Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(7): 704-710, 2021 Jul 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34382586

RESUMO

OBJECTIVES: To investigate the risk factors for serious infections among hospitalized systemic lupus erythematosus (SLE) patients, and to provide the advice for preventing serious infections in SLE patients. METHODS: Information of SLE patients hospitalized from March 2017 to February 2019 at the Department of Rheumatology and Immunology, Xiangya Hospital, Central South University was obtained. The patients were assigned into a serious infection group and a non-serious infection group. The risk factors for serious infections among SLE inpatients were identified by comparison between the 2 groups and multivariate logistic regression analysis. RESULTS: There were 463 SLE inpatients in total, and 144 were in the serious infection group and 319 in the non-serious infection group. Multivariate logistic regression analysis showed that age ≥54.50 years old (OR=4.958, P<0.001), cardiovascular involvement (OR=6.287, P<0.001), hematologic involvement (OR=2.643, P=0.003), serum albumin <20 g/L (OR=2.340, P=0.036), C-reaction protein (CRP)/erythrocyte sedimentation rate (ESR)≥0.12 (OR=2.430, P=0.002), glucocorticoid dose ≥8.75 mg/d prednisone-equivalent (OR=2.465, P=0.002), and the combined use of immunosuppressive agents (OR=2.847, P=0.037) were the risk factors for serious infections in SLE inpatients. CONCLUSIONS: SLE patients with older age, cardiovascular involvement, hematologic involvement, low serum albumin are prone to suffering serious infections. Increased CRP/ESR ratio indicates serious infections in SLE inpatients. High-dose glucocorticoid and the combined use of immunosuppressive agents can increase the risk of serious infections in SLE inpatients.


Assuntos
Pacientes Internados , Lúpus Eritematoso Sistêmico , Idoso , Glucocorticoides/efeitos adversos , Humanos , Lúpus Eritematoso Sistêmico/complicações , Pessoa de Meia-Idade , Prednisona , Fatores de Risco
2.
J Phys Chem C Nanomater Interfaces ; 125(26): 14338-14347, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34276869

RESUMO

Self-catalyzed AlGaAs nanowires (NWs) and NWs with a GaAs quantum dot (QD) were monolithically grown on Si(111) substrates via solid-source molecular beam epitaxy. This growth technique is advantageous in comparison to the previously employed Au-catalyzed approach, as it removes Au contamination issues and renders the structures compatible with complementary metal-oxide-semiconductor (CMOS) technology applications. Structural studies reveal the self-formation of an Al-rich AlGaAs shell, thicker at the NW base and thinning towards the tip, with the opposite behavior observed for the NW core. Wide alloy fluctuations in the shell region are also noticed. AlGaAs NW structures with nominal Al contents of 10, 20, and 30% have strong room temperature photoluminescence, with emission in the range of 1.50-1.72 eV. Individual NWs with an embedded 4.9 nm-thick GaAs region exhibit clear QD behavior, with spatially localized emission, both exciton and biexciton recombination lines, and an exciton line width of 490 µeV at low temperature. Our results demonstrate the properties and behavior of the AlGaAs NWs and AlGaAs/GaAs NWQDs grown via the self-catalyzed approach for the first time and exhibit their potential for a range of novel applications, including nanolasers and single-photon sources.

4.
Opt Express ; 29(10): 14231-14244, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33985147

RESUMO

We report on controllable cavity modes by controlling the backscattering by two identical scatterers. Periodic changes of the backscattering coupling between two degenerate cavity modes are observed with the changing angle between two scatterers and elucidated by a theoretical model using two-mode approximation and numerical simulations. The periodically appearing single-peak cavity modes indicate mode degeneracy at diabolical points. Interactions between single quantum dots and cavity modes are then investigated. Enhanced emission of a quantum dot with a six-fold intensity increase is obtained in a microdisk at a diabolical point. This method to control cavity modes allows large-scale integration, high reproducibility and flexible design of the size, the location, the quantity and the shape for scatterers, which can be applied for integrated photonic structures with scatterer-modified light-matter interaction.

5.
Front Microbiol ; 12: 625821, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679644

RESUMO

Shewanella species are widely distributed in the aquatic environment and aquatic organisms. They are opportunistic human pathogens with increasing clinical infections reported in recent years. However, there is a lack of a rapid and accurate method to identify Shewanella species. We evaluated here matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for rapid identification of Shewanella. A peptide mass reference spectra (PMRS) database was constructed for the type strains of 36 Shewanella species. The main spectrum projection (MSP) cluster dendrogram showed that the type strains of Shewanella species can be effectively distinguished according to the different MS fingerprinting. The PMRS database was validated using 125 Shewanella test strains isolated from various sources and periods; 92.8% (n = 116) of the strains were correctly identified at the species level, compared with the results of multilocus sequence analysis (MLSA), which was previously shown to be a method for identifying Shewanella at the species level. The misidentified strains (n = 9) by MALDI-TOF MS involved five species of two groups, i.e., Shewanella algae-Shewanella chilikensis-Shewanella indica and Shewanella seohaensis-Shewanella xiamenensis. We then identified and defined species-specific biomarker peaks of the 36 species using the type strains and validated these selected biomarkers using 125 test strains. Our study demonstrated that MALDI-TOF MS was a reliable and powerful tool for the rapid identification of Shewanella strains at the species level.

6.
BMC Pregnancy Childbirth ; 21(1): 17, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407258

RESUMO

BACKGROUND: This study aims to evaluate the efficacy and safety of the induction of labour in mid-trimester pregnancy using a double-balloon catheter (DBC) within 12 h versus within 12-24 h. METHODS: In this retrospective study, a total of 58 pregnant women at 14 + 0 weeks to 27 + 6 weeks of gestation were enrolled as research subjects, and they underwent the intended termination of pregnancy at our birth centre from January 1, 2017, to June 31, 2019. Based on the duration of DBC, the patients were divided into two groups, namely, the DBC group within 12 h and the DBC group within 12-24 h. RESULTS: All 58 cases were successful vaginal deliveries, and no one chose to undergo caesarean section. The success rate of induction (successful abortion of the foetus and placenta without the implementation of dilation and evacuation) was higher in the DBC group within 12-24 h (96.3%, 29/31) than in the DBC group within 12 h (71.0%, 18/27) (p < 0.05). Additionally, the time from DBC removal to delivery in the DBC group within 12-24 h was significantly shorter than that in the DBC group within 12 h (3.0 h versus 17.8 h) (p < 0.05), and the degree of cervical dilation after DBC removal in the DBC group within 12-24 h was larger than that in the DBC group within 12 h (p < 0.05). CONCLUSION: In the clinic, the placement time of DBC generally lasts for approximately 12 h. However, considering that the cervical condition is immature in the mid-trimester, properly extending the placement time of DBC to 24 h will benefit cervical ripening and reduce the chance of dilation and evacuation.


Assuntos
Cateterismo/métodos , Idade Gestacional , Trabalho de Parto Induzido/métodos , Aborto Induzido/métodos , Adulto , Cateterismo/instrumentação , Maturidade Cervical/fisiologia , Aberrações Cromossômicas , Parto Obstétrico/métodos , Feminino , Feto/anormalidades , Humanos , Primeira Fase do Trabalho de Parto/fisiologia , Gravidez , Segundo Trimestre da Gravidez , Estudos Retrospectivos , Fatores de Tempo
7.
Light Sci Appl ; 9: 6, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31969981

RESUMO

In single microdisks, embedded active emitters intrinsically affect the cavity modes of the microdisks, resulting in trivial symmetric backscattering and low controllability. Here we demonstrate macroscopic control of the backscattering direction by optimizing the cavity size. The signature of the positive and negative backscattering directions in each single microdisk is confirmed with two strongly coupled microdisks. Furthermore, diabolical points are achieved at the resonance of the two microdisks, which agrees well with theoretical calculations considering the backscattering directions. Diabolical points in active optical structures pave the way for an implementation of quantum information processing with geometric phase in quantum photonic networks.

8.
Phys Rev Lett ; 122(8): 087401, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30932617

RESUMO

Large coupling strengths in exciton-photon interactions are important for the quantum photonic network, while strong cavity-quantum dot interactions have been focused on s-shell excitons with small coupling strengths. Here we demonstrate strong interactions between cavities and p-shell excitons with a great enhancement by the in situ wave-function control. The p-shell excitons are demonstrated with much larger wave-function extents and nonlocal interactions beyond the dipole approximation. Then the interaction is tuned from the nonlocal to the local regime by the wave function shrinking, during which the enhancement is obtained. A large coupling strength of 210 µeV has been achieved, indicating the great potential of p-shell excitons for coherent information exchange. Furthermore, we propose a distributed delay model to quantitatively explain the coupling strength variation, revealing the intertwining of excitons and photons beyond the dipole approximation.

9.
Arthritis Res Ther ; 20(1): 263, 2018 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-30486874

RESUMO

BACKGROUND: The cholinergic anti-inflammatory pathway (CAP) has a strong anti-inflammatory effect on collagen-induced arthritis (CIA), a classic animal model of rheumatoid arthritis (RA). However, the underlying immune regulatory mechanism remains unclear. Here, we investigated the effect of the CAP on arthritis development and the involvement of dendritic cells (DCs). METHODS: Forty DBA/1 mice were randomly divided into five groups: a control group (sham vagotomy+ phosphate-buffered saline; shamVGX+PBS), a CIA group (shamVGX+CIA + PBS), a vagotomy group (VGX + CIA + PBS), a GTS-21 (4 mg/kg) group (shamVGX+CIA + GTS-4), and a GTS-21 (8 mg/kg) group (shamVGX+CIA + GTS-8). The vagotomy group underwent left cervical vagotomy 4 days before arthritis induction, whereas the sham-vagotomy group underwent vagus nerve exposure. Mice were pretreated with GTS-21 by intraperitoneal injection on the day of surgery. The degree of arthritis was measured by using the arthritis score, hematoxylin and eosin staining, and TRAP (tartrate-resistant acid phosphatase) staining. Flow cytometry was used to detect the expression of CD80 and major histocompatibility complex II (MHC II) on CD11c+ DCs in the spleen. Luminex was used to detect the serum concentration of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα), and IL-10. Immunohistochemistry was used to detect CD11c expression in the synovium. The effects of GTS-21 on DC differentiation and maturation were examined in vitro by treating bone marrow-derived DCs with GTS-21 and assessing differentiation and maturation. Flow cytometry was used to analyze CD80 and MHC II expression on the surface of DCs. RESULTS: GTS-21 treatment ameliorated clinical arthritis in a mouse model of CIA in vivo, decreasing the secretion of pro-inflammatory cytokines in the serum and downregulating CD80 and MHC II expression on DCs in the spleen of CIA mice. GTS-21 treatment strongly suppressed the infiltration of DCs into the synovium. Vagotomy itself did not exacerbate the severity of arthritis in CIA mice. In vitro, GTS-21 (10 µmol/L) significantly downregulated CD80 and MHC II in bone marrow-derived immature DCs and this effect was blocked by the α7-nicotinic acetylcholine receptor antagonist methyllycaconitine (MLA). However, GTS-21 had no effects on mature DCs. CONCLUSIONS: The present study provides new insight into the mechanism underlying the effects of the CAP on RA and indicates that the immunosuppressive effect of GTS-21 may be mediated by the inhibition of DC differentiation.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/prevenção & controle , Compostos de Benzilideno/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Agonistas Nicotínicos/farmacologia , Piridinas/farmacologia , Animais , Artrite Experimental/imunologia , Artrite Experimental/patologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Diferenciação Celular/imunologia , Células Cultivadas , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Distribuição Aleatória , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Vagotomia
10.
Phys Rev Lett ; 120(21): 213901, 2018 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-29883144

RESUMO

Two-photon Rabi splitting in a cavity-dot system provides a basis for multiqubit coherent control in a quantum photonic network. Here we report on two-photon Rabi splitting in a strongly coupled cavity-dot system. The quantum dot was grown intentionally large in size for a large oscillation strength and small biexciton binding energy. Both exciton and biexciton transitions couple to a high-quality-factor photonic crystal cavity with large coupling strengths over 130 µeV. Furthermore, the small binding energy enables the cavity to simultaneously couple with two exciton states. Thereby, two-photon Rabi splitting between the biexciton and cavity is achieved, which can be well reproduced by theoretical calculations with quantum master equations.

