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1.
Int J Mol Sci ; 21(3)2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32019072

RESUMO

Shiraia mycelial culture is a promising biotechnological alternative for the production of hypocrellin A (HA), a new photosensitizer for anticancer photodynamic therapy (PDT). The extractive fermentation of intracellular HA in the nonionic surfactant Triton X-100 (TX100) aqueous solution was studied in the present work. The addition of 25 g/L TX100 at 36 h of the fermentation not only enhanced HA exudation to the broth by 15.6-fold, but stimulated HA content in mycelia by 5.1-fold, leading to the higher production 206.2 mg/L, a 5.4-fold of the control on day 9. After the induced cell membrane permeabilization by TX100 addition, a rapid generation of nitric oxide (NO) and hydrogen peroxide (H2O2) was observed. The increase of NO level was suppressed by the scavenger vitamin C (VC) of reactive oxygen species (ROS), whereas the induced H2O2 production could not be prevented by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO), suggesting that NO production may occur downstream of ROS in the extractive fermentation. Both NO and H2O2 were proved to be involved in the expressions of HA biosynthetic genes (Mono, PKS and Omef) and HA production. NO was found to be able to up-regulate the expression of transporter genes (MFS and ABC) for HA exudation. Our results indicated the integrated role of NO and ROS in the extractive fermentation and provided a practical biotechnological process for HA production.

2.
Cell Immunol ; : 104047, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-32019673

RESUMO

The polarization of macrophages is critical to inflammation and tissue repair, with unbalanced macrophage polarization associated with critical dysfunctions of the immune system. Cytochrome P450 1A1 (CYP1A1) is a hydroxylase mainly controlled by the inflammation-limiting aryl hydrocarbon receptor (AhR), which plays a critical role in mycoplasma infection, oxidative stress injury, and cancer. Arginase-1 (Arg-1) is a surrogate for polarized alternative macrophages and is important to the production of nitric oxide (NO) by the modulation of arginine. In the present study, we found CYP1A1 to be upregulated in IL-4-stimulated mouse peritoneal macrophages (PMs) and human peripheral blood monocytes. Using CYP1A1-overexpressing RAW264.7 cells (CYP1A1/RAW) we found that CYP1A1 augmented Arg-1 expression by strengthening the activation of the JAK1/STAT6 signaling pathway in macrophages treated with IL-4. 15(S)-HETE, a metabolite of CYP1A1 hydroxylase, was elevated in IL-4-induced CYP1A1/RAW cells. Further, in macrophages, the loss-of-CYP1A1-hydroxylase activity was associated with reduced IL-4-induced Arg-1 expression due to impaired 15(S)-HETE generation. Of importance, CYP1A1 overexpressing macrophages reduced the inflammation associated with LPS-induced peritonitis. Taken together, these findings identified a novel signaling axis, CYP1A1-15(S)-HETE-JAK1-STAT6, that may be a promising target for the proper maintenance of macrophage polarization and may also be a means by which to treat immune-related disease due to macrophage dysfunction.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32020794

RESUMO

MOF-derived composites of transition metal oxide and porous carbon show great potential for energy storage applications. Selenylation is an effective strategy to improve the electrochemical properties of electrode materials. A facile one-step derivation and selenylation of MOFs is proposed here to obtain CoSe2 nanoparticles embedded into a N-doped carbon framework material (CoSe2/NC). Moreover, the composite is directly grown on nickel foam as nanosheet arrays, rather than other materials representing as powders. The CoSe2/NC electrode with special construction exhibits high capacity of 120.2 mAh g-1 at 1 A g-1 and excellent cyclic ability of 8% loss after 10000 cycles. An asymmetric supercapacitor of CoSe2/NC-NF//AC displays a maximum energy density of 40.9 Wh kg-1 at 980 W kg-1. Moreover, the device has demonstrated that it can successfully charge a mobile phone. The outstanding performance indicates a promising potential of CoSe2/NC-NF electrodes for supercapacitors.

4.
Med Sci Monit ; 26: e918207, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32037392

RESUMO

BACKGROUND Clinical relapse in acute myeloid leukemia (AML) is associated with the reduced treatment response of leukemia stem cells (LSCs). This study aimed to investigate the effects of the ginseng derivative, ginsenoside Rg1 (Rg1), on CD34+CD38- LSCs derived from KG1a human acute myeloid leukemia cells. MATERIAL AND METHODS CD34+CD38- LSCs were isolated from KG1a human acute myeloid leukemia cells by cell sorting. CD34+CD38- KG1alpha LSCs were divided into the control group and the Rg1 group (treated with Rg1). The cell counting kit-8 (CCK-8) assay evaluated the proliferation of CD34+CD38- KG1alpha LSCs and flow cytometry studied the cell cycle. The mixed colony-forming unit (CFU-Mix) assay and staining for senescence-associated beta-galactosidase (SA-ß-Gal) evaluated cell senescence. Expression of sirtuin 1 (SIRT1) and tuberous sclerosis complex 2 (TSC2) were evaluated using Western blot and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS CD34+CD38- KG1alpha LSCs were isolated at 98.72%. Rg1 significantly reduced the proliferation of CD34+CD38- KG1alpha LSCs compared with the control group (p<0.05). Cells in the G0/G1 phase were significantly increased, and cells in the G2/M and S phase were significantly reduced compared with the control group (p<0.05). Rg1 significantly increased SA-ß-Gal and reduced CFU-Mix formation compared with the control group (p<0.05), significantly down-regulated SIRT1 expression in CD34+CD38- KG1alpha LSCs compared with the control group (p<0.05), and significantly reduced TSC2 expression in CD34+CD38- KG1alpha LSCs compared with the control group (p<0.05). CONCLUSIONS Rg1 inhibited cell proliferation and induced cell senescence markers in CD34+CD38- KG1alpha LSCs by activating the SIRT1/TSC2 signaling pathway.

5.
J Agric Food Chem ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32033515

RESUMO

The immunomodulatory activity of a few Lactobacillus exopolysaccharide (EPS) has been reported. However, whether Lactobacillus EPS can promote the differentiation of CD4 T lymphocytes (CD4+ T) cells into T-helper 17 cells (Th17 cells) in the Peyer's Patches (PPs) of mice has not been addressed. In this study, we found the molecular weight (Mw) of the purified EPS from L. casei ranged from 2.7 ×106 Da to 1.7×107 Da, and the average Mw was proximately 8.4×106 Da. In healthy BALB/c mice, EPS elevated the numbers of Th17 cells and levels of Th17-related cytokines. In vitro, EPS induced BMDCs to stimulate the differentiation of CD4+ T cells of PPs into Th17 cells and the related cytokine secretion. Results suggest that L. casei EPS can effectively induce and promote the differentiation of CD4+ T cells of PPs into Th17 cells in healthy mice and has the potential ability to improve intestinal mucosa immunity.

6.
FASEB J ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32027421

RESUMO

Intestinal barrier dysfunction is a major complication of total parenteral nutrition (TPN). Our preliminary study revealed that intestinal P-glycoprotein (P-gp) was significantly downregulated under TPN treatment followed by disruption of barrier function, and thus the significance of early downregulation of P-gp needs to be addressed. Herein, we report a pivotal role of P-gp in the development of intestinal barrier dysfunction under TPN. Functional suppression of P-gp may facilitate bacterial attachment to intestinal epithelial cells (IECs) and thereby induce degradation of tight junctions to trigger barrier dysfunction. By using a rat model of TPN, we found early downregulation of P-gp function in ileum after 3-day TPN, followed by disruption of barrier function after 7-day TPN. By using Escherichia coli (E. coli) k88 and DH5α as type strains, we found significantly increased bacterial attachment to IECs in TPN group compared to sham. By using Caco-2 cells as an IEC model in vitro, we found that functional suppression of P-gp remarkably facilitated bacterial attachment to Caco-2 cells, leading to subsequent disruption of intestinal barrier function. Of note, Occludin was significantly downregulated by bacterial attachment when P-gp was functionally suppressed. Mechanistically, changes on Occludin were attributed to enhanced protein degradation instead of suppressed protein translation. Despite the half-life of Occludin protein being unchanged by DH5α treatment alone, it was decreased by about 40% when P-gp was simultaneously suppressed. Taken together, our findings revealed that early downregulation of intestinal P-gp under TPN may be a potential therapeutic target to prevent the development of barrier dysfunction.

7.
Shock ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32028357

RESUMO

OBJECTIVE: Global cerebral ischemia induced neuroinflammation causes neurofunctional impairment following cardiac arrest. Previous studies have demonstrated that the activation of protease activated receptor-2 (PAR-2) contributes to neuroinflammation. In the present study, we aimed to determine the potential treatment effect of PAR-2 inhibition against neuroinflammation in the setting of asphyxial CA (ACA) in rats. METHODS: A total of 116 adult, male Sprague-Dawley rats were randomly divided into Sham (n = 18) and ACA (n = 98) groups. Time course, short-term outcome and mechanism studies were conducted. All drugs were delivered intranasally. The effect of PAR-2 inhibitor FSLLRY-NH2 on neurocognitive functions was assessed by neurologic deficit score, number of seizures and T-maze test while hippocampal neuronal degeneration was evaluated by Fluoro-Jade C staining after ACA. Western blotting was performed for the mechanism study at 24 hours following ACA. Selective PAR-2 agonist (AC55541) and ERK1/2 inhibitor (PD98059) were used for intervention. RESULTS: Inhibition of PAR-2 decreased neuroinflammation, reduced the number of degenerating hippocampal neurons and improved neurocognitive functions following ACA. PAR-2 activator alone exerted opposite effects to PAR-2 inhibitor. PAR-2 mediated the augmented brain levels of proinflammatory cytokines by promoting the phosphorylation of ERK1/2. CONCLUSIONS: PAR-2 inhibition diminished neuroinflammation and thereby reduced hippocampal neuronal degeneration and neurocognitive impairment following ACA. This effect was at least partly mediated via the PAR-2/ERK1/2 signaling.

8.
Environ Health Prev Med ; 25(1): 1, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898483

RESUMO

BACKGROUND: This study aimed to describe the changing distribution of human brucellosis between 2004 and 2017 in mainland China and seek scientific evidence of the relationship between socio-economic, environmental, and ecological factors and human brucellosis incidence. METHODS: The annual numbers of brucellosis cases and incidence rates from 31 provinces in mainland China between 2004 and 2017 were obtained from the Data-Center for China Public Health Science. The number of monthly brucellosis cases in 2018 was obtained from the Chinese Center for Disease Control and Prevention. The electronic map of the People's Republic of China was downloaded from the National Earth System Science Data Sharing Platform. Human population density, gross domestic product (GDP), and an inventory of cattle and sheep at the end of each year from 2004 to 2017 were obtained from the National Bureau of Statistics of China. Annual rainfall data from 31 provinces in the People's Republic of China from 2004 to 2017 were collected from the China Meteorological Data Service Center. The risk distribution and changing trends of human brucellosis were mapped with ArcGIS. A cluster analysis was employed to identify geographical areas and periods with statistically significant incidence rates. Multivariate linear regression was used to determine possible factors that were significantly correlated with the presence of human brucellosis cases. RESULTS: Human brucellosis cases have spread throughout the whole country. Human brucellosis cases occurred mostly from March to August and were concentrated from April to July. The inventory of sheep, GDP, and climate were significantly correlated with the presence of brucellosis cases in mainland China. CONCLUSIONS: The geographical expansion of human brucellosis in mainland China was observed, so did the high-incidence clusters between 2004 and 2017. Most of the cases were reported during the early spring to early summer (February-August). Results from the multivariate linear regression suggested that the inventory of sheep, GDP, and climate were significantly associated with the incidence of human brucellosis in mainland China.

9.
Calcif Tissue Int ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31912171

RESUMO

The aim of this study was to distinguish the characteristics of intervertebral disc degeneration (IVDD) originating from mechanics imbalance, biology disruption, and their communion, and to develop a composite IVDD model by ovariectomy combined with lumbar facetectomy for mimicking elderly IVDD with osteoporosis and lumbar spinal instability. Mice were randomly divided into four groups and subjected to sham surgery (CON), ovariectomy (OVX), facetectomy (mechanical instability, INS) or their combination (COM), respectively. Radiographical (n = 4) and histological changes (n = 8) of L4/5 spinal segments were analyzed. Tartrate-resistant acid phosphatase (TRAP) staining was conducted to detect osteoclasts, and expression of osterix (OSX), type I collagen (Col I), type II collagen (Col II) and vascular endothelial growth factor (VEGF) were evaluated by immunochemistry. OVX affected the body's metabolism but INS did not, as the body weight increased and uterus weight decreased in OVX and COM mice compared to CON and INS mice. OVX, INS, and COM caused IVDD in various degrees at 12 weeks after surgery. However, the major pathogeneses of OVX- and INS-induced IVDD were different, which focused on endplate (EP) remodeling and annulus fibrosus (AF) collapse, respectively. OVX induced osteopenia of vertebra. In contrast, INS promoted the stress-adaptive increase of subchondral bone trabeculae. The COM produced a reproducible severe IVDD model with characteristics of sparse vertebral trabeculae, cartilaginous EP ossification, subchondral bone sclerosis, fibrous matrix disorder, angiogenesis, disc stiffness, as well as space fusion. Additionally, all groups had elevated bone and cartilage turnover compared with CON group, as the quantity of trap + osteoclasts and the osteogenic OSX expression increased in these groups. Likewise, the VEGF expression levels were similar, accompanied by the altered matrix expression of disc, including the changed distribution and contents of Col II and Col I. The findings suggested that the composite mouse model to some extent could effectively mimic the interactions of biology and mechanics engaged in the onset and natural course of IVDD, which would be more compatible with the IVDD of elderly with vertebral osteoporosis and spinal instability and benefit to further clarify the complicated mechanobiological environment of elderly IVDD progression.

10.
Biostatistics ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31985009

RESUMO

The Cox model is the most popular tool for analyzing time-to-event data. The nonparametric baseline hazard function can be as important as the regression coefficients in practice, especially when prediction is needed. In the context of stochastic process control, we propose a simultaneous monitoring method that combines a multivariate control chart for the regression coefficients and a profile control chart for the cumulative baseline hazard function that allows for data blocks of possibly different censoring rates and sample sizes. The method can detect changes in either the parametric or the nonparametric part of the Cox model. In simulation studies, the proposed method maintains its size and has substantial power in detecting changes in either part of the Cox model. An application in lymphoma survival analysis in which patients were enrolled by 2-month intervals in the Surveillance, Epidemiology, and End Results program identifies data blocks with structural model changes.

11.
Bioorg Med Chem ; 28(4): 115214, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31932193

RESUMO

N-terminal heptad repeat (NHR)-derived peptide (N-peptide) fusion inhibitors, which are derived from human immunodeficiency virus (HIV) envelope glycoprotein 41 (gp41), are limited by aggregation and unstable trimer conformation. However, they could function as potent inhibitors of viral infection by forming a coiled-coil structure covalently stabilized by interchain disulfide bonds. We previously synthesized N-peptides with potent anti-HIV-1 activity and high stability by coiled-coil fusion and covalent stabilization. Here, we attempted to study the effects of NHRs of chimeric N-peptides by fusing de novo coiled-coil isopeptide bridge-tethered T21 peptides of different NHR lengths. Peptides (T21N23)3 and (T21N36)3 was a more potent HIV-1 fusion inhibitor than (T21N17)3. The site of isopeptide bond formation was precisely controlled and had little influence on N-peptide properties. The N-peptide (T21N36)3, which had a similar conformation as the NHR trimer and interacted well with the C34 peptide, may be useful for screening other C-peptides and small-molecule fusion inhibitors, and for studying the interactions between the NHR trimer and C-terminal heptad repeats.

12.
Int J Biol Macromol ; 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31987947

RESUMO

Nitrogen and sulfur co-doped carbon dots (N,S-CDs) have been widely studied with high quantum yield (QY). The experimental conditions of three different N,S-CDs were optimized. Emission peak position of three different N,S-CDs shown almost remains unchanged or obvious excitation-dependent PL properties, that was likely owed to size distribution. In order to discuss the N,S-CDs stability of photoluminescence property in environment, various experiments such as the photostability, different pH, ionic strengths and temperature were designed. To sum up, three different N,S-CDs exhibited discrepancy property. Molecular interaction of three different N,S-CDs were produced via vary carbon source with human serum albumins have been investigate by various methods. The quenching mechanism, thermodynamic and kinetic parameters, binding sites, electrochemical behavior of three different N,S-CDs with human serum albumins have some different, but conformational change of three different N,S-CDs with human serum albumins alike. The molecular docking had successful applied to study the N,S-CDs interaction with HSA. Different N,S-CDs possessed various characteristic that will have different quenching mechanism when they interaction with human serum albumin, study the mechanism of action at molecular level will help people to choose suitable CDs to apply in nanomedical.

13.
J Oleo Sci ; 69(2): 161-166, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31941867

RESUMO

Activity changes after olive oil (OO), pomegranate seed oil (PSO), and grape seed oil (GSO) were formulated into self-nanoemulsifying systems (SNES), were examined in this study. Only GSO SNES dramatically enhanced antioxidant activity of GSO. SNES from OO and PSO did not exert obvious impact on radical quenching ability of the oils. Though PSO exhibited significantly stronger strength over OO in suppressing E. coli (p < 0.05), the inhibitory effect of OO SNES against E. coli became slightly higher than that of PSO SNES. Similar phenomenon happened in GSO, OO, and their SNES for preventing Yeast growth. The study indicated that SNES sometimes reversed the strength order of the original oils in inhibiting bacteria.

14.
PLoS Genet ; 16(1): e1008577, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31929527

RESUMO

Circadian systems provide a fitness advantage to organisms by allowing them to adapt to daily changes of environmental cues, such as light/dark cycles. The molecular mechanism underlying the circadian clock has been well characterized. However, how internal circadian clocks are entrained with regular daily light/dark cycles remains unclear. By collecting and analyzing indirect calorimetry (IC) data from more than 2000 wild-type mice available from the International Mouse Phenotyping Consortium (IMPC), we show that the onset time and peak phase of activity and food intake rhythms are reliable parameters for screening defects of circadian misalignment. We developed a machine learning algorithm to quantify these two parameters in our misalignment screen (SyncScreener) with existing datasets and used it to screen 750 mutant mouse lines from five IMPC phenotyping centres. Mutants of five genes (Slc7a11, Rhbdl1, Spop, Ctc1 and Oxtr) were found to be associated with altered patterns of activity or food intake. By further studying the Slc7a11tm1a/tm1a mice, we confirmed its advanced activity phase phenotype in response to a simulated jetlag and skeleton photoperiod stimuli. Disruption of Slc7a11 affected the intercellular communication in the suprachiasmatic nucleus, suggesting a defect in synchronization of clock neurons. Our study has established a systematic phenotype analysis approach that can be used to uncover the mechanism of circadian entrainment in mice.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31935850

RESUMO

This study investigated the feasibility of using sodium hexametaphosphate (SHMP)- amended calcium (Ca) bentonite in backfills for slurry trench cutoff walls for the containment of lead (Pb) contamination in groundwater. Backfills composed of 80 wt% sand and 20 wt% either Ca-bentonite or SHMP-amended Ca-bentonite were tested for hydraulic conductivity and sorption properties by conducting laboratory flexible-wall hydraulic conductivity tests and batch isothermal sorption experiments, respectively. The results showed that the SHMP amendment causes a one order of magnitude decrease in hydraulic conductivity of the backfill using tap water (1.9 to 3.0 × 10-10 m/s). Testing using 1000 mg/L Pb solution resulted insignificant variation in hydraulic conductivity of the amended backfill. Moreover, SHMP-amendment induced favorable conditions for increased sorption capacity of the backfill, with 1.5 times higher retardation factor relative to the unamended backfill. The Pb transport modeling through an hypothetical 1-m-thick slurry wall composed of amended backfill revealed 12 to 24 times of longer breakthrough time for Pb migration as compared to results obtained for the same thickness slurry wall with unamended backfill, which is attributed to decrease in seepage velocity combined with increase in retardation factor of the backfill with SHMP amendment. Overall, SHMP is shown to be a promising Ca-bentontie modifier for use in backfill for slurry trench cutoff wall for effective containment of Pb-contaminated groundwater.

16.
PLoS One ; 15(1): e0227206, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31990933

RESUMO

Complexity modelling of economic efficiency and growth potential is increasingly essential for countries and provinces. Evaluating the monetary flows, kinetic energy (efficiency) and potential capacity (resilience) provides crucial information for economic development. In the paper, the authors analyze growth opportunities for the Chinese economy from a system science point of view, using the perspective of information entropy, based on the input-output tables. Over the past four decades of reform and opening-up, China has made remarkable progress in its economic development. In 2007, China's GDP was at its fastest pace in history at 14.2% growth. However, after the financial crisis in 2008, the global economy experienced a downward trend and China's economic development also settled on a medium-low level of development. The traditional perspective is to rank regional development only based on GDP growth, whereas here, the authors advocate another evaluation method based on efficiency and potential growth. Unbalanced regional economic development has become problematic and has become a barrier for sustainability of China's economy. The results of the research indicate firstly that China's regional development in 2007 and 2012 has been unequal between the provinces. Secondly, the authors found that Shandong province had significantly higher indicators for efficiency and potential growth than others in the same circumstances. Authors observe that provinces tend to carry out industrial policies and adjust the structure of industry on a local level. This analysis demonstrates that the spatial imbalance of efficiency and potential of economic development under the perspective of provincial-level regions. From the perspective of industry, it indicates that the supply chain is too short, mainly focusing on the mining and processing of resources and minerals in the original upstream industry chain, while the downstream is not fully utilized. These represent some unique insights yielded through this type of analysis that authors advocate applying more broadly.

17.
Clin Ther ; 42(1): 144-156.e1, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31932080

RESUMO

PURPOSE: In China, dabigatran and rivaroxaban are the only approved non-vitamin K antagonist oral anticoagulants for the treatment of atrial fibrillation (AF). The goal of this article was to assess the cost-effectiveness of dabigatran versus rivaroxaban for the prevention of stroke and systemic embolism in Chinese patients with AF from the perspective of the Chinese health care system. METHODS: A Markov model was constructed to estimate the cost-effectiveness of dabigatran versus rivaroxaban. Clinical events were modeled for a lifetime horizon, based on clinical efficacy data from indirect treatment comparisons. The weighted average of the most recent prices of these 2 drugs was used as the drug acquisition cost. Other costs, including follow-up costs and event costs, were collected by using a survey from a panel of local experts. Utility inputs (health state utilities, clinical event disutilities, and event history utility) were obtained from published literature. Sensitivity analyses that included scenario analyses and a probabilistic sensitivity analysis were conducted to examine the robustness of the economic model. FINDINGS: Over a lifetime, patients treated with dabigatran experienced fewer ischemic strokes (2.14 dabigatran vs 2.61 rivaroxaban) and fewer intracranial hemorrhage (0.48 vs 0.94) per 100 patient-years. In the base case analysis, dabigatran had an incremental cost of ¥28,128 but with higher life years (10.38 vs 10.14) and quality-adjusted life years (QALYs) (7.95 vs 7.70). The resulting incremental cost-effectiveness ratio of ¥112,910 per QALY gained and net monetary benefit of ¥12,214 versus rivaroxaban showed that dabigatran was a cost-effective alternative to rivaroxaban. Extensive sensitivity analyses indicated that the results were robust over a wide range of inputs. The probabilistic sensitivity analysis indicated that dabigatran was cost-effective in 84.2% of the 10,000 Monte Carlo simulations compared with rivaroxaban. IMPLICATIONS: Dabigatran reduced the occurrence of clinical events and increased QALYs compared with rivaroxaban. The use of dabigatran for the prevention of stroke and systemic embolism is a cost-effective option compared with rivaroxaban among patients with AF in China.

18.
Aquat Toxicol ; 220: 105408, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31935571

RESUMO

Tributyltin (TBT), an aromatase inhibitor, has been found to disrupt gametogenesis and reproductive behavior in several fish species. However, whether TBT is capable of affecting other behaviors such as aggressive behavior and fear response in fish and the underlying mode(s) of action remain unclear. To study aggressive behavior, adult zebrafish (Danio rerio) males were continuously exposed to two nominal concentrations of TBT (TBT-low, 100 ng/L and TBT-high, 500 ng/L) for 28 days. To study the fear response, the fish were divided into four groups (Blank and Control, 0 ng/L TBT; TBT-low, 100 ng/L; and TBT-high, 500 ng/L). The fish were then treated with DW (Blank) or with alarm substance (AS) (Control, TBT-low and TBT-high). After exposure, the aggressive behavior of the fish was tested using the mirror test (mirror-biting frequency, approaches to the mirror and duration in approach zone).and fighting test (fish-biting frequency) The mirror-biting frequency, approaches to the mirror, duration in approach zone and fish-biting frequency of the TBT-exposed fish increased significantly compared to those of the control fish, indicating enhanced aggressive behavior. The fear response parameters tested using the novel tank dive test (onset time to the higher half, total duration in the lower half and the frequency of turning) of the TBT-exposed fish were also significantly increased after AS administration, suggesting an enhanced fear response. Further investigation revealed that TBT treatment elevated the plasma level of 11-ketotestosterone (11-KT) and decreased the plasma level of estradiol (E2) in a concentration-dependent manner. Moreover, TBT up-regulated the mRNA levels of ar, c-fos and bdnf1, and suppressed the expression of btg-2 in fish. In addition, exposure to AS increased the plasma level of cortisol and down-regulated the mRNA expression levels of genes involved in 5-HT synthesis (such as tph1b and pet1) in both control and TBT-treated fish. AS significantly suppressed the mRNA level of tph1b, tph2, pet1 and npy in the TBT-high group compared to the control fish. The present study demonstrates that TBT enhances aggressive behavior and fear responses in male zebrafish probably through altering plasma levels of 11-KT, E2 and cortisol and altering the expression of genes involved in the regulation of aggressive behavior (ar, c-fos, bdnf1 and btg-2) and fear responses (tph1b, tph2, pet1 and npy). The present study greatly extends our understanding of the behavioral toxicity of TBT to fish.

19.
World Neurosurg ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31954905

RESUMO

BACKGROUND: The aim of this study was to observe the improvement in patients with dopa-responsive dystonia (DRD) after deep brain stimulation (DBS) of the globus pallidus internus (GPi). CASE DESCRIPTION: A 27-year-old woman with a 22-year history of DRD underwent GPi DBS. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD) were used to regularly assess changes in the patient's condition after DBS treatment. CONCLUSIONS: After 6 months of GPi DBS treatment, the total BFMDRS score of the patient was 5, a 94.28% improvement over the preoperative baseline score. In addition, the MMSE, MOCA, HAMA, and HAMD scores of the patient were 30, 30, 1, and 2, respectively. Intelligence and cognitive levels of the patient did not change significantly compared with the preoperative baseline level, whereas anxiety and depression status of the patient improved compared with the preoperative status. GPi DBS treatment can significantly improve the symptoms of systemic dystonia in patients with DRD, and to a certain extent improve the anxiety and depression status of these patients. Therefore, we conclude that GPi DBS is an alternative safe and effective treatment for patients with DRD.

20.
J Mol Recognit ; 33(3): e2816, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31945234

RESUMO

Cefixime is a third generation orally administered cephalosporin that is frequently used as a broad spectrum antibiotic against various gram-negative and gram-positive bacteria. In this study, a simple and sensitive fluorescent sensor for the determination of the cefixime and ctDNA was established based on the CdTe:Zn2+ quantum dots (QDs). The fluorescence of CdTe:Zn2+ QDs can be effectively quenched by cefixime in virtue of the surface binding of cefixime on CdTe:Zn2+ QDs and the subsequent photoinduced electron transfer process from CdTe:Zn2+ QDs to cefixime, in particular, the high sensitivity of QDs fluorescence emission to cefixime at the micromole per liter level, which render the cefixime-CdTe:Zn2+ QDs system into fluorescence "OFF" status, then turn on in the presence of ctDNA. Furthermore, the Fourier transform infrared (FTIR) spectra of characteristic bands of C-N and N-H groups of cefixime endow evidence for the interaction of cefixime with CdTe:Zn2+ QDs. The relative electrochemical behavior of the affinity of CdTe:Zn2+ QDs for cefixime and ctDNA reveals the potential molecular binding mechanism.

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