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1.
Cell Stem Cell ; 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31588047

RESUMO

To investigate the contribution of parental genomes to early embryogenesis, we profiled the single-cell transcriptomes of human biparental and uniparental embryos systematically from the 1-cell to the morula stage. We observed that uniparental embryos exhibited variable and decreased embryonic genome activation (EGA). Comparative transcriptome analysis identified 807 maternally biased expressed genes (MBGs) and 581 paternally biased expressed genes (PBGs) in the preimplantation stages. MBGs became apparent at the 4-cell stage and contributed to the initiation of EGA, whereas PBGs preferentially appeared at the 8-cell stage and might affect embryo compaction and trophectoderm specification. Regulatory network analysis revealed that DUX4, EGR2, and DUXA are key transcription factors in MBGs' expression; ZNF263 and KLF3 are important for PBGs' expression. We demonstrated that parent-specific DNA methylation might account for the expression of most PBGs. Our results provide a valuable resource to understand parental genome activation and might help to elucidate parent-of-origin effects in early human development.

2.
J Am Heart Assoc ; 8(20): e012556, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31576770

RESUMO

Background Active commuting is related to a higher level of physical activity but more exposure to ambient air pollutants. With the rather serious air pollution in urban China, we aimed to examine the association between active commuting and risk of incident cardiovascular disease in the Chinese population. Methods and Results A total of 104 170 urban commuters without major chronic diseases at baseline were included from China Kadoorie Biobank. Self-reported commuting mode was defined as nonactive commuting, work at home or near home, walking, and cycling. Multivariable Cox regression was used to examine associations between commuting mode and cardiovascular disease. Overall, 47.2% of the participants reported nonactive commuting, 13.4% reported work at home or work near home, 20.1% reported walking, and 19.4% reported cycling. During a median follow-up of 10 years, we identified 5374 incidents of ischemic heart disease, 664 events of hemorrhagic stroke, and 4834 events of ischemic stroke. After adjusting for sex, socioeconomic status, lifestyle factors, sedentary time, body mass index, comorbidities, household air pollution, passive smoking, and other domain physical activity, walking (hazard ratio, 0.90; 95% CI, 0.84-0.96) and cycling (hazard ratio, 0.81; 95% CI, 0.74-0.88) were associated with a lower risk of ischemic heart disease than nonactive commuting. Cycling was associated with a lower risk of ischemic stroke (hazard ratio, 0.92; 95% CI, 0.84-1.00). No significant association was found of walking or cycling with hemorrhagic stroke. The associations of commuting mode with major cardiovascular disease were consistent among men and women and across different levels of other domain physical activity. Conclusions In urban China, cycling was associated with a lower risk of ischemic heart disease and ischemic stroke. Walking was associated with a lower risk of ischemic heart disease.

3.
Acta Crystallogr C Struct Chem ; 75(Pt 10): 1344-1352, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31589150

RESUMO

A novel modified polyoxometalate, {PMo12O40[Cu(2,2'-bpy)]}[Cu(2,2'-bpy)(en)(H2O)]2 [2,2'-bpy is 2,2'-bipyridyl (C10H8N2) and en is ethylenediamine (C2H8N2)], has been synthesized hydrothermally and structurally characterized by elemental analysis, TG, IR, XPS and single-crystal X-ray diffraction. The structural analysis reveals that the compound contains the reduced Keggin polyanion [PMo12O40]6- as the parent unit, which is monocapped by [Cu(2,2'-bpy)]2+ fragments via four bridging O atoms on an {Mo4O4} pit and bi-supported by two [Cu(2,2'-bpy)(en)(H2O)]2+ coordination cations simultaneously. There exist strong intramolecular π-π stacking between the capping and supporting units, which play a stabilizing role during the crystallization of the compound. Adjacent POM clusters are further aggregated to form a three-dimensional supramolecular network through noncovalent forces, hydrogen bonding and π-π stacking interactions. In addition, the photocatalytic properties were investigated in detail, and the results indicated that the compound can be used as a photocatalyst towards the decomposition of the organic pollutant methylene blue (MB).

5.
Chem Commun (Camb) ; 55(76): 11354-11357, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31483423

RESUMO

In this work, we show that precise control of the pore size and functionality in an ultramicroporous metal-organic framework platform can finely tune the adsorption selectivity between acetylene and carbon dioxide at will.

6.
Aging (Albany NY) ; 11(17): 7307-7327, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31498116

RESUMO

The prevalence rates of heart failure (HF) are greater than 10% in individuals aged >75 years, indicating an intrinsic link between aging and HF. It has been recognized that mitochondrial dysfunction contributes to the pathology of HF. Mitokines are a type of cytokines, peptides, or signaling pathways produced or activated by the nucleus or the mitochondria through cell non-autonomous responses during cellular stress. In addition to promoting the communication between the mitochondria and the nucleus, mitokines also exert a systemic regulatory effect by circulating to distant tissues. It is noteworthy that increasing evidence has demonstrated that mitokines are capable of reducing the metabolic-related HF risk factors and are associated with HF severity. Consequently, mitokines might represent a potential therapy target for HF.

7.
ACS Appl Mater Interfaces ; 11(40): 36371-36382, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31490057

RESUMO

Combination of chemotherapeutics and immunomodulators can generate synergistic anticancer efficacy, exerting efficient chemoimmunotherapy for cancer treatment. Nanoparticulate delivery systems hold great promise to promote synergistic anticancer efficacy for the codelivery of drugs. However, there remain challenges to precisely coencapsulate and deliver combinational drugs at designed ratios due to the difference of compatibility between drugs and nanocarriers. In this study, coassembled nanoparticles of lipophilic prodrugs (LPs) were designed to codeliver chemotherapeutics and immunomodulators for cancer treatment. Such nanoassemblies (NAs) could act as platforms to ratiometrically coencapsulate chemotherapeutics and immunomodulators. Based on this method, NAs formed by the self-assembly of iRGD peptide derivatives, paclitaxel (PTX) LPs, and imiquimod (R837) LPs were demonstrated to target the tumor at unified pharmacokinetics, further inducing the effective tumor inhibition and tumor recurrence prevention. This work provided an alternative to prepare chemoimmunotherapeutic NAs with advantages of ratiometric drug coencapsulation and unified pharmacokinetics, which may advance the future cancer chemoimmunotherapy.

8.
BMC Med Inform Decis Mak ; 19(1): 185, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511006

RESUMO

BACKGROUND: The incidence of cardiac implantable electronic device infection (CIEDI) is low and usually belongs to the typical imbalanced dataset. We sought to describe our experience on the management of the imbalanced CIEDI dataset. METHODS: Database from two centers of patients undergoing device implantation from 2001 to 2016 were reviewed retrospectively. Re-sampling technique was used to improve the classifier accuracy. RESULTS: CIEDI was identified in 28 out of 4959 procedures (0.56%); a high imbalance existed in the sizes of the patient profiles. In univariate analyses, replacement procedure and male were significantly associated with an increase in CIEDI: (53.6% vs. 23.4, 0.8% vs. 0.3%, P < 0.01). Multivariate logistic regression analysis showed that gender (odds ratio, OR = 3.503), age (OR = 1.032), replacement procedure (OR = 3.503), and use of antibiotics (OR = 0.250) remained as independent predictors of CIEDI (all P < 0.05) after adjustment for diabetes, post-operation fever, and device style, device company. There were 616 under-sampled cases and 123 over-sampled cases in the analyzed cohort after re-sampling. The re-sampling and bootstrap results were robust and largely like the analysis results prior re-sampling method, while use of antibiotics lost the predicting capacity for CIEDI after re-sampling technique (P > 0.05). CONCLUSION: The application of re-sampling techniques can generate useful synthetic samples for the classification of imbalanced data and improve the accuracy of predicting efficacy of CIEDI. The peri-operative assessment should be intensified in male and aged patients as well as patients receiving replacement procedures for the risk of CIEDI.

9.
Mol Med Rep ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31485653

RESUMO

MicroRNA (miR)­101 copy loss is an early event in the development of human lung cancer, and it occurs in 29% of all lung cancer incidences. In addition, miR­101 expression in non­small cell lung cancer (NSCLC) is known to be downregulated. The aim of the present study was to explore the roles and mechanisms of the long non­coding (lnc)­RNA pro­transition associated RNA (PTAR) on NSCLC cell proliferation, migration and invasion in association with miR­101. Reverse transcription­quantitative PCR analysis was performed to detect the expression of lncRNA PTAR in 30 paired human NSCLC tissues and the corresponding para­tumor tissues. PTAR was amplified and cloned into the expression vector pCDNA3.1. Then, PTAR­overexpression plasmids or small interfering (si)­RNA­PTAR was transfected into A549 cells for 48 h, after which cell proliferation and the cell cycle distribution were evaluated. In addition, Transwell chamber and cell scratch­wound assays were conducted to analyze A549 cell migration and invasion. A luciferase activity assay was evaluated to determine the interaction between PTAR and miR­101. Furthermore, our results demonstrated that in human NSCLC tissues and cell lines, lncRNA PTAR expression was upregulated compared with normal lung tissues and cell lines, respectively. Additionally, PTAR transfection was observed to promote A549 cell proliferation, migration and invasion; opposing effects were observed with siRNA­PTAR transfection. The luciferase activity assay revealed that PTAR could act as a sponge to bind miR­101. Thus, miR­101 plays a role in NSCLC tumorigenesis and progression. In conclusion, lncRNA PTAR was proposed to promote NSCLC cell growth through sponging and inactivating miR­101, which may be a possible mechanism underlying miR­101 copy loss in human NSCLC.

10.
Neurol Sci ; 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31392640

RESUMO

The main purpose of this study was to systematically evaluate the accuracy of neuromelanin-sensitive magnetic resonance imaging (NM-MRI) in Parkinson's disease (PD) diagnosis using a meta-analysis method. In PubMed, Web of Science, Embase, and Google Scholar, the literatures were searched for the diagnostic value of neuromelanin-sensitive magnetic resonance imaging in PD. The literatures were screened in the light of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data analysis was processed by Stata 12.0 software to obtain meta-analysis, heterogeneity analysis, and publication bias. Meta-analysis results showed by using NM-MRI observed substantia nigra pars compacta (SNpc) on PD, the pooled diagnostic sensitivity and specificity were 0.82 (95% CI, 0.74-0.87) and 0.82 (95% CI, 0.73-0.89), respectively. And the pooled positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 4.58 (95% CI, 3.08-6.82) and 0.22 (95% CI, 0.16-0.31), respectively. Moreover, subgroup analysis according to the measurement criteria of SNpc showed the SNpc volume should be used as good a marker for diagnosing PD. Finally, Fagan test demonstrated that when PLR was equal to 5, the posterior probability is significantly enhanced to 53%, compared with prior probability (20%). As for NLR (0.22), the prior probability is 20%, while the posterior probability remarkably dropped to 5%. In conclusion, SNpc signal detected by NM-MRI exhibited high sensitivity and specificity for diagnosis of PD, which was a high-performance imaging diagnostic method for PD. We recommend NM-MRI imaging technology to be widely used in Parkinson's diagnosis.

11.
Molecules ; 24(15)2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31366067

RESUMO

NCMN (N-(3-carboxy propyl)-4-methoxy-1,8-naphthalimide), a newly developed ratiometric two-photon fluorescent probe for human Cytochrome P450 1A (CYP1A), shows the best combination of specificity and reactivity for real-time detection of the enzymatic activities of CYP1A in complex biological systems. This study aimed to investigate the interspecies variation in NCMN-O-demethylation in commercially available liver microsomes from human, mouse, rat, beagle dog, minipig and cynomolgus monkey. Metabolite profiling demonstrated that NCMN could be O-demethylated in liver microsomes from all species but the reaction rate varied considerably. CYP1A was the major isoform involved in NCMN-O-demethylation in all examined liver microsomes based on the chemical inhibition assays. Furafylline, a specific inhibitor of mammalian CYP1A, displayed differential inhibitory effects on NCMN-O-demethylation in all tested species. Kinetic analyses demonstrated that NCMN-O-demethylation in liver microsomes form rat, minipig and cynomolgus monkey followed biphasic kinetics, while in liver microsomes form human, mouse and beagle dog obeyed Michaelis-Menten kinetics, the kinetic parameters from various species are much varied, while NCMN-O-demethylation in MLM exhibited the highest similarity of specificity, kinetic behavior and intrinsic clearance as that in HLM. These findings will be very helpful for the rational use of NCMN as a practical tool to decipher the functions of mammalian CYP1A or to study CYP1A associated drug-drug interactions in vivo.

12.
J Cell Mol Med ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454149

RESUMO

DYRK1A is considered a potential cancer therapeutic target, but the role of DYRK1A in NSCLC oncogenesis and treatment requires further investigation. In our study, high DYRK1A expression was observed in tumour samples from patients with lung cancer compared with normal lung tissues, and the high levels of DYRK1A were related to a reduced survival time in patients with lung cancer. Meanwhile, the DYRK1A inhibitor harmine could suppress the proliferation of NSCLC cells compared to that of the control. As DYRK1A suppression might be effective in treating NSCLC, we next explored the possible specific molecular mechanisms that were involved. We showed that DYRK1A suppression by siRNA could suppress the levels of EGFR and Met in NSCLC cells. Furthermore, DYRK1A siRNA could inhibit the expression and nuclear translocation of STAT3. Meanwhile, harmine could also regulate the STAT3/EGFR/Met signalling pathway in human NSCLC cells. AZD9291 is effective to treat NSCLC patients with EGFR-sensitivity mutation and T790 M resistance mutation, but the clinical efficacy in patients with wild-type EGFR remains modest. We showed that DYRK1A repression could enhance the anti-cancer effect of AZD9291 by inducing apoptosis and suppressing cell proliferation in EGFR wild-type NSCLC cells. In addition, harmine could enhance the anti-NSCLC activity of AZD9291 by modulating STAT3 pathway. Finally, harmine could enhance the anti-cancer activity of AZD9291 in primary NSCLC cells. Collectively, targeting DYRK1A might be an attractive target for AZD9291 sensitization in EGFR wild-type NSCLC patients.

13.
Neurol Sci ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31463680

RESUMO

The above article was published online with incorrect author name. The right spelling should be Xiangming Wang instead of Xiangmin Wang. The correct name is presented here. The original article has been corrected.

17.
BMC Med ; 17(1): 160, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31466528

RESUMO

BACKGROUND: Randomised control trials and genetic analyses have demonstrated that vitamin D or 25-hydroxyvitamin D (25[OH]D) levels may not play a causal role in the development of cardiovascular disease. However, it is unclear if 25(OH)D is causally associated with cause-specific vascular disease and lipids. Therefore, we examined the causal association of 25(OH)D with myocardial infarction, stroke, ischaemic heart disease, ischaemic stroke, subarachnoid haemorrhage, intracerebral haemorrhage, and lipid levels among both Chinese and Europeans. METHODS: We used a Mendelian randomisation (MR) design in the China Kadoorie Biobank, the Copenhagen City Heart Study, and the Copenhagen General Population Study. The 25(OH)D-related genetic variants in the CYP2R1 and DCHR7 genes were genotyped in 99,012 Chinese adults and 106,911 Danish adults. RESULTS: In Chinese adults, plasma 25(OH)D levels were not significantly associated with cause-specific vascular disease or mortality, with the exception of intracerebral haemorrhage (HR, 1.09 [95% CI, 1.01,1.18] per 25 nmol/L higher plasma 25(OH)D). In Europeans, plasma 25(OH)D levels were inversely associated with all types of vascular diseases and mortality. However, MR analysis did not demonstrate causal associations of genetically increased 25(OH)D levels with cause-specific vascular diseases, or mortality in both Chinese and European adults. In addition, each 25 nmol/L higher 25(OH)D was observationally associated with lower total cholesterol and low-density lipoprotein cholesterol levels, but higher high-density lipoprotein cholesterol levels. Likewise, MR analysis showed that 25(OH)D levels were not causally associated with lipids in both Chinese and European adults after Bonferroni correction. CONCLUSIONS: We found no evidence to support that genetically increased 25(OH)D was associated with a lower risk of ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and lipid levels in both Chinese and European adults. These results suggest that the inverse associations of vitamin D with vascular disease could be the result of confounding.

18.
Circ Genom Precis Med ; 12(9): 386-396, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31461308

RESUMO

BACKGROUND: Physical inactivity and sedentary behavior are associated with higher risk of cardiovascular disease (CVD). Little is known about the relevance of circulating metabolites for these associations. METHODS: A nested case-control study within the prospective China Kadoorie Biobank included 3195 incident CVD cases (2057 occlusive CVD and 1138 intracerebral hemorrhage) and 1465 controls aged 30 to 79 years without prior CVD or statin use at baseline. Nuclear magnetic resonance spectroscopy was used to measure 225 metabolic markers and derived traits in baseline plasma samples. Linear regression was used to relate self-reported physical activity and sedentary leisure time to biomarkers, adjusting for potential confounders. These were contrasted with associations of biomarkers with occlusive CVD risk. RESULTS: Physical activity and sedentary leisure time were associated with >100 metabolic markers, with patterns of associations generally mirroring each other. Physical activity was inversely associated with very low and low-density and positively with large and very large HDL (high-density lipoprotein) particle concentrations. Physical activity was also inversely associated with alanine, glucose, lactate, acetoacetate, and the inflammatory marker glycoprotein acetyls. In general, associations of physical activity and sedentary leisure time with specific metabolic markers were directionally consistent with the associations of these metabolic markers with occlusive CVD risk. Overall, metabolic markers potentially explained ≈70% of the protective associations of physical activity and ≈50% of the positive associations of sedentary leisure time with occlusive CVD. CONCLUSIONS: Among Chinese adults, physical activity and sedentary behavior have opposing associations with a diverse range of circulating metabolites, which may partially explain their associations with CVD risk.

19.
J Chin Med Assoc ; 82(7): 546-553, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31274786

RESUMO

BACKGROUND: It is importance to train the interprofessional collaboration (IPC) and team-efficiency (TE) of medical trainees. This prospective study evaluates whether implementation of scenario/video-created workshops in integrated IPC and TE (IIT) program provides additional benefits for IPC-TE skills of nursing trainees. METHODS: Mock simulation with two IIT scenarios was held as preintervention IPC-TE assessment. Basic and advanced workshops were arranged for teams of intervention groups for creation of discipline-specific scenario and video. Thirty-six nursing trainees were randomized into teams of five members (three nursing students, one standardized medical student, and one standardized trainees of other profession) in either intervention (scenario plus video and scenario) or control groups. After intervention, all groups received the formal simulation-based assessment using another two IIT scenario. In addition to instructors-based assessment of team' performance in mock and formal IIT simulation using interprofessional team collaboration scale (AITCS), self-assessment of attitudes and program-value score were completed by each trainee, using attitudes toward interprofessional health care teams scale (ATIHCTS) at all stages. RESULTS: Nursing trainees in intervention group gave high satisfaction score to this IIT intervention. In comparison with control group, greater increase in instructor-assessed team performance in the "partnership," "cooperation," and "shared decision making" domains of AITCS and the self-assessed "quality of care delivery" and TE domains of ATIHCTS were noted in the intervention groups. The overall improvement was greater in the scenario plus video group than those in the scenario group. Further, these improvements among nursing trainees persisted until follow-up stage at 4-weeks later. CONCLUSION: For nursing trainees, our study suggested that implementation of a scenario creation-based training resulted in additional improvement in trainee' IPC and TE behaviors and attitudes. Additionally, making video of newly created nurse-specific scenario enhances partnership and cooperation among nursing trainees and their interprofessional team members.

20.
Subst Use Misuse ; : 1-7, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31290365

RESUMO

Background: Many research studies reveal that both attentional bias and impaired cognitive control significantly influence heroin addiction. However, limited research has been conducted into how the interplay between attentional bias and cognitive control modulates heroin-seeking behavior. Objectives: A modified version of the flanker task was used to investigate whether attentional bias to drug-related stimuli is modulated by cognitive control mechanisms among heroin users. Methods: Sixty participants (30 male heroin users during their abstinence period and 30 normal controls) responded to the direction of the middle arrow, while ignoring the adjacent arrow and the pictures (drug-related cues and neutral cues) presented as part of the task. Results: The abstinent heroin users had a significantly larger flanker effect under drug-related cues compared to neutral cues, whereas the control group showed no such trend. This effect was primarily influenced by increased reaction times in the presence of drug-related cues relative to neutral cues in the incongruent condition among abstinent heroin users, but not in the control group. Conclusions/Importance: Among abstinent heroin users, attentional bias to drug-related cues was moderated by attentional control. Further, high cognitive control demand was found to reduce heroin users' ability to resist attentional capture from salient, but irrelevant, drug-related information, which may contribute to compulsive drug-seeking behavior and relapse in heroin users.

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