11.
Eur J Pharmacol ; 831: 38-45, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29715455

RESUMO

Previous research has demonstrated that nicotine have protective role in rheumatoid arthritis (RA). However, the immunologic mechanisms of nicotine's effect have not been fully elucidated. Herein, the effects of nicotine on the differentiation of Th1, Th2, and Th17 cells were assessed. Peripheral blood mononuclear cells (PBMCs) and CD4+T cells were separated from patients with RA. PBMCs were stimulated with anti-CD3/anti-CD28 in the absence or presence of nicotine. CD4+T cells were cultured in the Th cell differentiation condition in the absence of nicotine or nicotine and alpha- bungarotoxin (αBgt) (the antagonist of nicotine) combined. Levels of T cell cytokines were detected with ELISA and flow cytometry. The expression of specific transcription factors (retinoic orphan re- ceptor c (RORc), T-box transcription factor (T-bet), and GATA Binding Protein 3 (GATA-3)) and signaling molecules (P-ERK1/2 and T-ERK1/2) were determined by Western blot. The results showed nicotine reduced IL-17A and increased IL-4 produced by stimulated PBMCs. During Th17 differentiation conditions, nicotine reduced the levels of IL-17A and RORc, induced the phosphorylation of ERK1/2. Meanwhile, nicotine increased the levels of IL-4 and GATA3 during Th2 differentiation. α-Bgt blocked the effects of nicotine on Th2 and Th17 differentiation. However, nicotine had no effect on the expression of IFN-γ and T-bet in CD4+T cells during Th1differentiation. These results demonstrate that nicotine suppresses Th17 differentiation, promotes Th2 differentiation and improves Th1/Th2 imbalance in RA patients, providing a new justification for its application in the treatment of rheumatoid arthritis.


Assuntos
Artrite Reumatoide/imunologia , Diferenciação Celular/efeitos dos fármacos , Ativação Linfocitária/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Células Th1/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Células Th2/efeitos dos fármacos , Adulto , Idoso , Artrite Reumatoide/metabolismo , Biomarcadores/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocinas/imunologia , Citocinas/metabolismo , Relação Dose-Resposta a Droga , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Fator de Transcrição GATA3/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Fenótipo , Fosforilação , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Adulto Jovem , Receptor Nicotínico de Acetilcolina alfa7/agonistas , Receptor Nicotínico de Acetilcolina alfa7/imunologia , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
12.
Small ; 14(17): e1704429, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29611286

RESUMO

Defects are detrimental for optoelectronics devices, such as stacking faults can form carrier-transportation barriers, and foreign impurities (Au) with deep-energy levels can form carrier traps and nonradiative recombination centers. Here, self-catalyzed p-type GaAs nanowires (NWs) with a pure zinc blende (ZB) structure are first developed, and then a photodetector made from these NWs is fabricated. Due to the absence of stacking faults and suppression of large amount of defects with deep energy levels, the photodetector exhibits room-temperature high photoresponsivity of 1.45 × 105 A W-1 and excellent specific detectivity (D*) up to 1.48 × 1014 Jones for a low-intensity light signal of wavelength 632.8 nm, which outperforms previously reported NW-based photodetectors. These results demonstrate these self-catalyzed pure-ZB GaAs NWs to be promising candidates for optoelectronics applications.

