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Subclinical atherosclerosis may result in fatal cardiovascular (CV) events, but the underlying mechanisms and molecular players leading to disease are not entirely understood. Thus, novel approaches capable of identifying the factors involved in pathological progression and providing a better understanding of the subjacent mechanisms are needed. Extracellular vesicles (EVs) have been shown to have numerous biological functions, and their metabolome has recently generated interest as a source of novel biomarkers. The metabolic content of the exosomes has been so far unexplored in cardiovascular disease (CVD), and here, we developed an analytical strategy aimed at probing urinary exosomal metabolite content and its association to CV risk.
Direct analysis of the exosomes without metabolite extraction was evaluated by high-resolution magic angle spinning (
H HR-MAS). Other two methodologies for the analysis of exosomal metabolites by
H NMR were set up, based on methanol or organic solvents sequential extra to analyze metabolic alterations in urinary exosomes and identified a cardiometabolic signature in these microvesicles. This study constitutes the first evidence of a role for the exosomal metabolism in CVD and demonstrates the possibility to evaluate the urinary exosomal metabolic content by NMR and MS.
We set up a novel methodology to analyze metabolic alterations in urinary exosomes and identified a cardiometabolic signature in these microvesicles. This study constitutes the first evidence of a role for the exosomal metabolism in CVD and demonstrates the possibility to evaluate the urinary exosomal metabolic content by NMR and MS.Chronic fatigue often starts with an acute viral infection-as witnessed in the case of SARS-CoV-2-but indirect consequences of these infections are presumably the actual cause of the condition. As recently reviewed in this journal, the culprit could be a virus already present in the patient. The review covers several types of viruses, but concludes that the question is still open. The focus is on well known, pathogenic viruses for which there are ample diagnostic tools. I argue that there is one lesser-known group of viruses, the related anello- and circoviruses, which ought to be investigated. More or less everyone harbours at least one strain of these viruses in the blood, while not in the spinal fluid. They normally replicate at a low level, but their activity increases in an immune suppressed host; and there are cases where they do reach the brain. The initial infection could facilitate their access to the brain.
Elasticity prevents fatigue of tissues that are extensively and repeatedly deformed. Resilin is a resilient and elastic extracellular protein matrix in joints and hinges of insects. For its mechanical properties, Resilin is extensively analysed and applied in biomaterial and biomedical sciences. Selleckchem Eprosartan However, there is only indirect evidence for Resilin distribution and function in an insect. Commonly, the presence of dityrosines that covalently link Resilin protein monomers (Pro-Resilin), which are responsible for its mechanical properties and fluoresce upon UV excitation, has been considered to reflect Resilin incidence.
Using a GFP-tagged Resilin version, we directly identify Resilin in pliable regions of the Drosophila body, some of which were not described before. Interestingly, the amounts of dityrosines are not proportional to the amounts of Resilin in different areas of the fly body, arguing that the mechanical properties of Resilin matrices vary according to their need. For a functional analysis of Resilin matrices, applying the RNA interference and Crispr/Cas9 techniques, we generated flies with reduced or eliminated Resilin function, respectively. We find that these flies are flightless but capable of locomotion and viable suggesting that other proteins may partially compensate for Resilin function. Indeed, localizations of the potentially elastic protein Cpr56F and Resilin occasionally coincide.
Thus, Resilin-matrices are composite in the way that varying amounts of different elastic proteins and dityrosinylation define material properties. Understanding the biology of Resilin will have an impact on Resilin-based biomaterial and biomedical sciences.
Thus, Resilin-matrices are composite in the way that varying amounts of different elastic proteins and dityrosinylation define material properties. Understanding the biology of Resilin will have an impact on Resilin-based biomaterial and biomedical sciences.
Glutathione Peroxidase 8 (GPX8) as a member of the glutathione peroxidase (GPx) family plays an important role in anti-oxidation. Besides, dysregulation of GPX8 has been found in gastric cancer, but its detailed molecular mechanism in gastric cancer has not been reported.
Our study detected the expression of GPX8 in gastric cancer tissues and cell lines using immunohistochemistry (IHC), western blot and qRT-PCR, and determined the effect of GPX8 on gastric cancer cells using CCK-8, colony formation, transwell migration and invasion assays. Besides, the effect of GPX8 on the Wnt signaling pathway was determined by western blot. Furthermore, the transcription factor of GPX8 was identified by bioinformatics methods, dual luciferase reporter and chromatin immunoprecipitation (CHIP) assays. In addition, the effect of GPX8 on tumor formation was measured by IHC and western blot.
The over-expression of GPX8 was observed in gastric cancer tissues and cells, which facilitated the proliferation, migration and invasion of gastric cancer cells as well as the tumor growth. GPX8 knockdown effectively inhibited the growth of gastric cancer cells and tumors. Moreover, GPX8 could activate the Wnt signaling pathway to promote the cellular proliferation, migration and invasion through. Furthermore, FOXC1 was identified as a transcription factor of GPX8 and mediated GPX8 expression to affect cell development processes.
These findings contribute to understanding the molecular mechanism of GPX8 in gastric cancer. Additionally, GPX8 can be a potential biomarker for gastric cancer therapy.
These findings contribute to understanding the molecular mechanism of GPX8 in gastric cancer. Additionally, GPX8 can be a potential biomarker for gastric cancer therapy.
Type 2 diabetes (T2D) patients are at a greater risk of cardiovascular events due to aggravated atherosclerosis. Oxidized LDL (oxLDL) has been shown to be increased in T2D plaques and suggested to contribute to plaque ruptures. Despite intensified statin treatment during the last decade the higher risk for events remains. Here, we explored if intensified statin treatment was associated with reduced oxLDL in T2D plaques and if oxLDL predicts cardiovascular events, to elucidate whether further plaque oxLDL reduction would be a promising therapeutic target.
Carotid plaque OxLDL levels and plasma lipoproteins were assessed in 200 patients. Plaque oxLDL was located by immunohistochemistry. Plaque cytokines, cells and scavenger receptor gene expression were quantified by Luminex, immunohistochemistry and RNA sequencing, respectively. Clinical information and events during follow-up were obtained from national registers.
Plaque oxLDL levels correlated with markers of inflammatory activity, endothelial activati receiving statin treatment.
This study points out the importance of statin treatment in affecting plaque biology in T2D. It also implies that other biological components, beyond oxLDL, need to be identified and targeted to further reduce the risk of events among T2D patients receiving statin treatment.
Acute myocardial infarction (AMI) is a serious cardiovascular disease, followed by a high readmission rate within 30-days of discharge. Accurate prediction of AMI readmission is a crucial way to identify the high-risk group and optimize the distribution of medical resources.
In this study, we propose a stacking-based model to predict the risk of 30-day unplanned all-cause hospital readmissions for AMI patients based on clinical data. Firstly, we conducted an under-sampling method of neighborhood cleaning rule (NCR) to alleviate the class imbalance and then utilized a feature selection method of SelectFromModel (SFM) to select effective features. Secondly, we adopted a self-adaptive approach to select base classifiers from eight candidate models according to their performances in datasets. Finally, we constructed a three-layer stacking model in which layer 1 and layer 2 were base-layer and level 3 was meta-layer. The predictions of the base-layer were used to train the meta-layer in order to make the final forecast.
The results show that the proposed model exhibits the highest AUC (0.720), which is higher than that of decision tree (0.681), support vector machine (0.707), random forest (0.701), extra trees (0.709), adaBoost (0.702), bootstrap aggregating (0.704), gradient boosting decision tree (0.710) and extreme gradient enhancement (0.713).
It is evident that our model could effectively predict the risk of 30-day all cause hospital readmissions for AMI patients and provide decision support for the administration.
It is evident that our model could effectively predict the risk of 30-day all cause hospital readmissions for AMI patients and provide decision support for the administration.
Recent studies have revealed that serpin peptidase inhibitor clade E member 2 (SERPINE2) is associated with tumorigenesis. However, SERPINE2 expression and its role in lung adenocarcinomas are still unknown.
The expression levels of SERPINE2 in 74 consecutively resected lung adenocarcinomas were analyzed by using immunostaining. Inhibition of SERPINE2 expression by small interfering RNA (siRNA) was detected by quantitative PCR. Cell number assays and cell apoptosis assays were performed to clarify the cell-autonomous function of SERPINE2 in A549 and PC9 lung cancer cells.
The overall survival of patients with high SERPINE2 expression was significantly worse than that of patients with low SERPINE2 expression (P = 0.0172). Multivariate analysis revealed that SERPINE2 expression was an independent factor associated with poor prognosis (P = 0.03237). The interference of SERPINE2 decreased cell number and increased apoptosis in A549 and PC9 cells CONCLUSION These results suggest that SERPINE2 can be used as a novel prognostic marker of lung adenocarcinoma.
The overall survival of patients with high SERPINE2 expression was significantly worse than that of patients with low SERPINE2 expression (P = 0.0172). Multivariate analysis revealed that SERPINE2 expression was an independent factor associated with poor prognosis (P = 0.03237). The interference of SERPINE2 decreased cell number and increased apoptosis in A549 and PC9 cells CONCLUSION These results suggest that SERPINE2 can be used as a novel prognostic marker of lung adenocarcinoma.
Nursing education institutions are required to select and train applicants who have appropriate characteristics for delivering effective healthcare. Unlike other healthcare professions and despite the need to attract and select a competent workforce, there has been no comprehensive analysis of the selection criteria and methods used to recruit nursing students. As there is relatively limited prior research available, we conducted a scoping review to explore and synthesise the existing evidence regarding admission criteria and selection methods of nursing students and for the purpose of identifying an agenda for future research in this field.
Our scoping review follows the Arksey and O'Malley five-step proposition including identifying the research question and relevant studies, study selection, tabulation of data, and summarizing and reporting the results. Seven databases (PubMed, CINAHL, Scopus, ERIC, SID, Irandoc and PsycINFO) were searched systematically using relevant keywords. Articles on admission of undergraduate nursing students published in both English and/or Persian from 2006 to 2019 were retrieved.
