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1.
Oncotarget ; 10(57): 6045-6046, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31666936

RESUMO

[This corrects the article DOI: 10.18632/oncotarget.26740.].

2.
Drug Des Devel Ther ; 13: 3291-3306, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571831

RESUMO

Objectives: This study was performed to evaluate the effects of muscone on the proliferation, migration and differentiation of human gingival mesenchymal stem cells (GMSCs) and to explore the relevant mechanisms. Materials and methods: We performed studies to determine the effects and mechanisms of muscone on GMSC proliferation, migration and differentiation. We conducted CCK-8, colony formation, transwell chamber, scratch wound, alkaline phosphatase (ALP) staining and activity, and alizarin red and oil red O staining assays, as well as real-time quantitative polymerase chain reaction (qRT-PCR), to ascertain the effects of muscone on GMSC proliferation, migration and differentiation in vitro. The mechanism by which muscone influences the osteogenic and adipogenic differentiation of GMSCs was elucidated by qRT-PCR and Western blotting. Results: We found that muscone significantly promoted GMSC proliferation, chemotaxis, wound healing and fat droplet formation and inhibited ALP activity and mineral deposition. Notably, we observed that the Wnt/ß-catenin pathway was closely related to the ability of muscone to inhibit the osteogenic differentiation and promote the adipogenic differentiation of GMSCs. The effect of muscone on the multidirectional differentiation capacity of GMSCs was significantly reversed by the agonist lithium chloride through the Wnt/ß-catenin signaling pathway. Conclusion: Muscone effectively increased the proliferation and migration, promoted the adipogenic differentiation and inhibited the osteogenic differentiation of GMSCs by inhibiting the Wnt/ß-catenin signaling pathway. These results may provide a theoretical basis for the application of GMSCs and muscone in tissue engineering and regenerative medicine.

3.
Pest Manag Sci ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31595658

RESUMO

BACKGROUND: Precise regulation of oogenesis is crucial to female reproduction. 70% of pests belong to lepidopteran insect, so it would be interesting to explore the highly conserved genes involved in oogenesis that do not affect growth and development. This can provide potential target genes for pest control and promote the development of insect sterility technology. RESULTS: In lepidopteran species, ovarian serine protease (Osp), which encodes a member of the serine protease family, is essential for oogenesis. In this study, we used transgenic CRISPR/Cas9 technology to obtain Osp mutants in the model lepidopteran insect Bombyx mori and in the lepidopteran agricultural pest Spodoptera litura. Sequence analysis of mutants revealed an array of deletions in Osp loci in both species. We found that the deletion of Osp resulted in female sterility, whereas male fertility was not affected. Although B. mori and S. litura mutant females mated normally, they laid fewer eggs than wild-type females and eggs did not hatch. CONCLUSION: Osp is crucial for female reproductive success in two species of Lepidoptera. As the Osp gene is highly conserved in insect species, this gene is a potential molecular target for genetic-based pest management. This article is protected by copyright. All rights reserved.

4.
Int J Environ Health Res ; : 1-14, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31621395

RESUMO

Natural environment is an important factor affecting longevity. Soil, water and hair samples from Bama were assayed to investigate the effects of elements on the regional longevity. The concentrations of Cd, Co and Mg in soil and Co in drinking water were significantly higher in longevity area than those in non-longevity area (p < 0.05). The concentrations of K, Mo, Na, Pb and V in soil, Mg, Na, Fe, Li and Mn in drinking water and I, K, Mg, Mn, Na and Sr in hair were significantly lower in longevity area than those in non-longevity area (p < 0.05). Mg, Mn, Na and Sr in hair were affected by soil and drinking water. Our results indicate that adequate concentration of Mg in soil might benefit longevity, excessive concentrations of Na in soil, Mg, Mn and Na in drinking water and Mg, Mn, Na and Sr in hair might reduce lifespan of local residents.

5.
J Integr Neurosci ; 18(3): 253-259, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31601073

RESUMO

Executive functions are closely related to the prefrontal cortex, and inhibitory control is an important component of executive functioning. Previous studies have found that inhibitory control continues to develop after adolescence and that obesity is associated with executive functions. However, few studies have addressed whether obesity affects the development of inhibitory control. Hence, we focused on whether inhibitory control continues to develop after adolescence in obese individuals. We used a Stroop task to measure the inhibitory control of young obese subjects, and monitored accompanying brain activation by functional near-infrared spectroscopy technology. The findings suggest that brain activation due to Stroop interference does not increase with age in obese subjects and that early prevention of executive function deficit is recommended.

6.
Insect Biochem Mol Biol ; : 103243, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31541694

RESUMO

Sterile insect technology (SIT) is an environmentally friendly method for pest control. As part of our efforts to develop a strategy that results in engineered male-sterile strains with minimum effects on viability and mating competition, we used CRISPR/Cas9 technology to disrupt Ser2, which encodes a seminal fluid protein, in the model lepidopteran insect, Bombyx mori, and an important agricultural pest, Plutella xylostella. Disruption of Ser2 resulted in dominant heritable male sterility. Wild-type females mated with Ser2-deficient males laid eggs normally, but the eggs did not hatch. We detected no differences in other reproductive behaviors in the mutant males. These results support the conclusion that Ser2 gene is necessary for male reproductive success in diverse lepidopterans. Targeting Ser2 gene has the potential to form the basis for a new strategy for pest control.

7.
Chemosphere ; 235: 1089-1096, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31561299

RESUMO

WWTPs may be one of the important ways for MPs to enter surface water. In the present study, the influent and effluent from eleven WWTPs in Changzhou were collected and analyzed. At the same time, the abundance, size, color, and shape of MPs in influent and effluent were investigated. The average abundance of MPs in the influent and effluent were 196.00 ±â€¯11.89 n/L and 9.04 ±â€¯1.12 n/L respectively, and the MPs removal efficiency of eleven WWTPs was almost over 90% in which it could be up to 97.15%. MPs were divided into four particle size based on abundance changes, and the size of MPs with the highest abundant was mainly concentrated at 0.1-0.5 mm. Among these MPs, fibers were the main shape in wastewater, followed by fragments, flakes, spheres and films. The colors of MPs in wastewater were various and 14 types of plastics were detected from wastewater using attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Moreover, Rayon and PET were the dominant polymer types in eleven WWTPs. The research results provided basic data for the research and supervision of MPs pollution in WWTPs.


Assuntos
Plásticos/análise , Instalações de Eliminação de Resíduos/normas , Águas Residuárias/química , Poluentes Químicos da Água/análise , Celulose/análise , Cor , Tamanho da Partícula , Plásticos/isolamento & purificação , Polietilenotereftalatos/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Eliminação de Resíduos Líquidos
8.
J Chromatogr A ; : 460515, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31522803

RESUMO

Tandem mass spectrometry (MS/MS), in particular high-resolution MS/MS, is able to provide element compositions and substructures for the detected signals. However, it is still challenging to configure the whole structures via linking those substructures. Efforts were devoted here to propose and validate optimal collision energy (OCE) to be an auxiliary structural clue to mass-to-charge ratios (m/z), and online energy-resolved MS was developed to yield OCEs. Chlorogenic acid derivatives (CADs) were utilized as the proof-of-concept because diverse isomers usually initiated by the different linkage manners between the quinic acid/shikimic acid and cinnamoyl substituents(s), i.e. caffeoyl group, coumaroyl group, etc. Liquid chromatography-hybrid ion trap-time of flight MS (LC-IT-TOF-MS) was implemented to capture CADs in two well-known herbal medicines namely Lonicerae japonicae Flos and Inulae Flos. Afterwards, hybrid triple quadrupole-linear ion trap MS (Qtrap-MS) was deployed to acquire OCEs for the primary fragmentation pathways of all detected CADs through online energy-resolved MS. On the other side, structural calculations were conducted to figure out the relationships between OCEs and bond properties. Isomeric differences occurred for OCEs, and LC elution program as well as ionization parameters could not affect OCEs. Twenty-four and thirty-one CADs were hunted and putatively identified by LC-IT-TOF-MS in Lonicerae japonicae Flos and Inulae Flos, respectively, and the structural annotation was advanced by applying the OCE-bond property relationships. To verify the structures, CADs-of-interest were purified from Lonicerae japonicae Flos using an automated fraction collector and definitely identified with NMR spectroscopy. Exact consistence occurred for the structural identification of mono-caffeoylquinic acid isomers between LC-MS/MS and NMR analyses. Consequently, OCE is an inherent physicochemical parameter of a given compound and is an eligible structural descriptor to offset the ability of LC-MS/MS towards the chemical profiling of complex matrices.

9.
Gene ; 721: 144100, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31493508

RESUMO

BACKGROUND: Breast cancer (BRCA) is the most prevalent cancer that threatens female health. A growing body of evidence has demonstrated the non-negligible effects of messenger RNAs (mRNAs) on biological processes involved in cancers; however, there is no definite conclusion regarding the role of mRNAs in predicting the prognosis of BRCA patients. MATERIALS AND METHODS: We systematically screened the mRNA expression landscape and clinical data of samples from the Cancer Genome Atlas (TCGA). Univariate Cox analysis and robust likelihood-based survival analysis were conducted to identify key mRNAs associated with BRCA. Furthermore, risk scores based on multivariate Cox analysis divided the training set into high-risk and low-risk groups. ROC analysis determined the optimal cut-off point for patient classification of risk levels. The prognostic model was additionally validated in the testing set and complete dataset. Finally, we plotted the survival curves for the mRNAs used in our model. RESULTS: We obtained the original expression data of 13,617 mRNAs from a total of 1088 samples. After comprehensive survival analysis, the four-mRNA (ACSL1, OTUD3, PKD1L2, and WISP1) prognosis risk assessment model was constructed. Furthermore, the area under cure (AUC) was 0.834, indicating that the model was meaningful and reasonable. In each dataset, analysis based on the four-mRNA signature risk score indicated that the survival status of the group with high risk score was worse than that of the group with low risk scores. Patients with strong mRNA expression of OTUD3, PKD1L2, and WISP1 tended to have good prognosis, whereas patients with high ACSL1 expression tended to have poor prognosis. CONCLUSION: In summary, we constructed a four-mRNA prognosis risk assessment model for BRCA. The newly developed model offers more possibilities for assessing prognosis and guiding the selection of better treatment strategies for BRCA.

10.
Cancer Causes Control ; 30(11): 1201-1211, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31542834

RESUMO

PURPOSE: Menopausal hormone therapy (MHT) use induces alterations in circulating estrogens/estrogen metabolites, which may contribute to the altered risk of reproductive tract cancers among current users. Thus, the current study assessed associations between circulating estrogens/estrogen metabolites and ovarian and endometrial cancer risk among MHT users. METHODS: We conducted a nested case-control study among postmenopausal women using MHT at baseline in the Women's Health Initiative Observational Study (179 ovarian cancers, 396 controls; 230 endometrial cancers, 253 controls). Multivariable logistic regression was utilized to estimate odds ratios and 95% confidence intervals overall and by subtype. RESULTS: Estrogen/estrogen metabolite levels were not associated with overall or serous ovarian cancer risk, examined separately. However, unconjugated estradiol was positively associated with non-serous ovarian cancer risk [quintile 5 vs. quintile 1: 3.01 (1.17-7.73); p-trend = 0.03; p-het < 0.01]. Endometrial cancer risk was unrelated to estrogen/estrogen metabolite levels among women who took combined estrogen/progestin therapy (EPT). CONCLUSIONS: These findings provide novel evidence that may support a heterogeneous hormonal etiology across ovarian cancer subtypes. Circulating estrogens did not influence endometrial cancer risk among women with EPT-induced high-estrogen levels. Larger studies are needed to delineate the relationship between ovarian/endometrial cancer subtypes and estrogen levels in the context of MHT use.

11.
Eur J Pharmacol ; 861: 172587, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31377155

RESUMO

Oridonin is a diterpenoid isolated from Rabdosia rubescens (Hemsl.) Hara, a well-known herbal tea in China with many health benefits. To provide a better understanding of the potential cardioprotective effect of Oridonin, we investigated the metabolic alterations in heart tissue and serum of rat subjected to myocardial ischemia/reperfusion (MI/R) injury with or without pretreatment of Oridonin by UPLC-MS/MS metabolomics approach. Rats were randomly divided into groups as follows: Control, Sham, MI/R and pretreated with Oridonin (10 mg/kg)+MI/R. After 24 h of reperfusion, heart tissue and serum were collected for biochemical and metabolomic analysis. Pretreatment with Oridonin significantly decreased infarct size and reversed the abnormal elevated myocardial zymogram in serum. Moreover, Oridonin regulated several metabolic pathways, including glycolysis, branched chain amino acid, kynurenine, arginine, glutamine and bile acid metabolism. Our results suggest that Oridonin indeed displays outstanding cardioprotective effect mainly by regulating energy and amino acid metabolism.

12.
Hypertens Pregnancy ; 38(4): 217-222, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31366258

RESUMO

Objective: To assess whether supplementation with Coenzyme Q10 (CoQ10) during pregnancy alleviate preeclampsia symptoms and the underlying mechanism in the rats with preeclampsia. Methods: Forty-five pregnant Wistar rats were equally divided into three groups randomly and received subcutaneous saline injection (control group, n = 15) or 200 mg/kg L-NAME injection to induce preeclampsia symptoms (PE group, n = 30). The PE rats were treated by distilled water (PE+DW group, n = 15) and CoQ10 (PE+CoQ10 group, n = 15) on day 15 to 21 of gestation randomly. Physiological characteristics such as urine volume, total urine protein, blood pressure, number and weight of pups were recorded. Fluorescent dye was used to detect mitochondrial membrane potential in placenta. Real-time fluorescent quantitative PCR was used to detect the expression of mitochondrial DNA(mtDNA) in placenta. Results: There was no statistic difference among all the three groups on day 10 of gestation in SBP and 24-h proteinuria (P > 0.05). Whereas, SBP and 24-h proteinuria were significantly higher in PE group than control group on day 15 and 21 of gestation (P < 0.05). SBP and 24-h proteinuria were significantly lower in PE+CoQ10 group than PE+DW group on day 21 of gestation (P < 0.05). The number and weight of normal pups were significantly lower in PE group than the control group (P < 0.05), which were most notably in distilled water group, and the number and weight of normal pups were markedly bigger in PE+CoQ10 group rats compared to PE+DW (P < 0.05). The PE+CoQ10 group showed a significantly higher in level of mitochondrial membrane potential than PE+DW group. The expression of mtDNA was significantly higher in the PE+CoQ10 group compared with PE+DW group (P < 0.05). Conclusions: CoQ10 can alleviate preeclampsia symptoms and enhance the function of mitochondria in the placenta.

13.
Clin Lab ; 65(8)2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31414742

RESUMO

BACKGROUND: In order to establish suitable reference intervals (RIs) of serum cytokeratin-19 fragment (Cyfra211) and neuron specific enolase (NSE) for the healthy Chinese population in Chengdu, China, an indirect method was developed using the data from the people presented for routine health check-up. METHODS: All results for 4,988 healthy persons serum cytokeratin-19 fragment and 3,293 healthy persons neuron specific enolase were collected in our laboratory information system between January 2016 and December 2018. Outliers were identified and excluded using the stem-and-leaf and box plot methods. Mann-Whitney U test was used to observe the difference between sexes. Spearman's rank correlation analysis was used to evaluate the correlation between serum results and age. The RIs were defined by nonparametric 95th percentile interval. RESULTS: After statistical analysis the indirect RIs were 0.0 - 3.70 ng/mL (Cyfra211) and 0 - 17.26 ng/mL (NSE) in males and 0.0 - 3.35 ng/mL (Cyfra211) and 0.0 - 16.29 ng/mL (NSE) in females. Cyfra211 and NSE levels in males and females had no correlation with age. Therefore, there was no need to establish RIs according to age group. RIs of Cyfra211 and NSE were verified and passed the verification in the end. CONCLUSIONS: Using health check-up persons' laboratory data values is a relatively easy and cheap method of establishing laboratory specific references. This method deserves to be promoted and applied by other clinical laboratories.

14.
Drug Des Devel Ther ; 13: 2543-2552, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440036

RESUMO

Objectives: The aim of this study is to examine the roles of erythropoietin (EPO) in regulating proliferation and osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and analyze the underlying signaling of these processes. Materials and methods: PDLSCs were isolated and characterized. The PDLSCs were transfected with ß-catenin shRNA. qRT-PCR and Western blot analysis were used to examine the osteogenic effects of EPO on the expression of osteogenic-related genes and protein (Runx2, OCN and Osterix) in PDLSCs. Alizarin Red-S staining was used to detect mineralized nodule formation. In addition, the relationship between the Wnt/ß-catenin pathway and the effect of EPO on the osteogenesis of PDLSCs was investigated. Results: The results suggested that EPO exerts positive osteogenic effects on PDLSCs. The results showed that EPO decreased the growth of PDLSCs slightly and increased alkaline phosphatase activity and calcium deposition in a dose-dependent manner. The expression of Runx2, Osterix and OCN was increased after EPO administration. EPO increases ß-catenin and Cyclin D1 in PDLSCs. After transfected with ß-catenin shRNA, the osteogenic effect of EPO on PDLSCs was attenuated. Conclusion: EPO promotes osteogenic differentiation of PDLSCs. The underlying mechanism may be activating Wnt/ß-catenin signaling pathway.

15.
Zhongguo Zhong Yao Za Zhi ; 44(13): 2667-2674, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31359675

RESUMO

Chemical profiling of a given herbal medicine( HM) is the prerequisite for clarifying the effective material basis and therapeutic mechanisms,and it is an important integral part of traditional Chinese medicine chemical biology( TCMCB). In current study,we aimed to propose a new strategy for fast chemical characterization of HM by using reversed phase liquid chromatography-hydrophilic interaction chromatography-predictive multiple reaction monitoring( RPLC-HILIC-p MRM),and Artemisiae Scopariae Herba was employed in this study to illustrate the entire strategy. In response to wide polarity spanning of the diverse chemical clusters in Artemisiae Scopariae Herba,RPLC and HILIC were coupled in series to retain and separate hydrophilic and hydrophobic components simultaneously by identifying the characteristics of chromatographic separation. Most of the chemical constituents in traditional Chinese medicine can be predicted by summarizing the results of chemical constituents of the same genera and introducing primary metabolites and possible substitution reaction types. Therefore,we constructed predictive ion pairs to rapidly identify the chemical constituents of Artemisiae Scopariae Herba. After comparison with control products,discussion on fragmentation pattern,and access to relevant information from literature and databases,a total of 139 components were detected and structurally annotated by matching the obtained spectral data with the information of authentic compounds. Above all,RPLC-HILIC-p MRM could be used as an eligible analytical tool for the chemical profiling of HMs.


Assuntos
Artemisia/química , Cromatografia de Fase Reversa , Plantas Medicinais/química , Interações Hidrofóbicas e Hidrofílicas , Medicina Tradicional Chinesa
16.
Clin Rheumatol ; 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300980

RESUMO

OBJECTIVE: The association between hyperuricemia and insulin resistance (IR) has been demonstrated by many studies, but the traditional IR indexes are too impractical to be used in clinical practice for the recognition of the IR state in individuals with hyperuricemia. Therefore, we aimed to further investigate the association between hyperuricemia and three non-insulin-based IR indexes in this large-scale cross-sectional study. METHODS: A total of 174,695 adults without self-reported use of antihyperuricemic agents, hypoglycemic agents, or lipid-lowering drugs were included in the current analysis. The triglyceride to high-density lipoprotein cholesterol ratio (TG/HDLc), the product of fasting triglycerides and glucose (TyG), and metabolic score for IR (METS-IR) were calculated. Then, logistic regression analyses were applied to explore their association with hyperuricemia. RESULTS: The TG/HDLc, TyG, and METS-IR all had positive correlations with uric acid level. However, only TG/HDLc and TyG were significantly associated with hyperuricemia in both sexes and body mass index (BMI) classification (the ORs of the highest quartile for each were 6.751 and 1.505 in females and 6.487 and 1.646 in males, respectively). The AUC values of TG/HDLc and TyG to discriminate hyperuricemia were also statistically significant in both sexes and BMI classification (all greater than 0.7). CONCLUSIONS: TG/HDLc and TyG are strongly associated with hyperuricemia regardless of BMI classification. These two obtainable and cost-effective non-insulin-based IR indexes could be potential monitors during the management of hyperuricemia and prevention of its IR-driven comorbidities. Key Points • In this large-scale study, we identified TG/HDLc and TyG as indicators for identification of IR in patients with hyperuricemia. • These simple and practical IR indicators are of substantial clinical importance for implementing preventive strategies against IR-driven comorbidities of hyperuricemia.

17.
Cell Cycle ; 18(18): 2332-2343, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31345079

RESUMO

Objective: Long non-coding RNAs (lncRNAs) have recently been demonstrated to be involved in craniocerebral disease, but their expression in traumatic brain injury (TBI) is still unearthed. Therefore, we aimed to elucidate the effect of lncRNA CRNDE on TBI. Methods: Firstly, CRNDE expression was determined in serum of TBI patients and healthy controls. The TBI rat model was established based on Feeney's freefall impact method. The modeled rats were injected with siRNA against CRNDE, and the rats' neurobehavioral function were measured. Besides, expression of inflammatory factors, size, shape and number of hippocampal neurons, neuron apoptosis, Beclin I, LC3-I, LC3-II, glial fibrillary acidic protein (GFAP), BrdU, nerve growth factor (NGF), nestin, and neuronal nuclei (NeuN) expression were detected through different methods. Results: In TBI, CRNDE was found to be upregulated. Downregulated CRNDE improved neurobehavioral function, repressed expression of neuroinflammatory factors, elevated number of Nissl bodies, as well as restricted neuronal apoptosis and autophagy in TBI rats. Besides, downregulated CRNDE also promoted expression of GFAP, BrdU, NGF, nestin, and NeuN, thus induced the differentiation of neurons and the directional growth and regeneration of nerve fibers. Conclusion: Altogether, we found that silencing of CRNDE might be able to promote the nerve repair after TBI in rats.

19.
Antivir Ther ; 2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31355775

RESUMO

BACKGROUND: The safety and efficacy of doravirine were compared with that of efavirenz as initial treatment of adults living with HIV-1 infection (NCT01632345). METHODS: A Phase 2b double-blind trial with participants stratified by screening HIV-1 RNA (≤ or >100 000 copies/ml) and randomized 1:1:1:1:1 to receive once-daily doravirine (25, 50, 100, or 200 mg) or efavirenz 600 mg (Part I) for up to 96 weeks, with open-label tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (TDF/FTC). After dose selection at Week 24, doravirine 100 mg was provided to participants receiving the other doses of doravirine and additional participants were randomized 1:1 to receive once-daily doravirine 100 mg or efavirenz 600 mg for 96 weeks with TDF/FTC (Part II). Primary outcomes were the proportion of participants with HIV-1 RNA <40 copies/ml at Week 24, and central nervous system (CNS) adverse events (AEs) by Weeks 8 and 24 (Parts I+II combined). RESULTS: 210 and 132 participants were randomized in Parts I and II, respectively, and 216 (108 on doravirine 100 mg, 108 on efavirenz) were evaluable for Parts I+II combined. At Week 24, the proportion of participants with HIV-1 RNA <40 copies/ml was 72.9% for doravirine 100 mg and 73.1% for efavirenz (difference -0.5 [95% CI -12.3-11.2]). In addition, CNS AEs were reported by 26.9% and 47.2% of doravirine and efavirenz recipients, respectively (difference -20.4 [95% CI -32.6 to -7.5], p=0.002). CONCLUSIONS: Doravirine 100 mg with TDF/FTC demonstrated similar antiretroviral activity and superior CNS safety compared with efavirenz 600 mg with TDF/FTC.

20.
Medicine (Baltimore) ; 98(30): e16575, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31348290

RESUMO

BACKGROUND: Dapagliflozin, a novel inhibitor of sodium-glucose cotransporter-2 (SGLT-2), lowers blood glucose level by specifically inhibiting the activity of SGLT-2. Previous studies showed efficacy and safety of dapagliflozin combined with other antihyperglycemic agents in type 2 diabetes (T2DM), however, there are few studies for dapagliflozin as monotherapy. The aim of this study was to assess the efficacy and safety of dapagliflozin as a monotherapy in T2DM and provide theoretical basis for clinical rational use of drugs. METHODS: We did a systematic review and meta-analysis of randomized, placbo-controlled clinical studies in patients with type 2 diabetes. We searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, and VIP database through October 2018, we also manually screened list of references to the previous meta-analysis of dapagliflozin in the treatment of type 2 diabetes. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. A meta-analysis was conducted by using RevMan 5.3 software. RESULTS: Six randomized controlled trials (RCTs) including 2033 patients were analyzed. Compared with placebo, dapagliflozin monotherapy was associated with a reduction in glycosylated hemoglobin A1c (HbA1c) (weighted mean difference [WMD]: -0.60%; 95% confidence interval [CI]: -0.67%, -0.52%; P < .00001), fasting plasam glucose (FPG) (WMD: -1.30 mmol/L; 95% CI: -1.52, -1.08; P < .00001), and body weight (WMD: -1.50 kg; 95% CI: -1.67, -1.32; P < .00001). Dapagliflozin was associated with an increased risk of urinary tract infections (relative risk [RR]: 1.74; 95% CI: 1.21, 2.49; P = .003) and genital tract infections (RR: 3.52; 95% CI: 2.06, 6.03; P < .00001). CONCLUSIONS: Dapagliflozin monotherapy was well tolerated and effective in reducing the level of HbA1c, FPG, and body weight in patients with T2DM without increasing hypoglycaemia, although it may increase the risk of urinary tract infections and genital tract infections. This meta-analysis provides an evidence for the treatment in patients with T2DM. However, more randomized clinical evidences are still needed to verify the results.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/efeitos adversos , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Glucosídeos/administração & dosagem , Glucosídeos/efeitos adversos , Hemoglobina A Glicada , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
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