13.
Connect Tissue Res ; 59(3): 287-294, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28914550

RESUMO

Stimulation of the cholinergic inflammatory pathway can attenuate collagen-induced arthritis (CIA) and inhibit synovitis by Janus kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 signaling. Suppressor of cytokine signaling (SOCS) protein can also regulate the inflammatory processes and activate JAK/STAT signal transduction, but its involvement in rheumatoid arthritis (RA) has not been demonstrated. This study investigated the effect of SOCS on cholinergic pathway regulation of synovitis in the fibroblast-like synoviocytes (FLSs) of RA and CIA mice. The effects of nicotine on SOCS1 and SOCS3 protein expression in FLSs were assayed by western blotting before and after transfection with a small interfering RNA oligonucleotide (SOCS3-siRNA or control-siRNA). Interleukin-6 was measured by enzyme-linked immunosorbent assay of SOCS3-siRNA and control-siRNA transfected FLS culture supernatants. Histopathological evaluation and immunohistochemical staining of SOCS3 were performed in joint tissue sections of control, CIA model, vagotomy, and nicotine-treated DBA/1 mice. Nicotine increased SOCS3 expression in the FLSs of RA. The inhibitory effect of nicotine on inflammatory factors was abolished by siRNA knockdown of SOCS3 protein expression. Nicotine increased the expression of SOCS3 protein in the synovium and reduced synovitis and bone erosion in CIA mice.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Sinoviócitos/metabolismo , Animais , Artrite Experimental , Artrite Reumatoide/patologia , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Camundongos Endogâmicos DBA , Nicotina/farmacologia , Membrana Sinovial/citologia , Membrana Sinovial/efeitos dos fármacos , Sinoviócitos/efeitos dos fármacos , Sinovite/patologia
14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 42(8): 927-933, 2017 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-28872084

RESUMO

OBJECTIVE: To analyze the trend relevant factors leading to death and their patterns over a 10-year period in inpatients with connective tissue diseases (CTDs).
 Methods: All clinical data about death in inpatients with CTDs were retrospectively reviewed between 2005 and 2014 at the Department of Rheumatology and Immunology in Xiangya Hospital of Central South University.
 Results: In the 10-year time period, the overall hospital mortality was 15.68‰. The disease itself accounted for 44.71% of the total causes of death, infection accounted for 42.94%, and comorbidities accounted for 12.35%. The constituent ratio of deaths and the average hospital mortality caused by the disease itself declined gradually year by year, and the constituent ratio of deaths caused by infection and comorbidities increased gradually year by year (P<0.05). In 2013-2014, infection was the leading cause of death, which accounted for 51.06%. The survival time for CTDs inpatients with interstitial lung disease (ILD) was shorter than that of CTDs inpatients without ILD, and even the risk of death was 1.722 times of the latter. The proportion of deaths caused by the disease itself was the highest in systemic sclerosis and systemic lupus erythematosus, that by infection was the highest in idiopathic inflammatory myopathy (IIM), and that by comorbidities was the highest in rheumatoid arthritis.
 Conclusion: The proportion of deaths and the hospital mortality in CTDs inpatients caused by the disease itself show a declining trend, while the proportion of deaths caused by infection and comorbidities increase. CTDs patients with ILD have shorter survival time and an increase in risk of death.


Assuntos
Doenças do Tecido Conjuntivo , Pacientes Internados , Mortalidade Hospitalar , Humanos , Doenças Pulmonares Intersticiais , Estudos Retrospectivos
15.
Rev Sci Instrum ; 88(2): 024706, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28249504

RESUMO

This work provides a detailed analysis and simulation to demonstrate how to broaden the operating bandwidth of a circulator. A double-Y junction circulator is designed, and the shape of the central stripline is optimized with the knowledge of a modified equation. The equation predicts two resonant conditions. The overlapping of the two resonant conditions jointly constitutes the broad bandwidth. The bias magnetic field is simulated and then used in full electromagnetic-wave simulation. The designed circulator was fabricated in the S-band for communication purpose. The measured results agree very well with simulation. The overall operation range is from 1643 to 2027 MHz with the insertion loss less than 0.35 dB, reflection, and isolation better than 20 dB. The mechanism will be discussed.

16.
Rheumatol Int ; 37(4): 585-592, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27878344

RESUMO

The aim of the study was to measure the diagnostic values of biomarkers of bacterial infection in idiopathic inflammatory myopathy (IIM) patients. The serum and clinical data of 82 IIM patients with/without bacterial infection were collected. Concentrations of soluble urokinase plasminogen activator receptor (suPAR), soluble triggering receptor expressed on myeloid cells 1 (sTREM-1), procalcitonin (PCT) and C-reactive protein (CRP) were measured in IIM patients and healthy controls. There were no significant differences in serum suPAR and sTREM-1 levels between healthy controls and non-infection IIM patients. Serum levels of suPAR, sTREM-1, PCT and CRP measured in this study were significantly higher in the IIM patient group with concurrent infection than in the non-infection IIM patient group (p < 0.05). The biomarker suPAR showed the highest diagnostic value with sensitivity, specificity, positive predictive value and negative predictive value of 81.6, 77.3, 75.6 and 82.9%, respectively. Combining suPAR negative and CRP negative to rule out bacterial infection in IIM patients provides a very high specificity of 97.4%. Both suPAR and CRP positive to confirm bacterial infection give the specificity of 90.9%. The inflammatory biomarkers suPAR, sTREM-1, PCT and CRP offer diagnostic accuracy in detecting bacterial infection in IIM patients. Particularly, suPAR is the most sensitive and specific biomarker to predict bacterial infection in IIM patients. Combination of suPAR and CRP serum levels provides an even better confirmation of bacterial infection.


