Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Clin Rheumatol ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31950440

RESUMO

The first name of the co-author of the above article was presented incorrect in the published version. The author name "Miangliang Qiu" should read "Mingliang Qiu" as mentioned above.

2.
Clin Rheumatol ; 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31879859

RESUMO

OBJECTIVE: miR-150-5p has been implicated in the regulation and onset of immune diseases. We investigated the effects of miR-150-5p on the functions of RA synovial fibroblasts (RASFs). METHOD: The binding site between suppressor of cytokine signaling 1 (SOCS1) and miR-150-5p was analyzed using European Bioinformatics Institute database, and the 3' UTR of SOCS1 mRNA, including the binding site, was amplified and ligated to the 3'-end of LUC2 gene in the pmirGL0 dual-luciferase vector. The pmirGL0 vector and corresponding mimics were subsequently co-transfected into 293T cells to compare the relative fluorescence intensity of LUC2 between the miR-150-5p mimics and the negative control (NC) mimics groups. Further, the RASF cell line MH7A was transfected with miR-150-5p or NC mimics and subjected to flow cytometric analysis, cell counting kit-8 assay, western blot analysis, qPCR, and enzyme-linked immunosorbent (ELISA) assay 48 h after transfection. RESULTS: miR-150-5p mimics resulted in a lower cell apoptotic rate and proportion of cells in the S phase. Using a dual-luciferase reporter gene assay, we then found that SOCS1 is a potential target of miR-150-5p. Compared with NC mimics, miR-150-5p mimics significantly decreased the protein and mRNA expression levels of SOCS1. ELISA assay showed that miR-150-5p mimics increased interleukin-6 level in the cell culture medium but did not influence tumor necrosis factor-alpha levels. CONCLUSIONS: Overall, the growth-promoting effect of miR-150-5p on MH7A cells may be attributed to the miR-150-5p-induced degradation of SOCS1 mRNA, suggesting a potential therapeutic target for RA.Key Points• SOCS1 is a potential target of miR-150-5p.• miR-150-5p promoted the growth of RASF cell line MH7A.• miR-150-5p increased the secretion of IL-6 but did not significantly affect TNF-α levels in MH7A cells.

3.
Int J Rheum Dis ; 22(2): 200-206, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30338648

RESUMO

AIM: To study the influence of total glucosides of paeony (TGP) on the expression of peripheral blood programmed cell death protein 1 (PD-1) and its ligand (PD-L1) in patients with primary Sjögren's syndrome (pSS). METHOD: Ten patients with new-onset pSS were selected as the experimental group and were treated with 1.8 g of TGP (the main ingredient is Radix Paeoniae Alba) daily for 3 months; furthermore, 10 physically healthy individuals were selected as the control group. Peripheral blood mononuclear cells were isolated, and flow cytometry was used to detect PD-1 expression on the surface of CD4+ T and CD8+ T lymphocytes and PD-L1 expression on the surface of CD14+ monocytes and CD19+ B cells before and after treatment in the experimental and control groups. Furthermore, plasma levels of soluble PD-1 (sPD-1), interleukin (IL)-10, and IL-17A were also determined using enzyme-linked immunosorbent assay. RESULTS: The PD-1 expression on the surface of CD4+ T and CD8+ T lymphocytes in the peripheral blood of patients with pSS were significantly higher than in the control group (P < 0.001). However, PD-L1 expression on the surface of CD14+ monocytes declined but not significantly (P > 0.05), and PD-L1 expression on the surface of CD19+ B cells increased significantly (P < 0.001). Moreover, sPD-1 and IL-17A levels in the plasma of the experimental group were significantly higher than in the control group (P < 0.001), but the IL-10 level was significantly lower than in the control group (P < 0.001). After TGP treatment, PD-1 expression on the surface of CD4+ T and CD8+ lymphocytes in the peripheral blood of patients with pSS had decreased significantly (P < 0.001); the PD-L1 expression on the surface of CD19+ cells had decreased significantly (P < 0.001); and the PD-L1 expression on the surface of CD14+ monocytes did not differ significantly (P > 0.05). Furthermore, the levels of sPD-1 and IL-17A in plasma had decreased (P < 0.01) and IL-10 levels had increased after TGP treatment (P < 0.01). CONCLUSION: PD-1/PD-L1 molecules expressed on the surface of T cells, B cells, and monokaryon participated in the pathogenesis and development of SS through interactions. Therefore, TGP, which may increase the expression of PD-1 and its relevant ligand PD-L1 in the peripheral blood mononuclear cells, may play a role in the pathogenesis and development of SS through the PD-1/PD-L1 pathway by regulating regulatory T cells/T helper cell 17.


