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1.
J Endocrinol ; 244(1): 25-40, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31539873

RESUMO

Recent studies raise the possibility that eukaryotic translation elongation factor 1 alpha (eEF1A) may play a role in metabolism. One isoform, eEF1A2, is specifically expressed in skeletal muscle, heart and brain. It regulates translation elongation and signal transduction. Nonetheless, eEF1A2's function in skeletal muscle glucose metabolism remains unclear. In the present study, suppression subtractive hybridisation showed a decrease in Eef1a2 transcripts in the skeletal muscle of diabetic Mongolian gerbils. This was confirmed at mRNA and protein levels in hyperglycaemic gerbils, and in db/db and high-fat diet-fed mice. Further, this downregulation was independent of Eef1a2 promoter methylation. Interestingly, adeno-associated virus-mediated eEF1A2 overexpression in skeletal muscle aggravated fasting hyperglycaemia, hyperinsulinaemia and glucose intolerance in male diabetic gerbils but not in female gerbil models. The overexpression of eEF1A2 in skeletal muscle also resulted in promoted serum glucose levels and insulin resistance in male db/db mice. Up- and downregulation of eEF1A2 by lentiviral vector transfection confirmed its inhibitory effect on insulin-stimulated glucose uptake and signalling transduction in C2C12 myotubes with palmitate (PA)-induced insulin resistance. Furthermore, eEF1A2 bound PKCß and increased its activation in the cytoplasm, whereas suppression of PKCß by an inhibitor attenuated eEF1A2-mediated impairment of insulin sensitivity in insulin-resistant myotubes. Endoplasmic reticulum (ER) stress was elevated by eEF1A2, whereas suppression of ER stress or JNK partially restored insulin sensitivity in PA-treated myotubes. Additionally, eEF1A2 inhibited lipogenesis and lipid utilisation in insulin-resistant skeletal muscle. Collectively, we demonstrated that eEF1A2 exacerbates insulin resistance in male murine skeletal muscle via PKCß and ER stress.

2.
J Biochem Mol Toxicol ; : e22419, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31702098

RESUMO

Ionic liquids (ILs) as green alternatives for volatile organic solvents are increasingly used in commercial applications. It is necessary to explore the cytotoxic mechanism of ILs to reduce the risk to human health. For this purpose, cell viability, apoptosis, cytochrome P450 3A4 (CYP3A4), glucose transporter type 2 (GLUT2), and microRNA-122 (miR-122) gene expression in HepG2 cells was evaluated after IL exposure. The results showed that ILs reduced the viability of HepG2 cells through apoptotic cell death. Moreover, ILs markedly upregulated the transcription and protein levels of CYP3A4, but did not affect the expression of GLUT2 in either messenger RNA level or protein level. Finally, ILs increased the expression of miR-122 and inhibition of miR-122 with miR-122 inhibitor blocked ILs-induced apoptosis in HepG2 cells. This finding may contribute to an increased understanding of the in vitro molecular toxicity mechanism of ILs to further understand IL-related human health risks.

3.
Genes Genomics ; 2019 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-31736008

RESUMO

OBJECTIVES: MUC16 (mucin 16, also known as CA-125, cancer antigen 125, carcinoma antigen 125, or carbohydrate antigen 125) has been predicted as tumor biomarker for therapy. We determined to investigate effects and regulatory mechanism of MUC16 on cervical tumorigenesis. METHODS: Expression levels of MUC16 in cervical cancer cell lines was analyzed via qRT-PCR (quantitative real-time polymerase chain reaction). Knockdown of MUC16 was conducted via shRNA (Short hairpin RNA) transfection. MTT and colony formation assays were used to investigate effect of MUC16 on cell proliferation. Wound healing assay was utilized to detect migration and transwell assay to detect invasion. The underlying mechanism was demonstrated via western blot analysis. RESULTS: MUC16 was elevated in cervical cancer cell lines. MUC16 knockdown inhibited cell proliferation, invasion and migration. Gain- and loss-of functional assays revealed that over-expression of MUC16 activated Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) via phosphorylation, thus facilitating cyclooxygenase-2 (COX-2) expression, while knockdown of MUC16 demonstrated the reverse effect on JAK2/STAT3 activation and COX-2 expression. Moreover, inhibition of JAK2/STAT3 attenuated the regulation of MUC16 on COX-2. CONCLUSIONS: MUC16 enhanced proliferation and invasion of cervical cancer cells via JAK2/STAT3 phosphorylation-mediated cyclooxygenase-2 expression, suggesting the potential therapeutic target ability of MUC16 to treat cervical cancer.

4.
Gastrointest Endosc ; 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585126

RESUMO

BACKGROUND AND AIMS: Endoscopic resection is becoming an option in the management of gastric GI stromal tumors (GISTs). Although no consensus has been reached, patients with high malignancy potential GISTs are generally considered to be surgical candidates. However, no systematic preoperative evaluation strategy has yet been developed. The current study was performed to develop a preoperative multivariate model to predict the malignant potential of gastric GISTs. METHODS: This study consisted of 2 stages. First, a multivariate prediction model for gastric GISTs smaller than 5 cm was developed using a multivariate logistic regression analysis in a retrospective cohort. Next, the prediction model was validated further in a validation cohort of gastric GISTs. RESULTS: In the developing stage, 275 patients were included. The multivariate analysis demonstrated that independent risk factors for high malignancy potential gastric GISTs smaller than 5 cm were tumor size ≥2 cm (according to cutoff value), an irregular tumor shape, and mucosal ulceration (P < .05). Based on accordant regression coefficients, 3 risk factors were weighted with point values: 1 point for mucosal ulceration, 2 points for an irregular tumor shape, and 3 points for tumor size ≥2 cm. In the validation stage, 186 patients were included. The area under the curve of the prediction model was .80 (95% confidence interval, .73-.85), which was significantly higher than that of tumor size alone (P = .034). CONCLUSIONS: The independent risk factors for high malignancy potential gastric GISTs smaller than 5 cm were tumor size larger than 2 cm, an irregular tumor shape, and mucosal ulceration. These factors could be used to predict malignancy potential of gastric GISTs in a simple combination.

5.
J Agric Food Chem ; 67(39): 10863-10870, 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31507180

RESUMO

Mastitis, inflammation of the mammary gland, occurs in both humans and animals. Staphylococcus aureus is the most common infectious bacterial pathogen associated with mastitis. We investigated the effects of allicin on S. aureus-induced mastitis in mice. Pathological histology revealed that allicin inhibited S. aureus-induced pathological damage and myeloperoxidase activity in mammary tissues. Enzyme-linked immunosorbent assays demonstrated that allicin reduced the production of IL-1ß and TNF-α as well as inhibited the NF-κB and mitogen-activated protein kinase pathway by reducing phosphorylation of p65, IκBα, p38, JNK, and ERK. Western blotting revealed that allicin reduced TLR2 and TLR6 expression in mammary tissues and cells but not in HEK293 cells. The lipid raft content was reduced by allicin, which inhibited signaling downstream of TLR2 and TLR6. Liver X receptor α (LXRα) luciferase reporter assays and LXRα interference experiments showed that allicin improved the LXRα activity and adenosine 5'-triphosphate-binding cassette G and A1 (ABCG and ABCA1) expression, thereby reducing the cholesterol level, lipid raft formation, and downstream TLR2 and TLR6 pathway activity. These results demonstrated that allicin exerted anti-inflammatory effects against S. aureus mastitis by improving the LXRα activity and reducing lipid raft formation.


Assuntos
Mastite/tratamento farmacológico , Microdomínios da Membrana/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Ácidos Sulfínicos/administração & dosagem , Animais , Feminino , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , Mastite/genética , Mastite/metabolismo , Mastite/microbiologia , Microdomínios da Membrana/química , Microdomínios da Membrana/genética , Microdomínios da Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/genética , NF-kappa B/metabolismo , Infecções Estafilocócicas/genética , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/fisiologia , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo
6.
Food Funct ; 10(10): 6543-6555, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31545328

RESUMO

Mastitis, a major disease affecting dairy cows, is most commonly caused by Staphylococcus aureus (S. aureus). Selenium (Se) can activate pivotal proteins in immune responses and regulate the immune system, and microRNA-155 (miR-155) is a key transcriptional regulator for inflammation-related diseases. We constructed the model of mouse mastitis in vivo and primary mouse mammary epithelial cells (MMECs) in vitro, which were induced by S. aureus. Se content of the mammary was estimated using an atomic fluorescence spectrophotometer. Histopathological analysis was performed via hematoxylin and eosin (H&E) staining. The mmu-miR-155-5p mimic was transfected in MMECs, and viability was determined through the MTT assay. Transfected efficiency was evaluated by qPCR and fluorescence staining. Cytokines including TNF-α, IL-1ß, IL-10 and TLRs were detected with qPCR. In addition, western blotting was used to evaluate the expression of the NF-κB and MAPKs signaling pathways. The results demonstrated that a Se-supplemented diet improved the content of Se in mammary tissues. Histopathological studies indicated that the mammary glands were protected in the Se-supplemented group after S. aureus infection. Se-supplementation suppressed the production of MPO, mmu-miR-155, TNF-α, IL-1ß, and TLR2 and significantly inhibited the phosphorylation of NF-κB and MAPKs in vivo and in vitro. All the data indicated that mmu-miR-155 played a pro-inflammatory role in our study, and Se-supplementation could suppress the expression of mmu-miR-155 to inhibit inflammation in S. aureus-induced mastitis in mice.

7.
Neurol Sci ; 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31485861

RESUMO

STUDY OBJECTIVES: The aim was to investigate whether fatigue could predict the development of motor symptoms of Parkinson's disease (PD) in a southern Chinese population. METHODS: In total, 246 PD patients were recruited. All patients were evaluated by Fatigue Severity Scale (FSS), Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, and Unified PD Rating Scale provided by Movement Disorders Society (MDS-UPDRS). MDS-UPDRS was re-evaluated after 2 years. RESULTS: FSS scores were associated with total score and subparts of MDS-UPDRS (total: p 0.039, p 0.030, adjusted; part III: p 0.022, p 0.016, adjusted). CONCLUSIONS: The symptom of subjective fatigue could predict the progression of PD.

8.
Inorg Chem ; 58(20): 14167-14174, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31557004

RESUMO

A novel metal-organic framework (MOF), formulated as [Cd2(TTVTC)Cl2(H2O)3]·2H2O (1), was synthesized from a tetracarboxylate ligand ([TTVTC]2-) functionalized with the thiazolothiazole extended viologen (TTV2+) fluorophore. The MOF features three-dimensional (10,3)-d frameworks with 6-fold interpenetration. The MOF exhibits reversible photochromism, due to photoinduced electron transfer from carboxylate to TTV2+. The photoactivity benefits from the electron donor-acceptor contacts enabled by mutual interpenetration of the frameworks. This is the first demonstration of photochromism in TTV2+ derivatives. In addition, the fluorescence arising from the TTV2+ fluorophore can be reversibly modulated during the photochromic process. The work demonstrates the great potential of extended viologen based ligands in the construction of MOFs with dual photomodulable optical properties, which could find future applications in photoelectronics.

9.
Environ Pollut ; 254(Pt A): 112949, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31376599

RESUMO

In this study, various remote sensing data, modeling data and emission inventories were integrated to analyze the tempo-spatial distribution of biomass burning in mainland Southeast Asia and its effects on the local ambient air quality from 2001 to 2016. Land cover changes have been considered in dividing the biomass burning into four types: forest fires, shrubland fires, crop residue burning and other fires. The results show that the monthly average number of fire spots peaked at 34,512 in March and that the monthly variation followed a seasonal pattern, which was closely related to precipitation and farming activities. The four types of biomass burning fires presented different tempo-spatial distributions. Moreover, the monthly Aerosol Optical Depth (AOD), concentration of particulate matter with a diameter less than 2.5 µm (PM2.5) and carbon monoxide (CO) total column also peaked in March with values of 0.62, 45 µg/m3 and 3.25 × 1018 molecules/cm2, respectively. There are significant correlations between the monthly means of AOD (r = 0.74, P < 0.001), PM2.5 concentration (r = 0.88, P < 0.001), and CO total column (r = 0.82, P < 0.001) and the number of fire spots in the fire season. We used Positive Matrix Factorization (PMF) model to resolve the sources of PM2.5 into 3 factors. The result indicated that the largest contribution (48%) to annual average concentration of PM2.5 was from Factor 1 (dominated by biomass burning), followed by 27% from Factor 3 (dominated by anthropogenic emission), and 25% from Factor 2 (long-range transport/local nature source). The annually anthropogenic emission of CO and PM2.5 from 2001 to 2012 and the monthly emission from the Emission Database for Global Atmosphere Research (EDGAR) were consistent with PMF analysis and further prove that biomass burning is the dominant cause of the variation in the local air quality in mainland Southeast Asia.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/estatística & dados numéricos , Monitoramento Ambiental , Aerossóis/análise , Agricultura , Poluição do Ar/análise , Ásia Sudeste , Atmosfera/análise , Biomassa , Fogo , Material Particulado/análise , Estações do Ano , Incêndios Florestais
10.
Biochem Biophys Res Commun ; 516(3): 914-920, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31272717

RESUMO

The Ig superfamily member V-domain Ig-containing suppressor of T-cell activation (VISTA) is a negative regulator with broad-spectrum activities and has reported that blockade of VISTA or combination with other negative checkpoint receptors sufficiently break tumor tolerance. However, it remains unclear whether VISTA could induce allogeneic T-cell hyporesponsiveness and inhibit allograft rejection. Here we found VISTA treatment significantly inhibited lymphocyte proliferation and activation in allogeneic MLR assay through impairing SYK-VAV pathway. Interestingly, though neither VISTA protein nor VISTA-Fc fusion protein administration exerted satisfactory immunosuppressive effect on allograft survival due to their short half-life in circulation, this problem was solved by conjugating VISTA protein on liposome by biotin-streptavidin system, which markedly prolonged its circulating half-life to 60 h. With islet transplant model, administration of VISTA-conjugated liposome could markedly prolong allograft survival by inhibition of SYK-VAV pathway, thus maintained the normal blood glucose level of recipients during treatment period. The results indicate VISTA is a promising therapeutic target to treat allograft rejection of islet transplantation.

11.
Hereditas ; 156: 23, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31297041

RESUMO

Background: At present, the schizophrenia diagnoses are based on the clinical symptoms and behaviors neglecting the laboratory test indicators. Results: To better investigate the diagnostic potential of miRNAs for schizophrenia, we selected 14 candidate miRNAs and examined their expressions in the serums of 40 schizophrenia patients and 40 healthy controls by qRT-PCR. Ultimately three abnormally expressed microRNAs were identified, i.e., miR-34a-5p, miR-432-5p and miR-449a. Then, binary regression analysis was employed to combine 3 dysregulated miRNAs. ROC analysis revealed that the AUC of the combination of miR-432-5p + miR-449a in serums was 0.841 (95% CI: 0.791~0.887) with 90% sensitivity and 80% specificity. The AUC of the combination of miR-34a-5p + miR-432-5p + miR-449a in serums was 0.843 (95% CI: 0.791~0.887) with 90% sensitivity and 77.5% specificity. The results indicated that the combined model of miR-432-5p + miR-449a and miR-34a-5p + miR-432-5p + miR-449a have better prediction performances. Conclusions: The study concludes that the two miRNAs combinations have the potential to be used as biomarkers for schizophrenia diagnoses. The finding may be conducive to overcoming the dilemmas faced by current schizophrenia diagnosis.

12.
Medicine (Baltimore) ; 98(27): e15990, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277090

RESUMO

BACKGROUND: Recent studies have demonstrated that coronary microcirculation dysfunction (CMVD) is closely correlated with adverse clinical outcomes. In this study, quantitative stress myocardial contrast echocardiography (MCE) was used to evaluate the CMVD and to investigate its association with the prognosis of patients with nonobstructive coronary artery disease (CAD). MATERIAL AND METHODS: From 2006 to 2014, 227 consecutive patients with chest pain and a diagnostic coronary angiography without significant coronary artery stenosis (<50%) who underwent adenosine triphosphate disodium (ATP) stress MCE were enrolled. Quantitative MCE measurements were analyzed using replenishment curves. RESULTS: Median follow-up time of this study was 5.3 years. Predictors of impaired coronary flow reserve (CFR) were smoking, diabetes, high apolipoprotein B, high low-density lipoprotein, serum uric acid, and low apolipoprotein A. During follow-up, 22 patients were reported to have 30 cardiac events (21 unstable angina, 3 nonfatal myocardial infarctions, 6 percutaneous coronary interventions). Using multivariate analysis, abnormal ß reserve (≤1.6), impaired CFR (≤2.0), and diabetes were independent predictors of primary endpoint events in patients with nonobstructive CAD (P < .05). Multivariate analysis showed that CFR ≤2.0 (odds ratio [OR] =  25.21, 95% confidence interval [CI]: 3.01-182.32; P = .003), ß reserve ≤1.6 (OR = 29.96, 95% CI: 3.5-241.27; P = .002), and diabetic (OR = 33.11, 95% CI: 3.65-300.02; P = .002) significantly increased the risk of the primary endpoint events. CONCLUSIONS: ATP stress quantitative MCE is a feasible and effective method to evaluate microcirculation abnormalities in human coronary arteries and it can be used for the clinical analysis, risk stratification, and treatment of early CAD.


Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Estenose Coronária/diagnóstico por imagem , Ecocardiografia sob Estresse/métodos , Ecocardiografia/métodos , Microcirculação/fisiologia , Trifosfato de Adenosina/administração & dosagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco
13.
Chin J Nat Med ; 17(5): 363-371, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31171271

RESUMO

Flavonoids have been reported to exert protective effect against many inflammatory diseases, while the underlying cellular mechanisms are still not completely known. In the present study, we explored the anti-inflammation activity of 5, 7, 2', 4', 5'-pentamethoxyflavanone (abbreviated as Pen.), a kind of polymethoxylated flavonoid, both in vitro and in vivo experiments. Pen. was showed no obvious toxicity in macrophages even at high dosage treatment. Our results indicated that Pen. significantly inhibited both mRNA and protein level of proinflammatory cytokines, IL-1ß, IL-6, TNF-α and iNOS, which was characteristic expressed on M1 polarized macrophages. These effects of Pen. were further confirmed by diminished expression of CD11c, the M1 macrophage surface marker. Further researches showed that the mechanism was due to that Pen. downregulated the activity of p65, key transcription factor for M1 polarization. On the other hand, Pen. also enhanced M2 polarization with upregulation of anti-inflammatory factors and increase of M2 macrophage surface markers, which lead to the balance of M1 and M2 macrophages. Moreover, in vivo research verified that Pen. treatment alleviated LPS-induced sepsis in mice by increasing survival rate, decreasing inflammatory cytokines and improving lung tissue damage. In summary, our results suggested that Pen. modulated macrophage phenotype via suppressing p65 signal pathway to exert the anti-inflammation activity.

14.
Sci China Life Sci ; 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31231780

RESUMO

A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women. A randomized, immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in China. Girls aged 9-14 years were randomized to receive 2 doses at months 0 and 6 (n=301) or 3 doses at months 0, 1 and 6 (n=304). Girls aged 15-17 years (n=149) and women aged 18-26 years (n=225) received 3 doses. The objectives included noninferiority analysis of the IgG geometric mean concentration (GMC) ratio (95% CI, lower bound>0.5) to HPV-16 and HPV-18 at month 7 in girls compared with women. In the per-protocol set, the GMC ratio of IgG was noninferior for girls aged 9-17 years receiving 3 doses compared with women (1.76 (95% CI, 1.56, 1.99) for HPV-16 and 1.93 (95% CI, 1.69, 2.21) for HPV-18) and noninferior for girls aged 9-14 years receiving 2 doses compared with women (1.45 (95% CI, 1.25, 1.62) for HPV-16 and 1.17 (95% CI, 1.02, 1.33) for HPV-18). Noninferiority was also demonstrated for neutralizing antibodies. The immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.

15.
J Nanosci Nanotechnol ; 19(12): 7758-7763, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31196286

RESUMO

A novel Eu-TiO2 nanocomposite prepared by a sol-gel method is used for the degradation of rhodamine B (RhB) present in dyes wastewater. The X-ray diffraction (XRD), Raman spectroscopy and transmission electron microscopy (TEM) show the anatase phase and globular shape of Eu- TiO2 nanocomposite, UV-vis diffuse reflectance spectroscopy and low temperature N2 adsorption (BET) indicate Eu-TiO2 possesses a narrow band gap (2.98 eV) and a high specific surface area (112.1 m² · g-1), respectively. Furthermore, the prepared Eu-TiO2 exhibits unprecedented higher photocatalytic activity towards RhB than P25 TiO2. The degradation ratio of RhB is up to 93% within 100 min irradiation of simulated solar lights by the obtained Eu-TiO2, which demonstrated firstly by the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis. The high photocatalytic performance may be ascribed to the efficient Eu loading in favor of the absorption of visible-light and the separation of photogenerated charges.

16.
J Pharm Biomed Anal ; 174: 367-375, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31202879

RESUMO

Fufang Danshen Dripping Pill (FDDP) and Clopidogrel Bisulfate Tablet (CBT) are usually combined for treatment of coronary artery diseases in clinical. To investigate the pharmacokinetic interaction between FDDP and CBT after oral administration of FDDP, CBT and their combination in rats, a novel LC-MS method with segmented scan modes (multiple reaction monitoring and selected ion monitoring) and polarity (positive and negative ionization) was developed. Clopidogrel and the main active ingredients of FDDP, with different chemical and ionization properties, were simultaneously quantified in plasma in a single run. The method was validated in terms of specificity, linearity, precision, accuracy, recovery, matrix effect and stability. As a result, co-administration of FDDP and CBT significantly altered the pharmacokinetic parameters of danshensu, ginsenoside Rb1, dihydrotanshinone I, tanshinone I and tanshinone IIA of FDDP, as well as clopidogrel. Mechanism studies suggested that induction of liver cytochrome P450 isozymes CYP2C11 and CYP3A1 by co-administration, as well as inhibition of carboxyl esterase 1, was partly responsible for FDDP-CBT pharmacokinetic interactions. The developed LC-MS method could be used to simultaneously quantify different types of in vivo analytes in a single run, and the results could be used for clinical medication guidance of FDDP and CBT.

17.
J Chromatogr A ; 1601: 335-339, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31155143

RESUMO

Sodium valproate is the most commonly used antiepileptic drug that patients need to keep taking over a long period of time or on a permanent basis. Its blood concentration should be accurately detected to avoid toxicity or side-effects, especially for children and the aged. Dried blood spot (DBS) sampling from finger prick is a minimally invasive and patient-friendly procedure for blood collection. However, there are few studies about rapid detection of sodium valproate in DBS samples in current literatures. In this work, we developed an ink auxiliary headspace gas chromatography mass spectrometry (GC-MS) strategy for direct detection of sodium valproate in DBS from epilepsy patients, which does not need extra solvent extraction or elution. It was discovered that carbon black ink could provide better capacity of heat absorption and dissociation, and higher quality of headspace sampling. The detection sensitivity has been improved with reported headspace GC-MS methods, and the limit of quantitation could reach to 200 ng/mL. Finally, this strategy was practically applied to quantify sodium valproate in DBS samples from 29 epilepsy patients. The result showed higher accuracy with lower relative errors by comparing with the clinical immunoassay results. In conclusion, we developed a direct detection method for DBS samples that is suitable for high-throughput clinical test with great potential for clinical application.


Assuntos
Teste em Amostras de Sangue Seco/métodos , Cromatografia Gasosa-Espectrometria de Massas , Ácido Valproico/análise , Anticonvulsivantes/análise , Anticonvulsivantes/sangue , Criança , Monitoramento de Medicamentos , Humanos , Manejo de Espécimes , Ácido Valproico/sangue
18.
Zhongguo Zhen Jiu ; 39(6): 632-6, 2019 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-31190501

RESUMO

OBJECTIVE: To compare the effects of electroacupuncture (EA) at "Zusanli" (ST 36) versus "Yanglingquan" (GB 34) in the pregnant rats on perinatal nicotine-exposure-induced lung function and morphology of newborn rats and explore the rule of acupoint effect in EA for the prevention from lung dysplasia in newborn rats. METHODS: A total of 24 female SD rats were randomized into a normal saline group (S group), a nicotine group (N group), a nicotine-ST 36 group (N + ST 36 group) and a nicotine-GB 34 group (N+GB 34 group), 6 rats in each one. Starting at the 6th day of pregnancy, 0.9% sodium chloride solution was injected subcutaneously in the S group, 1 mg/kg; and in the rest 3 groups, nicotine of the same dose was injected through to the 21st postnatal day to establish the perinatal nicotine-exposure model. Simultaneously, during model preparation, EA was applied at "Zusanli" (ST 36) and "Yanglingquan" (GB 34) in the N+ST 36 group and the N+GB 34 group respectively, once a day, through to the 21st postnatal day. The lung function analytic system for small animal was adopted to observe the changes in lung function indicators in newborn rats, such as peak inspiratory flow (PIF), peak expiratory flow (PEF), expiratory resistance (RE), inspiratory resistance (RI) and dynamic compliance (Cdyn). HE staining was used to observe the morphological changes of lung, such as alveolar fusion and rupture. RESULTS: Compared with the S group, PEF and Cdyn were lower and PIF, RI and RE higher in the N group (all P<0.01), additionally, alveoli were fused and ruptured, alveolar wall thickened, the numbers of alveoli reduced, the interspace of alveoli enlarged and the diameter increased (P<0.01). Compared with the N group, in the N+ST 36 group, PEF and Cdyn were increased, PIF, RI and RE reduced (P<0.05, P<0.01), the alveolar fusion and rupture relieved, the numbers of alveoli increased, alveolar wall thinner, the interpsace of alveoli became normal and the diameter was reduced significantly (P<0.01). In the N+GB 34 group, the changes of lung function and morphological indicators were not significant (P>0.05). CONCLUSION: Electroacupuncture at "Zusanli" (ST 36) in the pregnant rats significantly improves the perinatal nicotine-exposure-induced lung function and morphology of newborn rats than electroacupuncture at "Yanglingquan" (GB 34).


Assuntos
Eletroacupuntura , Pulmão , Nicotina , Pontos de Acupuntura , Animais , Animais Recém-Nascidos , Feminino , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Nicotina/toxicidade , Gravidez , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
19.
Curr Drug Deliv ; 16(6): 500-510, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31244438

RESUMO

BACKGROUND: Olmesartan medoxomil (OLM) is a promising prodrug hydrolyzed to olmesartan (OL) during absorption from the gastrointestinal tract. OL is a selective angiotensin II receptor antagonist, with high drug resistance and low drug interaction. However, OLM has low solubility and low bioavailability. Therefore, it is extremely urgent to reduce the drug particle size to improve its biological bioavailability. OBJECTIVE: The aim of the study was to improve the oral bioavailability of poorly water-soluble olmesartan medoxomil (OLM) by using different particle size-reduction strategies. METHOD: Raw drug material was micronized or nanosized by either jet or wet milling processes, respectively. The particle sizes of the prepared nanocrystals (100-300 nm) and microcrystals (0.5-16 µm) were characterized by DLS, SEM, and TEM techniques. Solid state characterization by XPRD and DSC was used to confirm the crystalline state of OLM after the milling processes. RESULTS: We demonstrated that OLM nanocrystals enhanced solubility and dissolution in the non-sink condition in which high sensitivity was found in purified water. After 1 h, 65.4% of OLM was dissolved from nanocrystals, while microcrystals and OLMETEC® only showed 37.8% and 31.9% of drug dissolution, respectively. In the pharmacokinetic study using Beagle dogs, an increase in Cmax (~2 fold) and AUC (~1.6 fold) was observed after oral administration of OLM nanocrystals when compared to microcrystals and reference tablets, OLMETEC®. In contrast, OLM microcrystals failed to improve the oral bioavailability of the drugs. CONCLUSION: Particles size reduction to nano-scale by means of nanocrystals technology significantly increased in vitro dissolution rate and in vivo oral bioavailability of OLM.

20.
J Natl Cancer Inst ; 2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31086947

RESUMO

Background The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase 3 clinical trial was conducted to evaluate the efficacy, safety and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multi-centre, randomized, double-blind trial started on November 22, 2012, in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receiving 3 doses of the test or control (hepatitis E) vaccine at months 0, 1 and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received 3 doses of the vaccine. This report presents data from a pre-specified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval [CI] = 55.6% to 100.0%, 0/3306 in the vaccine group vs. 10/3296 in the control group) and 97.8% (95% CI = 87.1% to 99.9%, 1/3240 vs. 45/3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The Escherichia coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18 associated high-grade genital lesions and persistent infection in women.

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