumromide and scanning electron microscopy method. In comparison with pure SS/PNIPAm hydrogels, the introduction of certain GNP can accelerate cell adhesion and proliferation. Due to reversible change between hydrophobicity and hydrophilicity, by lowering temperature to 4°C from 37°C, L929 cells could spontaneously detach from the surface of hydrogels without the need for trypsin or ethylenediaminetetraacetic acid. The detached cells could subsequently be recultured. The prepared hydrogel and detached cells have potential applications in biomedical fields, such as organs or tissue regeneration and cancer or disease therapy.


Assuntos
Resinas Acrílicas , Proliferação de Células/efeitos dos fármacos , Hidrogéis , Iridoides , Sericinas , Resinas Acrílicas/química , Resinas Acrílicas/farmacologia , Animais , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Hidrogéis/química , Hidrogéis/farmacologia , Iridoides/química , Iridoides/farmacologia , Camundongos , Sericinas/química , Sericinas/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA