Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.718
Filtrar
1.
Int J Med Sci ; 17(17): 2888-2894, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33162817

RESUMO

Background: Fidgetin (FIGN), a conserved ATP-dependent enzyme, is regarded as a hepatocellular carcinoma (HCC) risk gene, but the prognostic implication of FIGN in HCC remains obscure. In this study, we investigate the expression of FIGN in HCC and to evaluate its prognostic value. Methods: A total of 216 patients with HCC who experienced hepatectomy were recruited in this study. The expression of FIGN in HCC samples was evaluated by quantitative real-time PCR, immunohistochemistry and immunoblotting analysis. And Cox regression model was used to evaluate the prognostic value of all covariates. Results: Of the 216 HCC patients, 67 (31.0%) had tumors with high FIGN expression and 149 (69.0%) had tumors with low FIGN expression. FIGN expression was positively correlated with TNM stage (P = 0.039), tumor with incomplete capsule (P = 0.036), microvascular invasion (P = 0.023), and portal vein tumor thrombus (P = 0.003). High expression of FIGN indicated shorter overall survival (OS) (hazard ratio: 4.569, P = 0.036) and disease-free survival (DFS) (hazard ratio: 6.487, P = 0.001). Conclusion: Our results indicate that high Fidgetin expression is associated with tumor progression and suggest a worse prognosis in HCC. Fidgetin might serve as a potential target for therapy.

2.
Behav Neurol ; 2020: 7029642, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178360

RESUMO

Aim: To identify the factors protecting Abeta-positive subjects with normal cognition (NC) or mild cognitive impairment (MCI) from conversion to Alzheimer's disease (AD). Methods: Subjects with MCI in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, with baseline data for neuropsychological tests, brain beta amyloid (Abeta), magnetic resonance imaging (MRI), APOE genotyping, and 18F-FDG-PET (FDG), were included for analysis. Results: Elevated brain amyloid was associated with a higher risk of conversion from MCI to AD (41.5%) relative to Abeta levels of <1.231 (5.5%) but was not associated with conversion from NC to AD (0.0 vs. 1.4%). In the multivariate Cox regression analyses, elevated Abeta increased the risk of AD, while higher whole-brain cerebral glucose metabolism (CGM) assessed by FDG decreased the risk of AD in subjects with the same amount of Abeta. Even in the patients with heavily elevated brain amyloid, those with FDG > 5.946 had a lower risk of AD. ApoE4 carrier status did not influence the protective effect. Conclusion: Higher average CGM based on FDG modified the progression to AD, indicating a protective function. The results suggest that the inclusion of this CGM measured by FDG would enrich clinical trial design and that increasing CGM along with the use of anti-Abeta agents might be a potential prevention strategy for AD.

3.
Chemosphere ; : 128800, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33143885

RESUMO

Modifying the electrodes of microbial fuel cells (MFCs) with iron oxides can improve the bacterial attachment performances and electrocatalytic activities for energy conversion, which is of significance in the fabrication of MFCs. However, the conventional modification methods usually result in the aggregation of iron sites, producing the electrodes of poor qualities. Herein, we report a novel method for the modification of electrochemical electrodes to boost the anode performance of MFC. The Shewanella precursor adhered on carbon felt electrode was directly carbonized to form a bacteria-derived biological iron oxide/carbon (Bio-FeOx/C) nanocomposite catalyst. The large spatial separation between the bacteria, as well as those between the iron containing proteins in the bacteria, deliver a highly dispersed Bio-FeOx/C nanocomposite with good electrocatalytic activities. The excellent microbial attachment performance and electron transfer rate of the Bio-FeOx/C modified electrode significantly promote the transfer of produced electrons between bacteria and electrode. Accordingly, the MFC with the Bio-FeOx/C electrode exhibits the maximum power density of 797.0 mW m-2, much higher than that obtained with the conventional carbon felt anode (226.1 mW m-2). Our works have paved a new avenue to the conversion of the natural bacterial precursors into active iron oxide nanoparticles as the anode catalyst of MFCs. The high catalytic activity of the prepared Bio-FeOx endows it great application potentials in the construction of high-performance electrodes.

5.
Clin Infect Dis ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33146720

RESUMO

BACKGROUND: Recurrent reports of suboptimal influenza vaccine effectiveness have renewed calls to develop improved, broadly cross-protective influenza vaccines. Here, we evaluated the safety and immunogenicity of a novel, saponin (Matrix-M)-adjuvanted, recombinant hemagglutinin (HA) quadrivalent nanoparticle influenza vaccine (qNIV). METHODS: We conducted a randomized, observer-blind, comparator-controlled (trivalent high-dose inactivated influenza vaccine [IIV3-HD], or quadrivalent recombinant influenza vaccine [RIV4]), safety and immunogenicity trial of qNIV (in 5 different doses/formulations) in healthy adults aged ≥65 years. Vaccine immunogenicity was measured by hemagglutination-inhibition assays using reagents expressing wild-type HA sequences (wt-HAI) and cell-mediated immune (CMI) responses. RESULTS: A total of 1375 participants were randomized, immunized, and followed for safety and immunogenicity. Matrix-M-adjuvanted qNIV induced superior wt-HAI antibody responses against 5 of 6 homologous or drifted strains evaluated compared to unadjuvanted qNIV. Adjuvanted qNIV induced post-vaccination wt-HAI antibody responses at Day 28 that were: statistically higher than IIV3-HD against a panel of homologous or drifted A/H3N2 strains; similar to IIV3-HD against homologous A/H1N1 and B (Victoria) strains; and similar to RIV4 against all homologous and drifted strains evaluated. The qNIV formulation with 75 µg Matrix-M adjuvant induced substantially higher post-vaccination geometric mean fold-increases of influenza HA-specific polyfunctional CD4+ T-cells compared to IIV3-HD or RIV4. Overall, similar frequencies of solicited and unsolicited adverse events (AEs) were reported in all treatment groups. CONCLUSIONS: qNIV with 75 µg Matrix-M adjuvant was well tolerated and induced robust antibody and cellular responses, notably against both homologous and drifted A/H3N2 viruses. Further investigation in a pivotal phase 3 trial is underway.

6.
Circ Res ; 127(11): 1381-1383, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33151797
7.
Int J Mol Sci ; 21(22)2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33212853

RESUMO

Research on the Aß cascade and alternations of biomarkers in neuro-inflammation, synaptic dysfunction, and neuronal injury followed by Aß have progressed. But the question is how to use the biomarkers. Here, we examine the evidence and pathogenic implications of protein interactions and the time order of alternation. After the deposition of Aß, the change of tau, neurofilament light chain (NFL), and neurogranin (Ng) is the main alternation and connection to others. Neuro-inflammation, synaptic dysfunction, and neuronal injury function is exhibited prior to the structural and metabolic changes in the brain following Aß deposition. The time order of such biomarkers compared to the tau protein is not clear. Despite the close relationship between biomarkers and plaque Aß deposition, several factors favor one or the other. There is an interaction between some proteins that can predict the brain amyloid burden. The Aß cascade hypothesis could be the pathway, but not all subjects suffer from Alzheimer's disease (AD) within a long follow-up, even with very elevated Aß. The interaction of biomarkers and the time order of change require further research to identify the right subjects and right molecular target for precision medicine therapies.

8.
PLoS One ; 15(11): e0242479, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33206711

RESUMO

Combining global gridded population and fossil fuel based CO2 emission data at 1 km scale, we investigate the spatial origin of CO2 emissions in relation to the population distribution within countries. We depict the correlations between these two datasets by a quasi-Lorenz curve which enables us to discern the individual contributions of densely and sparsely populated regions to the national CO2 emissions. We observe pronounced country-specific characteristics and quantify them using an indicator resembling the Gini-index. As demonstrated by a robustness test, the Gini-index for each country arise from a compound distribution between the population and emissions which differs among countries. Relating these indices with the degree of socio-economic development measured by per capita Gross Domestic Product (GDP) at purchase power parity, we find a strong negative correlation between the two quantities with a Pearson correlation coefficient of -0.71. More specifically, this implies that in developing countries locations with large population tend to emit relatively more CO2, and in developed countries the opposite tends to be the case. Based on the relation to urban scaling, we discuss the implications for CO2 emissions from cities. Our results show that general statements with regard to the (in)efficiency of large cities should be avoided as it is subject to the socio-economic development of respective countries. Concerning the political relevance, our results suggest a differentiated spatial prioritization in deploying climate change mitigation measures in cities for developed and developing countries.

10.
J Agric Food Chem ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33174430

RESUMO

There are multiple obstacles in the gastrointestinal tract (GIT) for oral administration of bioactive macromolecules. Here, we engineered an oral delivery vehicle (sporopollenin exine capsules with carboxymethylpachymaran (CMP)/metal ion modification) with targeted release based on food-grade ingredients and processing operations. Then, the interaction and binding mechanisms between CMP and metal ions in the vehicle were investigated. By using ß-galactosidase (ß-Gal) as a model protein, the systems were characterized for the surface morphology and monitored by the in vitro release profile of ß-Gal. Notably, the CMP/metal ion systems not only markedly decreased the CMP dosage but also achieved a valid long-term release compared with the previously reported CMP system. Among all the systems, the CMP/3% AlCl3 system showed the best ability to control the release with the maximum residual activity of ß-Gal at nearly 72% after 24 h of treatment. Subsequently, the interaction mechanism between CMP and metal ions within the system was characterized by the perspectives of microstructure, rheological properties, and spectroscopy characteristics. The results indicated that the low pH conditions are conducive to the further cross-linking of CMP and metal ions, resulting in a high gel strength and thus a dense structure, which can impact the controlled release of ß-Gal in the GIT. Overall, the system may be utilized in the administration of medical and functional foods, specifically for the delivery of bioactive proteins via the oral route.

11.
Mol Oncol ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33155364

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Here, we identified that increased miR-23a expression in HCC tissues was associated with worse survival. More importantly, we found that STAT5A was a target of miR-23a, whose levels significantly decreased in tumor tissues. Stable expression of STAT5A in Huh7 cells suppressed glucose metabolism and tumor growth. Finally, this study showed that increased miR-23a negatively regulated STAT5A, which further activated AKT signaling to enable rapid metabolism for accelerated tumor growth in HCC. Taken together, our results demonstrated that the miR-23a-STAT5A-AKT signaling pathway is critical to alter glucose metabolism in HCC and may offer new opportunities for effective therapy.

12.
Vaccine ; 38(50): 7892-7896, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33139139

RESUMO

There is an urgent need for a safe and protective vaccine to control the global spread of SARS-CoV-2 and prevent COVID-19. Here, we report the immunogenicity and protective efficacy of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length SARS-CoV-2 spike (S) glycoprotein stabilized in the prefusion conformation. Cynomolgus macaques (Macaca fascicularis) immunized with NVX-CoV2373 and the saponin-based Matrix-M™ adjuvant induced anti-S antibody that was neutralizing and blocked binding to the human angiotensin-converting enzyme 2 (hACE2) receptor. Following intranasal and intratracheal challenge with SARS-CoV-2, immunized macaques were protected against upper and lower infection and pulmonary disease. These results support ongoing phase 1/2 clinical studies of the safety and immunogenicity of NVX-CoV2327 vaccine (NCT04368988).

13.
BMC Neurosci ; 21(1): 46, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33218307

RESUMO

BACKGROUND: As a noninvasive perfusion-weighted MRI technique, arterial spin-labeling (ASL) was becoming increasingly used to evaluate cerebral hemodynamics in many studies. The relation between ASL-MRI and crossed cerebellar diaschisis (CCD) was rarely discussed. In this study, the aim of our study was to assess the performance of ASL-MRI in the detection of crossed cerebellar diaschisis after stroke in compared with single-photon emission CT (SPECT). RESULTS: 17 of 51(33.3%) patients revealed CCD phenomenon by the SPECT method. In CCD-positive group, CBFASL of ipsilateral cerebellar were significantly increased compared with contralateral cerebellar (p < 0.0001) while no significant differences (p = 0.063, > 0.001) in the CCD-negative group. Positive correlation was detected between admission National institute of health stroke scale (NIHSS) and asymmetry index of SPECT (AISPECT) (r = 0.351, p = 0.011), AIASL (r = 0.372, p = 0.007); infract volume and AISPECT (r = 0.443, p = 0.001), AIASL (r = 0.426, p = 0.002). Significant correlation was also found between cerebral blood flow of SPECT (CBFSPECT) and CBFASL, AISPECT and AIASL (r = 0.204, p = 0.04; r = 0.467, p = 0.001, respectively). Furthermore, the area under the receiver operating characteristic (ROC) curve value of AIASL was 0.829. CONCLUSIONS: CBF derived from ASL-MRI could be valuable for assessment of CCD in supratentorial stroke patients. Additionally, CCD was significantly associated with larger ischemic volume and higher initial NIHSS score.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33165604

RESUMO

OBJECTIVES: Muscle cell necrosis is the most common pathological manifestation of idiopathic inflammatory myopathies. Evidence suggests that glycolysis might participate in it. However, the mechanism is unclear. This study aimed to determine the role of glycolysis in the muscle damage that occurs in DM/PM. METHODS: Mass spectrometry was performed on muscle lesions from DM/PM and control subjects. The expression levels of pyruvate kinase isozyme M2 (PKM2), the nucleotide-binding and oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and pyroptosis-related genes in muscle tissues or plasma were determined by real-time PCR, western blot analysis, IF and ELISA. In addition, IFNγ was used to stimulate myotubes, and the relationships among PMK2 expression, NLRP3 inflammasome activation and pyroptosis were investigated. RESULTS: Mass spectrometry and bioinformatics analysis suggested that multiple glycolysis processes, the NLRP3 inflammasome and programmed cell death pathway-related proteins were dysregulated in the muscle tissues of DM/PM. PKM2 and the NLRP3 inflammasome were upregulated and positively correlated in the muscle fibres of DM/PM. Moreover, the pyroptosis-related proteins were increased in muscle tissues of DM/PM and were further increased in PM. The levels of PKM2 in muscle tissues and IL-1ß in plasma were high in patients with anti-signal recognition particle autoantibody expression. The pharmacological inhibition of PKM2 in IFNγ-stimulated myotubes attenuated NLRP3 inflammasome activation and subsequently inhibited pyroptosis. CONCLUSION: Our study revealed upregulated glycolysis in the lesioned muscle tissues of DM/PM, which activated the NLRP3 inflammasome and leaded to pyroptosis in muscle cells. The levels of PKM2 and IL-1ß were high in patients with anti-signal recognition particle autoantibody expression. These proteins might be used as new biomarkers for muscle damage.

15.
Chemosphere ; : 128736, 2020 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33131734

RESUMO

Depiction on an energetic chain in terms of assimilation, allocation and consumption as well as the linkage between energetic alteration and physiological process was performed in blue mussel Mytilus edulis coping with tetrabromodiphenyl ether (BDE-47) based on a 21-day bioassay to shed light on the possible mechanism from energetic perspective. The filtration was hindered along with BDE-47 concentration increment and the influence of digestion was suggested according to the combination of the digestive enzymatic activities' alteration and digestive gland tissue impairment, both of which decided the energy availability reduction. Energy consumption indicated by the electron transport system activity was firstly inhibited while was greatly increased with BDE-47 increment, and the cellular energy allocation and adenylate pool were decreased simultaneously. An energetic chain was thus depicted: it tended to reduce energy absorption, elevate the energy consumption and decrease the energy metabolism with BDE-47 exposure, and M. edulis adopted the energetic strategy with variation regarding to the stressing level, suggesting as the preference switched from protein utilization to lipid utilization with the concentration increment. A consistence was observed in index of growth and survival with the change of energy allocation, inferring the energetic involvement in sustaining the viability of the mussel.

16.
Biol Psychiatry ; 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-33190845

RESUMO

BACKGROUND: Deficiency in neuronal structural plasticity is involved in the development of major depressive disorder. TWIST1, a helix-loop-helix transcription factor that is essential for morphogenesis and organogenesis, is normally expressed at low levels in mature neurons. However, it is poorly understood what role TWIST1 plays in the brain and whether it is involved in the pathophysiology of depression. METHODS: Depressive-like behaviors in C57BL/6J mice were developed by chronic social defeat stress. Genetic and pharmacological approaches were used to investigate the role of the TWIST1-miR-214-PPAR-δ signaling pathway in depressive-like behaviors. Molecular biological and morphological studies were performed to define the molecular mechanisms downstream of TWIST1. RESULTS: The expression of TWIST1 was positively correlated with depressive behaviors in humans and mice. Chronic stress elevated TWIST1 expression in the medial prefrontal cortex of mice, which was reversed by fluoxetine treatment. While the overexpression of TWIST1 increased susceptibility to stress, the knockdown of TWIST1 prevented the defective morphogenesis of dendrites of pyramidal neurons in layer II/III of the medial prefrontal cortex and alleviated depressive-like behaviors. Mechanistically, this prodepressant property of TWIST1 was mediated, at least in part, through the repression of miR-214-PPAR-δ signaling and mitochondrial function, which was also mimicked by genetic and pharmacological inhibition of PPAR-δ. CONCLUSIONS: These results suggest that TWIST1 in the medial prefrontal cortex mediates chronic stress-induced dendritic remodeling and facilitates the occurrence of depressive-like behavior, providing new information for developing drug targets for depression therapy.

17.
Circulation ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33203221

RESUMO

Background: Recent discoveries have indicated that, in the developing heart, sinus venosus and endocardium provide major sources of endothelium for coronary vessel growth that supports the expanding myocardium. Here we set out to study the origin of the coronary vessels that develop in response to vascular endothelial growth factor B (VEGF-B) in the heart and the effect of VEGF-B on recovery from myocardial infarction. Methods: We used mice and rats expressing a VEGF-B transgene, VEGF-B-gene-deleted mice and rats, Apelin (Apln)-CreERT2 and Npr3-CreERT2 recombinase-mediated genetic cell lineage tracing and viral vector-mediated VEGF-B gene transfer in adult mice. Left anterior descending coronary vessel ligation was performed and EdU-mediated proliferating cell cycle labeling, flow cytometry, histological, immunohistochemical, and biochemical methods, single-cell RNA sequencing and subsequent bioinformatic analysis, micro-computed tomography, and fluorescent and tracer-mediated vascular perfusion imaging analyses were used to study the development and function of the VEGF-B-induced vessels in the heart. Results: We show that cardiomyocyte overexpression of VEGF-B in mice and rats during development promotes the growth of novel vessels that originate directly from the cardiac ventricles and maintain connection with the coronary vessels in subendocardial myocardium. In adult mice, endothelial proliferation induced by VEGF-B gene transfer was located predominantly in the subendocardial coronary vessels. Furthermore, VEGF-B gene transduction prior to or concomitantly with ligation of the left anterior descending coronary artery promoted endocardium-derived vessel development into the myocardium and improved cardiac tissue remodeling and cardiac function. Conclusions: The myocardial VEGF-B transgene promotes the formation of endocardium-derived coronary vessels during development, endothelial proliferation in subendocardial myocardium in adult mice, and structural and functional rescue of cardiac tissue after myocardial infarction. VEGF-B could provide a new therapeutic strategy for cardiac neovascularization after coronary occlusion to rescue the most vulnerable myocardial tissue.

18.
J Agric Food Chem ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33175506

RESUMO

Proanthocyanidins (PACs) are near-ubiquitous and chemically complex metabolites, prototypical of higher plants. Their roles in food/feed/nutrition and ethnomedicine are widely recognized but poorly understood. With the analysis of evidence that underlies this challenge, this perspective identifies shortcomings in capturing and delineating PAC structures as key factors. While several groups have forwarded new representations, a consensus method that captures PAC structures concisely and offers high integrity for electronic storage is required to reduce confusion in this expansive field. The PAC block arrays (PACBAR) system fills this gap by providing precise and human- and machine-readable structural descriptors that capture PAC metabolomic structural diversity. PACBAR enables communication of PAC structures for the development of precise structure-activity relationships and will assist in advancing PAC research to the next level.

19.
Nature ; 586(7831): 785-789, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33057196

RESUMO

In the mammalian lung, an apparently homogenous mesh of capillary vessels surrounds each alveolus, forming the vast respiratory surface across which oxygen transfers to the blood1. Here we use single-cell analysis to elucidate the cell types, development, renewal and evolution of the alveolar capillary endothelium. We show that alveolar capillaries are mosaics; similar to the epithelium that lines the alveolus, the alveolar endothelium is made up of two intermingled cell types, with complex 'Swiss-cheese'-like morphologies and distinct functions. The first cell type, which we term the 'aerocyte', is specialized for gas exchange and the trafficking of leukocytes, and is unique to the lung. The other cell type, termed gCap ('general' capillary), is specialized to regulate vasomotor tone, and functions as a stem/progenitor cell in capillary homeostasis and repair. The two cell types develop from bipotent progenitors, mature gradually and are affected differently in disease and during ageing. This cell-type specialization is conserved between mouse and human lungs but is not found in alligator or turtle lungs, suggesting it arose during the evolution of the mammalian lung. The discovery of cell type specialization in alveolar capillaries transforms our understanding of the structure, function, regulation and maintenance of the air-blood barrier and gas exchange in health, disease and evolution.

20.
Artigo em Inglês | MEDLINE | ID: mdl-33022772

RESUMO

BACKGROUND: Supraventricular tachycardia (SVT) with coronary sinus (CS) ostial atresia (CSA) or coronary sinus stenosis (CSS) causes difficulty in electrophysiological procedures, but its characteristics are poorly understood. OBJECTIVE: Study the anatomical and clinical features of SVT patients with CSA/CSS. METHODS: Of 6128 patients with SVT undergoing electrophysiological procedures, consecutive patients with CSA/CSS were enrolled, and the baseline characteristics, imaging materials, intraoperative data, and follow-up outcomes were analyzed. RESULTS: Thirteen patients, seven with CSA and six with CSS, underwent the electrophysiological procedure. Decapolar catheters were placed into the proximal CS in three cases, while the rest were placed at the free wall of the right atrium. Fourteen arrhythmias were confirmed: four atrioventricular nodal reentrant tachycardias, five left-sided accessory pathways, three paroxysmal atrial fibrillations, and two atrial flutters (AFLs). In addition to three patients who underwent only an electrophysiological study, the acute ablation success rate was 100% in 10 cases, with no procedure-related complications. After a median follow-up period of 59.6 months, only one case of atypical AFL recurred. For those cases (seven CSA and two CSS) with a total of 10 anomalous types of CS drainage, three types were classified: from the CS to the persistent left superior vena cava (n = 3), from an unroofed CS (n = 3), and from the CS to the small cardiac vein (n = 3) or Thebesian vein (n = 1). CONCLUSION: Patients with CSA/CSS may develop different kinds of SVT. Electrophysiological procedures for such patients are feasible and effective. An individualized mapping strategy based on the three types of CS drainage will be helpful.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA