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1.
Biofabrication ; 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32084655

RESUMO

Fabrication technique determines the physicochemical and biological properties of scaffold, including porosity, mechanical strength, osteoconductivity, and bone regenerative potential. Biphasic calcium phosphate (BCP)-based scaffolds are superior in bone tissue engineering due to their suitable physicochemical and biological properties. We developed an indirect selective laser sintering (SLS) printing strategy to fabricate 3D microporous BCP scaffolds for bone tissue engineering purposes. The green part of BCP scaffold was fabricated by SLS at relevantly low temperature in the presence of epoxy resin (EP) and the remaining EP was decomposed, and eliminated by a subsequent sintering process to obtain the microporous BCP scaffolds. Physicochemical properties, cell adhesion, biocompatibility, in vitro osteogenic potential and rabbit critical size cranial bone defect healing potential of the scaffolds were extensively evaluated. This indirect SLS printing eliminated the drawbacks of conventional direct SLS printing at high working temperatures, i.e., wavy deformation of the scaffold, hydroxyapatite decomposition, and conversion of ß-TCP to α-TCP. Among the scaffolds printed with various binder ratios (by weight) of BCP and EP, the scaffold with 50/50 binder ratio (S4) showed the highest mechanical strength and porosity with the smallest pore size. Scaffold S4 showed the highest effect on osteogenic differentiation of precursor cells in vitro, and this effect was ERK1/2 signaling dependent. Scaffold S4 robustly promoted precursor cells homing, endogenous bone regeneration, and vascularization in rabbit critical-size cranial defect. In conclusion, BCP scaffold fabricated by indirect SLS printing maintains the physicochemical properties of BCP and possess the capacity to recruit host precursor cells to the defect site and promote the endogenous bone regeneration possibly via activation of ERK1/2 signaling.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32088307

RESUMO

In a transcription-wide association study of nasal epithelium, we identify novel and previously reported susceptibility genes for atopic asthma in children and show that gene co-expression networks differ markedly between children with and without atopic asthma.

3.
Anal Chem ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32008316

RESUMO

Tiagabine hydrochloride (TGB) is a clinically frequently used drug for anticonvulsion and reducing epileptic frequency. Over administration of TGB could bring about adverse effects, such as speech disorder, depression, and even suicidal tendencies. Therefore, accessible and sensitive assay for analysis of TGB becomes an urgent need toward guiding clinical medication. Here, we present the first report on fluorescence turn-on detection of TGB in urine testing. In this protocol, a fluorescent dye, perylene tetracarboxylic acid imide derivative (PTAI), is found specifically occupying the Sudlow site II of human serum albumin (HSA) and displays a new phenomenon of binding-induced quenching (BIQ). In presence of TGB, competitive binding of the TGB to the site II of HSA will trigger release of PTAI, thus successfully lighting up the fluorescence of PTAI. This label-free assay enjoys a broader working range (1-350 µM) and lower detection limit (0.218 µM) than the traditional liquid chromatography method and is uninterfered by the miscellaneous in the artificial urine. The BIQ probe highlights the merits of HSA as a quencher and a molecular recognition unit, and it opens up a way for studying drug-HSA interaction mechanism and noninvasive pharmaceutical testing.

4.
Biochem Pharmacol ; 174: 113850, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32044355

RESUMO

The human cytochrome P450 enzyme CYP4Z1 remains an understudied enzyme despite its association with poor prognosis and overexpression in breast cancer. Hence, CYP4Z1 has previously been suggested as an anti-breast cancer target. In the present study we employed extended mutation analysis to increase our understanding of the substrate binding mode of this enzyme. In a combined in vitro and in silico approach we show for the first time that residue Arg487 plays an important role in substrate recognition and binding of CYP4Z1. Using a large array of recombinant CYP4Z1 mutants we show that, apart from Asn381, all other postulated binding residues only play an auxiliary role in substrate recognition and binding. Different substrate interaction motifs were identified via dynamic pharmacophores (dynophores) and their impact on catalytically competent substrate binding was classified. These new insights on the substrate recognition and binding mode represent an important step towards the rational design of CYP4Z1 prodrugs and guide further investigations into the so far poorly understood physiological role of CYP4Z1.

5.
Aging (Albany NY) ; 12(3): 2246-2260, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32023553

RESUMO

The treatment for intervertebral disc degeneration (IDD) has drawn great attention and recent studies have revealed that the p38 MAPK pathway is a potential therapeutic target for delaying the degeneration of intervertebral discs. In this study, we analyzed a nature-derived protein tyrosine kinase inhibitor, Genistein, and its function in delaying IDD in rats both in vitro and in vivo via the p38 MAPK pathway. Nucleus pulposus cells treated with Genistein showed better function compared with untreated cells. Further study revealed that Genistein could play a protective role in IDD by inhibiting phosphorylation of p38, consequently inhibiting the p38 pathway-mediated inflammatory response. The rat IDD model also demonstrated that Genistein could effectively delay the degeneration of intervertebral disc tissue. The current study reveals new biological functions of Genistein, further demonstrates the effects of the p38 MAPK pathway on intervertebral disc degeneration, and deepens our understanding of the treatment and prevention of IDD.

6.
Science ; 367(6476): 373, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31974238
7.
Inorg Chem ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31999443

RESUMO

Thiol-amine solvent mixtures have been widely applied in the solution processing of binary chalcogenide thin films due to their excellent ability to dissolve various bulk binary chalcogenides. However, application of this solvent system in preparing new crystalline chalcogenidometalates has not been explored. In this work, by using a thiol-amine solvent mixture of n-butylamine (BA) and 1,2-ethanedithiol (EDT) as the reaction medium and protonated piperazine (pip) cation as the template, we synthesized a series of new chalcogenidoarsenates with structures ranging from discrete clusters to two-dimensional layers, namely, [pipH2][pipH][AsS4] (1), [pipH2][pipH][As(Se0.4S0.6)4] (2), [pipH2]2[pipH]2[In2AsIII2AsV2S13.3(S2)0.7] (3), [pipH2]2[pipH]2[In2AsIII2AsV2S10.2Se3.1(Se2)0.7] (4), [pipH2]0.5[AsS(S2)] (5), [pipH2]0.5[AsS2] (6), [pipH]2[AgAsS4] (7), [pipH2]1.5[GaAsIIIAsVS7] (8), and Cs2[pipH]2[InAs6S12]Cl (9). Particularly, compounds 3, 4, and 8 contain mixed-valent AsIII and AsV ions in their discrete clusters and one-dimensional chain. In addition, compound 5 could thermodynamically transform to compound 6 with increasing reaction temperature, which may be attributed to the thermodynamically unstable S-S species in the chains of 5. The BA-EDT solvent mixture was crucial to the synthesis of these compounds, since no title crystals can be prepared by replacing the BA-EDT solvent mixture with other conventional solvents or removing one component of the BA-EDT solvent mixture from the reaction system. Our research demonstrates that thiol-amine solvent systems could be promising reaction media for growing novel crystalline chalcogenidometalates.

8.
Zhongguo Zhen Jiu ; 40(1): 79-83, 2020 Jan 12.
Artigo em Chinês | MEDLINE | ID: mdl-31930904

RESUMO

Professor CHEN Ri-xin has explored the causes of the characteristics of TCM syndromes in modern disease spectrum and pointed out that the TCM syndromes are generally characterized by "yang is often insufficient, but yin is often surplus". Based on the clinical experience and the understanding of TCM classics and ancient literature on tumor, professor CHEN has proposed that TCM syndromes of patients with advanced tumor are also generally characterized by "yang is often insufficient, but yin is often surplus". The heat-sensitive moxibustion has the functions of warming and nourishing yang-qi, eliminating dampness, warming meridians and dispersing cold, activating blood circulation and clearing collaterals, therefore tumor patients with deficiency syndrome (yang-deficiency, qi-deficiency), cold syndrome, dampness syndrome, phlegm syndrome and blood-stasis syndrome belonging to the indications of heat-sensitive moxibustion. The heat-sensitive moxibustion has unique advantages in treating spleen-stomach dysfunction after chemotherapy and radiotherapy, bone marrow suppression after chemotherapy and radiotherapy, cancerous deficiency, cancerous pain, pleural effusion, ascites, constipation, which has important clinical value in improving the quality of life and prolonging the life time for patients with advanced tumors.


