Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
2.
J Agric Food Chem ; 67(37): 10521-10533, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31461284

RESUMO

This work was designed to comparatively investigate 27 dietary flavonoids that act as α-glucosidase inhibitors and insulin sensitizers. On the basis of the results of an in vitro experiment of α-glucosidase inhibition, myricetin (IC50 = 11.63 ± 0.36 µM) possessed the strongest inhibitory effect, followed by apigenin-7-O-glucoside (IC50 = 22.80 ± 0.24 µM) and fisetin (IC50 = 46.39 ± 0.34 µM). A three-dimensional quantitative structure-activity relationship model of α-glucosidase inhibitors with good predictive capability [comparative molecular field analysis, q2 = 0.529, optimum number of components (ONC) = 10, R2 = 0.996, F = 250.843, standard error of estimation (SEE) = 0.064, and two descriptors; comparative similarity index analysis, q2 = 0.515, ONC = 10, R2 = 0.997, F = 348.301, SEE = 0.054, and four descriptors] was established and indicated that meta positions of ring B favored bulky and minor, electron-withdrawing, and hydrogen bond donor groups. The presence of electron-donating and hydrogen bond acceptor groups at position 4' of ring B could improve α-glucosidase activity. Position 3 of ring C favored minor, electron-donating, and hydrogen bond donor groups, whereas position 7 of ring A favored bulky and hydrogen bond acceptor groups. Molecular docking screened five flavonoids (baicalein, isorhamnetin-3-O-rutinoside, apigenin-7-O-glucoside, kaempferol-7-O-ß-glucoside, and cyanidin-3-O-glucoside) that can act as insulin sensitizers and form strong combinations with four key protein targets involved in the insulin signaling pathway. Apigenin-7-O-glucoside (60 µM) can effectively improve insulin resistance, and glucose uptake increased by approximately 73.06% relative to the model group of insulin-resistant HepG2 cells. Therefore, apigenin-7-O-glucoside might serve as the most effective α-glucosidase inhibitor and insulin sensitizer. This work may guide diabetes patients to improve their condition through dietary therapy.


Assuntos
Flavonoides/química , Inibidores de Glicosídeo Hidrolases/química , Insulina/metabolismo , Flavonoides/metabolismo , Flavonoides/farmacologia , Inibidores de Glicosídeo Hidrolases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Células Hep G2 , Humanos , Simulação de Acoplamento Molecular , Saccharomyces cerevisiae/enzimologia , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
3.
Wei Sheng Yan Jiu ; 48(1): 76-81, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31032772

RESUMO

OBJECTIVE: To explore influence of occupational stress on hypertension in Xinjiang Uygur Autonomous Region desert oilfield workers. METHODS: Cluster sampling was applied. A total of 1280 petroleum workers from 3 oil fields were used in Karamay City, Xinjiang. Occupational Stress Scale(OSI-R) was used to evaluate occupational stress and analyze the impact of occupational stress on hypertension. RESULTS: With the increase of occupational stress, the prevalence rate of hypertension is increasing(χ~2=21. 078, P<0. 001). Multivariate analysis showed that the risk of high blood pressure in the occupational task was 1. 562 times(95%CI 1. 072-2. 277)as high as that of the less occupational group, and the risk of high blood pressure in the group with strong individual tension reaction was 1. 701 times(95%CI 1. 158-2. 498)as much as that of the weak group(P<0. 05). Analysis of influencing factors of hypertension showed that the risk of high blood pressure in the shift was 1. 389 times(95%CI 1. 115-1. 730)as high as those without the shift, in the frequent drinkers was 1. 877 times(95%CI 1. 300-2. 710)that of the non drinkers, in the high salt patients was 1. 286 times(95%CI 1. 107-1. 691)that of the low salt, in the obese was 1. 564 times(95%CI 1. 249-2. 216)that of the normal people, and in the highly occupational stress was 1. 976 times(95%CI 1. 641-2. 336)as high as the low occupational stress. CONCLUSION: Heavy occupational tasks and strong individual strain can increase the risk of hypertension in desert oilfield workers. Shift, drinking history, salt consumption, BMI and occupational stress were the influencing factors of hypertension in desert oilfield workers.


Assuntos
Hipertensão , Estresse Ocupacional , Campos de Petróleo e Gás , Consumo de Bebidas Alcoólicas , China , Humanos , Hipertensão/epidemiologia , Prevalência , Fatores de Risco , Estresse Psicológico , Inquéritos e Questionários
4.
Cell Immunol ; 338: 9-20, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30826001

RESUMO

The emergence of alloreactive Th17 cells that mediate allograft rejection has provided an impetus to understand the factors affecting the generation of Th17 cells in allograft transplantation. How toll-like receptor 2 (TLR2) signalling regulates the generation of Th17 cells upon alloantigen stimuli remains unclear. In this study, we used a mouse model of cardiac allograft transplantation to investigate whether TLR2 signalling influences the development of Th17 cells. Here, we demonstrate that the TLR2-deficient recipient mice show high Th17 cells, both in spleens and allografts, as well as higher infiltrating inflammatory leukocytes in cardiac allografts compared to wild-type control recipient mice. mRNA expression of IL-17, IL-6, TNF-α, CCR6 and CCL20 within the allografts is markedly increased in TLR2-deficient recipient mice compared to wild-type recipient mice. In addition, TLR2 deficiency leads to upregulation of Signal transducer and activator of transcription 3 (STAT3) phosphorylation in both spleens and allografts. In an in vitro experiment, a mixed lymphocyte reaction was assessed, which further confirmed that TLR2 deficiency leads to a significant increase in the generation of Th17 cells compared with wild-type controls. Furthermore, IL-6 secreted by the dendritic cells of TLR2-deficient mice contributes to driving the generation of these Th17 cells. These results suggest that TLR2 signalling is important in regulating the development of Th17 cells after cardiac allograft transplantation.

5.
Int Immunopharmacol ; 68: 145-155, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30634142

RESUMO

Gasdermin D (GSDMD), a genetic substrate for inflammatory caspases, plays a central role in pyroptosis of macrophages and release of interleukin­1ß (IL-1ß), but was mainly referred to microbial infection. High mobility group box-1 (HMGB1), served as an alarm molecule during various pathological process, has been widely recognized to be involved in liver ischemia-reperfusion (I/R). Glycyrrhizin, a natural anti-inflammatory and antiviral triterpene in clinical use, was recently referred to have ability to prevent I/R induced liver injury by inhibiting HMGB1 expression and activity. However, the mechanisms responsible for damage amelioration subsequently to HMGB1 inhibition during liver I/R remain enigmatic. This study was designed to explore the functional role and molecular mechanism of glycyrrhizin in the regulation of I/R induced liver injury. We found that liver I/R promotes GSDMD-mediated pyroptotic cell death of Kupffer cells, which was inhibited by glycyrrhizin. Interestingly, endogenous HMGB1, not exogenous one, was involved in hypoxia-reoxygenation (H/R) induced pyroptosis. Moreover, GSDMD knockdown protects kupffer cells against H/R induced pyroptosis in vitro. Here, we report, for the first time, that glycyrrhizin attenuated tissue damage and kupffer cells pyroptosis during liver ischemia-reperfusion injury (LIRI) and identify a previously unrecognized HMGB1- dependent GSDMD- mediated signaling pathway in the mechanism of kupffer cells pyroptosis induced by H/R. Our findings provide the first demonstration of GSDMD-determined pyroptotic cell death responsible for I/R induced release of IL-1ß and this would provide a mandate to better understand the unconventional mechanisms of cytokine release in the sterile innate immune system.


Assuntos
Anti-Inflamatórios , Proteínas Reguladoras de Apoptose/fisiologia , Ácido Glicirrízico , Proteína HMGB1/metabolismo , Macrófagos do Fígado/efeitos dos fármacos , Hepatopatias , Piroptose/efeitos dos fármacos , Traumatismo por Reperfusão , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ácido Glicirrízico/farmacologia , Ácido Glicirrízico/uso terapêutico , Interleucina-1beta/metabolismo , Macrófagos do Fígado/fisiologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatopatias/tratamento farmacológico , Hepatopatias/metabolismo , Hepatopatias/patologia , Masculino , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
6.
Biomed Pharmacother ; 110: 692-699, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30553196

RESUMO

Glycyrrhizin, a triterpenoid compound, has been reported to be an anti-inflammatory agent for the treatment of a variety of inflammatory diseases including hepatitis. However, the mechanism by which glycyrrhizin inhibits inflammation is unclear. Using a Con A-induced hepatitis model in mice, we found that administration of glycyrrhizin ameliorates Con A-induced liver injury, which manifests as reduction in the production of inflammatory cytokines IFN-γ, IL-6 and IL-17, as well as serum alanine aminotransferase (ALT). Blockade of IL-17 dramatically mitigates liver injury resulting from Con A challenge. Interestingly, at both the mRNA and protein levels, the endogenous alarmin inflammatory molecule high-mobility group box 1 (HMGB1) is significantly decreased in mice injected with glycyrrhizin combined with Con A compared to those injected with Con A alone. In contrast, the administration of glycyrrhizin with Con A challenge up-regulates the production of IL-25. Furthermore, an increase in the proportion of protective lymphocyte subset, Gr-1+ CD11b+ (Myeloid-Derived Suppressor Cell, MDSCs), could be induced by increased IL-25 to restrain immune cell activation and favor the resolution of detrimental immune reactions caused by Con A challenge. The results indicate that glycyrrhizin plays a protective role in Con A-induced hepatitis. This protective role is particularly associated with reducing the production of IL-17 and enhancing the expression of IL-25. The present study may provide a new strategy for the treatment of acute hepatitis in the clinical setting.


