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1.
Evol Psychol ; 19(1): 1474704920986866, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33487056

RESUMO

Cyclical fluctuations of the ovarian hormones estrogen (E2) and progesterone (PROG) have multiple effects on reproduction and development. However, little is known about the roles of E2 and PROG in women's social behaviors. Here, based on evolutionary theory suggesting social sensitivity and inhibition ability are conductive to maintaining social relationships, we provide evidence for the association between menstrual phases and social orientation. In Study 1, 78 women provided saliva samples and reported their intensity of behavioral activation/inhibition system (BAS/BIS) and interpersonal sensitivity at either of two phases of the menstrual cycle: late follicular phase (FP), and mid-luteal phase (LP). A significant between-subject association emerged, revealing that women with higher PROG levels reported higher levels of social feedback sensitivity, and women with relatively high PROG levels showed a positive association between their E2 levels and inhibitory response. In Study 2, 30 women reported their interpersonal anxiety and finished the social value orientation (SVO) measures at both late FP and mid-LP. A significant within-person effect emerged: women in the mid-LP, which is characterized by higher PROG levels, reported higher levels of interpersonal anxiety and SVO. In sum, these findings revealed that women's social orientation could fluctuate naturally with ovarian hormones across the menstrual cycle.

2.
Front Hum Neurosci ; 14: 568399, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304251

RESUMO

Hormonal changes across the menstrual cycle have been shown to influence reward-related motivation and impulsive behaviors. Here, with the aim of examining the neural mechanisms underlying cognitive control of impulsivity, we compared event-related monetary delay discounting task behavior and concurrent functional magnetic resonance imaging (fMRI) revealed brain activity as well as resting state (rs)-fMRI activity, between women in the mid-luteal phase (LP) and women in the late follicular phase (FP). The behavioral data were analyzed and related to neural activation data. In the delay discounting task, women in the late FP were more responsive to short-term rewards (i.e., showed a greater discount rate) than women in the mid-LP, while also showing greater activity in the dorsal striatum (DS). Discount rate (transformed k) correlated with functional connectivity between the DS and dorsal lateral prefrontal cortex (dlPFC), consistent with previous findings indicating that DS-dlPFC circuitry may regulate impulsivity. Our rs-fMRI data further showed that the right dlPFC was significantly more active in the mid-LP than in late FP, and this effect was sensitive to absolute and relative estradiol levels during the mid-LP. DS-dlPFC functional connectivity magnitude correlated negatively with psychometric impulsivity scores during the late FP, consistent with our behavioral data and further indicating that relative estradiol levels may play an important role in augmenting cognitive control. These findings provide new insight into the treatment of conditions characterized by hyper-impulsivity, such as obsessive compulsive disorder, Parkinson disease, and attention deficit hyperactivity disorder. In conclusion, our results suggest that cyclical gonadal hormones affect cognitive control of impulsive behavior in a periodic manner, possibility via DS-dlPFC circuitry.

3.
Fitoterapia ; 146: 104710, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32882337

RESUMO

Three types of new Euphorbia diterpene pseudo-alkaloids possessing 5/6/7/3 (1), 5/6/6/4 (2-5), and 5/7/7/4 (6-7) fused ring skeletons were obtained through an unexpected BF3·Et2O/CH3CN-mediated structural conversion and amination of lathyrane diterpene (Euphorbia factor L1), in which the solution acetonitrile had been introduced into the Euphorbia diterpene as a nitrogen source and tandem amination/oxirane-opening (cyclopropane-opening)/oxa-Michael addition reaction was involved in the conversion. The structures of new Euphorbia diterpene pseudo-alkaloids were elucidated by a combination of spectroscopic data and single crystal X-ray diffraction analysis. The basic skeletons of Euphorbia diterpene pseudo-alkaloids 1 and 2-5 could fall into the structural types of euphoractine B and euphoractine A diterpenes, respectively, suggesting the possible biogenetic pathway relationship between lathyrane diterpene with euphoractines A and B types diterpenes. Pseudo-alkaloids 1-7 did not show any potential cytotoxicity against several tumor cell lines.

4.
PLoS One ; 15(8): e0237032, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790683

RESUMO

The behavioral activation system (BAS) and the behavioral inhibition system (BIS) have been proposed to relate to stable traits that predict inter-individual differences in motivation. Prior reports point dopamine (DA) pathways, mainly including ventral tegmental area (VTA) and substantia nigra (SN), implicate in subserving reward-related functions associated with BAS and inhibitory functions related with BIS. However, as an important factor that affects DA releasing, it remains an open question whether the ovarian hormones may also be related to BIS/BAS. Here, to investigate effects of the estradiol (E2) and progesterone (PROG) on BIS/BAS and related DA pathways, we employed a BIS/BAS scale and the resting-state functional magnetic resonance imaging (fMRI) during the late follicular phase (FP) and the mid-luteal phase (LP). On the behavioral level, when women had high PROG levels, their E2 levels were found positively correlated with BIS scores, but those women whose PROG levels were low, their E2 levels were negative correlation with BIS scores. On the neural level, we demonstrated BAS was related with the VTA pathway, included brain reward regions of nucleus accumbens (NAc) and orbitofrontal cortex (OFC). Meanwhile, the BIS was correlated with the SN-dorsolateral prefrontal cortex (dlPFC) pathway. ROI-based resting-state functional connectivity (RSFC) analyses further revealed that, RSFC between the SN and dlPFC was modulated by ovarian hormones. With higher PROG levels, increased E2 levels among women were accompanied by stronger RSFC of the SN-dlPFC, but when PROG levels were low, E2 levels were negatively correlated with the SN-dlPFC RSFC. These findings revealed a combined enhancement effect of E2 and PROG on BIS, and the SN-dlPFC pathway was mainly involved in this process.


Assuntos
Encéfalo/fisiologia , Dopamina/fisiologia , Inibição Psicológica , Motivação/fisiologia , Ovário/fisiologia , Adulto , Afeto/fisiologia , Encéfalo/diagnóstico por imagem , Neurônios Dopaminérgicos/fisiologia , Estradiol/fisiologia , Feminino , Neuroimagem Funcional , Humanos , Imagem por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Progesterona/fisiologia , Psicofisiologia , Substância Negra/diagnóstico por imagem , Substância Negra/fisiologia , Área Tegmentar Ventral/diagnóstico por imagem , Área Tegmentar Ventral/fisiologia , Adulto Jovem
5.
Neuroreport ; 31(10): 717-723, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32453019

RESUMO

The brain's default mode network (DMN) has become closely associated with self-referential mental activity, particularly in the resting-state. Prior reports point that the sex hormones are potent modulators of brain plasticity and functional connectivity. However, it is uncertain whether changes in ovarian hormones, as occur during the monthly menstrual cycle, substantially affects the functional connectivity of DMN. Here, we employed a Self-Awareness Scale (SAS) and the resting-state functional MRI in the late follicular phase and the mid-luteal phase to investigate the effect of the estradiol (E2) and progesterone on the SAS and DMN. On the behavioral level, increased progesterone facilitated women's other-focused attention. The regions of interest-based resting-state functional connectivity analyses continued to demonstrate a negative correlation of the relative progesterone and the medial prefrontal cortex-inferior temporal gyrus (mPFC-ITG) functional connectivity, and a facilitated effect of relative E2 on the mPFC-inferior parietal lobule functional connectivity in the DMN. Furthermore, as a core hub of the 'theory of mind', the functional connectivity between the ITG and thalamus was found negatively correlated with the relative E2. Meanwhile, the mid-luteal phase, which had significantly lower relative E2 levels, was indicated had stronger ITG-thalamus functional connectivity during the resting state. These results demonstrated an opposite effect of E2 and progesterone on the DMN and the other-focused preference in the mid-luteal phase, extended previous evidence of the potentially adaptive psychological effects of ovarian hormones on mapping self and others in the brain networks.

