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From 2015 to 2019, the annual average incidence rate of scarlet fever was 7.80/100 000 in Yantai City, which showed an increasing trend since 2017 (χ2trend=233.59, P<0.001). The peak period of this disease was from April to July and November to January of the next year. The ratio of male to female was 1.49â¶1, with a higher prevalence among cases aged 3 to 9 years (2 357/2 552, 92.36%). Children in kindergartens, primary and middle school students, and scattered children were the high risk population, with the incidence rate of 159.86/100 000, 25.57/100 000 and 26.77/100 000, respectively. The global spatial auto-correlation analysis showed that the global Moran's I index of the reported incidence rate of scarlet fever in Yantai from 2015 to 2019 was 0.28, 0.29, 0.44, 0.48, and 0.22, respectively (all P values<0.05), suggesting that the incidence rate of scarlet fever in Yantai from 2015 to 2019 was spatial clustering. The local spatial auto-correlation analysis showed that the "high-high" clustering areas were mainly located in Laizhou City, Zhifu District, Haiyang City, Fushan District and Kaifa District, while the "low-high" clustering areas were mainly located in Haiyang City and Fushan District.
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Escarlatina , Criança , Humanos , Masculino , Feminino , Escarlatina/epidemiologia , Análise Espacial , Cidades/epidemiologia , Estações do Ano , Fatores de Risco , Incidência , Análise por Conglomerados , China/epidemiologiaRESUMO
Objective: Takayasu's arteritis involving the pulmonary artery (PTA) is uncommon, and those with pulmonary hypertension (PH) are even rarer. This study investigated the clinical features and CT findings in PTA patients with PH. Methods: A total of 40 PTA patients were retrospective selected in the First Hospital of Air Force Medical University from January 2008 to January 2018. There were 14 PTA patients with PH, including 3 male and 11 female cases, aged from 18 to 53 (29.7±9.4) years, as the study group (PTA+PH group). There were 26 PTA patients without PH, including 4 males and 22 females, aged 15-52 (28.9±8.5) years, as the control group (PTA group). The Chi-square or Fisher's test, T test of two independent samples and Mann-Whitney U rank sum test were used to compare the general information, symptoms, signs, laboratory examination data, right ventricular and pulmonary artery measurement data, and pulmonary artery CT findings between the two groups. Results: Compared with the PTA group, the patients in the PTA+PH group had longer disease duration, fewer active cases, more shortness of breath, chest distress and lower limb edema, lower blood oxygen partial pressure (PaO2) and lower ESR (all P<0.05). The width of right atrium and right ventricle in PTA+PH group was greater than that in PTA group (all P<0.05). The main CT findings of the involved pulmonary artery included lumen stenosis (39 cases, 97.5%), lumen occlusion (16 cases, 40%), wall thickening (9 cases, 22.5%), and lumen dilation (2 cases, 5.0%). Patients in the PTA+PH group had less wall thickening and mild lumen stenosis (<50%), more severe lumen stenosis (≥50%) and occlusion than those in the PTA group (all P<0.05). Conclusions: PTA patients with PH showed certain characteristics in clinical, laboratory and CT findings, which may be correlated to the stage of the disease duration, the severity, and the prognosis.
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Hipertensão Pulmonar , Arterite de Takayasu , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Masculino , Artéria Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Arterite de Takayasu/complicações , Arterite de Takayasu/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are RNA molecules that do not translate into protein. Both miRNAs and lncRNAs are known to regulate gene expression and to play an essential role in T cell differentiation and function. Both systemic lupus erythematosus (SLE), a prototypic systemic autoimmune disease, and rheumatoid arthritis (RA), a representative disease of inflammatory arthritis, are characterized by a complex dysfunction in the innate and adaptive immunity. T cells play a central role in cell-mediated immune response and multiple defects in T cells from patients with SLE and RA have been observed. Abnormality in T cell signalling, cytokine and chemokine production, T cell activation and apoptosis, T cell differentiation and DNA methylation that are associated closely with the aberrant expression of a number of miRNAs and lncRNAs have been implicated in the immunopathogenesis of SLE and RA. This review aims to provide an overview of the current state of research on the abnormal expression of miRNAs and lncRNAs in T cells and their roles in the immunopathogenesis of SLE and RA. In addition, by comparing the differences in aberrant expression of miRNAs and lncRNAs in T cells between patients with SLE and RA, controversial areas are highlighted that warrant further investigation.