Assuntos
Moxibustão , Neoplasias , Temperatura Alta , Humanos , Medicina Tradicional Chinesa , Neoplasias/terapia , Qualidade de Vida
10.
DNA Cell Biol ; 39(2): 273-288, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31968175

RESUMO

Cleistogenes songorica is a cultivated turfgrass species that employs a mixed breeding system. To determine the morphological differences and molecular mechanisms of the chasmogamous (CH) and cleistogamous (CL) flowers of this species, we evaluated seed traits and analyzed six transcription factor (TF) families related to floral development. The seed traits from the CH and CL flowers were significantly different. In total, 12 CsAP2, 13 CsSPL, 9 CsGRF, 21 CsMYB, 15 CsMADS, and 1 CsLFY differentially expressed genes were identified from the transcriptome of the C. songorica flowers, which was further supported by evolutionary relationships and conserved motifs. All collinear gene pairs had a Ka/Ks ratio <1. Analysis of the promoters and miRNAs of the TFs revealed that the members of the six TF families may coregulate the divergence of CH and CL flowers during evolution. Two CsAP2, 8 CsSPL, 6 CsGRF, 3 CsMYB (targeted by miR172s, miR156s, miR396a/b and miR159a/b, respectively), and 15 CsMADS genes as well as 1 CsLFY gene may be involved in the development of CH and CL flowers. This study is the first to analyze the differences between CH and CL flowers at the TF-family level, which will help in the understanding of dimorphic turfgrasses.


Assuntos
Flores/genética , Poaceae/genética , Fatores de Transcrição/genética , Regulação da Expressão Gênica de Plantas/genética , MicroRNAs/genética , Fenótipo , Plantas/genética , RNA Mensageiro/genética , Sementes/genética , Fatores de Transcrição/metabolismo , Transcriptoma/genética
11.
Chem Commun (Camb) ; 56(12): 1843-1846, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-31950937

RESUMO

As the most abundant protein in blood, human serum albumin (HSA) is usually regarded as an interferent in clinical molecular diagnosis. Herein, we report that HSA is an endogenous signal amplifier for the detection of the prostate-specific antigen (PSA) in human plasma. This is the first study to utilize intrinsic biological components as the signal amplifier in blood tests.

12.
Biologicals ; 63: 74-80, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31753578

RESUMO

The traditional vaccine strains, such as LaSota, do not completely prevent the shedding of NDV. An ideal vaccine which could not only prevent the clinical signs, but significantly reduce the shedding of NDV is urgently needed for the eradication of ND. In this study, an NDV isolate APMV-1/Chicken/China (SC)/PT3/2016 (hereafter referred as PT3) was identified as a class Ⅰ NDV and a lentogenic strain. The antigenic relationship between PT3 and 3 other NDV strains, including vaccine strain LaSota and 2 prevalent genotype Ⅶd and Ⅵb strains were analyzed. The protective efficacy of PT3 and LaSota against challenge with genotype Ⅶd and Ⅵb strains were assessed. The antigenic analysis result showed that 4 strains belong to the single serotype and the PT3 antiserum exhibited the highest HI titer against 3 other NDV strains. The results of protective efficacy showed that both of LaSota and PT3 could provide 100% survivability for infected chickens. However, PT3 performed better in inducing higher humoral responses and reducing virus shedding than the LaSota strain. Lentogenic strains from Class I NDV appear to be promising vaccine candidates for the control of ND, and allows for the easy discrimination of field NDV and vaccine strains.

13.
IEEE Trans Cybern ; 50(3): 1347-1354, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30295641

RESUMO

Hidden Markov models (HMMs) underpin the solution to many problems in computational neuroscience. However, it is still unclear how to implement inference of HMMs with a network of neurons in the brain. The existing methods suffer from the problem of being nonspiking and inaccurate. Here, we build a precise equivalence between the inference equation of HMMs with time-invariant hidden variables and the dynamics of spiking winner-take-all (WTA) neural networks. We show that the membrane potential of each spiking neuron in the WTA circuit encodes the logarithm of the posterior probability of the hidden variable in each state, and the firing rate of each neuron is proportional to the posterior probability of the HMMs. We prove that the time course of the neural firing rate can implement posterior inference of HMMs. Theoretical analysis and experimental results show that the proposed WTA circuit can get accurate inference results of HMMs.

14.
Free Radic Biol Med ; 147: 262-270, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31883468

RESUMO

OBJECTIVES: The degeneration of intervertebral discs (IVD) is a risk factor for chronic low back pain. Anti-inflammation therapy could alleviate IVD degeneration. IL-10 is an important anti-inflammatory cytokine. However, the effect of IL-10 on IVD has not been fully revealed. The current study is to reveal the effect of IL-10 on IVD and its underlying mechanism. METHODS: IL-1ß was used to induce the degeneration of nucleus pulposus cells (NPCs). mRNA expression level was determined by qPCR. Protein expression level was determined by western blotting. Methylene blue was used to determined the expression of aggrecan. Immunocytochemical staining was used to determined the expression of collagen II. A rat caudal IVD degeneration model was established and used to evaluate the effect of IL-10 on IVD in vivo. RESULTS: IL10 could alleviated NPC degeneration in both morphology and extracellular matrix. IL-10 could increase the mRNA expression of Collagen II, Sox-9, but decrease the mRNA expression of IL-1ß, TNFα and Collagen X. IL-10 could also increase the protein level of Collagen II and aggrecan, but decrease that of Collagen X. Western blotting futher revealed the mechanism of the positive effect of IL-10 on IVD. IL-10 reduces phosphorylation level of p38 MAPK effectively. Rat caudal IVD degeneration model futher confirmed the positive effect of IL-10 on IVD degeneration and its mechanism in vivo. CONCLUSION: The current study demonstrates that exogenous IL-10 treatment can induce an anti-inflammatory response and inhibit p38 MAPK activation to delay IVD degeneration.

15.
Huan Jing Ke Xue ; 41(1): 31-38, 2020 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854901

RESUMO

Based on the source apportionment by positive matrix factorization (PMF) model, we analyze the main sources and characteristics of aerosol fine particulate matter (PM2.5) during winter and summer in the Hohhot-Baotou-Ordos region, China. We found that organic (19.9%-44.6%) and crustal compositions (9.7%-46.2%) accounted for a large proportion of aerosol PM2.5 according to the results of mass closure. The results of source apportionment showed that the contribution of sources rank as:secondary inorganic aerosol (26.7%) > coal (26.1%) > motor vehicle (19.1%) > dust (18.1%) during winter, and as:secondary inorganic aerosol (26.7%) > dust (22.3%) > coal (16.6%) > vehicle exhaust (15.1%) > SOC (8.7%) during summer. Findings suggest that the contribution of sources with secondary inorganic aerosol were the largest sources both in winter and summer, and that the Hohhot-Baotou-Ordos region was also affected by coal during the winter and dust during the summer. Corresponding to the source apportionment, analysis of typical heavy pollution episodes in winter and summer showed that the pollution sources during the winter were mainly secondary inorganic aerosol and coal, whereas they were mainly secondary inorganic aerosol during the summer.

17.
Environ Health Prev Med ; 24(1): 70, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31787069

RESUMO

AIMS: This study focused on the newest evidence of the relationship between forest environmental exposure and human health and assessed the health efficacy of forest bathing on the human body as well as the methodological quality of a single study, aiming to provide scientific guidance for interdisciplinary integration of forestry and medicine. METHOD: Through PubMed, Embase, and Cochrane Library, 210 papers from January 1, 2015, to April 1, 2019, were retrieved, and the final 28 papers meeting the inclusion criteria were included in the study. RESULT: The methodological quality of papers included in the study was assessed quantitatively with the Downs and Black checklist. The methodological quality of papers using randomized controlled trials is significantly higher than that of papers using non-randomized controlled trials (p < 0.05). Papers included in the study were analyzed qualitatively. The results demonstrated that forest bathing activities might have the following merits: remarkably improving cardiovascular function, hemodynamic indexes, neuroendocrine indexes, metabolic indexes, immunity and inflammatory indexes, antioxidant indexes, and electrophysiological indexes; significantly enhancing people's emotional state, attitude, and feelings towards things, physical and psychological recovery, and adaptive behaviors; and obvious alleviation of anxiety and depression. CONCLUSION: Forest bathing activities may significantly improve people's physical and psychological health. In the future, medical empirical studies of forest bathing should reinforce basic studies and interdisciplinary exchange to enhance the methodological quality of papers while decreasing the risk of bias, thereby raising the grade of paper evidence.


Assuntos
Ensaios Clínicos Controlados como Assunto , Exposição Ambiental , Florestas , Depressão/prevenção & controle , Depressão/terapia , Humanos , Saúde Mental , Aptidão Física/fisiologia , Terapia Recreacional
18.
Eur Respir J ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831581

RESUMO

The Trans-National Asthma Genetic Consortium (TAGC) identified 878 SNPs associated with asthma. We hypothesised that those SNPs affect asthma risk by regulating gene expression in airway epithelium, and conducted expression quantitative trait loci (eQTL) and mediation analyses to identify direct associations between the SNPs and expression levels of cis-genes (within 1 Mb) in nasal (airway) epithelium from Puerto Rican children with (n=228) and without (n=241) asthma. We then tested whether genes whose expression is associated with TAGC SNPs are differentially expressed (DE) in atopic asthma. We identified 1150 direct associations between 418 TAGC SNPs and the expression of 55 cis-genes. Most SNPs regulate distant cis-genes (average distance ∼200 kb). Our mediation analysis showed that 4571 (89.2%) of 5119 (direct and indirect) SNP-gene expression associations are mediated by methylation. Of 114 genes whose expression is associated with TAGC SNPs, 54 are DE in atopic asthma, including novel and previously reported genes. In an independent cohort of 72 African American children, 50 of the 54 DE genes were available, and 21 (42%) were also DE in atopic asthma. Thus, we show that many TAGC SNPs are associated with expression of distant cis-genes in airway epithelium, and that this is predominantly mediated by DNA methylation. Moreover, nearly half of the genes whose expression in airway epithelium is associated with TAGC SNPs are also DE in atopic asthma. Our findings support a key role of regulation of airway epithelial gene expression on atopic asthma in children.

19.
Huan Jing Ke Xue ; 40(6): 2565-2571, 2019 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854647

RESUMO

Based on the annual average concentration values, the health effects and health benefits as well as 95% confidence intervals of PM10 and PM2.5 pollution control from 2014 to 2016 in Zhengzhou were evaluated by applying the Poisson regression relative risk model. Results showed that the health benefits of PM10 pollution control were 18.18 billion RMB (15.04, 21.12), 24.25 billion RMB (20.25, 27.94), and 20.62 billion RMB (17.33, 23.92), which accounted for 2.7%, 3.3%, and 2.5% of the GDP of Zhengzhou, respectively, in 2014-2016. The health benefits of PM2.5 pollution control were 17.88 billion RMB (14.37, 21.16), 21.65 billion RMB (17.46, 25.53), and 17.25 billion RMB (13.78, 20.55), which accounted for 2.6%, 3.0%, and 2.1% of the GDP of Zhengzhou, respectively, in 2014-2016. After the PM10 and PM2.5 pollution was controlled, the number of urban beneficiaries was higher than that of rural areas, and acute bronchitis beneficiaries were higher than the beneficiaries of other health end-points. For chronic bronchitis, adults benefited more than children, while the opposite occurred for asthma. In this study, chronic bronchitis had the highest health benefit, followed by asthma, and outpatient and inpatient setting had the lower health benefits.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/prevenção & controle , Material Particulado/efeitos adversos , Adulto , Asma/prevenção & controle , Bronquite Crônica/prevenção & controle , Criança , China , Humanos , Análise de Regressão
20.
Huan Jing Ke Xue ; 40(11): 4774-4782, 2019 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854542

RESUMO

To study the pollution characteristics of atmospheric heavy metal elements in a living area of Zhengzhou City, assess the potential ecological risks, and determine risks to resident health in this city, the Wuhan Tianhong TH-16A Airborne Particles Intelligent Sampler was used to collect atmospheric PM2.5 in Zhengzhou City. The mass concentrations of 17 metal elements were analyzed by ambient air determination of inorganic elements by ambient particle matter wavelength dispersive X-ray fluorescence spectrometry. The source of heavy metals was analyzed by the enrichment factor method and principal component analysis. The ecological risk index method and the US Environmental Protection Agency's health risk assessment method were used to evaluate the potential ecological risks and residents' health risks from Cr, Cd, Cu, Zn, Ni, Pb, As, and other elements. The results showed that metals with higher enrichment factor values were Cd, Sb, Pb, and As, and Cd had the highest enrichment factor value. The sources of metal elements in a living area of Zhengzhou City were mainly crust/burning coal, fuel, garbage burning, metallurgical dust, and vehicle emission. The single factor potential ecological hazard index values of Cd, Pb, Zn, As, Cu, Ni, and Cr were 70420.2, 255.3, 204.6, 71.5, 36.9, 24.0, and 5.1, respectively. Cd, As, and Cr in a living area of Zhengzhou City posed a cancer risk, and Cd was the most harmful. Mn had a non-carcinogenic risk.


Assuntos
Saúde Ambiental , Monitoramento Ambiental , Poluição Ambiental , Metais Pesados , China , Cidades , Humanos , Medição de Risco
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