6.
Environ Pollut ; 247: 999-1008, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30823355

RESUMO

Endocrine disrupting compounds (EDCs) are becoming an increasing concern regarding bioaccumulation in aquatic biota. However, the effects of regional pollution levels and specific feeding habits on the bioaccumulation of EDCs in fish are rarely reported. 4-Nonylphenol (4-NP), bisphenol A (BPA), 4-tert-octylphenol (4-t-OP), triclocarban (TCC) and triclosan (TCS) were determined in abiotic compartments [water, sediment, suspended particulate matter (SPM)] and fish with different feeding habits along the Pearl River, China. EDCs in abiotic compartments exhibited significant (p < 0.05) spatial variations, forming five zones clustered based on site-specific EDC concentrations. 4-NP was the dominant compound, contributing 58-98% of the EDCs in fish, followed by BPA (<41%), 4-t-OP (<13%), and TCC and TCS (<4.7%). The concentrations of 4-NP and 4-t-OP, BPA, and TCC and TCS were the highest in brackish carnivorous, planktivorous, and detritivorous fish, respectively. The bioaccumulation factors (BAFs) showed that 4-NP accumulated (BAF > 5000) in all fish except for suck-feeding detritivores, while 4-t-OP and TCC accumulated in filter-feeding planktivores. The concentration of 4-NP in carnivores was significantly higher than that in detritivores, indicating the potential biomagnification of 4-NP along food chains. EDCs in sediment and SPM and those in water were most positively correlated with those in detritivores and planktivores, respectively, suggesting the potential of fish with these two feeding habits to act as bioindicators of EDC pollutants.


Assuntos
Disruptores Endócrinos/análise , Monitoramento Ambiental/métodos , Peixes , Rios/química , Poluentes Químicos da Água/análise , Animais , China
7.
Fitoterapia ; 133: 212-218, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30690124

RESUMO

Natural euphoractane and myrsinane diterpene skeletons, together with an unnatural 5/7/7/4 fused-ring diterpene skeleton were furnished via BF3·Et2O-mediated transformation of lathyrane-type diterpene, Euphorbia factor L1. The skeleton transformation process was mainly involved in the cascade oxirane-opening (cyclopropane-opening)/oxe-Micheal addition reaction. The structures of three diterpenes were confirmed by comprehensive spectra analysis and single crystals X-ray diffraction. Current results proved the biogenesis pathway between lathyrane with euphoractane and myrsinane by chemical transformation for the first time.


Assuntos
Diterpenos/química , Euphorbia/química , China , Ácidos de Lewis , Estrutura Molecular , Sementes/química
8.
Huan Jing Ke Xue ; 39(3): 1053-1064, 2018 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-29965449

RESUMO

This study aimed to investigate the occurrence and spatio-temporal distribution of 4-tert-octylphenol (4-t-OP), 4-nonylphenol (4-NP), triclosan (TCS), estrone (E1), 17ß-estradiol (E2), and bisphenol-A (BPA) as endocrine disrupting chemicals (EDCs) in the water of the Liuxi River and to evaluate the risks for estrogenic activity. The results showed that EDCs had been detected at the 14 monitoring sites and the total concentration ranged from 26.07 ng·L-1 to 7109.5 ng·L-1, with the highest contribution rate coming from 4-NP (78.62%), followed by BPA (11.91%), and the other four EDCs (≤ 4.92%). On a spatial and temporal scale, the EDC contents increased longitudinally from upstream to downstream, especially in the heavily-polluted Baiyun section where the water quality was lower than level Ⅴ. The EDC contents in the tributaries were much higher than those in the main channels. Influenced by the monsoon precipitation, the contents of 4-NP, 4-t-OP, and total EDCs in the rainy season were significantly (P<0.05) higher than those in the dry season, while the seasonal changes of E1 and E2 followed the opposite tendency. A Pearson correlation analysis showed that DO was significantly negatively correlated with all the EDCs, suggesting that the EDCs and reductive organic pollutants might coexist. As TN, TP, NH4+-N, permanganate index, and EC were significantly positively correlated with E1, E2, BPA, and TCS but not obviously correlated with 4-NP (P>0.05), we presumed that the pollution source of E1, E2, BPA, and TCS might be the same with nitrogen and phosphorus nutrition, originating from the point source emission of the domestic sewage, industrial, and agricultural wastewater. In contrast, 4-NP and 4-t-OP more likely originated from the non-point source pollution from agriculture. RDA results showed that the variation of the EDCs contents by season was more obvious than that in space (RDA1 56.14%>RDA2 14.20%), which was much more influenced by 4-NP in the rainy season and by BPA in the dry season. As E1, E2, and TCS were positively correlated with the Cu, Zn, cyanide, and fecal coliform, these three target compounds could be used to indicate the multiple pollution components for water quality. Compared with the worldwide reported EDC contents in waters, 4-NP, BPA, and TCS contents in the middle and lower reaches of the Liuxi River were at higher levels, while E1, E2, and 4-t-OP were at the middle and lower levels. The risk assessment for estrogenic activity showed that the RQ values in the middle and lower reaches of the Liuxi River were all greater than 1, indicating that the downstream river sections were under high risk for estrogenic activity. As a result, appropriate precautions are needed to improve environmental management.


Assuntos
Disruptores Endócrinos/análise , Monitoramento Ambiental , Rios/química , Poluentes Químicos da Água/análise , Compostos Benzidrílicos , China , Estradiol , Estrona , Fenóis , Análise Espaço-Temporal , Triclosan , Águas Residuárias
9.
Front Psychol ; 9: 465, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29681873

RESUMO

Correlations between memories and dreaming has typically been studied by linking conscious experiences and dream reports, which has illustrated that dreaming reflects waking life events, thoughts, and emotions. As some research suggests that sleep has a function of memory consolidation, and dreams reflect this, researching this relationship further may uncover more useful insights. However, most related research has been conducted using the self-report method which asks participants to judge the relationship between their own conscious experiences and dreams. This method may cause errors when the research purpose is to make comparisons between different groups, because individual differences cannot be balanced out when the results are compared among groups. Based on a knowledge of metaphors and symbols, we developed two operationalized definitions for independent judges to match conscious experiences and dreams, the descriptive incorporation and the metaphorical incorporation, and tested their reliability for the matching purpose. Two independent judges were asked to complete a linking task for 212 paired event-dreams. Results showed almost half dreams can be matched by independent judges, and the independent-judge method could provide similar proportions for the linking task, when compared with the self-report method.

10.
Chem Pharm Bull (Tokyo) ; 66(6): 674-677, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29593174

RESUMO

We isolated two new lathyrane-type diterpenes L27 (1) and L28 (2) along with seven known compounds (3-9) from the seeds of Euphorbia lathyris. These compounds were identified by NMR, high-resolution electrospray ionisation (HR-ESI)-MS as well as IR spectroscopy. Compounds 1 and 2 were assigned NMR spectrums with 1H-NMR, 13C-NMR, distortionless enhancement by polarization (DEPT), correlation spectroscopy (COSY), heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple bond connectivity (HMBC) and nuclear Overhauser effect spectroscopy (NOESY). Stereo configuration of 1 and 2 were confirmed by comprehensive interpretation of their nuclear Overhauser effect (NOE) relationship and showed they were first natural lathyrane-type diterpenes possessing α-configuration substitutes at C-3. Cytotoxicity assay of isolated compounds were evaluated against breast cancer cell lines MCF-7 or MDA-MB-231, 786-0 and liver cancer cell lines HepG2. As a result, Euphorbia factor L28 (2) showed strongly cytotoxicity to the 786-0 and HepG2 cell lines, with an IC50 value of 9.43 and 13.22 µM, respectively, which preliminarily suggested that the configuration of lathyrane-type diterpene at C-3 has a significant effect on its bioactivity.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Euphorbia/química , Extratos Vegetais/farmacologia , Sementes/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Células MCF-7 , Conformação Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade
11.
Exp Neurol ; 297: 1-13, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28602833

RESUMO

Neuroinflammation and oxidative stress are involved in cerebral ischemia-reperfusion, in which Interleukin 1 (IL-1), as an effective intervention target, is implicated. Interleukin-1 receptor antagonist (IL-1RA) is the natural inhibitor of IL-1, but blood-brain barrier (BBB) limits the brain penetration of intravenously administered IL-1RA, thereby restricting its therapeutic effect against neuroinflammation. In this study, we evaluated the potential effects of anti-inflammation and anti-oxidative stress of a novel protein IL-1RA-PEP, which fused IL-1RA with a cell penetrating peptide (CPP). Studies were carried out in transient middle cerebral artery occlusion (MCAO) in rats and oxygen glucose deprivation/reoxygenation (OGD/R) in primary cortical neurons. In MCAO rat model, IL-1RA-PEP (50mg/kg) injected i.v., penetrated BBB effectively, and alleviated brain infarction, cerebral edema, neurological deficit score and motor performance as well as inhibited the inflammatory cytokines expression. Furthermore, our results firstly showed that IL-1RA-PEP also regulated the oxidases expression, decreased the levels of NO, MDA and ROS. In addition, the inhibitory effects of IL-1RA-PEP on oxidative stress and inflammation were confirmed in rat cortical neurons induced by OGD/R, it reduced ROS, IL-6 and TNF-α. Further study showed that the effects of IL-1RA-PEP were closely associated with the NF-κB and p38 pathways which were proved respectively by their inhibitors JSH-23 and SB203580. Our results indicated that IL-1RA-PEP could effectively penetrate the brain of MCAO rats, alleviated the cerebral ischemia reperfusion injury by inhibiting neuroinflammation and oxidative stress, showing a great clinical potential for stroke.


Assuntos
Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Estresse Oxidativo/fisiologia , Traumatismo por Reperfusão/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Masculino , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico
12.
PLoS One ; 9(9): e106407, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25180577

RESUMO

The present study examined women's attentional bias toward ornamental objects in relation to their menstrual phase as well as to motivations of intersexual courtship or intrasexual competition. In Experiment 1, 33 healthy heterosexual women were tested in a bias-assessment visual cuing task twice: once on a high-fertility day (during the ovulatory phase) and once on a low-fertility day (during the luteal phase). They paid greater attention to pictures of ornamental objects than to pictures of non-ornamental objects near ovulation, but not during the luteal phase, suggesting an ornamental bias during the high-fertility phase. In Experiment 2, before the visual cuing task, 40 participants viewed 10 same-sex or opposite-sex facial photographs with either high or low attractiveness as priming tasks to activate the intrasexual competition or intersexual courtship motives. Results showed that women's ornamental bias was dependent on the interaction of menstrual phase and mating motive. Specifically, the ornamental bias was observed on the high-fertility day when the subjects were primed with high-attractive same-sex images (intrasexual competition) and was observed on the low-fertility day when they were primed with high-attractive opposite-sex photographs (intersexual courtship). In conclusion, the present findings confirm the hypothesis that, during the high-fertility phase, women have an attentional bias toward ornamental objects and further support the hypothesis that the ornamental bias is driven by intrasexual competition motivation near ovulation, but driven by intersexual courtship motivation during the luteal phase.


Assuntos
Comportamento Competitivo , Corte , Fase Luteal/fisiologia , Ovulação/fisiologia , Adulto , Atenção , Feminino , Humanos , Tempo de Reação , Análise e Desempenho de Tarefas , Adulto Jovem
13.
J Asthma ; 50(2): 209-14, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23294145

RESUMO

BACKGROUND: The presence of transient receptor potential vanilloid 2 (TRPV2) in human peripheral blood cells may suggest a role under pathological conditions. The aim of this study was to explore the relationship between the expression profile of TRPV2 gene and childhood asthma in the north of China. The effects of allergens exposure on the expression of TRPV2 gene were also investigated. METHODS: Sixty asthmatics children confirmed by physician diagnosis and 60 healthy children as a control group were recruited. Serum total IgE and specific IgE were measured. Using quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), TRPV2 was detected in total RNA extracted from peripheral blood lymphocytes. Student's t-test and chi-square test were used to analyze the relationship between TRPV2 transcript and different parameter variables on susceptibility of childhood asthma. Multiple logistic regression was used to analyze the associations between TRPV2 gene and allergens. RESULTS: The expression level of TRPV2 gene was increased 2.6 times in asthmatic children compared with controls (p < .01). The up-regulation of TRPV2 gene and sensitization to one of three the allergens-spring pollen, dust mite, and dog and cat hair-were correlated with childhood asthma. In addition, the hypersensitivity to spring pollen, cockroach, and dust mite and up-regulation of TRPV2 gene expression may be the risk factors for the childhood asthma in Beijing. CONCLUSIONS: The increased expression of TRPV2 gene in peripheral lymphocytes is closely correlated with childhood asthma in the north of China. This study provides a potential new biomarker of childhood asthma and lays the basis for further clarification of the pathogenesis underlying asthma.


Assuntos
Asma/metabolismo , Canais de Cátion TRPV/metabolismo , Alérgenos/imunologia , Asma/sangue , Asma/genética , Asma/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Feminino , Regulação da Expressão Gênica , Humanos , Imunoglobulina E/sangue , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Modelos Logísticos , Masculino , RNA/química , RNA/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Canais de Cátion TRPV/sangue , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/imunologia , População Urbana
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(6): 1492-5, 2012 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-23257460

RESUMO

This study was aimed to set up and evaluate a quantitative method for detecting lumbrokinase level in plasma. The lumbrokinase was used to immunize rabbit and BALB/c mouse for preparation of rabbit or mouse-derived polyclonal antibodies, and then the standard curves were drawn up by detecting the lumbrokinase diluted in PBS using the double antibody sandwich ELISA. This method further was analyzed for its specificity, precision and recovery rate. This established double antibody sandwich ELISA was used to assay the lumbrokinase in human plasma, and the assayed results were assessed. The results showed that a double antibody sandwich ELISA for the detection of lumbrokinase has been established. And the standard curve fitting R value > 0.99, the precision assessment showed that the measured values of coefficient of variation (CV) in 3 batches were all < 15%; recovery assessment in 3 batches showed that all the measured recovery rates were > 80%; the quantitative low limit was assessed as 5 ng/ml (precision CV < 15%, recovery rate > 85%). It is concluded that this method is consistent with the criteria stipulated by the Pharmacopeia, which provides a reliable measurement method for quantitative detection of plasma lumbrokinase in clinical trials.


Assuntos
Endopeptidases/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Animais , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Plasma , Coelhos
15.
Cytokine ; 56(2): 174-9, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21843953

RESUMO

Interleukin-22 (IL-22), a member of the IL-10 cytokine family that is produced by activated Th22, Th1 and Th17 cells as well as natural killer cells, plays an important role in increase of innate immunity, protection from damage and enhancement of regeneration. Here, we examined the effects of IL-22 on acute liver failure model induced by d-galactosamine (GalN) and lipopolysaccharide (LPS). Administration of recombinant human IL-22 (rhIL-22) reduced the death rate markedly and prevented mice from severe hepatic injury, as evidenced by decreased serum alanine aminotransferase (ALT) and total bilirubin (T.Bil) activity as well as improved histological signs in liver. Furthermore, IL-22 treatment decreased the hepatic malondialdehyde (MDA) contents and increased the reduced glutathione levels. Serum tumor necrosis factor α (TNF-α) level and hepatic caspase-3 activity were significantly lower in mice administrated with IL-22. Moreover, IL-22 treatment significantly enhanced activation of STAT3 and up-regulated the expression of Bcl-xL, heme oxygenase-1 (HO-1) and redox factor-1 (Ref-1) in the liver injury induced by GalN/LPS. Collectively, these data indicate that IL-22 can provide critical protection against GalN/LPS-induced liver injury through anti-apoptotic, anti-oxidant and anti-inflammatory actions.


Assuntos
Galactosamina/toxicidade , Interleucinas/farmacologia , Lipopolissacarídeos/toxicidade , Falência Hepática Aguda/tratamento farmacológico , Alanina Transaminase/sangue , Animais , Sequência de Bases , Bilirrubina/sangue , Caspase 3/sangue , Primers do DNA , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Glutationa/metabolismo , Heme Oxigenase-1/genética , Interleucina-1/sangue , Interleucinas/administração & dosagem , Interleucinas/sangue , Fígado/metabolismo , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/sangue , Proteínas Recombinantes/farmacologia , Fator de Transcrição STAT3/metabolismo , Fator de Necrose Tumoral alfa/sangue , Proteína bcl-X/metabolismo
16.
Biosci Biotechnol Biochem ; 75(7): 1290-4, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21737938

RESUMO

The protective effects of interleukin-22 (IL-22) on acute alcohol-induced liver injury were investigated. Mice were gavaged with 7 doses of alcohol (56% wt/vol, 15.2 mL/kg of body weight for each dose) over the 24 h, and IL-22 (0.5 mg/kg BW) was given to the mice by injection into the tail vein 1 h after alcohol administration. The results indicated that acute alcohol administration caused prominent hepatic microvesicular steatosis and an elevation of serum transaminase activities, induced a significant decrease in hepatic glutathione in conjunction with enhanced lipid peroxidation, and increased hepatocyte apoptosis as well as hepatic TNF-alpha production. IL-22 treatment attenuated these adverse changes induced by acute alcohol administration. The protective effects of IL-22 on alcohol-induced hepatotoxicity were due mainly to its anti-inflammatory, anti-oxidant, and anti-apoptotic features.


Assuntos
Etanol/toxicidade , Fígado Gorduroso Alcoólico/prevenção & controle , Hepatite Alcoólica/prevenção & controle , Interleucinas/administração & dosagem , Fígado/patologia , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Alanina Transaminase/sangue , Alanina Transaminase/efeitos dos fármacos , Alanina Transaminase/metabolismo , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Fígado Gorduroso Alcoólico/etiologia , Fígado Gorduroso Alcoólico/metabolismo , Fígado Gorduroso Alcoólico/patologia , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Hepatite Alcoólica/etiologia , Hepatite Alcoólica/metabolismo , Hepatite Alcoólica/patologia , Inflamação , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/citologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Fator de Necrose Tumoral alfa/metabolismo
17.
Cytokine ; 49(3): 338-43, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20036575

RESUMO

Fibroblast growth factor 10 (FGF10) plays important roles in vertebrate limb development, lung branching morphogenesis, and epidermis regeneration. The receptor (FGFR2b) binding specificity is an essential element in regulating the diverse functions of FGF10. Analyzing the FGF10:FGFR2b complex we found that Thr-114 in beta4 of FGF10 could form specific interactions with D3 of FGFR2b. To investigate the role of Thr-114 played on functions of FGF10, two mutants of FGF10 were constructed, named TA (Thr-114-->Ala) and TR (Thr-114-->Arg), respectively. The biological activity assays showed that the receptor-binding affinity, the stimulating growth effect on rat tracheal epithelium (RTE) cells, and the inducing ability in receptor phosphorylation of both mutants were decreased, which were consistent with the interaction analysis of the TA:FGFR2b and TR:FGFR2b complexes. These results suggested that Thr-114 is a crucial functional residue for FGF10, and mutating Thr-114 to Ala or Arg would lead to great decrease in receptor-binding affinity and biological activity of FGF10.


Assuntos
Análise Mutacional de DNA , Fator 10 de Crescimento de Fibroblastos , Conformação Proteica , Treonina/metabolismo , Animais , Fator 10 de Crescimento de Fibroblastos/química , Fator 10 de Crescimento de Fibroblastos/genética , Fator 10 de Crescimento de Fibroblastos/metabolismo , Humanos , Camundongos , Modelos Moleculares , Células NIH 3T3 , Mutação Puntual , Ratos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/química , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Treonina/genética
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 17(3): 670-3, 2009 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-19549385

RESUMO

This study was aimed to explore the influence of staphylokinase derivative (SAKD) on the hemoagglutinative and fibrinolytic systems, and to determine the safety of the staphylokinase derivative in application. The normal and model rats each 30 were divided into normal saline, SAKD and rSAK groups. The hemorrhage, bleeding time (BT), blood platelet count (BPC), activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (Fg), D-dimer (D-D), plasminogen (PLG) and plasmin inhibitor activity (PI) were detected before and after the administration with staphylokinase derivative 0.5 mg/kg body weight, once three days for consecutive 15 days. The results indicated that one case of normal rats with SAKD and two cases of high fat diet model group had mild hemorrhage, all of which showed automatic hemostasis; and 3 cases in rSAK group had mild hemorrhage. And the platelet counting, D-D, PLG and PI in all groups did not significantly change. The rats of high fat diet group treated with SAKD showed the significant extension of APTT, PT and TT times, and the decrease of Fg time (p < 0.05). All the experimental results demonstrated that the influence of SAKD on the hemagglutination of the normal animals was lower, however, which can improve the high-hemagglutination status of the rats with high fat diet. It is concluded that the SAKD at the dosage of this study has the higher safety, which can alleviate the high hemagglutination symptoms of the rats with high fat diet.


Assuntos
Fibrinólise/efeitos dos fármacos , Fibrinolíticos/efeitos adversos , Hemaglutinação/efeitos dos fármacos , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/farmacologia , Terapia Trombolítica , Animais , Gorduras na Dieta , Produtos de Degradação da Fibrina e do Fibrinogênio , Fibrinolíticos/farmacologia , Hemostasia , Masculino , Metaloendopeptidases/farmacologia , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Tempo de Protrombina , Ratos , Ratos Wistar , Tempo de Trombina
19.
Zhonghua Yi Xue Za Zhi ; 88(34): 2432-6, 2008 Sep 09.
Artigo em Chinês | MEDLINE | ID: mdl-19087723

RESUMO

OBJECTIVE: To study the effects of interleukin 1 receptor antagonist (IL-Ira) on allergy asthma and its mechanism. METHODS: Thirty female SD rats underwent intraperitoneal and hypodermic injection of ovalbumin (OVA) on days 1 and 14, and then underwent spraying of OVA aerosol since day 21 for 7 days so as to provoke asthma, and then the rats were randomly divided into 3 equal groups: asthma model group, low dose IL-1ra treatment group undergoing intravenous injection of IL-1ra 6 mg/kg before each provocation (low dose treatment group), and high dose IL-1ra treatment group undergoing intravenous injection of IL-1ra 30 mg/kg before each provocation (high dose treatment group). Another 10 rats were used as normal controls. Twenty-four hours after the last provocation physiological monitoring equipment was used to detect the pulmonary function. Then the rats were killed. Bronchoalveolar lavage fluid (BALF) was collected. ELISA was used to detect the serum IgE content. The ratio of inflammatory cells from the BALF was calculated. Microscopy was conducted to observe the histopathology of lung. RT-PCR was used to examine the mRNA expression of NF-kappaB and signal transducer and activator of the transcription 6 (STAT6). RESULTS: The respiratory rate, expiratory flow, percentage of eosinophils in BALF inflammatory cells, peripheral blood IgE concentration, mRNA expression of STAT6 and NF-kappaB of the asthma group were (206 +/- 11) times/min, (77 +/- 8) microl/s, 24.8% +/- 1.3%, (72.5 +/- 8.1) ng/ml, 0.294 +/- 0.048, and 0.686 +/- 0.052 respectively, all significantly higher than those of the low dose treatment group [(183 +/- 9) times/min, (64 +/- 5) microl/s, 18.5% +/- 3.1%, (63.4 +/- 4.8) ng/ml, 0.229 +/- 0.038, and 0.613 +/- 0.062 respectively, all P < 0.05] and those of the high dose treatment group [(181 +/- 11) times/min, (57 +/- 4) microl/s, 14.7% +/- 2.1%, (41.4 +/- 7.4) ng/ml, 0.194 +/- 0.076, and 0.352 +/- 0.267, all P < 0.05]. The therapeutic effect of high dose treatment group is superior to that of low dose treatment group (P < 0.05). CONCLUSION: IL-1ra is significantly effective in treatment of allergic asthma, and its potential mechanism is through regulating both STAT6 mRNA and NF-kappaB mRNA expression simultaneously.


Assuntos
Asma/tratamento farmacológico , Asma/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Animais , Asma/etiologia , Modelos Animais de Doenças , Feminino , Hipersensibilidade/complicações , NF-kappa B/biossíntese , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT6/biossíntese
20.
Fen Zi Xi Bao Sheng Wu Xue Bao ; 41(4): 309-16, 2008 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-18959005

RESUMO

The cDNA of IgE constant domain of rat was cloned from the spleen of allergy asthma rat by RT-PCR. The IL-1ra segment was obtained from intermediate vector pBV220-IL-1ra. By overlap extension PCR, the fusion gene IL-1ra-Fcepsilon was cloned, then inserted into the eukaryotic expression plasmid pIRES2-EGFP to obtain a recombinant expression plasmid pIRES2-EGFP-IL-1ra-Fcepsilon. The recombinant expression plasmid was transfected into 293T cells using lipofectamin and instillated into the rat lung through trachea. The expression of IL-1ra-Fcepsilon was identified by Western blot, RT-PCR, and this protein could inhibit the activity of IL-1 in vitro. Green fluorescent protein could be detected in the transfected 293T cells and the rat lungs at different times. The research paved the way for the gene therapy of allergy asthma.


Assuntos
Vetores Genéticos/genética , Proteínas de Fluorescência Verde/genética , Fragmentos Fab das Imunoglobulinas/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Plasmídeos/genética , Proteínas Recombinantes de Fusão/genética , Animais , Linhagem Celular , Feminino , Humanos , Imunoglobulina E/química , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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