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Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , RNA não Traduzido/genética , Linfócitos T/imunologia , Imunidade Adaptativa/genética , Imunidade Adaptativa/imunologia , Animais , Apoptose/genética , Apoptose/imunologia , Artrite Reumatoide/genética , Metilação de DNA/genética , Metilação de DNA/imunologia , Humanos , Lúpus Eritematoso Sistêmico/genética , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , MicroRNAs/genéticaRESUMO
BACKGROUND: Schizophrenia is a complex disease which proceeds from an interaction between genetic background and environmental factors. Recent studies showed T helper 17 (Th17) signalling, which is the main downstream immune response of psoriasis, is activated in schizophrenia. OBJECTIVE: To investigate whether patients with schizophrenia have higher risk of psoriasis. METHODS: In this nationwide retrospective cohort study, we analysed the 1 million enrollees' cohort from Taiwan's National Health Insurance Research Database. Psoriasis and schizophrenia were ascertained by International Classification of Diseases, 9th revision, Clinical Modification coding. The study cohort was comprised of enrollees diagnosed with schizophrenia during the period from 1 January 1996 through 31 December 2010, while the comparison population consisted of enrollees who had not been diagnosed with schizophrenia during the study period. Hazard ratio (HR) and 95% confidence interval (CI) were calculated for the risk of psoriasis associated with schizophrenia using Cox proportional hazard regression. RESULTS: The adjusted HR of psoriasis associated with schizophrenia was 2.32 (95% CI = 1.81-2.98). After 15 years, the cumulative incidence of psoriasis in patients with schizophrenia and comparison population was 2.82% and 1.17%, respectively. The Kaplan-Meier curves for the cumulative incidence of psoriasis in individuals with and without schizophrenia differed significantly (P < 0.0001, log-rank test). CONCLUSIONS: Patients with schizophrenia have higher risk of psoriasis, which may be due to common genetic susceptibilities and/or immunologic mechanisms in both diseases. Th17 signalling and pro-inflammatory cytokines may act as a link between these two diseases and are potential therapeutic targets for schizophrenia.
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Psoríase/complicações , Esquizofrenia/complicações , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Psoríase/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Esquizofrenia/epidemiologia , Taiwan/epidemiologia , Adulto JovemRESUMO
Objective: To explore the CT findings of the Takayasu's arteritis (TA)with pulmonary artery (PA) involvement and its clinical significance. Methods: A total of 35 patients with TA involving the PA in Xijing Hospital from November 2007 to November 2016, 6 male cases, 29 female cases, the age was 15-52 (28±9) years old, were retrospectively collected and included in the study group (TA+ P group), meanwhile 40 patients with TA but not involving the pulmonary artery in this hospital from January 2015 to November 2016 were collected as control group, 5 male cases, 35 female cases, the age was 7-67 (28±12) years old.The clinical and laboratory data, the pulmonary artery and right heart measurement data of the two groups were compared by using t test, χ(2) test , and rank sum test.The CT signs of pulmonary artery involvement in the TA+ P group were analyzed. Results: TA+ P group patients had shortness of breath, wheezing(54.3% vs 10.0%), cough(31.4% vs 12.5%)and palpitations(11.4% vs 0)mostly, and there were statistical difference between TA+ P group and TA group (all P<0.05), However, there was no difference between the two groups in the activity and duration of disease (all P>0.05). In TA+ P group, a total of 312 pulmonary artery segments were involved in 35 patients.The lumen stenosis of PA was more common(35 cases, 211 segments), followed by occlusion(14 cases, 94 segments), bilateral PA (23 cases, 217 segments) and multiple branches of PA involvement(34 cases, 311 segments) were more common.The PA systolic pressure, the diameter of main pulmonary artery, right atrium and right ventricular width of the TA+ P group patients were significantly higher than those of the TA group (all P<0.05). Conclusions: There are some CT certain characteristics in TA pulmonary arterial involvement, and they are not related to the activity and duration of the disease.Most patients with PA involvement present pulmonary hypertension and a series of special clinical manifestations.
