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1.
Molecules ; 29(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38338425

RESUMO

Organophosphorus flame retardants (OPFRs) have been widely used in polymeric materials owing to their flame retardant and plasticizing effects. Investigating the fragmentation pathway of OPFRs is of great necessity for further discovering and identifying novel pollutants using orbitrap-based high-resolution mass spectrometry (HRMS). A total of 25 OPFRs, including alkyl, halogenated, and aromatic types, were analyzed in this study. The fragmentation pathways of the OPFRs were investigated using orbitrap-based HRMS with high-energy collision dissociation (HCD) in positive mode. The major fragmentation pathways for the three types of OPFRs are greatly affected by the substituents. In detail, the alkyl and halogenated OPFRs underwent three McLafferty hydrogen rearrangements, wherein the substituents were gradually cleaved to form the structurally stable [H4PO4]+ (m/z = 98.9845) ions. In contrast, the aromatic OPFRs would cleave not only the C-O bond but also the P-O bond, depending on the substituents, to form fragment ions such as [C6H7O]+ (m/z = 95.0495) or [C7H7]+ (m/z = 91.0530), among others. Using HRMS improved the accuracy of fragment ion identification, and the pathway became more evident. These fragmentation laws can provide identification information in pollutant screening work and theoretical references for the structural characterization of compounds with diverse substituent structures.

2.
Molecules ; 29(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731466

RESUMO

Tripropyl phosphate (TnPP) is a commonly used organic phosphate flame retardant in the textiles, plastics, and coating industries. Residues are commonly detected in samples from the environment and food. The availability of certified reference materials (CRMs) is essential to ensure the accuracy and traceability of detection results. In this study, a comprehensive characterization of a CRM for TnPP was carried out, and its purity was evaluated using two distinct methodologies: mass balance (MB) and quantitative nuclear magnetic resonance spectroscopy (qNMR). In the MB method, the levels of structurally related organic impurities are 1.37 mg/g. The water content was determined to be 3.16 mg/g, while inorganic impurities were found to be 0.87 mg/g, and no residual organic solvents were detected. Benzoic acid and monocrotophos were chosen as internal standards for 1H-qNMR and 31P-qNMR, respectively. The purity of the TnPP CRM was assessed as 994.6 mg/g, 994.1 mg/g, and 993.5 mg/g using MB, 1H-qNMR, and 31P-qNMR techniques, respectively. The verified purity of the TnPP CRM was ultimately determined to be 994.1 mg/g, with an expanded uncertainty of 3.4 mg/g (k = 2), ensuring traceability to the International System of Units (SI). This CRM can be effectively utilized for preparing calibration solutions suitable for the routine monitoring of TnPP residues in plastics and food samples.

3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 316-323, 2024 Jun.
Artigo em Zh | MEDLINE | ID: mdl-38953254

RESUMO

Objective To investigate the expression levels of selenoprotein genes in the patients with coronavirus disease 2019 (COVID-19) and the possible regulatory mechanisms.Methods The dataset GSE177477 was obtained from the Gene Expression Omnibus,consisting of a symptomatic group (n=11),an asymptomatic group (n=18),and a healthy control group (n=18).The dataset was preprocessed to screen the differentially expressed genes (DEG) related to COVID-19,and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analysis were performed for the DEGs.The protein-protein interaction network of DEGs was established,and multivariate Logistic regression was employed to analyze the effects of selenoprotein genes on the presence/absence of symptoms in the patients with COVID-19.Results Compared with the healthy control,the symptomatic COVID-19 patients presented up-regulated expression of GPX1,GPX4,GPX6,DIO2,TXNRD1,SELENOF,SELENOK,SELENOS,SELENOT,and SELENOW and down-regulated expression of TXNRD2 and SELENON (all P<0.05).The asymptomatic patients showcased up-regulated expression of GPX2,SELENOI,SELENOO,SELENOS,SELENOT,and SELENOW and down-regulated expression of SELP (all P<0.05).The results of multivariate Logistic regression analysis showed that the abnormally high expression of GPX1 (OR=0.067,95%CI=0.005-0.904,P=0.042) and SELENON (OR=56.663,95%CI=3.114-856.999,P=0.006) was the risk factor for symptomatic COVID-19,and the abnormally high expression of SELP was a risk factor for asymptomatic COVID-19 (OR=15.000,95%CI=2.537-88.701,P=0.003).Conclusions Selenoprotein genes with differential expression are involved in the regulation of COVID-19 development.The findings provide a new reference for the prevention and treatment of COVID-19.


Assuntos
COVID-19 , Selenoproteínas , Humanos , Selenoproteínas/genética , Selenoproteínas/metabolismo , COVID-19/genética , COVID-19/metabolismo , SARS-CoV-2 , Mapas de Interação de Proteínas/genética
4.
Anal Chem ; 95(42): 15673-15680, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37843007

RESUMO

A new method accompanied by a derived equation for accurate determination of trace water was developed by using quantitative 1H nuclear magnetic resonance (qNMR) spectroscopy. Given that the response for each chemically distinct moiety is uniformly proportional to the number of the corresponding resonant nuclei within the analyte, it is practicable to directly quantify the water content via its proton number using qNMR. In this study, three water standards with known water contents (e.g., 10.02, 1.006, and 0.103 mg/g), which were accurately determined by a well-established Coulometric Karl Fischer (CKF) titration method, were measured by using the developed qNMR method. An excellent agreement between the results from these two methods was obtained. Then, the water content of Sudan I was determined by high-field NMR (HF-NMR) spectroscopy, and the water contents of acetone and bioethanol were measured by low-field NMR (LF-NMR) spectroscopy. These results were compared with the water content measured by the CKF method to confirm the applicability of the established qNMR method. The developed method can eliminate the influences of environmental humidity and background water in the solvent; subsequently, the results calculated by the derived equation were comparable to the nominal values. Under the optimal conditions, the limit of quantitation of this method was as low as 6.7 µg. The recommended sample sizes for practical samples with various water contents (e.g., 10.02, 1.006, and 0.103 mg/g) were determined to be 5, 50, and 60 mg, respectively, which are much smaller than those required for the CKF method. The new method has a static and stable process without any side reactions, and the traceability to the SI unit can be directly achieved through the NMR internal standard. This method overcomes the limitations of the CKF method, especially for measuring methanol-insoluble substances.

6.
Acta Pharmacol Sin ; 44(10): 2048-2064, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37225848

RESUMO

Autoimmune hepatitis (AIH) is a progressive hepatitis syndrome characterized by high transaminase levels, interface hepatitis, hypergammaglobulinemia, and the presence of autoantibodies. Misdiagnosis or delayed treatment of AIH can lead to cirrhosis or liver failure, which poses a major risk to human health. ß-Arrestin2, a key scaffold protein for intracellular signaling pathways, has been found to be involved in many autoimmune diseases such as Sjogren's syndrome and rheumatoid arthritis. However, whether ß-arrestin2 plays a role in AIH remains unknown. In the present study, S-100-induced AIH was established in both wild-type mice and ß-arrestin2 knockout (Arrb2 KO) mice, and the experiments identified that liver ß-arrestin2 expression was gradually increased, and positively correlated to serum ANA, ALT and AST levels during AIH progression. Furthermore, ß-arrestin2 deficiency ameliorated hepatic pathological damage, decreased serum autoantibody and inflammatory cytokine levels. ß-arrestin2 deficiency also inhibited hepatocyte apoptosis and prevented the infiltration of monocyte-derived macrophages into the damaged liver. In vitro experiments revealed that ß-arrestin2 knockdown suppressed the migration and differentiation of THP-1 cells, whereas ß-arrestin2 overexpression promoted the migration of THP-1 cells, which was regulated by the activation of the ERK and p38 MAPK pathways. In addition, ß-arrestin2 deficiency attenuated TNF-α-induced primary hepatocyte apoptosis by activating the Akt/GSK-3ß pathway. These results suggest that ß-arrestin2 deficiency ameliorates AIH by inhibiting the migration and differentiation of monocytes, decreasing the infiltration of monocyte-derived macrophages into the liver, thereby reducing inflammatory cytokines-induced hepatocytes apoptosis. Therefore, ß-arrestin2 may act as an effective therapeutic target for AIH.


