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1.
Small ; : e2001987, 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32583970

RESUMO

Two identical layered metal-organic frameworks (MOFs) (CoFRS and NiFRS) are constructed by using flexible 1,10-bis(1,2,4-triazol-1-yl)decane as pillars and 1,4-benzenedicarboxylic acid as rigid linkers. The single-crystal structure analysis indicates that the as-synthesized MOFs possess fluctuant 2D networks with large interlayer lattices. Serving as active electrode elements in supercapacitors, both MOFs deliver excellent rate capabilities, high capacities, and longstanding endurances. Moreover, the new intermediates in two electrodes before and after long-lifespan cycling are also examined, which cannot be identified as metal hydroxides in the peer reports. After assembled into battery-supercapacitor (BatCap) hybrid devices, the NiFRS//activated carbon (AC) device displays better electrochemical results in terms of gravimetric capacitance and cycling performance than CoFRS//AC devices, and a higher energy-density value of 28.7 Wh kg-1 compared to other peer references with MOFs-based electrodes. Furthermore, the possible factors to support the distinct performances are discussed and analyzed.

2.
Eur J Drug Metab Pharmacokinet ; 45(4): 523-533, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32304023

RESUMO

BACKGROUND AND OBJECTIVES: As a traditional Chinese Materia Medica (CMM), the Compound Danshen Dripping Pill (CDDP) is widely used for the treatments of cardiovascular diseases. In view of its undefined applicable population and dosage, a population pharmacokinetic (PPK) study is required. The objective of this study was to explore the feasibility of multi-component CMM PPK in rat plasma after oral administration of CDDP based on sparse sampling. METHODS: In this research, a simple, rapid and highly sensitive UFLC-MS/MS method for the simultaneous determination of tanshinol (TSL), ginsenoside Rb1 (GRb1) and ginsenoside Rg1 (GRg1) has been successfully developed in rat plasma. Moreover, the validated method has been applied to a PPK study of CDDP based on sparse data. We established the PPK models for these three main active constituents using a nonlinear mixed-effects model, taking into account of factors such as gender, age in weeks and weight. RESULTS: The PPK models of TSL and GRb1 were best described by a one-compartment model with linear elimination and first-order absorption. The model of GRg1 was best described by a two-compartment model with first-order absorption. Bootstrap validation and a visual predictive check confirmed the predictive ability, the model stability and the precision of the parameter estimates from these models. CONCLUSION: As a preliminary exploration toward the clinical population pharmacokinetic research, this study provides a reference for the population pharmacokinetic study of traditional CMM.

3.
BMC Complement Med Ther ; 20(1): 126, 2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32336289

RESUMO

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes. Diosgenin is a natural steroidal saponin with a variety of beneficial effects, including antidiabetic effects, and is a raw material for the synthesis of carrier hormones. In our study, we aimed to assess the antioxidant effects of diosgenin in diabetic mice. METHODS: Male C57 mice were fed a high-fat diet for 8 weeks and intraperitoneally injected with streptozotocin (STZ) at a dose of 100 mg/kg for 2 consecutive days. Eligible mice were divided into the normal control group (CON), diabetic group (DM), low-dose diosgenin (50 mg/kg) group (DIO50) and high-dose diosgenin (100 mg/kg) group (DIO100). Treatment was started 6 weeks after the induction of diabetes by STZ and continued for 8 weeks. Blood sugar and body weight were monitored dynamically. The behavioural effects of diosgenin were detected by a hot tail immersion test and paw tactile responses. HE staining was used to evaluate edema and degeneration of the sciatic nerve. The levels of SOD, MDA and GPx were tested according to the instructions of the respective kits. The levels of Nrf2, HO-1 and NQO1 were detected by immunofluorescence and Western blotting. Statistical analysis was performed using SPSS, and P < 0.05 was considered statistically significant. RESULTS: Diosgenin decreased the blood glucose levels and increased the body weight of diabetic mice. There was a significant increase in the tail withdrawal latency of diabetic animals, and mechanical hyperalgesia was significantly alleviated after diosgenin treatment. Histopathological micrographs of HE-stained sciatic nerves showed improvement after diosgenin treatment. Diosgenin attenuated the level of MDA but increased the activities of SOD and GPx. Diosgenin increased the expression of Nrf2, HO-1 and NQO1. CONCLUSIONS: Our results demonstrate that diosgenin can ameliorate behavioural and morphological changes in DPN by reducing oxidative stress. The Nrf2/HO-1 signalling pathway was involved in its neuroprotective effects.

4.
Yi Chuan ; 42(3): 309-320, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32217516

RESUMO

Excessive accumulation of fat is harmful to human health. The preadipocyte differentiation is a critical process of fat development. Studying the expression profiles of genes related to preadipocyte differentiation contributes to understanding of the mechanism of fat accumulation. Despite being considered an ideal animal model for studying adipogenesis, little is known about the gene expression profiles at different stages during preadipocyte differentiation in rabbits. In the present study, rabbit preadipocytes were cultured in vitro and induced for differentiation, and gene expression profiles of adipocytes collected at days 0, 3, and 9 of differentiation were analyzed by RNA-seq. We identified 1352 differentially expressed genes (DEGs) when comparing day 3 with day 0 and identified 888 DEGs when comparing day 9 with day 3. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the PPAR signaling pathway and PI3K-Akt signaling pathway were significantly enriched by the DEGs that up-regulated within the period of day 0 - day 3, and the GO terms and KEGG pathways that were associated with cell cycle were enriched by the DEGs that up-regulated within the period of day 3 - day 9. The DEGs that specifically up-regulated within the period of day 0 - day 3 might play roles in the cytoplasm, and the DEGs that specifically up-regulated within the period of day 3 - day 9 might act in the nucleus. The protein-protein interaction (PPI) network constructed by DEGs showed that hub node genes might modulate rabbit preadipocyte differentiation via regulating cell cycle.


Assuntos
Adipócitos/citologia , Adipogenia , Diferenciação Celular , Transcriptoma , Animais , Perfilação da Expressão Gênica , Coelhos , Transdução de Sinais
5.
J Ethnopharmacol ; 256: 112780, 2020 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-32222575

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Si-miao-yong-an decoction (SMYAD) is a famous traditional Chinese medicinal formula that has been used for centuries in ancient China for treating thromboangiitis obliterans. Because of its long history of use, it has been used to treat patients in China for thousands of years. In recent years, SMYAD has been widely used for treating cardiovascular and endocrine diseases. It was shown to significantly increase high-density lipoprotein-cholesterol levels and reduce total cholesterol and low-density lipoprotein-cholesterol levels in the serum. AIM OF THE STUDY: Herein, a serum metabonomics approach based on the HPLC-MS/MS method was adopted to evaluate the therapeutic effect of SMYAD on high-fat diet-induced hyperlipidemia, and investigate the mechanisms for treating hyperlipidemia. MATERIALS AND METHODS: Firstly, the change in body weight, liver histopathology, and serum biochemistry, including that in the levels of hepatotoxicity-related enzymes, oxidative stress indexes, and inflammatory factors were monitored in rats, to evaluate the therapeutic effect of SMYAD on high-fat diet-induced hyperlipidemia. Then, a serum metabolomics approach was applied, to cluster different groups using principle component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), as well as to screen out sensitive and reliable biomarkers. Finally, the metabolic pathways associated with specific biomarkers were analyzed, to understand the possible mechanism underlying the action of SMYAD. RESULTS: The results indicated that SMYAD had significant anti-hyperlipidemic, anti-oxidant, and anti-inflammatory effects. Based on the results of serum metabolomics analysis, the hyperlipidemic rats showed completely different results compared to the control rats; metabolite profiles of rats from the SMYAD treatment groups showed a trend comparable to those of the normal control group in a dose-dependent manner. Besides, twelve biomarkers associated with pyruvate metabolism, taurine and hypotaurine metabolism, TCA cycle, bile acid metabolism, and glucose metabolism were identified and confirmed, to clarify the mechanism of action of SMYAD. CONCLUSION: Using metabonomics technology, it was predicted that the therapeutic effects of SMYAD were associated with its anti-oxidation as well as anti-inflammatory activities and the adjustment of the pyruvate, taurine as well as hypotaurine metabolism pathways in the hyperlipidemic state. This study provided evidence regarding the clinical application of SMYAD and thoroughly explored the mechanism underlying the action of this traditional Chinese medicine.

6.
Bioorg Med Chem Lett ; 30(8): 127046, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32122739

RESUMO

A series of novel vorapaxar analogues with different amino substitutes at the C-7, C-9a and aromatic substitutes at the C-4 position were designed, synthesized, and evaluated for their inhibitory activity to PAR-1. Several compounds showed good potency in antagonist activity based on the intracellular calcium mobilization assay and excellent pharmacokinetics profile in rats. Among these analogues, 3d exhibited excellent PAR-1 inhibitory activity (IC50 = 0.18 µM) and the lower ability to cross the blood-brain barrier compared with vorapaxar (IC50 = 0.25 µM). Compound 3d has the potential to be developed as a new generation of PAR-1 antagonists with a better therapeutic window.

7.
BMC Complement Med Ther ; 20(1): 29, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32020873

RESUMO

BACKGROUND: Crocetin is a major active component of saffron, which has a wide range of pharmacological effects. However, due to its low solubility, the pharmacological effects of crocetin cannot be better utilized. METHODS: In this study, we modified the chemical structure of crocetin by conjugating with ethylamine and 4-Fluorbenzylamine to enhance its solubility and biological activities. The solubility and the influence of synthesized derivatives on the proliferation of tumor cells and the inflammatory effect of macrophage were investigated. RESULTS: It was shown that, compared with the crocetin, the synthesized derivatives have much higher solubility. Moreover, the inhibitory effect of the derivatives on varieties of tumor cells, including human ovarian carcinoma cell line, human lung cancer cell line, rat melanoma cell line was enhanced after the modification. Besides that, the derivatives were improved for the anti-inflammatory efficacy with the cytotoxicity decreased. CONCLUSIONS: The synthesized derivatives were shown for their good solubility and the great potential in tumor and inflammation treatment.


Assuntos
Anti-Inflamatórios/farmacologia , Carotenoides/química , Carotenoides/farmacologia , Proliferação de Células/efeitos dos fármacos , Macrófagos/metabolismo , Animais , Linhagem Celular Tumoral , Crocus , Humanos , Camundongos , Ratos
8.
Clin Chem ; 66(2): 302-315, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-32040589

RESUMO

BACKGROUND: Rapid detection of Shiga toxin-producing Escherichia coli (STEC) enables appropriate monitoring and treatment. We synthesized available evidence to compare the performance of enzyme immunoassay (EIA) and PCR tests for the detection of STEC. METHODS: We searched published and gray literature for studies of STEC EIA and/or PCR diagnostic test accuracy relative to reference standards including at least one nucleic acid amplification test. Two reviewers independently screened studies, extracted data, and assessed quality with the second version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Bivariate random effects models were used to meta-analyze the clinical sensitivity and specificity of commercial EIA and PCR STEC diagnostic tests, and summary receiver operator characteristic curves were constructed. We evaluated the certainty of evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We identified 43 articles reflecting 25 260 specimens. Meta-analysis of EIA and PCR accuracy included 25 and 22 articles, respectively. STEC EIA pooled sensitivity and specificity were 0.681 (95% CI, 0.571-0.773; very low certainty of evidence) and 1.00 (95% CI, 0.998-1.00; moderate certainty of evidence), respectively. STEC PCR pooled sensitivity and specificity were 1.00 (95% CI, 0.904-1.00; low certainty of evidence) and 0.999 (95% CI, 0.997-0.999; low certainty of evidence), respectively. Certainty of evidence was downgraded because of high risk of bias. CONCLUSIONS: PCR tests to identify the presence of STEC are more sensitive than EIA tests, with no meaningful loss of specificity. However, given the low certainty of evidence, our results may overestimate the difference in performance.


Assuntos
Infecções por Escherichia coli/diagnóstico , Toxina Shiga/análise , Escherichia coli Shiga Toxigênica/patogenicidade , Testes Diagnósticos de Rotina/métodos , Escherichia coli/enzimologia , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Técnicas Imunoenzimáticas/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade , Toxina Shiga/metabolismo , Escherichia coli Shiga Toxigênica/genética , Escherichia coli Shiga Toxigênica/metabolismo
9.
Genet Test Mol Biomarkers ; 24(3): 138-144, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32101051

RESUMO

Objective: Carotid atherosclerosis is one of the major risk factors for ischemic stroke. The presence of carotid plaque has been widely used to assess the risk of clinical atherosclerotic disease. Lectin-type oxidized LDL (low-density lipoprotein) receptor 1 (LOX-1), lysosomal acid lipase (LAL), and acyl-CoA:cholesterol acyltransferase 1 (ACAT1) are important for lipid accumulation in atherosclerosis. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in the LOX-1, LAL, and ACAT1 genes and the presence of carotid plaque in a Northern Chinese population. Methods: Three polymorphisms in LOX-1 (rs1050286), LAL (rs11203042), and ACAT1 (rs11576517) were identified and genotyped in 215 patients with carotid plaque and 252 controls using the polymerase chain reaction with high-resolution melting analysis. Results: The LOX-1 (rs1050286) AA and LAL (rs11203042) TT genotypes were significantly associated with increased risk of carotid plaque, whereas a ACAT1 (rs11576517) TT genotype was shown to be protective against carotid plaque in a Northern Chinese population (p < 0.05). Even after the Bonferroni correction, the LAL (rs11203042) TT genotype (odds ratio = 3.838, 95% confidence interval = 1.748-8.426, p < 0.001) was still associated with an increased risk for carotid plaque. Conclusions: These results suggest that the LAL (rs11203042) TT genotype is associated with increased risk for carotid plaque in a Northern Chinese population, and that the LOX-1 (rs1050286) AA genotype shows a nonstatistically significant trend towards association. However, no association was found between the ACAT1 (rs11576517) polymorphisms and carotid plaque presence.

10.
J Infect Public Health ; 13(4): 591-597, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31530441

RESUMO

OBJECTIVE: The clinical use of intermittent infusion of vancomycin (IIV) and continuous infusion of vancomycin (CIV) is controversial. The aim of this study was to assess the effectiveness and safety of IIV and CIV by using a meta-analysis for cohort studies and randomized controlled trials. METHODS: We compared the probabilities of target attainment (PTA) for the measured concentration (Cm) ≥the target concentration (Ct), the PTA for the area under the drug concentration curve/minimal inhibitory concentration (AUC/MIC) ≥400, the duration of treatment, nephrotoxicity, and overall mortality after vancomycin treatment as reported in PubMed, Embase, Cochrane, and Web of Science. RESULTS: A total of 14 studies with 1640 patients were included in the meta-analysis. For IIV, the PTA of Cm≥Ct (RR=0.72, 95% CI=0.60-0.88), and nephrotoxicity (RR=1.70, 95% CI=1.34-2.14) were significantly different from those of CIV. The treatment duration (SMD=0.08, 95% CI=-0.08-0.25), the PTA of AUC/MIC ≥ 400 (RR=0.84, 95% CI=0.70-1.00) and mortality (RR=0.94, 95% CI=0.72-1.25) were not significantly different from those of CIV. CONCLUSIONS: The results showed that CIV was easier to achieve Ct and safer than IIV. Additional randomized controlled trials focusing on the concentration of vancomycin are needed for further analysis.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Vancomicina/uso terapêutico , Antibacterianos/administração & dosagem , Esquema de Medicação , Humanos , Infusões Intravenosas/métodos , Vancomicina/administração & dosagem
11.
J Infect Public Health ; 13(1): 68-74, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31277936

RESUMO

BACKGROUND: Augmented renal clearance (ARC) refers to enhanced renal elimination of circulating solute has attracted attention widely and in recent years increasing attention has been paid to patients with ARC. A population pharmacokinetic (PPK) analysis was performed to provide a reference for clinical individual therapy of vancomycin in in ARC patients. METHODS: Patients hospitalized in the First Affiliated Hospital of China Medical University from July 2013 to December 2015 and suspected or confirmed infection caused by gram-positive bacteria were enrolled in this study. The serum concentrations were determined by enzyme multiplied immunoassay technique. A nonlinear mixed effects model (NONMEM) was used to evaluate the influence of covariates on vancomycin pharmacokinetics and obtain the PPK model. Bootstrap, visual predictive checks and normalized prediction distribution errors were used to evaluate the estabolishe model. RESULTS: A total of 186 vancomycin serum samples from 95 patients, including 24 females and 71 males were studied. The final model was as follows: [Formula: see text] and [Formula: see text] . The final PPK model in ARC patients was proved to be robust and reliable. Age was identified as the most significant covariate in the final model. CONCLUSIONS: In this study, a simple population pharmacokinetic (PPK) model of vancomycin in Chinese patients with ARC was established using a nonlinear mixed-effects model (NONMEM). The final PPK model could achieve a good predictive effect, which provides a reference for clinical individual therapy.

12.
Food Chem ; 303: 125363, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31472383

RESUMO

Present in many plant foods, biogenic phenolic compounds are important bioactive phytonutrients with high anti-oxidant activity and thereby are praised for their health-promoting properties. However, current food nutrient improvement by high phenolic content in staples is limited by the shortage of genetic resources rich in phenolic compounds. To resolve this obstacle, we developed a non-destructive massive analytical approach to screen wheat phenolic mutants. In grains, multiple mutant lines showed significantly higher contents of flavonoids or cell wall-bound phenolic esters. Moreover, five mutants showed higher anti-oxidant potentials in wall-bound phenolic compounds ranging from 15% to 20%, with the maximal close to natural black wheat. In contrast to black wheat, two mutants accumulated higher phenolic compounds in the endosperm. lrf4 was mapped by BSR to a concentrated genomic region in the short arm of chromosome 1A. The present work represents an efficient high-throughput strategy to increase wheat anti-oxidant potential through traditional mutagenesis.


Assuntos
Antioxidantes/metabolismo , Mutação , Fenóis/metabolismo , Triticum/genética , Triticum/metabolismo , Flavonoides/metabolismo
13.
Metabolomics ; 15(10): 128, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31541307

RESUMO

INTRODUCTION: Clinical trials of Compound danshen dripping pills (CDDP) indicated distinct improvement in patients with chronic stable angina. Daily fluctuation of therapeutic effect agreed with a peak-valley PK profile during a 4-week CDDP regimen, but stabilized after 8-week treatment. OBJECTIVES: This article aims to explore the underlying mechanism for the time-dependent drug efficacy of the up-down fluctuation or stabilization in clinic trials. METHODS: A rat model of myocardial ischemia was established via isoproterenol induction. Metabolomics was employed to analyze the energy-related substances both in circulatory system and myocardium in the myocardial ischemia model. RESULTS: CDDP treatment ameliorated myocardial ischemia, reversed the reprogramming of the metabolism induced by ISO and normalized the level of most myocardial substrates and the genes/enzymes associated with those metabolic changes. After 1- or 2-week treatment, CDDP regulated plasma and myocardial metabolome in an analogous, time-dependent way, and modulated metabolic patterns of ischemic rats that perfectly matched with the fluctuated or stabilized effects observed in clinical trials with 4 or 8-week treatment, respectively. CONCLUSION: Metabolic modulation by CDDP contributes to the fluctuated or stabilized therapeutic outcome, and is a potential therapeutic approach for myocardial ischemia diseases.

14.
Front Cell Neurosci ; 13: 349, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440142

RESUMO

Hydrogen sulfide (H2S), an important endogenous signaling molecule, has a significant neuroprotective role in the central nervous system. In this study, we examined the protective effects of exogenous H2S against intracerebral hemorrhage (ICH), as well as its underlying mechanisms. We investigated the effects of exogenous H2S on ICH using Western blotting, injury volume, measurement of brain edema, propidium iodide (PI) staining, and behavior assessment, respectively. We found that endogenous H2S production was downregulated in the brain after ICH, which is caused by the decrease in cystathionine ß-synthase (CBS) as the predominant cerebral H2S-generating enzyme in the brain. Treatment with sodium hydrosulfide (NaHS; an H2S producer) could restore the H2S production and the expression of CBS. NaHS could also attenuate brain edema, injury volume, and neurological deficits in the Morris water maze test after ICH. Western blotting results indicated that H2S pretreatment reversed the increase in caspase 3 cleavage and the decrease in Bcl-2, suppressed the activation of autophagy marker (LC3II and Beclin-1), and maintained the p62 level in injured striatum post-ICH. However, H2S could not restore brain CBS expression and H2S content, reduce brain edema, and improve motor performance and memory function after ICH through modulating autophagy and apoptosis when pretreated with the CBS inhibitor aminooxyacetic acid (AOAA). We also found that AOAA reduced the endogenous H2S production through inhibiting the enzyme activity of CBS rather than modulating the expression of CBS protein level. These present results indicate that H2S may possess potential therapeutic value in the treatment of brain injury after ICH, and the protective effect of exogenous H2S against ICH may be not a direct action but an indirect effect through inducing endogenous H2S metabolism responses.

15.
Colloids Surf B Biointerfaces ; 181: 910-917, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31382340

RESUMO

The purpose of this study was to investigate the effects of soybean phospholipid, as a steric stabilizer, on improving dissolution rate, storage stability and bioavailability of ginkgolides. The ginkgolides coarse powder, hydroxypropyl methylcellulose (HPMC), soybean phospholipid and sodium dodecyl sulfate (SDS) were mixed and wet-milled to prepare nanosuspension S1. Nanosuspension S2 was obtained by the same technique except adding the soybean phospholipid. Results of particle size showed that particle size (D50) of S1 significantly decreased from 44.25 µm to 0.373 µm. Results of differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and transmission electron microscope (TEM) showed that ginkgolides in nanosuspension still maintained its crystallinity, and the nanoparticles were all nearly circular and uniformly dispersed. Then, pellets F1 and F2 were prepared by layering S1 and S2 onto the microcrystalline cellulose (MCC) spheres, respectively. The dissolution rate of ginkgolide A (GA) and ginkgolide B (GB) in F1 was 98.3% and 97.7% in 30 min, respectively. It was much higher than F2 (89.0% and 86.5%) and coarse powder of ginkgolides (22.3% and 24.6%). According to the results of stability test, the storage stability of F1 was improved compared with F2. In addition, compared with coarse powder of ginkgolides, the relative bioavailability of GA and GB in F1 were up to (221.84 ±â€¯106.67) % and (437.45 ±â€¯336.43) %, respectively. The above results demonstrated that soybean phospholipid added to the nanosuspension played an important role in improving drug dissolution rate, storage stability and in vivo bioavailability: (1) The amphiphilic soybean phospholipid interacted with the drug, with the hydrophobic part adsorbed on the surface of the poorly soluble drug and the hydrophilic part exposed to the aqueous medium. This increases the wettability of the nanoparticles, which ensure a good redispersibility of the drug particles. (2) It could self-assemble to form an interfacial phospholipid film by surrounding the individual nanoparticles, which can produce enough steric hindrance to prevent nanoparticles from aggregation and ensure a rapid dissolution rate. (3) Soybean phospholipid and its hydrolysate formed strong micellar solubilizing vehicles with bile salts in vivo, stimulated the absorption process of ginkgolides. Thus, soybean phospholipid was a promising steric stabilizer in nanosuspension drug delivery system.


Assuntos
Ginkgolídeos/química , Nanopartículas/química , Fosfolipídeos/química , Soja/química , Administração Oral , Animais , Disponibilidade Biológica , Cães , Sistemas de Liberação de Medicamentos , Ginkgolídeos/administração & dosagem , Ginkgolídeos/sangue , Tamanho da Partícula , Fosfolipídeos/administração & dosagem , Fosfolipídeos/sangue , Propriedades de Superfície , Suspensões/química
16.
Rev Cardiovasc Med ; 20(2): 91-98, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31345001

RESUMO

A meta-analysis was performed to compare the antihypertensive efficacy of morning and evening dosing. Database of Pubmed, Embase, Cochrane, Web of Science CNKI, VIP, and Wanfang were searched up to December 2018. A total of 19 randomized control trials and 1215 participants were included in this meta-analysis. Administration time of amlodipine did not affect the office blood pressure (RR = -0.03, 95% CI -0.93-0.88, P = 0.96), daytime blood pressure (RR = -0.30, 95% CI -1.05-0.46, P = 0.44), 24 h mean blood pressure (RR = 1.15, 95% CI -0.39-2.70, P = 0.14), or heart rate (RR = 0.11, 95% CI -1.22-1.45, P = 0.87). Administration of amlodipine in the evening could significantly reduce the nighttime blood pressure (RR = 2.04, 95% CI 1.27-2.81, P < 0.00001), increased non-dipper alteration (RR = 0.51, 95% CI 0.41-0.63, P < 0.00001), and contained better anti-hypertension efficacy (RR = 0.64, 95% CI 0.55-0.74, P < 0.00001). For patients with hypertension, especially for non-dipper hypertension, taking amlodipine in the evening will be more beneficial. Better quality trials conducted in different regions and with larger sample size are necessary to verify the conclusion of this study.


Assuntos
Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , Hipertensão/tratamento farmacológico , Anlodipino/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Cronoterapia Farmacológica , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
Gene ; 710: 24-29, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31075410

RESUMO

BACKGROUND: Pulmonary tuberculosis caused by an intracellular pathogen, Mycobacterium tuberculosis continues to exist as a hazardous disease to human life globally. Genetic polymorphisms regulate resistance and susceptibility to tuberculosis. The C-type lectin receptor of family 4 member E (CLEC4E) confers protection against tuberculosis in laboratory animals but its function in influencing exposure or resistance to pulmonary tuberculosis (PTB) in humans remains obscure. AIM: We conducted this research to analyze the effects or concomitance of CLEC4E gene variations with susceptibility to pulmonary tuberculosis in a northern Chinese population. METHOD: In this study, 202 participants with pulmonary tuberculosis and 214 controls without PTB were enrolled. Two single nucleotide polymorphisms (SNPs) for CLEC4E on chromosome 12 were selected with a minor allele frequency of >0.05. All the SNPs were genotyped using high resolution melting analysis-PCR. RESULTS: We estimated and compared two SNPs, rs10841845 and rs10841847. From our study findings, CLEC4E rs10841845 conferred protection against the development of pulmonary TB with a P value of <0.05 and odds ratio of <1 for all models of genetic inheritance. CLEC4E rs10841847 genotypes in co-dominant, Recessive, Dominant models and alleles had a significant statistical difference between patients and controls associated with resistance against the development of PTB (P<0.05 and OR<1). CONCLUSION: Our findings suggest that variations at rs10841845 and rs10841847 of CLEC4E genes are associated with increased individual protection against PTB.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Resistência à Doença , Lectinas Tipo C/genética , Polimorfismo de Nucleotídeo Único , Receptores Imunológicos/genética , Tuberculose Pulmonar/epidemiologia , Estudos de Casos e Controles , Cromossomos Humanos Par 12/genética , Feminino , Frequência do Gene , Humanos , Masculino , Razão de Chances , Tuberculose Pulmonar/genética
18.
Genet Test Mol Biomarkers ; 23(4): 235-240, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30986097

RESUMO

AIMS: Evaluation of nucleic acids in plasma exosomes is a noninvasive method that can be used to detect different types of cancer. The aim of this study was to determine the value of exosomal long noncoding RNAs (lncRNAs) in detecting lung squamous cell carcinoma (LSCC). MATERIALS AND METHODS: A total of 75 LSCC patients and 79 negative control subjects were enrolled in the study. Twenty differentially expressed lncRNAs were evaluated as potential candidates. Exosomes were isolated by ultracentrifugation, and lncRNA levels in exosomes were determined using real-time polymerase chain reaction. Receiver Operating Characteristic (ROC) curves were used to determine specificity and sensitivity. RESULTS: Exosomal SOX2-OT was significantly upregulated in LSCC patients and showed the strongest power in detecting LSCC. The area under the ROC curve was 0.815, and the sensitivity and specificity were 76% and 73.17%, respectively. Moreover, exosomal SOX2-OT levels were significantly correlated with tumor size, TNM stage, and lymph node metastasis. Exosomal SOX2-OT levels were significantly decreased in the postoperative plasma of LSCC patients. CONCLUSION: SOX2-OT may serve as a promising noninvasive plasma-based tumor biomarker for LSCC.


Assuntos
Carcinoma de Células Escamosas/genética , Complexo Multienzimático de Ribonucleases do Exossomo/genética , Fatores de Transcrição SOXB1/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Complexo Multienzimático de Ribonucleases do Exossomo/sangue , Exossomos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Homologia de Genes/genética , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Metástase Linfática , Masculino , Pessoa de Meia-Idade , RNA Longo não Codificante/análise , RNA Longo não Codificante/genética , Curva ROC , Sensibilidade e Especificidade
19.
J Pharm Biomed Anal ; 169: 254-259, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30878903

RESUMO

As one of the main constituents of Compound Danshen Dripping Pills (CDDP), Panax notoginseng (PN) plays a pivotal role in the treatment of cardiovascular diseases. Numerous researches have proved that the dammarane type saponins including notoginsenoside R1 (NR1), ginsenoside Rg1 (GRg1) and ginsenoside Rb1 (GRb1) are the main bioactive components of PN in CDDP. An efficient, realiable and sensitive liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis method for simultaneously detecting NR1, GRg1 and GRb1 in human plasma was established and applied to the pharmacokinetics study of the three PN saponins after oral administration of CDDP. The human plasma samples were processed using acetonitrile and the target materials were separated on an Eclipse plus C18 column (100 × 4.6 mm, 3.5 µm) with a gradient mobile phase consisted of water (containing 0.1% formic acid) and methanol. Within the concentration ranges of 0.25-50 ng/mL, each calibration curve exhibited an excellent linear relationship (r>0.998). The precision deviations of intra-day and inter-day analysis were lower than 9.0%, and accuracy error (RE%) ranged between 1.5% and 10.5%. The average recoveries of analytes were >64.0%. The established method was successfully applied to determine the pharmacokinetics of the three saponins in human plasma. In addition to providing guidance for clinical safe medication, the experimental results also provided a valuable and reliable basis for further pharmacological studies of PN in the human body after oral administration of CDDP.


Assuntos
Medicamentos de Ervas Chinesas/química , Plasma/química , Saponinas/sangue , Saponinas/farmacocinética , Administração Oral , Adulto , Cromatografia Líquida/métodos , Ginsenosídeos/sangue , Ginsenosídeos/química , Ginsenosídeos/farmacocinética , Humanos , Masculino , Pessoa de Meia-Idade , Panax notoginseng/química , Saponinas/química , Espectrometria de Massas em Tandem/métodos , Triterpenos/sangue , Triterpenos/química , Triterpenos/farmacocinética , Adulto Jovem
20.
BMJ Open ; 9(3): e025950, 2019 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-30850413

RESUMO

INTRODUCTION: Rapid detection of Shiga toxin-producing Escherichia coli (STEC) enables appropriate treatment. Numerous commercially available molecular tests exist, but they vary in clinical performance. This systematic review aims to synthesise available evidence to compare the clinical performance of enzyme immunoassay (EIA) and nucleic acid amplification tests (NAATs) for the detection of STEC. METHODS AND ANALYSIS: The following databases will be searched employing a standardised search strategy: Medline, Embase, Cochrane CENTRAL Register of Controlled Trials, Cochrane Database of Systematic Reviews, PubMed, Scopus and Web of Science. Grey literature will be searched under advice from a medical librarian. Independent reviewers will screen titles, abstracts and full texts of retrieved studies for relevant studies. Data will be extracted independently by two reviewers, using a piloted template. Quality Assessment of Diagnostic Accuracy Studies-2 will be employed to assess the risk of bias of individual studies, and the quality of evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation approach. A bivariate random-effects model will be used to meta-analyse the sensitivity and specificity of commercial STEC diagnostic tests, and a hierarchical summary receiver operator characteristic curve will be constructed. Studies of single test accuracy of EIA and NAATs and studies of comparative accuracy will be analysed separately. ETHICS AND DISSEMINATION: Ethics approval was not required for this systematic review and meta-analysis. Findings will be disseminated in conferences, through a peer-reviewed journal and via personal interactions with relevant stakeholders. PROSPERO REGISTRATION NUMBER: CRD42018099119.


Assuntos
Infecções por Escherichia coli/diagnóstico , Técnicas Imunoenzimáticas/normas , Técnicas de Amplificação de Ácido Nucleico/normas , Escherichia coli Shiga Toxigênica/isolamento & purificação , Comércio , Diagnóstico Precoce , Humanos , Sensibilidade e Especificidade
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