Assuntos
Hipertensão Pulmonar/etiologia , Artéria Pulmonar/diagnóstico por imagem , Arterite de Takayasu/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Constrição Patológica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Arterite de Takayasu/complicações , Adulto JovemRESUMO
Objective: To evaluate the application of the BACspreader™ Microbe Dispersion Counter in drug susceptibility test (DST) on Mycobacterium tuberculosis (MTB). Methods: The MTB strains were dispersed and diluted to 1.0 McFarland standard turbidity, by means of BACspreader™ Microbe Dispersion Counter and manual grinding method, respectively. The bacterial dispersion effect and bacterial activity were tested by microscope and colony counting method. During Jan. 2015 to June 2015, a total of 726 isolates of MTB were collected in all district tuberculosis hospitals of Shanghai. The bacterial suspension dispersed by instrument and manual grinding, were inoculated in slant medium for DST (Proportion Method), and then incubated in 37 â incubator for 28 days and the DST results were reported. The effects of the 2 different bacterial dispersion methods were compared by comparing DST results and counting the bacterial colony which grew in high and low concentration control media. Paired chi-square test was used for statistical analysis, and the significance level was 0.05. Results: Compared to the manual grinding method, the MTB colony could be better dispersed by BACspreader™ Microbe Dispersion Counter, without reducing the bacterial activity. The DST results of 726 mycobacterial isolates were the same by different bacterial dispersion methods. The count of bacterial colony growing in high concentration control medium was significantly different between of the 2 dispersion methods (χ(2)=8.0, P<0.01). When counting the bacterial colony growing in low concentration control medium, the numerable rate was 97.7% by BACspreader™ Microbe Dispersion Counter, and 4.3% by manual grinding method; the difference being significant between the 2 dispersion methods (χ(2)=674, P<0.001). Conclusions: Compared to the manual grinding method, the slant medium inoculated with bacterial suspension obtained by BACspreader™ Microbe Dispersion Counter had better countability in low concentration control slants, and had more significant contrast between high and low concentration control slants, which was useful to determine the DST results. Introducing the BACspreader™ Microbe Dispersion Counter to MTB DST could automate the DST process, make the testing results objective and standardized, and reduce personal error in the tests.
Assuntos
Antituberculosos/farmacologia , Testes de Sensibilidade Microbiana/métodos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , China , Contagem de Colônia Microbiana , Humanos , Sensibilidade e Especificidade , Tuberculose/tratamento farmacológicoRESUMO
We hypothesized that the aberrant expression of microRNAs (miRNAs) in rheumatoid arthritis (RA) T cells was involved in the pathogenesis of RA. The expression profile of 270 human miRNAs in T cells from the first five RA patients and five controls were analysed by real-time polymerase chain reaction. Twelve miRNAs exhibited potentially aberrant expression in RA T cells compared to normal T cells. After validation with another 22 RA patients and 19 controls, miR-223 and miR-34b were over-expressed in RA T cells. The expression levels of miR-223 were correlated positively with the titre of rheumatoid factor (RF) in RA patients. Transfection of Jurkat cells with miR-223 mimic suppressed insulin-like growth factor-1 receptor (IGF-1R) and transfection with miR-34b mimic suppressed cAMP response element binding protein (CREB) protein expression by Western blotting. The protein expression of IGF-1R but not CREB was decreased in RA T cells. The addition of recombinant IGF-1-stimulated interleukin (IL)-10 production by activated normal T cells, but not RA T cells. The transfection of miR-223 mimic impaired IGF-1-mediated IL-10 production in activated normal T cells. The expression levels of SCD5, targeted by miR-34b, were decreased in RA T cells after microarray analysis. In conclusion, both miR-223 and miR-34b were over-expressed in RA T cells, but only the miR-223 expression levels were correlated positively with RF titre in RA patients. Functionally, the increased miR-223 expression could impair the IGF-1-mediated IL-10 production in activated RA T cells in vivo, which might contribute to the imbalance between proinflammatory and anti-inflammatory cytokines.
Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-10/biossíntese , MicroRNAs/genética , Linfócitos T/metabolismo , Adulto , Idoso , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Antígenos CD28/imunologia , Complexo CD3/imunologia , Estudos de Casos e Controles , Linhagem Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Interferência de RNA , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , Linfócitos T/efeitos dos fármacos , TransfecçãoRESUMO
Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by dysregulated T cells. We hypothesized that the aberrant expression of microRNAs (miRNAs) in AS T cells involved in the pathogenesis of AS. The expression profile of 270 miRNAs in T cells from five AS patients and five healthy controls were analysed by real-time polymerase chain reaction (PCR). Thirteen miRNAs were found potentially differential expression. After validation, we confirmed that miR-16, miR-221 and let-7i were over-expressed in AS T cells and the expression of miR-221 and let-7i were correlated positively with the Bath Ankylosing Spondylitis Radiology Index (BASRI) of lumbar spine in AS patients. The protein molecules regulated by miR-16, miR-221 and let-7i were measured by Western blotting. We found that the protein levels of Toll-like receptor-4 (TLR-4), a target of let-7i, in T cells from AS patients were decreased. In addition, the mRNA expression of interferon (IFN)-γ was elevated in AS T cells. Lipopolysaccharide (LPS), a TLR-4 agonist, inhibited IFN-γ secretion by anti-CD3(+) anti-CD28 antibodies-stimulated normal T cells but not AS T cells. In the transfection studies, we found the increased expression of let-7i enhanced IFN-γ production by anti-CD3(+) anti-CD28(+) lipopolysaccharide (LPS)-stimulated normal T cells. In contrast, the decreased expression of let-7i suppressed IFN-γ production by anti-CD3(+) anti-CD28(+) LPS-stimulated AS T cells. In conclusion, we found that miR-16, miR-221 and let-7i were over-expressed in AS T cells, but only miR-221 and let-7i were associated with BASRI of lumbar spine. In the functional studies, the increased let-7i expression facilitated the T helper type 1 (IFN-γ) immune response in T cells.
Assuntos
MicroRNAs/biossíntese , Espondilite Anquilosante/imunologia , Células Th1/metabolismo , Adulto , Artrite Reumatoide/metabolismo , Estudos de Casos e Controles , Células Cultivadas/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Interferon gama/biossíntese , Interferon gama/genética , Interferon gama/metabolismo , Células Jurkat/metabolismo , Lipopolissacarídeos/farmacologia , Vértebras Lombares/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/metabolismo , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , MicroRNAs/fisiologia , Pessoa de Meia-Idade , RNA Mensageiro/biossíntese , Radiografia , Índice de Gravidade de Doença , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/etiologia , Espondilite Anquilosante/genética , Células Th1/imunologia , Receptor 4 Toll-Like/biossíntese , Receptor 4 Toll-Like/genética , Adulto JovemRESUMO
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with abnormal T cell immune responses. We hypothesized that aberrant expression of microRNAs (miRNAs) in T cells may contribute to the pathogenesis of SLE. First, we analysed the expression profiles of 270 human miRNAs in T cells from five SLE patients and five healthy controls and then validated those potentially aberrant-expressed miRNAs using real-time polymerase chain reaction (PCR). Then, the expression of mRNAs regulated by these aberrant-expressed miRNAs was detected using real-time PCR. Finally, miRNA transfection into Jurkat T cells was conducted for confirming further the biological functions of these miRNAs. The initial analysis indicated that seven miRNAs, including miR-145, miR-224, miR-513-5p, miR-150, miR-516a-5p, miR-483-5p and miR-629, were found to be potentially abnormally expressed in SLE T cells. After validation, under-expressed miR-145 and over-expressed miR-224 were noted. We further found that STAT1 mRNA targeted by miR-145 was over-expressed and apoptosis inhibitory protein 5 (API5) mRNA targeted by miR-224 was under-expressed in SLE T cells. Transfection of Jurkat cells with miR-145 suppressed STAT1 and miR-224 transfection suppressed API5 protein expression. Over-expression of miR-224 facilitates activation-induced cell death in Jurkat cells. In the clinical setting, the increased transcript levels of STAT1 were associated significantly with lupus nephritis. In conclusion, we first demonstrated that miR-145 and miR-224 were expressed aberrantly in SLE T cells that modulated the protein expression of their target genes, STAT1 and API5, respectively. These miRNA aberrations accelerated T cell activation-induced cell death by suppressing API5 expression and associated with lupus nephritis by enhancing signal transducer and activator of transcription-1 (STAT)-1 expression in patients with SLE.
Assuntos
Lúpus Eritematoso Sistêmico/imunologia , MicroRNAs/biossíntese , Linfócitos T/imunologia , Adulto , Apoptose/genética , Proteínas Reguladoras de Apoptose/biossíntese , Feminino , Humanos , Células Jurkat , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Nucleares/biossíntese , Fator de Transcrição STAT1/biossíntese , Transcriptoma , TransfecçãoRESUMO
Control over the interaction between single photons and individual optical emitters is an outstanding problem in quantum science and engineering. It is of interest for ultimate control over light quanta, as well as for potential applications such as efficient photon collection, single-photon switching and transistors, and long-range optical coupling of quantum bits. Recently, substantial advances have been made towards these goals, based on modifying photon fields around an emitter using high-finesse optical cavities. Here we demonstrate a cavity-free, broadband approach for engineering photon-emitter interactions via subwavelength confinement of optical fields near metallic nanostructures. When a single CdSe quantum dot is optically excited in close proximity to a silver nanowire, emission from the quantum dot couples directly to guided surface plasmons in the nanowire, causing the wire's ends to light up. Non-classical photon correlations between the emission from the quantum dot and the ends of the nanowire demonstrate that the latter stems from the generation of single, quantized plasmons. Results from a large number of devices show that efficient coupling is accompanied by more than 2.5-fold enhancement of the quantum dot spontaneous emission, in good agreement with theoretical predictions.
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Semiconductor InSb nanowires are expected to provide an excellent material platform for the study of Majorana fermions in solid state systems. Here, we report on the realization of a Nb-InSb nanowire-Nb hybrid quantum device and the observation of a zero-bias conductance peak structure in the device. An InSb nanowire quantum dot is formed in the device between the two Nb contacts. Due to the proximity effect, the InSb nanowire segments covered by the superconductor Nb contacts turn to superconductors with a superconducting energy gap Δ(InSb) â¼ 0.25 meV. A tunable critical supercurrent is observed in the device in high back gate voltage regions in which the Fermi level in the InSb nanowire is located above the tunneling barriers of the quantum dot and the device is open to conduction. When a perpendicular magnetic field is applied to the devices, the critical supercurrent is seen to decrease as the magnetic field increases. However, at sufficiently low back gate voltages, the device shows the quasi-particle Coulomb blockade characteristics and the supercurrent is strongly suppressed even at zero magnetic field. This transport characteristic changes when a perpendicular magnetic field stronger than a critical value, at which the Zeeman energy in the InSb nanowire is E(z) â¼ Δ(InSb), is applied to the device. In this case, the transport measurements show a conductance peak at the zero bias voltage and the entire InSb nanowire in the device behaves as in a topological superconductor phase. We also show that this zero-bias conductance peak structure can persist over a large range of applied magnetic fields and could be interpreted as a transport signature of Majorana fermions in the InSb nanowire.
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Neuronal CX3CL1 suppressed microglial inflammation by binding to its receptor CX3CR1 expressed on microglia. Neuronal autophagy was prominently activated by cerebral ischemia, whereas CX3CL1 expression in autophagic neurons was conversely down-regulated to exacerbate microglial inflammation. Accordingly, this study was meant to investigate whether ischemia-activated microglial inflammation could be repressed by promoting CX3CL1 expression via the attenuation of neuronal autophagy. Immunofluorescence showed that autophagy predominantly occurred in neurons but barely in microglia. Western blot and immunofluorescence demonstrated that attenuating HT22 autophagy significantly increased its CX3CL1 expression and subsequently mitigated the BV2-mediated inflammatory responses, as indicated by decreased inflammatory factors of NF-κB-p65, IL-6, IL-1ß, TNF-α, and PGE2. Meanwhile, CCK-8, Nissl staining, and FJC staining showed that an OGD (Oxygen-glycogen deprivation)-created neuronal injury was greatly alleviated by CX3CL1-suppressed microglial inflammation. Contrarily, elevating HT22 autophagy markedly decreased its CX3CL1 expression, which consequently worsened microglial inflammation and the neuronal injury. Our data suggests that attenuating neuronal autophagy may be an effective method to alleviate a microglial inflammatory injury after an ischemic stroke.
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Abnormal Ca(2+) -mediated signalling contributes to the pathogenesis of rheumatoid arthritis (RA). However, the potential implication of calcium channel blocker in RA remained unknown. We hypothesized that nifedipine, an L-type calcium channel blocker, combined with a calcineurin inhibitor, could suppress T cell activation via targeting different level of the Ca(2+) signalling pathway. The percentage of activated T cells and the apoptotic rate of mononuclear cells (MNCs) was measured by flow cytometry. The MNC viability, cytokine production, cytosolic Ca(2+) level and activity of the nuclear factor of activated T cells (NFAT) were measured by enzyme-linked immunosorbent assay (ELISA). The NFAT-regulated gene expression, including interleukin (IL)-2, interferon (IFN)-γ and granulocyte-macrophage colony-stimulating factor (GM-CSF), was measured by real-time polymerase chain reaction (PCR). We found that the percentage of activated T cells in anti-CD3 + anti-CD28-activated MNC was higher in RA patients. High doses of nifedipine (50 µM) increased MNCs apoptosis, inhibited T cell activation and decreased T helper type 2 (Th1) (IFN-γ)/Th2 (IL-10) cytokine production in both groups. The Ca(2+) influx was lower in anti-CD3 + anti-CD28-activated MNC from RA patients than healthy volunteers and suppressed by nifedipine. When combined with a subtherapeutic dose (50 ng/ml) of cyclosporin, 1 µM nifedipine suppressed the percentage of activated T cells in both groups. Moreover, this combination suppressed more IFN-γ secretion and NFAT-regulated gene (GM-CSF and IFN-γ) expression in RA-MNCs than normal MNCs via decreasing the activity of NFATc1. In conclusion, we found that L-type Ca(2+) channel blockers and subtherapeutic doses of cyclosporin act additively to suppress the Ca(2+) -calcineurin-NFAT signalling pathway, leading to inhibition of T cell activity. We propose that this combination may become a potential treatment of RA.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Calcineurina/metabolismo , Ciclosporina/administração & dosagem , Leucócitos Mononucleares/imunologia , Nifedipino/administração & dosagem , Linfócitos T/imunologia , Adulto , Idoso , Apoptose/efeitos dos fármacos , Artrite Reumatoide/metabolismo , Inibidores de Calcineurina , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Ciclosporina/farmacologia , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/biossíntese , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Humanos , Interferon gama/antagonistas & inibidores , Interferon gama/biossíntese , Interferon gama/genética , Interleucina-10/metabolismo , Interleucina-2/biossíntese , Interleucina-2/genética , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Fatores de Transcrição NFATC/biossíntese , Nifedipino/farmacologia , Nifedipino/uso terapêutico , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/metabolismoRESUMO
OBJECTIVE: Long noncoding RNAs (lncRNAs) play critical roles in osteosarcoma (OS) progression. LncRNA DSCAM-AS1 has been reported to function as a tumor promoter in various cancers. However, the potential mechanism of DSCAM-AS1 in OS remains rarely know. PATIENTS AND METHODS: The expression levels of DSCAM-AS1 and miR-101 were detected by RT-qPCR. The correlation between DSCAM-AS1 and miR-101 expression was analyzed by Pearson's correlation. Kaplan-Meier analysis was used to assess the overall survival rate. Cell viability and invasion were assessed by MTT assay and transwell assays, respectively. A Luciferase reporter assay was used to identify the relationship between DSCAM-AS1 and miR-101. RESULTS: In the present study, it was demonstrated that DSCAM-AS1 expression was significantly upregulated in OS tissues and cells and high expression of DSCAM-AS1 predicted poor prognosis in OS patients. In addition, the silencing of DSCAM-AS1 suppressed the viability and invasion of OS cells, while DSCAM-AS1 overexpression promoted cell viability and invasion. Furthermore, we found that DSCAM-AS1 inhibited miR-101 expression by direct interaction and DSCAM-AS1 promoted OS progression by sponging miR-101. In addition, miR-101 expression was negatively correlated with DSCAM-AS1 expression. Patients with low miR-101 expression had a shorter overall survival time compared with those with high miR-101 expression. CONCLUSIONS: The present study demonstrated that DSCAM-AS1 accelerated OS cell progression by sponging miR-101, which might provide a new sight in the treatment of OS.
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Neoplasias Ósseas/metabolismo , Movimento Celular , Proliferação de Células , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias Ósseas/genética , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Invasividade Neoplásica , Osteossarcoma/genética , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Prognóstico , RNA Longo não Codificante/genética , Transdução de Sinais , Adulto JovemRESUMO
A cytoplasmic protein has been identified that inhibits the guanosine triphosphatase (GTPase) activity of bacterially synthesized, cellular H-Ras protein. This GTPase inhibiting protein is able to counteract the activity of GTPase activating protein (GAP), which has been postulated to function as a negative regulator of Ras activity. The potential biological importance of the GTPase inhibiting protein is further supported by its interaction with lipids. Phospholipids produced in cells as a consequence of mitogenic stimulation increase the activity of the GTPase inhibiting protein, as well as inhibit the activity of GAP. The interaction of such lipids with each of these two regulatory proteins would, therefore, tend to increase the biological activity of Ras and stimulate cell proliferation.
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GTP Fosfo-Hidrolases/antagonistas & inibidores , Fosfolipídeos/farmacologia , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Animais , Divisão Celular , Relação Dose-Resposta a Droga , Proteínas Ativadoras de GTPase , Camundongos , Proteínas/antagonistas & inibidores , Proteínas Ativadoras de ras GTPaseRESUMO
Bacterially synthesized c-Ha-ras protein (Ras) was incubated with guanosine triphosphatase (GTPase) activating (GA) protein in the presence of various phospholipids. The stimulation of Ras GTPase activity by GA protein was inhibited in some cases. Among the lipids most active in blocking GA protein activity were lipids that show altered metabolism during mitogenic stimulation. These included phosphatidic acid (containing arachidonic acid), phosphatidylinositol phosphates, and arachidonic acid. Other lipids, including phosphatidic acid with long, saturated side chains, diacylglycerols, and many other common phospholipids, were unable to alter GA protein activity. The interaction of lipids with GA protein might be important in the regulation of Ras activity during mitogenic stimulation.
Assuntos
Mitógenos , Fosfolipídeos/farmacologia , Proteínas/farmacologia , Proteínas Proto-Oncogênicas/metabolismo , Animais , Ácido Araquidônico , Ácidos Araquidônicos/farmacologia , Diglicerídeos/farmacologia , GTP Fosfo-Hidrolases/metabolismo , Proteínas Ativadoras de GTPase , Guanosina Trifosfato/metabolismo , Lipossomos , Camundongos , Ácidos Fosfatídicos/farmacologia , Fosfatidilinositóis/farmacologia , Proteínas/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras) , Proteínas Ativadoras de ras GTPaseRESUMO
Cytokines and growth factors induce tyrosine phosphorylation of signal transducers and activators of transcription (STATs) that directly activate gene expression. Cells stably transformed by the Src oncogene tyrosine kinase were examined for STAT protein activation. Assays of electrophoretic mobility, DNA-binding specificity, and antigenicity indicated that Stat3 or a closely related STAT family member was constitutively activated by the Src oncoprotein. Induction of this DNA-binding activity was accompanied by tyrosine phosphorylation of Stat3 and correlated with Src transformation. These findings demonstrate that Src can activate STAT signaling pathways and raise the possibility that Stat3 contributes to oncogenesis by Src.
Assuntos
Transformação Celular Neoplásica , Proteínas de Ligação a DNA/metabolismo , DNA/metabolismo , Interleucina-6 , Proteína Oncogênica pp60(v-src)/fisiologia , Transdução de Sinais , Transativadores/metabolismo , Animais , Sequência de Bases , Linhagem Celular Transformada , Inibidores do Crescimento/farmacologia , Interferon gama/farmacologia , Fator Inibidor de Leucemia , Linfocinas/farmacologia , Camundongos , Dados de Sequência Molecular , Fosforilação , Fosfotirosina , Fator de Transcrição STAT3 , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
Abstract The current practice for cellulitis in diagnosis and treatment is mainly based on subjective clinical judgement without validated objective guidance. For patients with non-purulent cellulitis needing intravenous antibiotic treatment in hospital, we found soft tissue sonography performed around 4 days after initiation of antibiotics might have prognostic values. The patients with soft tissue sonographic pattern of subcutaneous thickening alone had shorter duration of antibiotic treatment and higher rate of early treatment response to antibiotics than those with the pattern of cobblestone appearance. Larger-scale research may be warranted to validate the prognostic roles of sonography in cellulitis management.
Assuntos
Celulite (Flegmão)/diagnóstico por imagem , Infecções dos Tecidos Moles/diagnóstico por imagem , Abscesso , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/uso terapêutico , Celulite (Flegmão)/tratamento farmacológico , Celulite (Flegmão)/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções dos Tecidos Moles/microbiologia , Supuração , UltrassonografiaRESUMO
OBJECTIVE: To elucidate the molecular basis of hyporesponsiveness of polymorphonuclear neutrophils (PMN) to interleukin-8 (IL-8) stimulation in patients with active SLE. METHODS: PMN obtained from active SLE and well-matched healthy individuals were studied. The expression of two IL-8 receptors, CXCR1 and CXCR2, in PMN were detected by flow cytometry and reverse transcriptase-polymerase chain reaction. The binding affinity of PMN with IL-8 was calculated by Scatchard plotting. Soluble CXCR2 level in IL-8-stimulated PMN culture supernatant was measured by sandwich enzyme-linked immunosorbent assay. The resting and IL-8-stimulated membrane potential (MP) changes, and membrane expression of cationic ion transporters including Na+-K+-ATPase, renal epithelial Na+ channel (ENaC) and renal outer medullary epithelial K+ channel 1 (ROMK1) on PMN were detected by flow cytometry. RESULTS: Compared with normal PMN, decreased CXCR2 gene expression, but normal IL-8-binding affinity of SLE-PMN, was found. For exploring the molecular basis of the defect, the modulation of CXCR2 in SLE-PMN was intensively investigated. We found that increased cytosolic CXCR2 expression in SLE-PMN was due to defective surface translocation, increased spontaneous internalization and/or increased spontaneous synthesis. The IL-8-induced CXCR2 down-regulation in SLE-PMN was also impaired due to decreased proteolytic cleavage of IL-8-IL-8 receptor complexes from the cell surface whereas IL-8-induced internalization of the complexes was normal. In addition, we originally found that increased resting but decreased IL-8-stimulated MP in SLE-PMN was relevant to defective expression of Na+-K+-ATPase, ENaC and ROMK1 on the cell surface. CONCLUSION: The abnormal CXCR2 modulation and impaired cationic ion transporter expression cause SLE-PMN hyporesponsiveness to IL-8 stimulation in vitro.
Assuntos
Interleucina-8/farmacologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Neutrófilos/imunologia , Receptores de Interleucina-8B/genética , Feminino , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Humanos , Interleucina-8/biossíntese , Lipopolissacarídeos/farmacologia , Masculino , Neutrófilos/efeitos dos fármacos , RNA Mensageiro/genética , Receptores de Interleucina-8A/genética , Valores de Referência , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
UNLABELLED: Multidrug resistance-associated proteins (MRPs, ATP binding cassette sub-family C), P-glycoprotein (P-gp) and ATP binding cassette (ABC) sub-family G member 2 (ABCG2) are important drug efflux pumps emerging after long-term medications. We intended to detect whether these molecules are expressed in immune-related cells of patients with systemic lupus erythematosus (SLE) on long-term immunosuppressants. METHODS: Mono nuclear cells (MNC) and polymorphonuclear neutrophils (PMN) were isolated from healthy volunteers and SLE patients. The MPR-mediated transport activity of these cells was measured by using carboxy-2',7'-dichlorofluorescein diacetate (CFDA) efflux assay. P-gp-mediated transport activity of cells was detected by rhodamine 123 efflux assay. ABCG2-mediated transport assay was evaluated by mitoxantrone efflux assay. The intracellular expression of MRP1, MRP2, and MRP3 molecules in MNC was detected by flow cytometry. The results were compared between MNC and PMN derived from normal and SLE groups. RESULTS: The specific dye-efflux function of MRPs in SLE-MNC is significantly higher than normal MNC. However, the expression of MRP1, MRP2, and MRP3 molecules in SLE-MNC was not different from normal MNC. We also noted that only the duration of corticosteroid treatment in different clinical/laboratory parameters was significantly correlated with the increased activity of MRPs in SLE-MNC. CONCLUSIONS: These results suggest that increased activity of MRPs in SLE-MNC is elicited by long-term corticosteroid therapy.