Assuntos
Infecções Bacterianas/diagnóstico , Proteína C-Reativa/metabolismo , Calcitonina/sangue , Glicoproteínas de Membrana/sangue , Miosite/diagnóstico , Receptores Imunológicos/sangue , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Adulto , Infecções Bacterianas/sangue , Biomarcadores/sangue , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Receptor Gatilho 1 Expresso em Células Mieloides
17.
Mol Med Rep ; 12(2): 2765-70, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25955496

RESUMO

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, characterized by the development of a pathogenic autoantibodies. Lupus nephritis is a major cause of mortality in patients with SLE. Glucocorticoids are used for the treatment of lupus, however, corticosteroids have no effect on the expression of Toll-like receptor 9 (TLR9), which may limit response to corticosteroids in certain patients with SLR. The expression of TLR9 can be used as a predictor of glucocorticoid response in patients with active SLE. The present study analyzed urine proteins and pathological kidney sections of BABL/C-lpr mice and found that, following the inhibition of Notch1, glucocorticoid treatment improved the symptoms of lupus nephritis. Furthermore, glucocorticoid treatment reduced the expression of TLR9 in the BABL/C-lpr mouse kidneys, according to immunohistochemical and western blot analyses. These results suggested that inhibition of the expression of Notch-1 enhanced corticosteroid sensitivity in BABL/C-lpr mice.


Assuntos
Glucocorticoides/uso terapêutico , Rim/efeitos dos fármacos , Nefrite Lúpica/tratamento farmacológico , Receptor Notch1/antagonistas & inibidores , Receptor Toll-Like 9/análise , Animais , Feminino , Humanos , Rim/patologia , Nefrite Lúpica/patologia , Camundongos Endogâmicos BALB C
18.
Inflammation ; 38(4): 1424-33, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25616906

RESUMO

It was recently demonstrated that stimulation of the nicotine receptor attenuates collagen-induced arthritis and inhibits cytokine release in mice. We elucidated the possible intracellular signaling mechanism of the cholinergic anti-inflammatory pathway in fibroblast-like synoviocytes (FLSs). Levels of interleukin (IL)-6, IL-10, and monocyte chemoattractant protein (MCP)-1 in culture supernatants of tumor necrosis factor (TNF)-α-stimulated FLSs were measured using an enzyme-linked immunosorbent assay (ELISA). FLSs were transfected with a small interfering RNA oligonucleotide (STAT3 siRNA or control siRNA). AG490, a specific inhibitor of JAK2, was added 16 h before nicotine, and blocker of nAChR was added 30 min before nicotine. Activation of signal transducers and activators of transcription (STAT) such as STAT1 and STAT3 were detected using Western blotting. Nicotine downregulated production of IL-6 and MCP-1 in RA-FLSs induced by TNFα in a concentration-dependent manner, and IL-10 levels were not significantly different after nicotine pretreatment. Nicotine-induced activation of STAT3 (but not STAT1) and deactivation of STAT3 decreased the anti-inflammatory effect of nicotine. AG490 inhibited the phosphorylation of STAT1 and STAT3 and decreased the TNF-α-induced production of pro-inflammatory mediators in RA-FLSs. A α7nAChR antagonist abrogated the anti-inflammatory effects of nicotine and suppressed STAT3 activity. In conclusion, nicotine has an anti-inflammatory effect on RA by downregulating production of IL-6 and MCP-1 in FLSs, and this is mediated through activation of the JAK2-STAT3 signal pathway.


Assuntos
Fibroblastos/metabolismo , Mediadores da Inflamação/metabolismo , Janus Quinase 2/metabolismo , Receptores Nicotínicos/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Células Cultivadas , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Nicotina/farmacologia , Fator de Transcrição STAT3/agonistas , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Membrana Sinovial/citologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
19.
Exp Ther Med ; 8(2): 557-562, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25009619

RESUMO

GTS-21 (also known as DMBX-anabaseine), a selective α7 nicotinic acetylcholine receptor (α7nAChR) agonist, has previously been found to inhibit the inflammation associated with rheumatoid arthritis (RA). RA is an autoimmune disease, where an abnormal immune system plays a critical role in the occurrence and development of synovium inflammation and bone damage. However, prior to this study, the immunological mechanism by which GTS-21 protects against RA had not been elucidated. In the present study, the effects of GTS-21 on T helper 1 (Th1) cells, which have an important role in the inflammation associated with RA, were investigated. Peripheral blood mononuclear cells (PBMCs) and cluster of differentiation (CD)4+ T cells were separated from patients with RA, and the effects of GTS-21 on PBMCs stimulated with anti-CD3/-CD28 antibodies and CD4+ T cells were investigated in the context of Th1-cell differentiation. ELISA was used to analyze interferon (IFN)-γ expression and flow cytometric analysis was used to detect the percentage of IFN-γ+ CD3+CD8- T cells. In addition, western blotting was employed to detect the levels of the T-box transcription factor TBX21, which is a Th1 cell-specific transcription factor. The present study showed that GTS-21 reduced IFN-γ production in PBMCs from patients with RA. Under conditions of Th1-cell differentiation, GTS-21 reduced the percentage of IFNγ+CD3+CD8- T cells and IFN-γ production in the culture supernatant and also inhibited the expression of the Th1 cell-specific transcription factor TBX21. The effects of GTS-21 were blocked by the α7nAchR antagonist α-bungarotoxin, which increased the expression of IFN-γ and TBX21. This study demonstrated that GTS-21 is able to inhibit RA Th1-cell differentiation through activation of the α7nAchR.

20.
Eur J Pharmacol ; 735: 97-104, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24755145

RESUMO

The cholinergic anti-inflammatory pathway can inhibit the inflammation of collagen induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). However, the immunologic mechanisms that provide a therapeutic effect against the auto-inflammatory disease are not yet elucidated. The present study explores the effect of cholinergic anti-inflammatory pathway on CD4+ T cell responses in CIA. Forty DBA/1 mice were divided into 4 groups: a control group, a CIA group, a vagotomy group, and a nicotine group. The degree of arthritis was measured by arthritis score and hematoxylin and eosin. ELISA was used to detect the serum concentration of IFN-γ, IL-4 and IL-17A. Flow cytometry was used to detect the cytokines and transcription factors (TFs) (the TFs of Th1, Th2, and Th17 cells are T-bet, RORγτ and GATA3 respectively) in the spleen. Immunohistochemistry was used to analyze RORγτ expression in the joint synovium. Arthritis in the nicotine group was significantly lightened compared with that in the CIA group and in the vagotomy group. Nicotine attenuated Th17 lineage by reducing IL-17A production and RORγτ expression. The expressions of IL-4 and GATA3 were increased in the same setting. However, the expressions of IFN-γ and T-bet had no difference between the nicotine and the CIA group. Nicotine may induce a shift to the Th2 lineage and improve the Th1/Th2 imbalance. Activating the cholinergic anti-inflammatory pathway with nicotine can inhibit Th17 cell responses and may improve the Th1/Th2 imbalance in CIA, providing a new justification for its application in the treatment of rheumatoid arthritis.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/imunologia , Nicotina/farmacologia , Células Th17/imunologia , Animais , Articulação do Tornozelo/efeitos dos fármacos , Articulação do Tornozelo/patologia , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Citocinas/sangue , Citocinas/imunologia , Fator de Transcrição GATA3/imunologia , Masculino , Camundongos Endogâmicos DBA , Nicotina/uso terapêutico , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/imunologia , Baço/efeitos dos fármacos , Baço/imunologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/imunologia , Proteínas com Domínio T/imunologia , Células Th1/imunologia , Células Th2/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...