Assuntos
Antígeno B7-H1/sangue , Glucosídeos/uso terapêutico , Fatores Imunológicos/uso terapêutico , Leucócitos Mononucleares/efeitos dos fármacos , Paeonia , Extratos Vegetais/uso terapêutico , Receptor de Morte Celular Programada 1/sangue , Síndrome de Sjogren/tratamento farmacológico , Adulto , Idoso , Antígeno B7-H1/imunologia , Estudos de Casos e Controles , Feminino , Glucosídeos/isolamento & purificação , Humanos , Fatores Imunológicos/isolamento & purificação , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-17/sangue , Interleucina-17/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Paeonia/química , Extratos Vegetais/isolamento & purificação , Receptor de Morte Celular Programada 1/imunologia , Síndrome de Sjogren/sangue , Síndrome de Sjogren/imunologia , Fatores de Tempo , Resultado do Tratamento
4.
Front Immunol ; 9: 2228, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319663

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory arthropathy associated with articular damage and attendant comorbidities. Even although RA treatment has advanced remarkably over the last decade, a significant proportion of patients still do not achieve sustained remission. The cause of RA is not yet known despite the many potential mechanisms proposed. It has been confirmed that RA is associated with dysregulated immune system and persistent inflammation. Therefore, management of inflammation is always the target of therapy. Sinomenine (SIN) is the prescription drug approved by the Chinese government for RA treatment. A previous study found that SIN was a robust anti-inflammation drug. In this study, we screened the different secretory cytokines using inflammation antibody arrays and qRT-PCR in both LPS-induced and SIN-treated RAW264.7 cells followed by evaluation of the ability of SIN to modulate cytokine secretion in a cell model, collagen-induced arthritis (CIA) mouse model, and RA patients. Several clinical indexes affecting the 28-joint disease activity score (DAS28) were determined before and after SIN treatment. Clinical indexes, inflammatory cytokine secretion, and DAS28 were compared among RA patients treated with either SIN or methotrexate (MTX). To explore the mechanism of SIN anti-inflammatory function, RA-associated monocyte/macrophage subsets were determined using flow cytometry in CIA mouse model and RA patients, both treated with SIN. The results demonstrated that SIN regulated IL-6, GM-CSF, IL-12 p40, IL-1α, TNF-α, IL-1ß, KC (CXCL1), Eotaxin-2, IL-10, M-CSF, RANTES, and MCP-1 secretion in vivo and in vitro and reduced RA activity and DAS28 in a clinical setting. Furthermore, SIN attenuated CD11b+F4/80+CD64+ resident macrophages in the synovial tissue, CD11b+Ly6C+CD43+ macrophages in the spleen and draining lymph nodes of CIA mice. The percentage of CD14+CD16+ peripheral blood mononuclear cells was reduced by SIN in RA patients. These data indicated that SIN regulates the secretion of multiple inflammatory cytokines and monocyte/macrophage subsets, thereby suppressing RA progression. Therefore, along with MTX, SIN could be an alternative cost-effective anti-inflammatory agent for treating RA.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Morfinanos/uso terapêutico , Adulto , Idoso , Animais , Antirreumáticos/farmacologia , Artrite Experimental/sangue , Artrite Experimental/diagnóstico , Artrite Experimental/imunologia , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Colágeno/administração & dosagem , Colágeno/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Diclofenaco/uso terapêutico , Progressão da Doença , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Metotrexato/uso terapêutico , Camundongos , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Morfinanos/farmacologia , Células RAW 264.7 , Índice de Gravidade de Doença , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/imunologia , Membrana Sinovial/metabolismo , Resultado do Tratamento
5.
Zhen Ci Yan Jiu ; 43(2): 75-9, 2018 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-29516693