Assuntos
Hepatite Autoimune , Hepatopatias , beta-Arrestina 2 , Animais , Camundongos , Apoptose , Autoanticorpos/metabolismo , beta-Arrestina 2/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Hepatócitos/metabolismo , Fígado/metabolismo , Hepatopatias/metabolismo , Macrófagos/metabolismo , Proteínas S100/metabolismo
7.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(4): 563-570, 2023 Aug.
Artigo em Zh | MEDLINE | ID: mdl-37654136

RESUMO

Objective To study the expression of selenoprotein genes in human immunodeficiency virus(HIV)infection and its mother-to-child transmission,so as to provide a theoretical basis for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.Methods The dataset GSE4124 was downloaded from the Gene Expression Omnibus(GEO).Two groups of HIV-positive mothers(n=25)and HIV-negative mothers(n=20)were designed.HIV-positive mothers included a subset of transmitter(TR)mothers(n=11)and non-transmitter(NTR)mothers(n=14).Then,t-test was carried out to compare the expression levels of selenoprotein genes between the four groups(HIV-positive vs. HIV-negative,NTR vs. HIV-negative,TR vs. HIV-negative,TR vs. NTR).Univariate and multivariate Logistic regression were adopted to analyze the effects of differentially expressed genes on HIV infection and mother-to-child transmission.R software was used to establish a nomogram prediction model and evaluate the model performance.Results Compared with the HIV-negative group,HIV-positive,NTR,and TR groups had 8,5 and 8 down-regulated selenoprotein genes,respectively.Compared with the NTR group,the TR group had 4 down-regulated selenoprotein genes.Univariate Logistic regression analysis showed that abnormally high expression of GPX1,GPX3,GPX4,TXNRD1,TXNRD3,and SEPHS2 affected HIV infection and had no effect on mother-to-child transmission.The multivariate Logistic regression analysis showed that the abnormally high expression of TXNRD3(OR=0.032,95%CI=0.002-0.607,P=0.022)was positively correlated with HIV infection.As for the nomogram prediction model,the area under the receiver-operating characteristic curve for 1-year survival of HIV-infected patients was 0.840(95%CI=0.690-1.000),and that for 3-year survival of HIV-infected patients was 0.870(95%CI=0.730-1.000).Conclusions Multiple selenoprotein genes with down-regulated expression levels were involved in the regulation of HIV infection and mother-to-child transmission.The abnormal high expression of TXNRD3 was positively correlated with HIV infection.The findings provide new ideas for the prevention,diagnosis,and treatment of acquired immunodeficiency syndrome.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Humanos , Feminino , Transmissão Vertical de Doenças Infecciosas , Nomogramas , Selenoproteínas/genética
8.
Anal Bioanal Chem ; 414(12): 3631-3641, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35305116

RESUMO

In this study, a trans-zearalenone (trans-ZEN) calibrant in acetonitrile as certified reference material (CRM) was prepared and intensively investigated the stability by high performance liquid chromatography coupled diode array detection and triple quadrupole tandem mass spectrometry (HPLC-DAD-MS/MS). The photoisomerization and degradation of main component and related impurities in trans-ZEN calibrant CRM was studied in detail under different light conditions such as UV light (254 nm), sunlight, and visible light. Trans-ZEN in acetonitrile was confirmed a significant shift toward cis-ZEN up to a 52% cis-isomerization rate after exposing to UV light (254 nm) in transparent ampule for 1 day. The unsaturated double bond photosensitive groups of trans-ZEN and cis-ZEN will further undergo photoreaction to generate more isomers and related products with the increase of UV irradiation time. The calibrant in amber ampules was relatively stable after exposing to sunlight for 28 days, with only 0.35% cis-isomer observed. The results indicated that trans-ZEN solution calibrant should be packed in amber ampules to avoid UV rays. Thermal stability test exhibited this calibrant was stable over 6 weeks even at 60 °C. Trans-ZEN was found to be more stable in acetonitrile than in methanol since an unknown impurity was observed in methanol after 6 weeks placed at 25 °C. The stability study of trans-ZEN calibrant provided a basis for the usage, storage, and transportation of the CRM. A concentration and expanded uncertainty of the trans-ZEN calibrant CRM of 11.01 ± 0.18 µg/mL was developed.


Assuntos
Zearalenona , Âmbar , Cromatografia Líquida de Alta Pressão/métodos , Metanol , Espectrometria de Massas em Tandem/métodos , Zearalenona/análise
9.
Eur J Nutr ; 61(7): 3487-3497, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35596007

RESUMO

PURPOSE: Previous studies have indicated that dietary consumption of calcium (Ca), magnesium (Mg), and the Ca-to-Mg (Ca:Mg) ratio were associated with different health outcomes. However, no study has evaluated the association of pre-diagnostic Ca, Mg, and Ca:Mg ratio consumption with ovarian cancer (OC) survival. METHODS: The aforementioned associations were investigated in a cohort of 853 Chinese women diagnosed with OC between 2015 and 2020. A validated food frequency questionnaire was used to evaluate pre-diagnostic diet information. Deaths were recorded until March 31, 2021 via medical records and active follow-up. Cox proportional hazards model was applied to calculate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 130 deaths were observed during a median follow-up of 37.2 months. After adjustment for potential confounders, pre-diagnostic Ca (HR< 600 vs. > 1000 = 1.45, 95% CI = 0.47-4.46, p for trend = 0.69) and Mg (HR< 250 vs. > 330 = 0.90, 95% CI = 0.39-2.08, p for trend = 0.77) intakes were found to be unrelated to OC survival, whereas a higher Ca:Mg intake ratio was significantly associated with worse survival (HR< 1.7 vs. > 2.5 = 2.72, 95% CI = 1.28-5.78, p for trend < 0.05). A significant result was also observed when treating the Ca:Mg ratio as a continuous variable (HR = 1.69, 95% CI = 1.12-2.55) for one-unit increment. CONCLUSION: Pre-diagnostic consumption of Ca and Mg was unrelated to OC survival, while a higher Ca:Mg intake ratio was strongly associated with worse survival among OC patients.


Assuntos
Magnésio , Neoplasias Ovarianas , Cálcio , Cálcio da Dieta , Dieta , Feminino , Seguimentos , Humanos , Modelos de Riscos Proporcionais , Fatores de Risco
10.
Acta Pharmacol Sin ; 42(7): 1090-1100, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33116250

RESUMO

Hepatic fibrosis is a disease characterized by excessive deposition of extracellular matrix (ECM) in the liver. Activation of hepatic stellate cells (HSCs) is responsible for most of ECM production. Oxidative stress and reactive oxygen species (ROS) may be important factors leading to liver fibrosis. NADPH oxidase 4 (NOX4) is the main source of ROS in hepatic fibrosis, but the mechanism by which NOX4 regulates oxidative stress is not fully understood. ß-Arrestin2 is a multifunctional scaffold protein that regulates receptor endocytosis, signaling and trafficking. In this study, we investigated whether ß-arrestin2 regulated oxidative stress in hepatic fibrosis. Both ß-arrestin2 knockout (Arrb2 KO) mice and wild-type mice were intraperitoneally injected with carbon tetrachloride (CCl4) to induce hepatic fibrosis. Arrb2 KO mice showed significantly attenuated liver fibrosis, decreased ROS levels and NOX4 expression, and reduced collagen levels in their livers. In vitro, NOX4 knockdown significantly inhibited ROS production, and decreased expression of alpha-smooth muscle actin in angiotensin II-stimulated human HSC cell line LX-2. Through overexpression or depletion of ß-arrestin2 in LX-2 cells, we revealed that decreased ß-arrestin2 inhibited ROS levels and NOX4 expression, and reduced collagen production; it also inhibited activation of ERK and JNK signaling pathways. These results demonstrate that ß-arrestin2 deficiency protects against liver fibrosis by downregulating ROS production through NOX4. This effect appears to be mediated by ERK and JNK signaling pathways. Thus, targeted inhibition of ß-arrestin2 might reduce oxidative stress and inhibit the progression of liver fibrosis.


Assuntos
Cirrose Hepática/metabolismo , NADPH Oxidase 4/metabolismo , Estresse Oxidativo/fisiologia , beta-Arrestina 2/deficiência , Animais , Tetracloreto de Carbono , Colágeno/metabolismo , Regulação para Baixo/fisiologia , Técnicas de Inativação de Genes , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Metaloproteinase 13 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/fisiologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , beta-Arrestina 2/genética
11.
J Fish Biol ; 99(5): 1746-1751, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34270090

RESUMO

Fish eggs of the ovate sole Solea ovata and black porgy Acanthopagrus schlegelii were identified through DNA barcoding of cytochrome c oxidase subunit I (COX1). Visual taxonomic features were achieved, and photographs of the eggs of both species at different developmental stages were reported for the first time. In addition, the dissolution of oil globules caused by ethanol as egg fixatives was observed. This result showed the importance of using formalin as egg fixatives in the case of morphometric analysis and the necessity of combining molecular and visual taxonomic method for morphological study.


Assuntos
Linguados , Perciformes , Animais , Perciformes/genética
12.
J Cell Biochem ; 121(2): 1409-1419, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31502352

RESUMO

DNA methylation markers in the peripheral blood are able to be applied to treat epithelial cancer. Nevertheless, the diagnostic potential value of it for ovarian cancer (OV) has not been studied. The study aimed to explore the difference of DNA methylation in peripheral blood between OV patients and healthy women. Firstly, the whole blood of DNA methylation data was provided by the Gene Expression Omnibus (GEO) database. The linear model was applied to the identification of significantly differentially expressed methylated CpG sites (differentially methylation sites [DMP]), and the further screen of co-expression CpG sites (Co-DMP). A total of 2812 DMPs were identified, and weighted gene co-expression network analysis helped to obtain seven co-expression modules. Among them, the yellow module was the most related to OV. Co-DMPs (167) in the yellow module were mainly distributed near the transcription start sites. However, most of them were not in the CpG island. Least absolute shrinkage and selection operator (LASSO) regression analysis was applied to the identification of stable OV-related blood biomarkers that six Co-DMPs (cg00134539, cg00226923, cg25268718, cg25697314, cg25839227, cg26574610) with the highest frequency were found as potential biomarkers. Finally, the diagnostic classifier was established using the support vector machine (SVM) with the accuracy rate of 87.1% and 74.5% in training data set and validation data set, respectively. To sum up, a new feature was provided here for the diagnosis of OV, which is helpful for the diagnosis and individualized treatments of early OV.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Ilhas de CpG , Metilação de DNA , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Ovarianas/diagnóstico , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/genética , Prognóstico
13.
Int J Cancer ; 147(8): 2121-2130, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32285933

RESUMO

Epidemiological studies have investigated the relationship between infertility and the risk of ovarian cancer (OC); however, the results have been inconsistent. We therefore conducted the first meta-analysis to update and quantify the aforementioned association based on prospective cohort studies. Studies were identified by searching PubMed, EMBASE and Web of Science databases up to January 8, 2020. We extracted data from the studies and performed quality assessments. Summary relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Publication bias, and subgroup, meta-regression and sensitivity analyses were also conducted. Nine prospective cohort studies with a total of 10 383 OC cases and 6 278 830 participants were included in the present study. The summary RR of the association between infertility and the risk of OC was 1.51 (95% CI: 1.35-1.69), with low heterogeneity. Positive associations were observed in most subgroup analyses stratified by predefined factors, including region, duration of follow-up, study quality, causes of infertility, invasiveness of OC, infertility treatment status and adjustment of potential confounding parameters. No significant publication bias was detected. Our findings suggest that infertility in women were associated with an increased risk of OC.


Assuntos
Infertilidade/complicações , Neoplasias Ovarianas/etiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Infertilidade/patologia , Neoplasias Ovarianas/patologia , Ovário/patologia , Estudos Prospectivos , Fatores de Risco
14.
Biochem Biophys Res Commun ; 522(2): 485-491, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-31780259

RESUMO

Acute liver injury can be caused by oxidative stress within a short period and is a common pathway to many liver diseases. The liver is vulnerable to reactive oxygen species (ROS) and free radical-mediated disorders. ß-arrestin2 was initially discovered to be a negative regulator of G protein-coupled receptor signaling. Recently, ß-arrestin2 has been found to act as a multifunctional adaptor protein and play new roles in regulating intracellular signaling networks. However, the role of ß-arrestin2 in the pathogenesis of acute liver injury is unclear. In this study, we hypothesize that ß-arrestin2 regulates acute liver injury via modulation of oxidative stress. ß-arrestin2 knockout mice were used to investigate the impacts of ß-arrestin2 on carbon tetrachloride (CCl4)-induced acute liver injury and oxidative stress. Results here suggested that ß-arrestin2 deficiency decreased serum activities of aminotransferase and alleviated liver injury induced by CCl4 injection as compared with wildtype mice. ß-arrestin2 knockout mice exhibited stronger tolerance in oxidative stress compared with wild-type mice, which was demonstrated by decreased ROS level and increased superoxide dismutase (SOD) and glutathione (GSH) in the liver. Furthermore, ß-arrestin2 deficiency significantly inhibited NOX4 (a major source of ROS) expression and the activation of the extracellular regulated kinase (ERK) and, c-Jun NH2-terminal kinase (JNK) pathways. These results suggest that ß-arrestin2 deficiency protects against CCl4-induced acute liver injury through attenuating oxidative damage and decreased ERK and JNK phosphorylation.


Assuntos
Fígado/lesões , Fígado/metabolismo , Substâncias Protetoras/metabolismo , beta-Arrestina 2/metabolismo , Animais , Antioxidantes/metabolismo , Tetracloreto de Carbono , Deleção de Genes , Glutationa/metabolismo , Fígado/patologia , Fígado/fisiopatologia , Sistema de Sinalização das MAP Quinases , Malondialdeído/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , NADPH Oxidase 4/metabolismo , Especificidade de Órgãos , Oxirredução , Espécies Reativas de Oxigênio/metabolismo
15.
Wei Sheng Yan Jiu ; 49(4): 580-584, 2020 Jul.
Artigo em Zh | MEDLINE | ID: mdl-32928348

RESUMO

OBJECTIVE: To observe the changes of neuropeptide Y(NPY) expression in perirenal adipose tissue and its relationship with insulin resistance in the nutritional transition models of refeeding after calorie restriction. METHODS: SPF Male SD rats, aged 8 weeks, were randomly divided into normal chow group and refeeding with normal chow after calorie restriction for 4 weeks group. NPY gene expression in perirenal adipose tissue were detected by real-time quantitative PCR at the end of 4 and 12 weeks, along with fasting plasma glucose, fasting serum lisulin, free fatty acids and average glucose infusion rate(GIR_(60-120)) of hyperinsulinemic-euglycemic clamp test for 60-120 minutes. NPY gene mRNA expression in perirenal adipose tissue was detected by real-time quantitative PCR. And the relationship between NPY gene expression and insulin resistance was detected by Spearman correlation analysis. RESULTS: The expression level of NPY gene in perirenal adipose tissue in caloric restriction for 4 weeks group was significantly increased by calorie restriction(P<0. 01). After refeeding, the expression level of NPY gene in refeeding with normal group was still slightly increased, which was significantly higher than that in normal group at the end of the experiment(P<0. 01). The levels of fasting plasma glucose and fasting insulin in caloric restriction for 4 weeks group decreased slightly, GIR_(60-120) increased slightly, but there were no statistical differences compared with normal group(P>0. 05), but free fatty acid levels increased significantly(P<0. 01). After refeeding, the levels of fasting insulin, free fatty acid in refeeding with normal group increased significantly, GIR_(60-120) decreased evidently(P<0. 01), but the changes of fasting blood glucose were not obvious. The result of stepwise regression showed that the expression level of NPY gene in perirenal adipose tissue was closely related to GIR_(60-120) and fasting insulin, with R values of-0. 816 and 0. 789 respectively(R~2=0. 892, P<0. 01). The result of correlation analysis showed that in the 4-week group, the mRNA expression level of NPY gene in perirenal adipose tissue was closely related to GIR_( 60-120)、fasting insulin and free fatty acid, with R values of-0. 765, 0. 716 and 0. 657 respectively(P<0. 01). In the 12 week group, the mRNA expression level of NPY gene in perirenal adipose tissue was closely related to GIR_(60-120), fasting insulin and free fatty acid, with R values of-0. 853, 0. 622 and 0. 608 respectively(P<0. 01). CONCLUSION: The mRNA expression of NPY gene in perirenal adipose tissue was closely related to indicators of insulin resistance. It is an important factor affecting insulin sensitivity.


Assuntos
Resistência à Insulina , Tecido Adiposo , Animais , Insulina , Masculino , Neuropeptídeo Y , Ratos , Ratos Sprague-Dawley
16.
J Cell Physiol ; 234(8): 12604-12614, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30306574

RESUMO

BACKGROUND: DL-3-n-butylphthalide (NBP) has been approved to be effective in improving cognitive deficits. The aim of the current study was to determine whether NBP protects against cognitive deficits in a rat model of vascular dementia (VD) induced by chronic cerebral hypoperfusion (CCH) by regulating the sonic hedgehog (Shh)/patched1 (Ptch1) pathway and endoplasmic reticulum stress (ERS)-related markers. METHODS: Adult male Sprague-Dawley rats were subjected to permanent bilateral occlusion of the common carotid arteries (2VO) to established the model of VD. These rats were randomly divided into five groups: sham, model, NBP30 (30 mg/kg), NBP 60 (60 mg/kg), and NBP 120 (120 mg/kg) groups. The Morris water maze test was used to assess for cognitive function at 4 weeks after operation. RESULTS: NBP significantly alleviated spatial learning and memory impairment, and inhibited the loss of neurons in the CA1 region of the hippocampus. Western blot analysis and real-time quantitative polymerase chain reaction analysis revealed that plasticity-related synaptic markers and the Shh/Ptch1 pathway significantly increased in the NBP treated groups, while ERS-related markers decreased. CONCLUSION: The results of the current study prove that the Shh/Ptch1 pathway plays an essential role in the model of VD. NBP had protective effects on cognitive impairment induced by CCH. This mechanism was associated with ERS and the Shh/Ptch1 pathway. Meanwhile, the Shh/Ptch1 pathway and ERS may interact with each other.


Assuntos
Benzofuranos/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Receptor Patched-1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Cognição/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
17.
Behav Pharmacol ; 29(4): 306-315, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29035920

RESUMO

Sinomenine is a bioactive alkaloid extracted from Sinomenium acutum. Here, we investigated the antidepressant effects of sinomenine in mice. The antidepressant actions of sinomenine were first examined in the forced-swim test and the tail-suspension test, and then assessed in the chronic social defeat stress (CSDS) model of depression. Changes in the brain-derived neurotrophic factor (BDNF) signaling pathway after CSDS and sinomenine treatment were also investigated. A tryptophan hydroxylase inhibitor and a BDNF signaling inhibitor were also used to determine the pharmacological mechanisms of sinomenine. It was found that sinomenine induced antidepressant-like effects in the forced-swim test and tail-suspension test without affecting the locomotor activity of mice. Sinomenine also prevented the CSDS-induced depressive-like symptoms. Moreover, sinomenine fully restored the CSDS-induced decrease in the hippocampal BDNF signaling pathway, whereas a BDNF signaling inhibitor, but not a tryptophan hydroxylase inhibitor, blocked the antidepressant effects of sinomenine. In conclusion, sinomenine exerts antidepressant effects in mice by promoting the hippocampal BDNF signaling pathway.


Assuntos
Depressão/tratamento farmacológico , Morfinanos/farmacologia , Animais , Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtorno Depressivo/tratamento farmacológico , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Morfinanos/metabolismo , Neurogênese/efeitos dos fármacos , Serotonina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/tratamento farmacológico
18.
Int J Clin Oncol ; 23(6): 1160-1166, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30078140

RESUMO

BACKGROUND: This study aimed to explore the potential risk factors of platinum allergy and follow-up treatment to provide a reference for the clinical prevention and treatment of platinum allergic reactions in patients with gynecological tumors. METHODS: The study retrospectively analyzed 45 cases of platinum allergic reactions that occurred in Shengjing Hospital affiliated to China Medical University from August 2010 to July 2016. Analysis of risk factors included the cumulative dose, treatment course and time intervals. RESULTS: The cumulative carboplatin dose in allergic patients ranged from 900 to 10250 mg (average 4845 mg). The 45 allergic reactions occurred between the 3rd and 25th course of treatment (average 11.4 courses). The average re-treatment interval of carboplatin-allergic patients was 28.1 months, including 93.3% of patients with platinum re-treatment interval of more than 1 year. The allergic reaction occurred in the 2nd or 3rd course of re-treatment in 26 patients, accounting for 70.3% of all patients with recurrence. Seventeen patients were subjected to desensitization therapy, among which 13 cases were well tolerated. CONCLUSIONS: Patients who received more than 8 courses of carboplatin or a cumulative dose of more than 3500 mg were the high-risk population for platinum allergy. The 2nd and 3rd treatment course after restarting carboplatin treatment after an interval time of more than 1 year was the high incident period of carboplatin allergy. Skin tests should be conducted in patients with high risk of carboplatin allergy. In cases of carboplatin allergy, patients could receive carboplatin or oxaliplatin desensitization therapy.


Assuntos
Dessensibilização Imunológica , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/prevenção & controle , Neoplasias dos Genitais Femininos/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Platina/efeitos adversos , Adulto , Idoso , China , Hipersensibilidade a Drogas/diagnóstico , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Fatores de Risco , Testes Cutâneos
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(7): 1879-84, 2015 Jul.
Artigo em Zh | MEDLINE | ID: mdl-26717744

RESUMO

A rapid discrimination method of edible oils, KL-BP model, was proposed by attenuated total reflectance infrared spectroscopy. The model extracts the characteristic of classification from source data by KL and reduces data dimension at the same time. Then the neural network model is constructed by the new data which as the input of the model. 84 edible oil samples which include sesame oil, corn oil, canola oil, blend oil, sunflower oil, peanut oil, olive oil, soybean oil and tea seed oil, were collected and their infrared spectra determined using an ATR FT-IR spectrometer. In order to compare the method performance, principal component analysis (PCA) direct-classification model, KL direct-classification model, PLS-DA model, PCA-BP model and KL-BP model are constructed in this paper. The results show that the recognition rates of PCA, PCA-BP, KL, PLS-DA and KL-BP are 59.1%, 68.2%, 77.3%, 77.3% and 90.9% for discriminating the 9 kinds of edible oils, respectively. KL extracts the eigenvector which make the distance between different class and distance of every class ratio is the largest. So the method can get much more classify information than PCA. BP neural network can effectively enhance the classification ability and accuracy. Taking full of the advantages of KL in extracting more category information in dimension reducing and the features of BP neural network in self-learning, adaptive, nonlinear, the KL-BP method has the best classification ability and recognition accuracy and great importance for rapidly recognizing edible oil in practice.


Assuntos
Óleos de Plantas/análise , Modelos Teóricos , Redes Neurais de Computação , Óleos de Plantas/classificação , Análise de Componente Principal , Espectrofotometria Infravermelho
20.
Tumour Biol ; 35(5): 5013-9, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24488668

RESUMO

Polyamidoamine dendrimer (PAMAM) is a new nanometer material, which can transfer the target genes to cells with high efficiency and lower toxicity. This study aims to evaluate antitumor effects of survivin antisense oligonucleotide (survivin-asODN) (carried by polyamidoamine dendrimer liposome) on hepatic cancer in nude mice. Hepatic cancer model was established by injecting SMMC-7721 cells subcutaneously into flanks of nude mice. Polyamidoamine dendrimer and liposome were mixed with survivin-asODN, respectively. The shape and size of complex were observed by transmission electron microscope, and zeta potential was measured by an analytical tool. Encapsulation efficiency and DNA loading level were determined by an ultraviolet spectrophotometer in centrifuging method. Expression of survivin in transplant tumor was measured by Western blotting. No significant difference appeared for diameter and envelopment ratio between PAMAM liposome-survivin-asODN and PAMAM-survivin-asODN (P > 0.05). Both zeta potential and transfection efficiency in PAMAM liposome-survivin-asODN were higher than that in PAMAM-survivin-asODN complex (P < 0.05). Expression of survivin protein and weight of tumors in transplanted tumors in PAMAM liposome-survivin-asODN group was less than that in PAMAM-survivin-asODN group (P < 0.05). Cell apoptosis rate in PAMAM liposome-survivin-asODN group was higher than that of PAMAM-survivin-asODN group (P < 0.05). In conclusion, polyamidoamine dendrimer liposome can deliver survivin-asODN into hepatic transplanted tumor cells effectively. Ployamidoamine dendrimer liposome-mediated survivin-asODN can inhibit hepatic cell proliferation by inducing apoptosis.


Assuntos
Apoptose , Dendrímeros/administração & dosagem , Terapia Genética , Proteínas Inibidoras de Apoptose/genética , Neoplasias Hepáticas/terapia , Oligonucleotídeos Antissenso/genética , Poliaminas/administração & dosagem , Animais , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Lipossomos , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Survivina
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