Assuntos
Concanavalina A/toxicidade , Ácido Glicirrízico/uso terapêutico , Hepatite/tratamento farmacológico , Hepatite/metabolismo , Interleucina-17/biossíntese , Interleucinas/biossíntese , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Ácido Glicirrízico/farmacologia , Interleucina-17/antagonistas & inibidores , Interleucinas/agonistas , Masculino , Camundongos , Camundongos Endogâmicos C57BL
7.
Front Psychol ; 9: 2048, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30405509

RESUMO

Second language (L2) learners need to continually learn new L2 words as well as additional meanings of previously learned L2 words. The present study investigated the influence of semantic similarity on the growth curve of learning of artificially paired new meanings of previously known L2 words in Chinese-English bilinguals. The results of a translation recognition task showed that related meanings are learned faster and more accurately than unrelated meanings. The advantage of learning related new meaning persisted and increased for a week after learning the new meanings. These results suggest that semantic similarities impact the learning of new meanings for known L2 words, and that the shared features between previously known and new meanings of a word facilitate the process of incorporating the related new meaning into the lexical semantic network. Our results are discussed under the framework of the connectionist model.

8.
Inflamm Res ; 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30430216

RESUMO

BACKGROUND: Previous studies showed that CD4+ T cells play a critical role in Con A-induced hepatitis in wild-type mice. However, the role of CD8+ T cells in the setting of Con A-induced hepatitis is enigmatic. The aim of study is to investigate the function of CD8+ T cells in the context of Con-A-induced hepatitis. MATERIALS AND SUBJECTS: Two different mouse models of Con A-induced hepatitis, T cell-transferred Rag2-/- mice and wild-type C57BL/6 mice, were used in the present study. IL-33 gene knockout mice were used to confirm the role of alarmin in Con A-induced hepatitis. RESULTS: Opposing to the previous results obtained in wild-type mice, transferred CD4+ T cells alone into Rag2-knockout mice cannot cause hepatitis upon Con A challenge. In stark contrast, transferred CD8+ T cells play an important role in the pathogenesis of Con A-induced liver injury in T cell-transferred Rag2-deficient mice. Furthermore, we found that hepatocytes injured by perforin-based CD8+ T cell cytotoxicity release the alarmin IL-33. This cytokine promotes ST2+ ILC2 development and the secretion of cytokines IL-5 and IL-13 to mediate liver inflammation triggered by Con A challenge. In addition, these type 2 cytokines, including those originated from CD4+ T cells, result in eosinophils accumulation in liver to exacerbate the liver injury after Con A administration. CONCLUSION: Our data for the first time revealed that CD8+ T cells play an indispensable role in the pathogenesis of Con A-induced liver injury in T cell-transferred Rag2-deficient mice. Therefore, the CD8+ T cell/IL-33/ILC2 axis is a potential therapeutic target for acute immune-mediated liver injury.

9.
Oncogene ; 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30185813

RESUMO

Overexpression of Jumonji domain-containing 6 (JMJD6) has been reported to be associated with more aggressive breast cancer characteristics. However, the precise role of JMJD6 in breast cancer development remains unclear. Here, we demonstrate that JMJD6 has intrinsic tyrosine kinase activity and can utilize ATP and GTP as phosphate donors to phosphorylate Y39 of histone H2A.X (H2A.XY39ph). High JMJD6 levels promoted autophagy in triple negative breast cancer (TNBC) cells by regulating the expression of autophagy-related genes. The JMJD6-H2A.XY39ph axis promoted TNBC cell growth via the autophagy pathway. We show that combined inhibition of JMJD6 kinase activity and autophagy efficiently decreases TNBC growth. Together, these findings suggest an effective strategy for TNBC treatment.

