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1.
PLoS One ; 15(1): e0227190, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31917784

RESUMO

STUDY OBJECTIVES: Insomnia is the most common sleep disorder with significant psychiatric/physical comorbidities in the general population. The aim of this study is to investigate whether socioeconomic and demographic factors are associated with gender differences in insomnia and subtypes in Korean population. METHOD: The present study used data from the nationwide, cross-sectional study on sleep among all Koreans aged 19 to 69 years. The Insomnia Severity Index (ISI) was used to classify insomnia symptoms and their subtypes (cutoff value: 9.5). The Pittsburgh Sleep Quality Index (PSQI), Goldberg Anxiety Scale (GAS) and Patient Health Questionnaire-9 (PHQ-9) were used to measure sleep quality, anxiety and depression. RESULTS: A total of 2695 participants completed the survey. The overall prevalence of insomnia symptoms was 10.7%, including difficulty in initiating sleep (DIS) (6.8%), difficulty in maintaining sleep (DMS) (6.5%) and early morning awakening (EMA) (6.5%), and these symptoms were more prevalent in women than in men. Multivariate analysis showed that female gender, shorter sleep time and psychiatric complications were found to be independent predictors for insomnia symptoms and subtypes. After adjusting for covariates among these factors, female gender remained a significant risk factor for insomnia symptoms and their subtypes. As for men, low income was related to insomnia. CONCLUSION: Approximately one-tenth of the sample from the Korean general population had insomnia symptoms. The prevalence of insomnia symptom and the subtypes were more prevalent in women than men. Gender is an independent factor for insomnia symptoms.

2.
Biosci Biotechnol Biochem ; : 1-13, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900049

RESUMO

In this study, we investigated the role and mechanism of imperatorin (IMP) in chronic inflammation and airway remodeling. The levels of TNF-α, IL-1ß, IL-6, IL-8, VEGF, α-SMA, and ROS were detected by ELISA, immunohistochemistry (IHC), immunofluorescence, and Western blot. In addition, we evaluated the effect of IMP on MAPK, PI3K/Akt, NF-κB, and Nrf2/HO-1 signaling pathways. IMP treatment obviously attenuated the production of inflammatory cytokines and inflammatory cells in bronchoalveolar lavage fluid of OVA-induced airway remodeling model. Meanwhile, it significantly inhibited inflammatory cell infiltration, goblet cell hyperplasia, collagen deposition, VEGF production, α-SMA, and ROS expression. Our study has shown that IMP could regulate the signaling pathways including MAPK, PI3K/Akt, NF-κB, and Nrf2/HO-1 to release the inflammatory responses. IMP might attenuate airway remodeling by the down-regulation of Nrf2/HO-1/ROS/PI3K/Akt, Nrf2/HO-1/ROS/MAPK, and Nrf2/HO-1/ROS/NF-κB signaling pathways.

3.
BMC Neurol ; 19(1): 292, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31739779

RESUMO

BACKGROUND: Antiepileptic drug (AED) induced dyskinesia is an unusual manifestation in the medical field. In the previous case reports describing first generation-AED related involuntary movements, the authors suggested that a plausible cause is pharmacokinetic interactions between two or more AEDs. To date, development of dyskinesia after levetiracetam (LEV) has not been reported. CASE PRESENTATION: A 28-year-old woman with a history of brain metastasis from spinal cord glioblastoma presented with several generalized tonic-clonic seizures without restored consciousness. LEV was administered intravenously. Thereafter no more clinical or electroencephalographic seizures were noted on video-EEG monitoring, while chorea movement was observed in her face and bilateral upper limbs. DISCUSSION AND CONCLUSIONS: To our knowledge, there is no case report of dyskinesia after administration of LEV. Considering the temporal relationship and absence of ictal video-EEG findings, we suggest that development of choreoathetosis was closely associated with the undesirable effects of LEV. We propose that dopaminergic system dysregulation and genetic susceptibility might underlie this unusual phenomenon after LEV treatment.

4.
Biol Pharm Bull ; 42(10): 1665-1673, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582654

RESUMO

Houttuynia cordata (HC) is a traditional oriental herbal medicinal plant widely used as a component of complex prescriptions in Asia for alopecia treatment. The effect of HC on hair growth and its underlying mechanism, however, have not been demonstrated or clarified. In this study, we investigated the hair growth promoting effect of HC in cultured human dermal papilla cells (hDPCs). HC extract was found to stimulate the proliferation of hDPCs and this stimulation might be in part a consequence of activated cellular energy metabolism, because treatment of HC extract increased the generation of nicotinamide adenine dinucleotide (NADH) and ATP through increasing the mitochondrial membrane potential (ΔΨ). In the context of cell cycle, HC extract increased the expression of CDK4 and decreased the expression of CCNA2 and CCNB1, implying that HC extract might induce G1 phase progression of DPCs which resulted in enhanced proliferation. HC extract increased the expression of Bcl2 essential for maintaining hair follicle anagen stage and cell survival. On the contrary, the expression of p16 and p21 was down-regulated by HC extract. In addition, HC extract enhanced the secretion of platelet-derived growth factor (PDGF)-aa and vascular endothelial growth factor (VEGF) and induced phosphorylation of extracellular signal-regulated kinase (ERK) and AKT. Furthermore, HC extract prolonged anagen stage in organ cultured human hair follicles. Our data strongly suggest that HC extract could support hair growth by stimulating proliferation of DPCs and elongating anagen stage, resulted from enhanced cellular energy metabolism and modulation of gene expression related to cell cycle, apoptosis, and growth factors.

5.
Front Neurol ; 10: 819, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31417490

RESUMO

Study Objectives: Coronary artery disease is considered to be the major cause of death amongst patients with ischemic stroke. The coronary artery calcium (CAC) score is related not only to sleep-disordered breathing, but also with future risk of cardiovascular mortality. We investigated the association between the severity of sleep-disordered breathing and CAC score in patients with ischemic stroke. Methods: We included 32 patients who underwent coronary multichannel computed tomography and polysomnography (within 2 years of the stroke event) amongst the patients admitted to our clinic due to acute ischemic stroke. We investigated vascular risk factors, polysomnography findings, and sleep questionnaire scores, and their relationships with the CAC score. Results: All patients were found to have sleep apnea of any degree, and 23 (72%) had severe sleep apnea. Twenty-three (72%) patients had a positive CAC score. Higher CAC scores were associated with elevated respiratory disturbance index (RDI), apnea index, oxygen desaturation index, and STOP-BANG test scores. Multivariate analysis after adjusting for potential confounding factors revealed independent relationships between the CAC score and the RDI (ß [SE] = 5.3 [2.1], p = 0.01), oxygen desaturation index (ß [SE] = 6.8 [2.8], p = 0.02), and STOP-BANG test score (ß [SE] = 90.3 [37.7], p = 0.02). Conclusion: Our findings indicate a relationship between coronary atherosclerotic burden measured by the CAC score and the severity of sleep apnea. Performing polysomnography could be useful for investigating the severity of hidden coronary artery disease among these patients. Brief Summary: Current Knowledge/Study Rationale: The effect of sleep apnea on coronary artery disease in patients with ischemic stroke has not been explored. We investigated the relationship between sleep apnea, its related characteristics and the coronary artery calcium score in patients with stroke.Study Impact: Our findings reveal a close relationship between the atherosclerosis-related burden measured by the coronary artery calcium score and the severity of sleep apnea that persisted after adjusting for confounding variables related to the risk of coronary artery disease. Proper detection and treatment of sleep apnea might mitigate the risk of future coronary events in patients with ischemic stroke.

6.
Mol Neurobiol ; 56(7): 4894-4903, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30411306

RESUMO

In pathological conditions such as status epilepticus (SE), neuronal cell death can occur due to oxidative stress that is caused by an excessive production and accumulation of reactive oxygen species (ROS). Sirtuin3 (Sirt3) plays an important role in maintaining appropriate ROS levels by regulating manganese superoxide dismutase (MnSOD), which scavenges ROS in mitochondria. Using a SE model, we demonstrated that Sirt3 directly regulated MnSOD activity by deacetylation, which protects hippocampal cells against damage from ROS. Furthermore, we showed that after formation in the nucleus, Sirt3 is primarily located in the mitochondria, where it is activated and exerts its major function. Sirt3 then completed its pathway and moved back into the nucleus. Our data indicate that Sirt3 has an important function in regulating MnSOD, which results in decreased ROS in hippocampal cells. Sirt3 may have potential as an effective therapeutic target in SE conditions that would delay the progression of epileptogenesis.


Assuntos
Núcleo Celular/metabolismo , Neurônios/metabolismo , Neuroproteção/fisiologia , Sirtuína 3/metabolismo , Estado Epiléptico/metabolismo , Animais , Núcleo Celular/patologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Feminino , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/patologia , Gravidez , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Estado Epiléptico/patologia , Superóxido Dismutase/metabolismo
7.
Scand J Immunol ; 89(1): e12720, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30589094

RESUMO

Pyrin domain (PYD), a subclass of protein motif known as the death fold, is frequently involved in inflammation and immune responses. PYD modulates nuclear factor-kappa B (NF-κB) signalling pathway upon various stimuli. Herein, a novel recombinant pyrin domain protein (RPYD) was generated. Its role and mechanism in inflammatory response in an ovalbumin (OVA) induced asthma model was investigated. After OVA challenge, there was inflammatory cell infiltration in the lung, as well as airway hyper-responsiveness (AHR) to inhaled methacholine. In addition, eosinophils increased in the bronchoalveolar lavage fluids, alone with the elevated levels of Th-2 type cytokines [interleukin (IL)-4, IL-5 and IL-13], eotaxin, and adhesion molecules. However, the transnasal administration of RPYD before the OVA challenge significantly inhibited these asthmatic reactions. Moreover, RPYD markedly suppressed NF-κB translocation, reduced phosphorylation of p38 MAPK, and thus attenuated the expression of intercellular adhesion molecule 1 and IL-6 in the BEAS-2B cells stimulated by proinflammatory cytokines in vitro. These findings indicate that RPYD can protect asthma host from OVA-induced airway inflammation and AHR via down-regulation of NF-κB and p38 MAPK activities. RPYD may be used as a potential medicine for the treatment of asthma in clinic.


Assuntos
Asma/imunologia , Hipersensibilidade/imunologia , Inflamação/imunologia , NF-kappa B/imunologia , Domínio Pirina/imunologia , Animais , Asma/metabolismo , Feminino , Hipersensibilidade/metabolismo , Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo
8.
Int Immunopharmacol ; 65: 571-579, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30415164

RESUMO

To explore the effects of aloperine (ALO) on allergic airway inflammation, we investigated whether its mechanism is related with NF-κB, MAPK, and Nrf2/HO-1 signaling pathways. Histochemical staining and inflammatory cell count were used to observe lung histopathological changes in mice. ELISA was used to detect the content of inflammatory cytokines and IgE in the mouse bronchoalveolar lavage fluid (BALF). Airway hyperresponsiveness (AHR) to inhale methacholine was measured by the plethysmography in conscious mice. Immunohistochemical method was used to detect the expression levels of Nrf2 and HO-1 in lung tissues. The key proteins of MAPK, NF-κB, and Nrf2/HO-1 in lung tissues were quantitatively analyzed by Western blot. Finally, the in vitro effect of ALO on the production of pro-inflammatory mediators and cytokines by lipopolysaccharide-stimulated RAW 264.7 cells was also evaluated. In the ovalbumin (OVA)-induced asthma mouse model, ALO reduced the exudation and infiltration of inflammatory cells and suppressed goblet cell hyperplasia. ALO-treated asthmatic mice also decreased the protein levels of interleukin (IL)-4, IL-5, IL-13, IFN-γ, and IgE in BALF and attenuated AHR. Furthermore, ALO inhibited the expression of key proteins of MAPK and NF-κB pathways, and increased the expression of Nrf2/HO-1 in OVA-challenged mice. Additional in vitro study has shown that ALO abrogates the macrophage production of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, IL-6, and IL-1ß. Taken together, ALO attenuated allergic airway inflammation through regulating NF-κB, MAPK, and Nrf2/HO-1 signaling pathways. The results suggest the utility of ALO as an anti-inflammatory agent for the treatment of asthma.


Assuntos
Anti-Inflamatórios/uso terapêutico , Hipersensibilidade/tratamento farmacológico , Inflamação/tratamento farmacológico , Piperidinas/uso terapêutico , Sistema Respiratório/imunologia , Animais , Células Cultivadas , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Heme Oxigenase-1/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais
9.
Med Sci Monit ; 24: 7186-7198, 2018 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-30296789

RESUMO

BACKGROUND This study investigated the role and mechanism of alprostadil in acute respiratory distress syndrome (ARDS) induced by oleic acid (OA) in rats. MATERIAL AND METHODS Sprague-Dawley rats were randomly divided into control, OA model, and OA + Alprostadil (2.5, 5, and 10 µg/kg, respectively) groups. The ARDS model was induced by femoral vein injection of OA, and alprostadil was administrated immediately. Lung injury was evaluated by lung wet-dry weight ratio (W/D) and histological analyses. Expressions of ACE, inflammatory mediators, apoptotic-related proteins, and proteins in the MAPKs and NF-κB signaling pathways were determined by Western blot or immunohistochemical staining. RESULTS Compared with the control group, the OA model group had significantly increased W/D, lung injury score, and collagen deposition at 3 h after OA injection. However, alprostadil (10 µg/kg) treatment significantly reduced OA-induced elevation of these indicators. Additionally, OA-induced expression of TNF-α and IL-1ß were suppressed by alprostadil. The OA-induced activation of nuclear factor (NF) κB p65 was also reduced by alprostadil. Furthermore, we found that Alprostadil had an inhibitory effect on the phosphorylation of JNK, ERK1/2, and p38 MAPKs. Alprostadil inhibited Bax but increased Bcl-2, indicating a suppressive role in apoptosis. Remarkably increased expression of ACE in the OA model group was observed, which was decreased by alprostadil. CONCLUSIONS Alprostadil has a protective effect on ARDS induced by OA in rats, possibly through inhibiting apoptosis, suppressing the activation of MAPKs and NF-κB signaling pathways, and decreasing ACE protein expression. Therefore, the use of alprostadil in clinical ARDS treatment is promising.


Assuntos
Alprostadil/farmacologia , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/citologia , Modelos Animais de Doenças , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Ácido Oleico/toxicidade , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Síndrome do Desconforto Respiratório do Adulto/induzido quimicamente , Síndrome do Desconforto Respiratório do Adulto/metabolismo , Síndrome do Desconforto Respiratório do Adulto/patologia , Transdução de Sinais/efeitos dos fármacos
10.
Epilepsy Res ; 147: 58-61, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30253317

RESUMO

Granule cell dispersion (GCD) is a common neuropathological feature of hippocampal sclerosis (HS) in patients with temporal lobe epilepsy (TLE). However, the underlying molecular mechanism of GCD formation remains unclear. The present study aimed to investigate the expressional changes of With No Lysine protein kinase subtype 3 (WNK3), a molecule upstream of cation-chloride cotransporters with reciprocal expression in sclerosed hippocampus of TLE patients. Using immunofluorescence staining, we analyzed WNK3 immunoreactivity in hippocampal specimens from histologically normal controls and TLE patients with HS. Our results showed that WNK3 expression was significantly increased in dispersed granule neurons in hippocampal tissues from patients with TLE compared with histologically normal hippocampus. These findings demonstrate a potential association between an increased expression of WNK3 and GCD formation during the chronic phase of epilepsy. Controlling WNK3 expression may thus be a novel therapeutic target in epileptogenesis.


Assuntos
Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Neurônios/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Regulação para Cima/fisiologia , Adolescente , Adulto , Criança , Pré-Escolar , Epilepsia do Lobo Temporal/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfopiruvato Hidratase/metabolismo , Esclerose/etiologia , Esclerose/patologia , Estatísticas não Paramétricas , Adulto Jovem
11.
BMC Musculoskelet Disord ; 19(1): 184, 2018 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-29866097

RESUMO

BACKGROUND: Sciatic nerve injuries following total hip arthroplasty are disabling complications. Although degrees of injury are variable from neuropraxia to neurotmesis, mechanical irritation of sciatic nerve might be occurred by protruding hardware. This case shows endoscopic decompression for protruded acetabular screw irritating sciatic nerve, the techniques described herein may permit broader arthroscopic/endoscopic applications for management of complications after reconstructive hip surgery. CASE PRESENTATION: An 80-year-old man complained of severe pain and paresthesias following acetabular component revision surgery. Physical findings included right buttock pain with radiating pain to lower extremity. Radiographs and computed tomography imaging showed that the sharp end of protruded screw invaded greater sciatic foramen anterior to posterior and distal to proximal direction at sciatic notch level. A protruding tip of the acetabular screw at the sciatic notch was decompressed by use of techniques gained from experience performing endoscopic sciatic nerve decompression. The pre-operative pain and paresthesias resolved post-operatively after recovering from anesthesia. CONCLUSIONS: This case report describes the first documented endoscopic resection of the tip of the acetabular screw irritating sciatic nerve after total hip arthroplasty. If endoscopic resection of an offending acetabular screw can be performed in a safe and minimally invasive manner, one can envision a future expansion of the role of hip arthroscopic surgery in several complications management after total hip arthroplasty.


Assuntos
Acetábulo/cirurgia , Parafusos Ósseos/efeitos adversos , Descompressão Cirúrgica/métodos , Neuroendoscopia/métodos , Nervo Isquiático/cirurgia , Acetábulo/diagnóstico por imagem , Idoso de 80 Anos ou mais , Humanos , Masculino , Nervo Isquiático/diagnóstico por imagem
12.
ISA Trans ; 77: 77-89, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29729975

RESUMO

This paper investigates the event-triggered decentralized adaptive tracking problem of a class of uncertain interconnected nonlinear systems with unexpected actuator failures. It is assumed that local control signals are transmitted to local actuators with time-varying faults whenever predefined conditions for triggering events are satisfied. Compared with the existing control-input-based event-triggering strategy for adaptive control of uncertain nonlinear systems, the aim of this paper is to propose a tracking-error-based event-triggering strategy in the decentralized adaptive fault-tolerant tracking framework. The proposed approach can relax drastic changes in control inputs caused by actuator faults in the existing triggering strategy. The stability of the proposed event-triggering control system is analyzed in the Lyapunov sense. Finally, simulation comparisons of the proposed and existing approaches are provided to show the effectiveness of the proposed theoretical result in the presence of actuator faults.

13.
Phytother Res ; 32(2): 290-297, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29210121

RESUMO

Mast cells play a critical role in the effector phase of immediate hypersensitivity and allergic reactions. Pinus radiata bark extract exerts multiple biological effects and exhibits immunomodulatory and antioxidant properties. However, its role in mast cell-mediated anaphylactic reactions has not been thoroughly investigated. In this study, we examined the effects of proanthocyanidin-rich water extract (PAWE) isolated from P. radiata bark on compound 48/80-induced or antidinitrophenyl (DNP) immunoglobulin E (IgE)-mediated anaphylaxis-like reactions in vivo. In addition, we evaluated the mechanism underlying the inhibitory effect of PAWE on mast cell activation, with a specific focus on histamine release, using rat peritoneal mast cells. PAWE attenuated compound 48/80-induced or anti-DNP IgE-mediated passive cutaneous anaphylaxis-like reactions in mice, and it inhibited histamine release triggered by compound 48/80, ionophore A23187, or anti-DNP IgE in rat peritoneal mast cells in vitro. Moreover, PAWE suppressed compound 48/80-elicited calcium uptake in a concentration-dependent manner and promoted a transient increase in intracellular cyclic adenosine-3',5'-monophosphate levels. Together, these results suggest that proanthocyanidin-rich P. radiata bark extract effectively inhibits anaphylaxis-like reactions.


Assuntos
Anafilaxia/etiologia , Mastócitos/efeitos dos fármacos , Pinus/química , Extratos Vegetais/farmacologia , Proantocianidinas/química , Animais , Hipersensibilidade Imediata , Masculino , Camundongos , Ratos
14.
J Agric Food Chem ; 65(37): 8128-8135, 2017 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-28891650

RESUMO

The effects of asiaticoside (AS) on allergic responses mediated by mast cells were investigated. AS showed no obvious cytotoxicity on RPMCs (rat peritoneal mast cells). AS reduced the intracellular calcium in RPMCs and deprived the histamine release and degranulation. AS also decreased the generation of antigen-induced tumor necrosis factor α, interleukin (IL)-4, IL-8, and IL-1ß in RBL-2H3 cells sensitized by IgE. The suppression of AS on pro-inflammatory cytokines was related with the activation of the intracellular FcεRI and the inhibition of the nuclear factor-κB signaling pathway. In addition, AS disabled the phosphorylation of antigen-induced Syk, Lyn, Gab2, and PLCγ1, thus suppressing the downstream Akt phosphorylation and MAPKs pathways. It also increased HO-1 and Nrf2 expression time dependently. In summary, we demonstrate that AS suppresses the allergic inflammation mediated by mast cells and this effect might be mediated by FcεRI-dependent signaling pathways.


Assuntos
Hipersensibilidade/diagnóstico por imagem , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Triterpenos/administração & dosagem , Animais , Degranulação Celular/efeitos dos fármacos , Células Cultivadas , Liberação de Histamina/efeitos dos fármacos , Hipersensibilidade/imunologia , Imunoglobulina E/imunologia , Interleucina-8/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/imunologia , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
15.
Sci Rep ; 7(1): 11895, 2017 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-28928455

RESUMO

Polydatin(PD) shows anti-allergic inflammatory effect, and this study investigated its underlying mechanisms in in vitro and in vivo models. IgE-mediated passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis (PSA) models were used to confirm PD effect in vivo. Various signaling pathway proteins in mast cell were examined. RT-PCR, ELISA and western blotting were applied when appropriate. Activity of Lyn and Fyn kinases in vitro was measured using the Kinase Enzyme System. PD dose-dependently reduced the pigmentation of Evans blue in the PCA model and decreased the concentration of serum histamine in PSA model, and attenuated the degranulation of mast cells without generating cytotoxicity. PD decreased pro-inflammatory cytokine expression (TNF-α, IL-4, IL-1ß, and IL-8). PD directly inhibited activity of Lyn and Syk kinases and down-regulated downstream signaling pathway including MAPK, PI3K/AKT and NF-kB. In addition, PD also targets Nrf2/HO-1 pathway to inhibit mast cell-derived allergic inflammatory reactions. In conclusion, the study demonstrates that PD is a possible therapeutic candidate for allergic inflammatory diseases. It directly inhibited activity of Lyn and Syk kinases and down-regulates the signaling pathway of MAPK, PI3K/AKT and NF-κB, and up-regulates the signaling pathway of Nrf2/HO-1 to inhibit the degranulation of mast cells.


Assuntos
Anafilaxia/tratamento farmacológico , Degranulação Celular/efeitos dos fármacos , Dermatite Atópica/tratamento farmacológico , Glucosídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mastócitos/imunologia , Estilbenos/farmacologia , Anafilaxia/imunologia , Anafilaxia/patologia , Animais , Degranulação Celular/imunologia , Citocinas/imunologia , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , MAP Quinases Reguladas por Sinal Extracelular/imunologia , Heme Oxigenase-1/imunologia , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Sistema de Sinalização das MAP Quinases/imunologia , Masculino , Mastócitos/patologia , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/imunologia , Fosfatidilinositol 3-Quinases/imunologia , Proteínas Proto-Oncogênicas c-akt/imunologia
16.
BMB Rep ; 49(6): 349-54, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27222124

RESUMO

The archaeon Sulfolobus solfataricus P1 carboxylesterase is a thermostable enzyme with a molecular mass of 33.5 kDa belonging to the mammalian hormone-sensitive lipase (HSL) family. In our previous study, we purified the enzyme and suggested the expected amino acids related to its catalysis by chemical modification and a sequence homology search. For further validating these amino acids in this study, we modified them using site-directed mutagenesis and examined the activity of the mutant enzymes using spectrophotometric analysis and then estimated by homology modeling and fluorescence analysis. As a result, it was identified that Ser151, Asp244, and His274 consist of a catalytic triad, and Gly80, Gly81, and Ala152 compose an oxyanion hole of the enzyme. In addition, it was also determined that the cysteine residues are located near the active site or at the positions inducing any conformational changes of the enzyme by their replacement with serine residues. [BMB Reports 2016; 49(6): 349-354].


Assuntos
Aminoácidos/metabolismo , Biocatálise , Carboxilesterase/química , Carboxilesterase/metabolismo , Modelos Moleculares , Mutagênese Sítio-Dirigida , Sulfolobus solfataricus/enzimologia , Sequência de Aminoácidos , Carboxilesterase/genética , Cisteína/metabolismo , Fluorescência , Proteínas Mutantes/química , Proteínas Mutantes/isolamento & purificação , Mutação/genética , Plasmídeos/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Homologia Estrutural de Proteína , Relação Estrutura-Atividade
17.
Reprod Toxicol ; 60: 156-66, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26867867

RESUMO

The endocrine-disrupting effects of androgenic signaling play crucial roles in several androgen-related diseases. In attempting to develop an in vitro cell line to be used in androgen receptor (AR)-mediated reporter gene assays, we developed a stable 22Rv1/MMTV cell line, which is a human prostate cancer cell line that endogenously expresses functional AR, to evaluate AR-mediated transcriptional activation (TA). Using 22Rv1/MMTV cells, we established and optimized a test protocol for the AR-TA assay and validated the proposed assay using 20 compounds recommended by the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). All the performance parameters for agonist and antagonist assays were 91-100% comparable between the 22Rv1/MMTV assay and the ICCVAM report. In conclusion, the AR-TA assay using 22Rv1/MMTV cells might be a quick and relatively inexpensive method for screening large numbers of chemicals for their potential to activate or inhibit AR-mediated gene transcription.


Assuntos
Antagonistas de Androgênios/farmacologia , Androgênios/farmacologia , Receptores Androgênicos/genética , Ativação Transcricional/efeitos dos fármacos , Bioensaio , Linhagem Celular Tumoral , Genes Reporter , Humanos , Luciferases/metabolismo
18.
IEEE Trans Cybern ; 46(12): 3401-3413, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26731788

RESUMO

A decentralized adaptive backstepping control design using minimal function approximators is proposed for nonlinear large-scale systems with unknown unmatched time-varying delayed interactions and unknown backlash-like hysteresis nonlinearities. Compared with existing decentralized backstepping methods, the contribution of this paper is to design a simple local control law for each subsystem, consisting of an actual control with one adaptive function approximator, without requiring the use of multiple function approximators and regardless of the order of each subsystem. The virtual controllers for each subsystem are used as intermediate signals for designing a local actual control at the last step. For each subsystem, a lumped unknown function including the unknown nonlinear terms and the hysteresis nonlinearities is derived at the last step and is estimated by one function approximator. Thus, the proposed approach only uses one function approximator to implement each local controller, while existing decentralized backstepping control methods require the number of function approximators equal to the order of each subsystem and a calculation of virtual controllers to implement each local actual controller. The stability of the total controlled closed-loop system is analyzed using the Lyapunov stability theorem.

19.
Mol Med Rep ; 12(5): 6946-54, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26502836

RESUMO

Allergic asthma is a chronic inflammatory disease that is regulated by coordination of T-helper type 2 cell cytokines and inflammatory signaling molecules. Ginsenoside Rh2 (G-Rh2) is an active component of ginseng with anti-inflammatory and anti-tumor effects. The aim of the present study was to determine the inhibitory effects of G-Rh2 on allergic airway inflammation in a murine model of asthma, in which mice develop the following pathophysiological features of asthma: Increased abundance of inflammatory cells; increased levels of interleukin-4 (IL-4), IL-5 and IL-13; decreased abundance of interferon gamma in the bronchoalveolar lavage fluid and lung tissue; increased total and ovalbumin (OVA)-specific immunoglobulin E (IgE) levels in the serum; increased airway hyperresponsiveness (AHR); and activation of nuclear factor kappa B (NF-κB) in lung tissue. In the asthmatic mice, administration of G-Rh2 markedly reduced peribronchiolar inflammation, recruitment of airway inflammatory cells, cytokine production, total and OVA-specific IgE levels and AHR. G-Rh2 administration inhibited NF-κB activation and p38 mitogen-activated protein kinase (MAPK) phosphorylation induced by OVA inhalation. These results suggested that G-Rh2 attenuates allergic airway inflammation by regulating NF-κB activation and p38 MAPK phosphorylation. The present study identified the molecular mechanisms of action of G-Rh2, which supported the potential use of G-Rh2 to prevent and/or treat asthma and other airway inflammatory disorders.


Assuntos
Antiasmáticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Asma/imunologia , Ginsenosídeos/uso terapêutico , Pulmão/efeitos dos fármacos , NF-kappa B/imunologia , Animais , Asma/sangue , Asma/patologia , Feminino , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Interleucina-13/imunologia , Interleucina-4/imunologia , Interleucina-5/imunologia , Pulmão/imunologia , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/sangue , Ovalbumina/imunologia
20.
Korean J Gastroenterol ; 64(5): 278-83, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25420737

RESUMO

BACKGROUND/AIMS: Adequate screening colonoscopy in the general population decreases the mortality associated with colorectal cancer through detection and removal of adenomatous polyps. Prolonged colonoscopic withdrawal times (>6 min) are reportedly beneficial for adenoma detection rates (ADRs). However, the quality of the endoscopist compared with colonoscopic withdrawal times is not known. The aims of this study were to investigate the difference in ADRs between trainees and experienced examiners. METHODS: A total of 967 consecutive patients who underwent screening colonoscopy in a single University hospital from June 2010 to November 2011 were enrolled in this prospective observational study. Colonoscopy was performed by four experienced staff and seven gastroenterology fellows. RESULTS: Seven gastroenterology fellows performed 633 colonoscopies and four experienced staff performed 334 colonoscopies. The overall detection rates of colorectal adenoma were 31.5% with ADRs of fellows and staff of 29.4% and 35.6%, respectively (p=0.047). Fellows also showed lower advanced ADRs (5.7% vs. 9.9%, p=0.016), and fellows had longer mean withdrawal times than staff (12.4±B1;4.9 min vs. 8.2±B1;4.1 min, p<0.001). Multivariate analysis showed significantly increased ADRs and advanced ADRs for staff compared with fellows (adjusted OR 2.41, 95% CI 1.70-3.43; adjusted OR 2.55, 95% CI 1.47-4.45, respectively). CONCLUSIONS: ADRs were significantly lower when colonoscopy was performed by trainees, although withdrawal times were longer than those of staff. Our results demonstrated that the quality of colonoscopy, as measured by ADRs, may be improved by experienced examiners.


Assuntos
Adenoma/diagnóstico , Neoplasias Colorretais/diagnóstico , Competência Profissional , Adenoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Colonoscopia , Neoplasias Colorretais/patologia , Feminino , Hospitais Universitários , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Fumar , Fatores de Tempo , Adulto Jovem
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