RESUMO

OBJECTIVE: To study the protective effect of moxibustion for tripterygium-induced premature ovarian failure (POF) and its underlying mechanisms in rats. METHODS: Forty-five female SD rats were randomly divided into normal control, POF model and moxibustion groups (n=15/group). The POF model was induced by intragastric administration of Triptolide (40 mg/kg), once daily for 6 weeks. From the 4th week after modeling, moxibustion was given at "Guanyuan" (CV 4) and bilateral "Sanyinjiao" (SP 6) for 10 min, once daily for 3 weeks. Pathological changes of ovary tissues were determined by hematoxylin-eosin (HE) staining. The serum estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), interleukin-6 (IL-6) and interleukin-1 ß (IL-1 ß) contents were measured by enzyme-linked immunosorbent assay (ELISA). The expression levels of phosphatidyl inositol 3- kinase (PI 3 K), protein kinase B (Akt) and mammalian target of rapamycin (mTOR) proteins of the ovarian tissue were detected by Western blot. RESULTS: After modeling, HE staining showed that the numbers of ovarian follicles and follicular granulocytes and corpora luteum layers were decreased, and the number of corpora atretica was increased in the model group. The content of serum E2 was markedly decreased and those of serum LH, FSH, IL-6 and IL-1 ß were markedly increased in the model group (P<0.01), and the expression levels of ovarian p-PI 3 K, p-Akt and p-mTOR were markedly increased after modeling relevant to the control group (P<0.01). Following moxibustion, the pathological damage of ovarian tissue was improved, the contents of serum LH, FSH, IL-6, IL-1 ß, and the levels of p-PI 3 K, p-Akt and p-mTOR proteins in the ovarian tissue were significantly decreased (P<0.05, P<0.01), and the content of serum E2 was markedly increased (P<0.05) in comparison with the model group. CONCLUSION: Moxibustion can improve POF in POF rats, which may be related to its actions in inhibiting PI 3 K/Akt/mTOR signaling, down-regulating serum IL-6, IL-1 ß, and regulating serum hormones.


Assuntos
Moxibustão , Insuficiência Ovariana Primária , Pontos de Acupuntura , Animais , Feminino , Fosfatidilinositol 3-Quinases , Insuficiência Ovariana Primária/terapia , Proteínas Proto-Oncogênicas c-akt , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Sirolimo , Serina-Treonina Quinases TOR
6.
J Vis ; 18(1): 12, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29362805

RESUMO

The study of how visual processing functions in the absence of visual awareness has become a major research interest in the vision-science community. One of the main sources of evidence that stimuli that do not reach conscious awareness-and are thus "invisible"-are still processed to some degree by the visual system comes from studies using continuous flash suppression (CFS). Why and how CFS works may provide more general insight into how stimuli access awareness. As spatial and temporal properties of stimuli are major determinants of visual perception, we hypothesized that these properties of the CFS masks would be of significant importance to the achieved suppression depth. In previous studies however, the spatial and temporal properties of the masks themselves have received little study, and masking parameters vary widely across studies, making a metacomparison difficult. To investigate the factors that determine the effectiveness of CFS, we varied both the temporal frequency and the spatial density of Mondrian-style masks. We consistently found the longest suppression duration for a mask temporal frequency of around 6 Hz. In trials using masks with reduced spatial density, suppression was weaker and frequency tuning was less precise. In contrast, removing color reduced mask effectiveness but did not change the pattern of suppression strength as a function of frequency. Overall, this pattern of results stresses the importance of CFS mask parameters and is consistent with the idea that CFS works by disrupting the spatiotemporal mechanisms that underlie conscious access to visual input.


Assuntos
Conscientização , Mascaramento Perceptivo/fisiologia , Retina/efeitos da radiação , Processamento Espacial/fisiologia , Percepção Visual/fisiologia , Adulto , Cor , Feminino , Humanos , Masculino , Máscaras , Estimulação Luminosa/métodos , Fatores de Tempo , Vias Visuais/fisiologia , Adulto Jovem
7.
J Cell Mol Med ; 21(12): 3761-3775, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28767194

RESUMO

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Recent epidemiological studies suggest that echinacoside (ECH), a phenylethanoid glycoside found in Cistanche deserticola, has a protective effect against the development of PD. However, the detailed mechanisms of how ECH suppresses neuronal death have not been fully elucidated. In this study, we confirmed that ECH protects nigrostriatal neurons against 6-hydroxydopamine (6-OHDA)-induced endoplasmic reticulum stress (ERS) in vivo and in vitro. ECH rescued cell viability in damaged cells and decreased 6-OHDA-induced reactive oxygen species accumulation in vitro. It also rescued tyrosine hydroxylase and dopamine transporter expression in the striatum, and decreased α-synuclein aggregation following 6-OHDA treatment in vivo. The validated mechanism of ECH activity was the reduction in the 6-OHDA-induced accumulation of seipin (Berardinelli-Seip congenital lipodystrophy 2). Seipin has been shown to be a key molecule related to motor neuron disease and was tightly associated with ERS in a series of in vivo studies. ECH attenuated seipinopathy by promoting seipin degradation via ubiquitination. ERS was relieved by ECH through the Grp94/Bip-ATF4-CHOP signal pathway.


Assuntos
Corpo Estriado/efeitos dos fármacos , Glicosídeos/farmacologia , Proteínas Heterotriméricas de Ligação ao GTP/genética , Fármacos Neuroprotetores/farmacologia , Oxidopamina/antagonistas & inibidores , Parte Compacta da Substância Negra/efeitos dos fármacos , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Adrenérgicos/farmacologia , Animais , Linhagem Celular Tumoral , Cistanche/química , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Regulação da Expressão Gênica , Glicosídeos/isolamento & purificação , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Proteínas Heterotriméricas de Ligação ao GTP/antagonistas & inibidores , Proteínas Heterotriméricas de Ligação ao GTP/metabolismo , Injeções Intraventriculares , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/isolamento & purificação , Oxidopamina/farmacologia , Parte Compacta da Substância Negra/metabolismo , Parte Compacta da Substância Negra/patologia , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Técnicas Estereotáxicas , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo
8.
BMC Complement Altern Med ; 17(1): 15, 2017 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-28056947

RESUMO

BACKGROUND: Triptolide (TP), an active constituent of Tripterygium wilfordii, possesses numerous pharmacological activities. However, its effects on cytochrome P450 enzymes (CYP450s) in rats remain unexplored. METHODS: In this study, the effects of triptolide on the six main CYP450 isoforms (1A2, 2C9, 2C19, 2D6, 2E1, and 3A) were investigated both in vivo and in vitro. We monitored the body weight, survival proportions, liver index, changes in pathology, and biochemical index upon TP administration, in vivo. Using a cocktail probe of CYP450 isoform-specific substrates and their metabolites, we then carried out in vitro enzymatic studies in liver microsomal incubation systems via ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Finally, we verified our results at the messenger ribonucleic acid (mRNA) and protein level through quantitative real-time polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemical detection. RESULTS: The in vivo toxicity study confirmed that Sprague-Dawley (SD) rats exhibited dose-dependent hepatotoxicity after intragastric administration of TP [200, 400, and 600 µg/(kg.day)] for 28 days. In case of the CYP450 isoforms 3A, 2C9, 2C19, and 2E1, the in vitro metabolic study demonstrated a decrease in the substrate metabolic rate, metabolite production rate, and Vmax, with an increase in the Km value, compared with that observed in the control group. Additionally, a TP dose-dependent decrease in the mRNA levels was observed in the four major isoforms of CYP3A subfamily (3A1/3A23, 3A2, 3A9, and 3A62) and CYP2C9. A similar effect was also observed with respect to the protein levels of CYP2C19 and CYP2E1. CONCLUSIONS: This study suggests that TP can cause hepatotoxicity by reducing the substrate affinity, activity, and expression at the transcriptional and protein levels of the CYP450 isoforms 3A, 2C9, 2C19, and 2E1. TP also has the potential to cause pharmacokinetic drug interactions when co-administered with drugs metabolized by these four isoforms. However, further clinical studies are needed to evaluate the significance of this interaction.


Assuntos
Inibidores das Enzimas do Citocromo P-450/toxicidade , Diterpenos/toxicidade , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Fenantrenos/toxicidade , Animais , Inibidores das Enzimas do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Diterpenos/química , Compostos de Epóxi/química , Compostos de Epóxi/toxicidade , Isoenzimas/antagonistas & inibidores , Isoenzimas/química , Isoenzimas/metabolismo , Cinética , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Microssomos Hepáticos/química , Fenantrenos/química , Ratos , Ratos Sprague-Dawley
9.
Mol Immunol ; 82: 123-136, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28073079

RESUMO

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is known as a key molecule to induce cancer cell apoptosis, has also been found to participate in the process of ischemia/reperfusion (I/R) injury. Infiltrated macrophages play dual roles in inflammatory injury and healing following I/R. Whether TRAIL has any effect on macrophages during this process remains elusive. Here we showed that I/R triggered the expressions of TRAIL, DR5 and cytokines (IL-1ß, TNFα, CCL-2 and ICAM-1), in addition to macrophage infiltration, which could be abolished by TRAIL neutralizing antibody. In vitro, TRAIL enhanced DR5 expression and facilitated the macrophages migration following hypoxia/reoxygenation (H/R) treatment in a dose-dependent manner via ER stress and NF-κB signaling pathways, which is accompanied by inflammatory factors expression. The increased cytokines production (such as TNFα and IL-1ß) stimulated by TRAIL can be blocked by the NF-κB and ER stress inhibitor. The results also suggested that NF-κB activation of macrophages during H/R was regulated by ER stress. Thus, our research present that TRAIL affects functional activities of macrophages during I/R injury, which may be a potential therapeutic target for ischemic heart disease.


Assuntos
Macrófagos/metabolismo , Isquemia Miocárdica/metabolismo , NF-kappa B/metabolismo , Traumatismo por Reperfusão/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Animais , Movimento Celular/imunologia , Citocinas/biossíntese , Estresse do Retículo Endoplasmático/imunologia , Citometria de Fluxo , Immunoblotting , Imuno-Histoquímica , Macrófagos/imunologia , NF-kappa B/imunologia , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Traumatismo por Reperfusão/imunologia , Ligante Indutor de Apoptose Relacionado a TNF/imunologia
10.
Biomed Pharmacother ; 85: 679-686, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27899253

RESUMO

The purpose of the present study was to evaluate the protective effect of betulin (BE) on CS (cigarette smoke)-induced COPD in mice and explore its underlying mechanisms. 60 male ICR mice were randomly assigned to five groups: control group, model group, dexamethasone (2mg/kg) group, BE (20mg/kg) group and BE (40mg/kg) group. The COPD mice were induced by cigarette smoke exposure for 8 weeks. The result of H&E staining demonstrated that BE inhibited CS-induced pathological injury in lung tissue. Besides, BE could restore the activities of superoxide dismutase (SOD) in serum and in lung, catalase (CAT) in serum and reduce the content of malondialdehyde (MDA) in serum and in lung. BE also inhibited the overproductions of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß). Furthermore, the administration of BE significantly inhibited the protein expression of ROCK/NF-κB pathway in CS-induced mice. Our findings suggested that BE might effectively ameliorate the progression of COPD via ROCK/NF-κB pathway in mice.


Assuntos
Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Fumaça/efeitos adversos , Triterpenos/farmacologia , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Citocinas/genética , Citocinas/metabolismo , Dexametasona/administração & dosagem , Dexametasona/farmacologia , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Peroxidação de Lipídeos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Distribuição Aleatória , Poluição por Fumaça de Tabaco/efeitos adversos , Triterpenos/administração & dosagem
11.
Front Hum Neurosci ; 10: 513, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27790106

RESUMO

The human visual system can quickly and efficiently extract categorical information from a complex natural scene. The rapid detection of animals in a scene is one compelling example of this phenomenon, and it suggests the automatic processing of at least some types of categories with little or no attentional requirements (Li et al., 2002, 2005). The aim of this study is to investigate whether the remarkable capability to categorize complex natural scenes exist in the absence of awareness, based on recent reports that "invisible" stimuli, which do not reach conscious awareness, can still be processed by the human visual system (Pasley et al., 2004; Williams et al., 2004; Fang and He, 2005; Jiang et al., 2006, 2007; Kaunitz et al., 2011a). In two experiments, we recorded event-related potentials (ERPs) in response to animal and non-animal/vehicle stimuli in both aware and unaware conditions in a continuous flash suppression (CFS) paradigm. Our results indicate that even in the "unseen" condition, the brain responds differently to animal and non-animal/vehicle images, consistent with rapid activation of animal-selective feature detectors prior to, or outside of, suppression by the CFS mask.

12.
PLoS One ; 11(7): e0159206, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27416317

RESUMO

Visual processing is not instantaneous, but instead our conscious perception depends on the integration of sensory input over time. In the case of Continuous Flash Suppression (CFS), masks are flashed to one eye, suppressing awareness of stimuli presented to the other eye. One potential explanation of CFS is that it depends, at least in part, on the flashing mask continually interrupting visual processing before the stimulus reaches awareness. We investigated the temporal features of masks in two ways. First, we measured the suppression effectiveness of a wide range of masking frequencies (0-32Hz), using both complex (faces/houses) and simple (closed/open geometric shapes) stimuli. Second, we varied whether the different frequencies were interleaved within blocks or separated in homogenous blocks, in order to see if suppression was stronger or weaker when the frequency remained constant across trials. We found that break-through contrast differed dramatically between masking frequencies, with mask effectiveness following a skewed-normal curve peaking around 6Hz and little or no masking for low and high temporal frequencies. Peak frequency was similar for trial-randomized and block randomized conditions. In terms of type of stimulus, we found no significant difference in peak frequency between the stimulus groups (complex/simple, face/house, closed/open). These findings suggest that temporal factors play a critical role in perceptual awareness, perhaps due to interactions between mask frequency and the time frame of visual processing.


Assuntos
Mascaramento Perceptivo/fisiologia , Percepção Visual/fisiologia , Adulto , Conscientização/fisiologia , Feminino , Humanos , Masculino , Estimulação Luminosa , Fatores de Tempo , Percepção do Tempo/fisiologia , Adulto Jovem
13.
J Neurosci ; 36(1): 185-92, 2016 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-26740660

RESUMO

UNLABELLED: The human visual system must extract reliable object information from cluttered visual scenes several times per second, and this temporal constraint has been taken as evidence that the underlying cortical processing must be strictly feedforward. Here we use a novel rapid reinforcement paradigm to probe the temporal dynamics of the neural circuit underlying rapid object shape perception and thus test this feedforward assumption. Our results show that two shape stimuli are optimally reinforcing when separated in time by ∼60 ms, suggesting an underlying recurrent circuit with a time constant (feedforward + feedback) of 60 ms. A control experiment demonstrates that this is not an attentional cueing effect. Instead, it appears to reflect the time course of feedback processing underlying the rapid perceptual organization of shape. SIGNIFICANCE STATEMENT: Human and nonhuman primates can spot an animal shape in complex natural scenes with striking speed, and this has been taken as evidence that the underlying cortical mechanisms are strictly feedforward. Using a novel paradigm to probe the dynamics of shape perception, we find that two shape stimuli are optimally reinforcing when separated in time by 60 ms, suggesting a fast but recurrent neural circuit. This work (1) introduces a novel method for probing the temporal dynamics of cortical circuits underlying perception, (2) provides direct evidence against the feedforward assumption for rapid shape perception, and (3) yields insight into the role of feedback connections in the object pathway.


Assuntos
Retroalimentação Fisiológica/fisiologia , Percepção de Forma/fisiologia , Plasticidade Neuronal/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Tempo de Reação/fisiologia , Córtex Visual/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Sci Rep ; 5: 16290, 2015 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-26542183

RESUMO

Perceptual systems must create discrete objects and events out of a continuous flow of sensory information. Previous studies have demonstrated oscillatory effects in the behavioral outcome of low-level visual tasks, suggesting a cyclic nature of visual processing as the solution. To investigate whether these effects extend to more complex tasks, a stream of "neutral" photographic images (not containing targets) was rapidly presented (20 ms/image). Embedded were one or two presentations of a randomly selected target image (vehicles and animals). Subjects reported the perceived target category. On dual-presentation trials, the ISI varied systematically from 0 to 600 ms. At randomized timing before first target presentation, the screen was flashed with the intent of creating a phase reset in the visual system. Sorting trials by temporal distance between flash and first target presentation revealed strong oscillations in behavioral performance, peaking at 5 Hz. On dual-target trials, longer ISIs led to reduced performance, implying a temporal integration window for object category discrimination. The "animal" trials exhibited a significant oscillatory component around 5 Hz. Our results indicate that oscillatory effects are not mere fringe effects relevant only with simple stimuli, but are resultant from the core mechanisms of visual processing and may well extend into real-life scenarios.


Assuntos
Comportamento , Percepção Visual , Humanos
15.
Int Immunopharmacol ; 29(2): 599-606, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26428851

RESUMO

Acute lung injury (ALI) is a critical manifestation of sepsis/septic shock. Heat shock protein A12B (HSPA12B), an endothelial cell-expressed heat shock protein, shows a negative regulation of lipopolysaccharide (LPS)-induced inflammation in myocardium and endothelial cells. However, it is unclear whether HSPA12B exerts protective effects against ALI during sepsis/septic shock. In this study, we treated HSPA12B transgenic mice (Tg) and wild type littermates (WT) with LPS for 6h to induce endotoxemia. LPS treatment significantly caused pulmonary injuries as evidenced by microarchitecture destruction, vascular leakage and neutrophil recruitment in lungs of WT mice. However, the LPS-induced pulmonary injuries were significantly attenuated in Tg mice. Moreover, the LPS-induced activation of extracellular signal-regulated kinases (ERKs) and upregulation of intercellular adhesion molecule-1 (ICAM-1) and Cyclooxygenase-2 (Cox-2) were inhibited in Tg lungs compared with that in WT mice. Additionally, Tg lungs showed a significant lower level of vascular endothelial growth factor (VEGF) compared with WT mice. Our results demonstrate a pulmonary protective effect of HSPA12B against endotoxin challenge, which indicates management of HSPA12B expression could serve as a potential therapeutic target for ALI during sepsis/septic shock.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Endotoxemia/induzido quimicamente , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/metabolismo , Lesão Pulmonar Aguda/metabolismo , Animais , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas de Choque Térmico HSP70/genética , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Lipopolissacarídeos/toxicidade , Pulmão/metabolismo , Camundongos , Camundongos Transgênicos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
Sheng Li Xue Bao ; 67(4): 423-30, 2015 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-26300255

RESUMO

To improve a fast and high-quality isolation method for culturing the primary cardiomyocyte and fibroblast in vitro, the neonatal Wistar rats were decapitated accordingly and left ventricles were isolated under the sterile condition. The ventricles were chopped and digested in the enzyme solution containing 0.5 mg/mL type II collagenase. During this process, the digesting time, frequency and stirring speed, centrifuging frequency and speed were strictly controlled. The cardiomyocytes were separated from the cardiac fibroblast by using the Percoll density gradient centrifugation. The cell viability was tested by staining with 0.2% trypan blue. The purity of cardiomyocytes and fibroblasts were determined by immunoflourescent staining with anti-cTnI, anti-Vimentin and anti-α-SMA antibodies. The results indicated that with this protocol, the viability and purity of cardiomyocytes were 92% and 95%. The automobile pulse of the adhered cardiomyocyte was visible. For fibroblasts, the cell viability and purity were 96% and 94%. Our results demonstrate that this advanced isolation method is reproducible, and can simultaneously produce high-quality primary cardiomyocytes and fibroblasts for the future study.


Assuntos
Separação Celular/métodos , Centrifugação com Gradiente de Concentração , Fibroblastos , Miócitos Cardíacos , Animais , Sobrevivência Celular , Ventrículos do Coração/citologia , Povidona , Ratos , Ratos Wistar , Dióxido de Silício
17.
PLoS One ; 9(10): e111197, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25338168

RESUMO

Camera-based eye trackers are the mainstay of eye movement research and countless practical applications of eye tracking. Recently, a significant impact of changes in pupil size on gaze position as measured by camera-based eye trackers has been reported. In an attempt to improve the understanding of the magnitude and population-wise distribution of the pupil-size dependent shift in reported gaze position, we present the first collection of binocular pupil drift measurements recorded from 39 subjects. The pupil-size dependent shift varied greatly between subjects (from 0.3 to 5.2 deg of deviation, mean 2.6 deg), but also between the eyes of individual subjects (0.1 to 3.0 deg difference, mean difference 1.0 deg). We observed a wide range of drift direction, mostly downward and nasal. We demonstrate two methods to partially compensate the pupil-based shift using separate calibrations in pupil-constricted and pupil-dilated conditions, and evaluate an improved method of compensation based on individual look-up-tables, achieving up to 74% of compensation.


Assuntos
Movimentos Oculares , Pupila , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
18.
Vision Res ; 105: 21-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25220538

RESUMO

The visual system constructs a percept of the world across multiple spatial and temporal scales. This raises the questions of whether different scales involve separate integration mechanisms and whether spatial and temporal factors are linked via spatio-temporal reference frames. We investigated this using Vernier fusion, a phenomenon in which the features of two Vernier stimuli presented in close spatio-temporal proximity are fused into a single percept. With increasing spatial offset, perception changes dramatically from a single percept into apparent motion and later, at larger offsets, into two separately perceived stimuli. We tested the link between spatial and temporal integration by presenting two successive Vernier stimuli presented at varying spatial and temporal offsets. The second Vernier either had the same or the opposite offset as the first. We found that the type of percept depended not only on spatial offset, as reported previously, but interacted with the temporal parameter as well. At temporal separations around 30-40 ms the majority of trials were perceived as motion, while above 70 ms predominantly two separate stimuli were reported. The dominance of the second Vernier varied systematically with temporal offset, peaking around 40 ms ISI. Same-offset conditions showed increasing amounts of perceived separation at large ISIs, but little dependence on spatial offset. As subjects did not always completely fuse stimuli, we separated trials by reported percept (single/fusion, motion, double/segregation). We found systematic indications of spatial fusion even on trials in which subjects perceived temporal segregation. These findings imply that spatial integration/fusion may occur even when the stimuli are perceived as temporally separate entities, suggesting that the mechanisms responsible for temporal segregation and spatial integration may not be mutually exclusive.


Assuntos
Percepção Espacial/fisiologia , Percepção do Tempo/fisiologia , Análise de Variância , Humanos , Percepção de Movimento/fisiologia , Estimulação Luminosa , Visão Ocular
19.
Toxicol In Vitro ; 28(8): 1461-73, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25193743

RESUMO

It has been long noted that cardiac cell apoptosis provoked by excessive production of nitric oxide (NO) plays important roles in the pathogenesis of variant cardiac diseases. Attenuation of NO-induced injury would be an alternative therapeutic approach for the development of cardiac disorders. This study investigated the effects of α-lipoic acid (LA) on the injury induced by sodium nitroprusside (SNP), a widely used NO donor, in rat cardiomyoblast H9c2 cells. SNP challenge significantly decreased cell viability and increased apoptosis, as evidenced by morphological abnormalities, nuclear condensation and decline of mitochondrial potential (ΔΨm). These changes induced by SNP were significantly attenuated by LA pretreatment. Furthermore, LA pretreatment prevented the SNP-triggered suppression of Akt and Gsk-3ß activation. Blockade of Akt activation with triciribin (API) completely abolished the cytoprotection of LA against SNP challenge. In addition, LA moderately increased intracellular ROS production. Interestingly, inhibition of ROS with N-acetylcysteine abrogated Akt/Gsk-3ß activation and the LA-induced cytoprotection following SNP stimulation. Taken together, the results indicate that LA protected the SNP-induced injury in cardiac H9c2 cells through, at least in part, the activation of Akt/Gsk-3ß signaling in a ROS-dependent mechanism.


Assuntos
Citoproteção , Quinase 3 da Glicogênio Sintase/fisiologia , Mioblastos Cardíacos/efeitos dos fármacos , Nitroprussiato/toxicidade , Proteínas Proto-Oncogênicas c-akt/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Ácido Tióctico/farmacologia , Acetilcisteína/farmacologia , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Glicogênio Sintase Quinase 3 beta , Mioblastos Cardíacos/metabolismo , Ratos
20.
Cardiovasc Res ; 102(1): 46-55, 2014 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24442869

RESUMO

AIMS: Pellino1 is an evolutionally conserved immune regulator and participates in the regulation of Toll-like receptor/interleukin-1 receptor (TLR/IL-1R)-mediated signalling. Recent studies have shown that TLR/IL-1R contributes to the left ventricular (LV) remodelling after myocardial infarction (MI). However, the role of Pellino1 in LV remodelling following MI has not been investigated. This study examined the effect of Pellino1 silencing on cardiac function and LV remodelling after MI. METHODS AND RESULTS: Male C57BL/6 mice were subjected to permanent ligation of left anterior descending coronary artery (LAD) to induce MI. The levels of Pellino1 were significantly increased in the myocardium 3 days and sustained for 4 weeks after MI, when compared with the sham control. Hypoxia increased Pellino1 expression in cultured cardiomyocytes and fibroblasts. To examine whether Pellino1 plays a role in MI-induced cardiac dysfunction and the LV remodelling, we suppressed the expression of Pellino1 either by intramyocardial delivery of adenovirus expressing siRNA for Pellino1 (AdsiPeli1) or by Cre-LoxP-mediated conditional deletion of Pellino1 from the myocardium. In both models, silencing of Pellino1 significantly attenuated MI-induced cardiac dysfunction, decreased scar size, and reduced collagen deposition, when compared with the control groups. Pellino1 silencing in mice also attenuated MI-induced Pellino1 E3 ligase activity, receptor-interacting protein 1 and tumor necrosis factor receptor associated factor 6 (TRAF6) ubiquitination, nuclear factor Kappa B (NF-κB) activity, cytokine production, and inflammatory cell infiltration into the myocardium when compared with the MI group. CONCLUSIONS: Our data demonstrate that Pellino1 plays an important role in the pathogenesis of MI. Targeting Pellino1 may ameliorate cardiac dysfunction and remodelling following MI.


Assuntos
Proteínas Nucleares/metabolismo , Disfunção Ventricular Esquerda/metabolismo , Remodelação Ventricular/genética , Animais , Modelos Animais de Doenças , Inativação Gênica , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Proteínas Nucleares/genética , Receptores de Interleucina-1/metabolismo , Receptores Toll-Like/metabolismo , Ubiquitina-Proteína Ligases , Disfunção Ventricular Esquerda/genética , Remodelação Ventricular/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA