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1.
Front Pharmacol ; 12: 739749, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744722

RESUMO

Objective: The aim of the present study is to explore the combination of dexmedetomidine (DXM) and tramadol (TMD) on sedative effect in patients with pregnancy-induced hypertension (PIH). Methods: A total of 356 patients with pregnancy-induced hypertension (PIH) were randomly divided into three groups: DXM, TMD and DXM + TMD groups. These patients were treated with different doses of DXM, TMD or combination of DXM and TMD by a patient-controlled intravenous injection device. The scores of static pain and dynamic pain, sedation degree, and adverse reaction were recorded. The plasma levels of inflammatory mediators IL-10 and C-reactive protein (CRP), and the serum level of p-p38-MAPK were evaluated. Results: It was found that administration with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg result in stronger sedative effect than single administration with DXM or TMD. The mean arterial pressure (MAP) and heart rate (HR) of patients with PIH were decreased with the combinational treatment of DXM and TMD. Interestingly, the PIH patients injected with DXM 1.0 µg/kg/h + TMD 700 mg and DXM 2.0 µg/kg/h + TMD 600 mg showed stronger sedative effect. In addition, the plasma level of level of IL-10 was increased and CRP decreased. The serum level of p-p38/MAPK was decreased. Conclusion: Taken together, our study indicates that combination of DXM and TMD effectively lowers blood pressure and reduces inflammation through increasing the level of IL-10, reducing CRP and inhibiting p-p38/MAPK in patients with PIH. This study suggests that the combination of DXM and TMD could be an anesthetic choice in the management of PIH.

2.
J Epidemiol Community Health ; 75(9): 836-842, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33632722

RESUMO

BACKGROUND: The COVID-19 has had an enormous impact worldwide and is still spreading. Globally confirmed infections have surpassed 41.1 million, of which more than 1 million resulted in deaths. Considering the relationship between public health disasters and emotional disorders, it is essential to examine psychological well-being related to this pandemic. METHOD: We performed a systematic search on psychological problems from PubMed to 10 October 2020, and conducted a meta-analysis using Comprehensive Meta-Analysis V.3 software. RESULTS: The results showed a 19.4% and 26.8% pooled incidence for depression and post-traumatic stress disorder (PTSD), respectively, during the SARS and Middle East Respiratory Syndrome (MERS)-related coronavirus outbreaks. However, overall prevalence of depression was somewhat higher at 27.0% during the COVID-19 period. The pooled incidence of PTSD during COVID-19 compared with SARS and MERS outbreaks, was lower, at 16.4%. CONCLUSION: The results suggest that there are shared and distinct psychological responses following SARS, MERS and COVID-19, and show pessimistic estimates of a wide range of potentially upcoming psychological problems.


Assuntos
COVID-19 , Surtos de Doenças , Transtornos Mentais , COVID-19/epidemiologia , COVID-19/psicologia , Humanos , Incidência , Transtornos Mentais/epidemiologia
3.
Schizophr Bull ; 47(3): 615-623, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33159208

RESUMO

Exosomes have been suggested as promising targets for the diagnosis and treatment of neurological diseases, including schizophrenia (SCZ), but the potential role of exosome-derived metabolites in these diseases was rarely studied. Using ultra-performance liquid chromatography-tandem mass spectrometry, we performed the first metabolomic study of serum-derived exosomes from patients with SCZ. Our sample comprised 385 patients and 332 healthy controls recruited from 3 clinical centers and 4 independent cohorts. We identified 25 perturbed metabolites in patients that can be used to classify samples from patients and control participants with 95.7% accuracy (95% CI: 92.6%-98.9%) in the training samples (78 patients and 66 controls). These metabolites also showed good to excellent performance in differentiating between patients and controls in the 3 test sets of participants, with accuracies 91.0% (95% CI: 85.7%-96.3%; 107 patients and 62 controls), 82.7% (95% CI: 77.6%-87.9%; 104 patients and 142 controls), and 99.0% (95% CI: 97.7%-100%; 96 patients and 62 controls), respectively. Bioinformatic analysis suggested that these metabolites were enriched in pathways implicated in SCZ, such as glycerophospholipid metabolism. Taken together, our findings support a role for exosomal metabolite dysregulation in the pathophysiology of SCZ and indicate a strong potential for exosome-derived metabolites to inform the diagnosis of SCZ.


Assuntos
Exossomos/metabolismo , Metaboloma/fisiologia , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Adulto , Biomarcadores/metabolismo , Cromatografia Líquida , Feminino , Humanos , Masculino , Metabolômica , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem
4.
Front Neurosci ; 14: 823, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982663

RESUMO

Oxidative stress has been suggested to play a key role in multiple sclerosis (MS), but clinical data on oxidative stress markers in MS patients were inconsistent. This study sought to quantitatively summarize the data of oxidative stress markers in the blood and cerebrospinal fluid (CSF) of patients with MS in the literature. We conducted a systematic search of PubMed and Web of Science and included studies if they provided data on the concentrations of oxidative stress markers in the peripheral blood and CSF of MS patients and healthy control (HC) subjects. The systematic search resulted in the inclusion of 31 studies with 2,001 MS patients and 2,212 HC subjects for meta-analysis. Random-effects meta-analysis demonstrated that patients with MS had significantly increased concentrations of blood oxidative stress markers compared with HC subjects for malondialdehyde (MDA; Hedges' g, 2.252; 95% CI, 1.080 to 3.424; p < 0.001) and lipid hydroperoxide by tert-butyl hydroperoxide-initiated chemiluminescence (CL-LOOH; Hedges' g, 0.383; 95% CI, 0.065 to 0.702; p = 0.018). In contrast, concentrations of albumin (Hedges' g, -1.036; CI, -1.679 to -0.394; p = 0.002) were significantly decreased in MS patients when compared with those in HC subjects. However, the other analyzed blood oxidative stress markers did not show significant differences between cases and controls. Furthermore, this meta-analysis showed significant association between CSF MDA and MS (Hedges' g, 3.275; 95% CI, 0.859 to 5.691; p = 0.008). Taken together, our results revealed increased blood and CSF MDA and decreased blood albumin levels in patients with MS, strengthening the clinical evidence of increased oxidative stress in MS.

5.
Ther Adv Med Oncol ; 11: 1758835919838958, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019568

RESUMO

Background: Genome-wide sequencing investigations have identified numerous long noncoding RNAs (lncRNAs) among mammals, many of which exhibit aberrant expression in cancers, including esophageal squamous cell carcinoma (ESCC). Herein, this study elucidates the role and mechanism by which LINC01419 regulates the DNA methylation of glutathione S-transferase pi 1 (GSTP1) in relation to ESCC progression and the sensitivity of ESCC cells to 5-fluorouracil (5-FU). Methods: LINC01419 and GSTP1 levels were quantified among 38 paired ESCC and adjacent tissue samples collected from patients with ESCC. To ascertain the contributory role of LINC01419 in the progression of ESCC and identify the interaction between LINC01419 and GSTP1 promoter methylation, LINC01419 was overexpressed or silenced, and the DNA methyltransferase inhibitor 5-Aza-CdR was treated. Results: Data from the GEO database (GSE21362) and the Cancer Genome Atlas displayed elevated levels of LINC01419 and downregulated levels of GSTP1 in the ESCC tissues and cells. The silencing of LINC01419 led to decreased proliferation, increased apoptosis, and enhanced sensitivity to 5-FU in ESCC cells. Notably, LINC01419 could bind to the promoter region of the GSTP1 gene, resulting in elevated GSTP1 methylation and reduced GSTP1 levels via the recruitment of DNA methyltransferase among ESCC cells, whereby ESCC progression was stimulated accompanied by reduced ESCC cell sensitivity to 5-FU. GSTP1 demethylation by 5-Aza-CdR was observed to reverse the effects of LINC01419 overexpression in ESCC cells and the response to 5-FU. Conclusion: Highly expressed LINC01419 in ESCC promotes GSTP1 methylation, which ultimately acts to promote the event of ESCC and diminish the sensitivity of ESCC cells to 5-FU, highlighting a novel potential strategy to improve 5-FU-based chemotherapy in ESCC.

6.
Artigo em Inglês | MEDLINE | ID: mdl-30696365

RESUMO

Predictions of aflatoxin (AF) in grain at post-harvest can be useful for ensuring the safety of stored grain. Versicolorin (Ver) A, a precursor of AFB1, can serve as an early indicator of AF contamination, even when AFs themselves are present at undetectable levels. In the current research, we developed a probabilistic model based on logistic regression and Ver A levels to estimate the risk of AF contamination in stored corn. Moisture content, aflatoxigenic fungal load, and initial and maximum values of Ver A in the first three sampling cycles were experimentally determined as the four important factors for the probabilistic model. Both internal and external model validations were shown to be high at 96.4% and 93.3%, respectively. For high-risk samples, a precise model was developed to predict the maximum period of safe storage, which can be useful for decision-making by the stakeholders in feed and food supply chain. Our findings provide a basis tool for establishing an early warning system for AF contamination in granaries, which can improve global food safety.


Assuntos
Aflatoxinas/análise , Antraquinonas/análise , Contaminação de Alimentos/análise , Armazenamento de Alimentos , Zea mays/química , Inocuidade dos Alimentos , Humanos , Modelos Logísticos , Medição de Risco
7.
FASEB J ; 33(2): 1972-1988, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30226808

RESUMO

Approximately 85% of a single administered dose of 5-fluorouracil (5-FU) will be degraded by dihydropyrimidine dehydrogenase (DYPD). Studies have highlighted a link between the complete or partial loss of DYPD function and clinical responses to 5-FU; however, the underlying molecular basis of DPD deficiency remains poorly understood. Hence, the aim of the present study was to evaluate the prevailing hypothesis which suggests that overexpression of LINC00261 possesses the ability to modulate the methylation-dependent repression of DPYD, ultimately resulting in an elevation of the sensitivity of human esophageal cancer cells to 5-FU. LINC00261 levels were initially quantified, followed by analysis of DYPD methylation within the cancerous tissues collected from 75 patients diagnosed with esophageal cancer undergoing 5-FU-based adjuvant chemotherapy. In an attempt to determine the levels of LINC00261 related to the esophageal cancer cell resistance to 5-FU and to identify the interaction between the levels of LINC00261 and methylation of the DYPD promoter, esophageal cancer cells TE-1 and -5 were prepared, in which LINC00261 and the 5-FU-resistant TE-1 and -5 cells were overexpressed. The levels of LINC00261 were reduced among the cancerous tissues obtained from patients exhibiting resistance to 5-FU. Overexpression of LINC00261 was determined to dramatically inhibit proliferation and resistance to apoptosis among 5-FU-resistant TE-1 and -5 cells, whereas silencing of LINC00261 was determined to enhance proliferation and resistance to apoptosis among the TE-1 and -5 cells. DPYD, a confirmed target of LINC00261, displayed a greater incidence of DNA methylation among patient's sensitive to 5-FU. A key finding revealed that overexpressed LINC00261 could increase the methylation of the DPYD promoter through the recruitment of DNA methyltransferase (DNMT), which, in turn, acts to decrease DPYD activity in 5-FU-resistant TE-1 cells, whereas a reversible change was recorded once the demethylation reagent 5-aza-2'-deoxyctidine was employed to treat the 5-FU-resistant TE-1 cells. Taken together, the results of the study provided evidence emphasizing the distinct antitumor ability of LINC00261 in cases of esophageal cancer, which was manifested by overexpression of LINC00261 detected to increase the sensitivity of human esophageal cancer cells to 5-FU by mediating methylation-dependent repression of DPYD. Our study highlighted the potential of LINC00261 as a novel target capable of improving the chemotherapeutic response and survival of patients with esophageal cancer.-Lin, K., Jiang, H., Zhuang, S.-S., Qin, Y.-S., Qiu, G.-D., She, Y.-Q., Zheng, J.-T., Chen, C., Fang, L., Zhang, S.-Y. Long noncoding RNA LINC00261 induces chemosensitization to 5-fluorouracil by mediating methylation-dependent repression of DPYD in human esophageal cancer.


Assuntos
Metilação de DNA/efeitos dos fármacos , DNA de Neoplasias/metabolismo , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Esofágicas/metabolismo , Fluoruracila/farmacologia , Proteínas de Neoplasias/metabolismo , Regiões Promotoras Genéticas , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Animais , Linhagem Celular Tumoral , Metilação de DNA/genética , DNA de Neoplasias/genética , Di-Hidrouracila Desidrogenase (NADP)/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas de Neoplasias/genética , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Dig Dis Sci ; 63(9): 2320-2331, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29808247

RESUMO

BACKGROUND AND AIM: HOX transcript antisense intergenic RNA (HOTAIR) is a relatively well-understood RNA, which plays a central role in the pathogenesis of various tumors. The aim of the present study was to investigate the effect by which HOTAIR acts to influence the biological processes of colorectal cancer (CRC) through p21. METHODS: Reverse transcription quantitative polymerase chain reaction and Western blot methods were employed to provide verification regarding the changes in HOTAIR, PCNA, Ki67, p21, cyclin E, and CDK2 among the CRC tissues and cells. The correlation between the clinicopathological characteristics of patients and expression of HOTAIR and p21 was subsequently evaluated, followed by an analysis into the effects of HOTAIR on the biological processes of M5 cells. RESULTS: HOTAIR was found to be expressed at high levels, while p21 was determined to be at a low level among both the CRC tissues and the CRC cell lines. The expressions of HOTAIR and p21 were determined to be related to lymph node metastasis, tumor node metastasis, Dukes staging, distant metastases, histological types, and the degree of differentiation. Cells transfected with HOTAIR siRNA displayed inhibited rates of proliferation, invasion, and migration, as well as decreased cyclin E and CDK2, while apoptosis and p21 were increased. CONCLUSION: The principal findings demonstrated that down-regulation of HOTAIR elicits an inhibitory effect on proliferation, invasion, and migration, while promoting the apoptosis of CRC cells through the up-regulation of p21. We believe that HOTAIR could represent a novel target for the treatment of CRC.


Assuntos
Movimento Celular , Proliferação de Células , Neoplasias Colorretais/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , RNA Longo não Codificante/metabolismo , Adulto , Idoso , Apoptose , Células CACO-2 , Diferenciação Celular , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Ciclina E/genética , Ciclina E/metabolismo , Quinase 2 Dependente de Ciclina/genética , Quinase 2 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Regulação para Baixo , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HT29 , Humanos , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais , Fatores de Tempo , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-29337658

RESUMO

The objective of this study was to evaluate the feasibility of the predictive monitoring of aflatoxin B1 (AFB1) under granary conditions, since mycotoxin contamination of the stored grain represents an important issue. Using the storage test, we investigated the relationship between versicolorin A (Ver A, an intermediate in AFB1 biosynthesis) levels and the levels of aflatoxigenic fungi, and their relationship with aflatoxin production. All samples, except for one, were found to be contaminated with aflatoxigenic fungi using PCR analyses, while their AFB1 levels were not detectable before the storage test using an enzyme-linked immunosorbent assay (ELISA) method with an LOD of 2 µg/kg. Aflatoxigenic fungi levels were analysed, as well as Ver A levels prior to the accumulation of AFB1 (Levels were ≥5 µg/kg; the permissible levels of AFB1 in corn intended for direct consumption are <5 µg/kg (EC)). Statistical analyses demonstrated that aflatoxin levels after both actual storage and safe storage (AFB1˂5µg/kg) times are significantly correlated with the Ver A levels and the changes in Ver A levels (ΔVer A). Both high and variable Ver A levels were indicative of the vigorous metabolic activity of aflatoxigenic fungi. In contrast, steady Ver A levels showed that aflatoxin production by the fungi was not active. Monitoring Ver A levels and their changes may allow an earlier detection of harmful aflatoxin contamination in the stored grain. Additionally, the toxicity of Ver A should be further examined. The results of our study indicate that the monitoring of Ver A levels, even when the AFB1 levels are very low, may increase the safety of grain consumption, especially considering Ver A toxicity.


Assuntos
Aflatoxina B1/análise , Antraquinonas/análise , Contaminação de Alimentos/análise , Armazenamento de Alimentos , Zea mays/química , Biomarcadores/análise , Ensaio de Imunoadsorção Enzimática
10.
Eur J Drug Metab Pharmacokinet ; 40(1): 111-4, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24590313

RESUMO

Droperidol, an antidopaminergic drug clinically used as an antiemetic and antipsychotic, has been reported to induce cardiac toxicity in patients. Due to the close relationship between drug metabolism and efficiency and toxicity, the present study aims to investigate the phase I metabolites using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. The NADPH-supplemented phase I incubation system was used to elucidate the in vitro phase I metabolites. Five metabolites were detected after droperidol was incubated with phase I incubation mixture, including one hydrogenated droperidol, three oxidative metabolites, and one N-dealkylated droperidol, elucidated by individual retention time and MS/MS fragmentation. Due to the existed phase II metabolic reaction, further phase II metabolism should be investigated in the future. In conclusion, the phase I metabolism of droperidol was investigated in the present study, and five new metabolites were identified. The efficiency and toxicity of these phase I metabolites should be investigated in the future.


Assuntos
Cromatografia Líquida/métodos , Antagonistas dos Receptores de Dopamina D2/metabolismo , Droperidol/metabolismo , Espectrometria de Massas em Tandem/métodos , Adulto , Remoção de Radical Alquila , Antagonistas dos Receptores de Dopamina D2/química , Droperidol/química , Humanos , Hidrogenação , Masculino , Desentoxicação Metabólica Fase I , Microssomos Hepáticos/metabolismo , Pessoa de Meia-Idade , Estrutura Molecular , Oxirredução
11.
Eur J Drug Metab Pharmacokinet ; 39(2): 99-102, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23807732

RESUMO

The disturbance of estradiol level might induce the occurence of some diseases, including cancer. Estradiol is mainly metabolized through the conjugation reactions, including the sulfation and glucuronidation reactions. The present study tried to evaluate the inhibition of estradiol glucuronidation by the major ingredients of Tripterygium wilfordii Hook F. demethylzeylasteral. Selective ion monitoring at negative ion mode ([M⁺ H⁻] = 447) was employed to monitor the two glucuronides of estradiol. The reaction rate was determined through comparison of peak area of these two glucuronides. Lineweaver-Burk plot and Dixon plot were utilized to determine the inhibition kinetic type, and the inhibition kinetic parameters (K i) were calculated using the second plot. Competitive inhibition of demethylzeylasteral towards the formation of two glucuronides of estradiol was demonstrated, and the K i values were calculated to be 453.3 and 110.9 µM, respectively. All these results will remind us the risk of elevated serum concentrations of estradiol due to the inhibition of estradiol glucuronidation by demethylzeylasteral.


Assuntos
Estradiol/metabolismo , Glucuronídeos/metabolismo , Triterpenos/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Humanos
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