10.
Innate Immun ; 24(4): 231-239, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29673286

RESUMO

Here, the regulatory role of autophagy is examined in both an LPS-induced lethal endotoxic shock mouse model and cecal ligation and puncture (CLP) mouse model. Autophagy-inhibitor 3-methyladenine (3-MA) and autophagy-enhancer rapamycin were administrated to mice challenged with LPS or CLP. Animals challenged with LPS or CLP combined with 3-MA displayed increased survival after endotoxemia, but LPS combined with rapamycin worsened the endotoxic shock of the mice. Among the different organs studied, the lungs and intestines exhibited significant differences among LPS alone, LPS combined with 3-MA and LPS combined with rapamycin. LPS combined with 3-MA attenuated the inflammatory damages of these organs as compared with LPS alone. In contrast, LPS combined with rapamycin increased damage in these organs. Consistently, serum inflammatory mediators TNF-α and IL-6 were decreased by the treatment of LPS combined with 3-MA as compared with LPS alone, while administration of LPS combined with rapamycin increased the serum TNF-α and IL-6 levels. Similar results were found in mouse bone marrow-derived macrophages exposed to LPS. Moreover, the regulatory effect of autophagy to endotoxic shock is dependent on the TLR4 signaling pathway. Our results demonstrate the central role of autophagy in the regulation of endotoxic shock and its potential modulation for endotoxic shock treatment.

11.
Tumour Biol ; 35(6): 5237-44, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24523018

RESUMO

Apurinic/apyrimidinic endonuclease 1 (APE1) is a key enzyme in base excision repair (BER) pathway for the removal of many oxidized and alkylated bases. Single-nucleotide polymorphisms of the APE1gene have been demonstrated to be involved in carcinogenesis. However, the association between APE1 Asp148Glu polymorphism and lung cancer risk remains inconclusive. To derive a precise estimate for this association, we carried out an updated meta-analysis by pooling data thus far published. The pooled odds ratio (OR) with 95 % confidence interval (95 % CI) was calculated to assess the role of APE1 Asp148Glu polymorphism in lung carcinogenesis. The pooled ORs suggested that variant genotypes of APE1 Asp148Glu were modestly associated with an elevated risk of lung cancer (GluGlu vs. AspAsp, OR=1.22, 95 % CI 1.01-1.48, P=0.038; GluGlu vs. AspAsp + AspGlu, OR=1.19, 95 % CI 1.02-1.39, P=0.023). The relationship was also observed in studies conducted among Asians, but not Caucasians. Sensitivity analysis further confirmed the findings. The meta-analysis shows that the polymorphism of APE1 Asp148Glu exerts risk effect on lung cancer development.


Assuntos
DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Polimorfismo de Nucleotídeo Único , Humanos , Risco
12.
Tumour Biol ; 35(2): 1323-30, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24068566

RESUMO

The relationship between the vitamin D receptor (VDR) polymorphisms and the susceptibility to lung cancer remains unclear. The present meta-analysis was performed to estimate the polymorphisms of VDR and lung cancer risk. The pooled odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were calculated. Subgroup analysis by smoking status was carried out for further elucidation. The VDR BsmI polymorphism seemed to be negatively associated with the lung cancer risk (A vs. G, OR = 0.71, 95 % CI, 0.52-0.96; GA vs. GG, OR = 0.54, 95 % CI, 0.35-0.83; AA + GA vs. GG, OR = 0.55, 95 % CI, 0.36-0.84), particularly among the smokers (AA + GA vs. GG, OR = 0.39, 95 % CI, 0.21-0.72). The VDR ApaI variant genotypes did not alter the risk of lung cancer under all gene models in overall analysis. However, smokers carrying the variant G allele were more susceptible to lung cancer (G vs. T, OR = 1.60, 95 % CI, 1.14-2.25). The polymorphism of VDR TaqI was related to a decreased risk of lung cancer (C vs. T, OR = 0.62, 95 % CI, 0.26-1.46; CC vs. TT, OR = 0.44, 95 % CI, 0.21-0.91; TC vs. TT, OR = 0.58, 95 % CI, 0.38-0.90; CC + TC vs. TT, OR = 0.55, 95 % CI, 0.36-0.84). Besides, the CC + TC carriers in the smokers were at a significantly reduced risk of lung cancer (CC + TC vs. TT, OR = 0.48, 95 % CI, 0.16-1.44). The study supports that the polymorphisms of VDR BsmI and TaqI play protective roles in the lung carcinogenesis, particularly among the smokers. The association of VDR ApaI polymorphism with the lung cancer risk needs to be further elucidated.


Assuntos
Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Receptores de Calcitriol/genética , Alelos , Estudos de Associação Genética , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA