The effects of quercetin on the gene expression of arginine metabolism key enzymes in human embryonic kidney 293 cells

Background: Arginine metabolism is an important factor involved in tumorigenesis, progression, and survival of tumor cells. Besides, other metabolites produced in the arginine metabolism process, such as polyamines, nitric oxide, argininosuccinate, and agmatine, play key roles in different stages of tumor development. On the other hand, herbal metabolites are widely used to treat cancer. One of these herbal flavonoids is quercetin. Methods: In this study, according to MTT assay data, two concentrations of quercetin flavonoid were selected (57.5 and 115 μM) to treat human embryonic kidney 293 (HEK293) cells. Then RNA was extracted from the cells and used as a template for cDNA synthesis. Using real-time PCR, the expression of key enzymes involved in arginine metabolism was evaluated, including arginase 2 (Arg2), ornithine carbamoyl transferase (OTC), agmatinase (AGMAT), arginase 1 (Arg1), nitric oxide synthase 1 (nNOS), arginine decarboxylase (ADC), ornithine decarboxylase 1 (ODC), ornithine carbamoyl transferase (OCT), spermidine synthase (SRM), spermine synthase (SMS), argininosuccinate synthase 1 (ASS1), and argininosuccinate lyase (ASL). The Student t-test was used to analyze the data considering a P value of < 0.05 as the significance level. Results: Our results indicated significant changes in the expression of arginine metabolism enzymes after quercetin exposure, confirming a role for quercetin plant flavonoid in regulating arginine metabolism in HEK293 cells. Conclusions: Quercetin could alter the gene expression of the key enzymes involved in arginine metabolism. This was the first study investigating the effects of quercetin on arginine metabolism in HEK293 cells. © 2021 The Authors

Electronic Medical Record Inaccuracies: Multicenter Analysis of Challenges with Modified Lung Cancer Screening Criteria.

The National Comprehensive Cancer Network expanded their lung cancer screening (LCS) criteria to comprise one additional clinical risk factor, including chronic obstructive pulmonary disease (COPD). The electronic medical record (EMR) is a source of clinical information that could identify high-risk populations for LCS, including a diagnosis of COPD; however, an unsubstantiated COPD diagnosis in the EMR may lead to inappropriate LCS referrals. We aimed to detect the prevalence of unsubstantiated COPD diagnosis in the EMR for LCS referrals, to determine the efficacy of utilizing the EMR as an accurate population-based eligibility screening trigger using modified clinical criteria. We performed a multicenter review of all individuals referred to three LCS programs from 2012 to 2015. Each individual\u27s EMR was searched for COPD diagnostic terms and the presence of a diagnostic pulmonary functionality test (PFT). An unsubstantiated COPD diagnosis was defined by an individual\u27s EMR containing a COPD term with no PFTs present, or the presence of PFTs without evidence of obstruction. A total of 2834 referred individuals were identified, of which 30% (840/2834) had a COPD term present in their EMR. Of these, 68% (571/840) were considered unsubstantiated diagnoses: 86% (489/571) due to absent PFTs and 14% (82/571) due to PFTs demonstrating no evidence of postbronchodilation obstruction. A large proportion of individuals referred for LCS may have an unsubstantiated COPD diagnosis within their EMR. Thus, utilizing the EMR as a population-based eligibility screening tool, employing expanded criteria, may lead to individuals being referred, potentially, inappropriately for LCS

Minimally Invasive Mitral Valve Surgery I: Patient Selection, Evaluation, and Planning.

Widespread adoption of minimally invasive mitral valve repair and replacement may be fostered by practice consensus and standardization. This expert opinion, first of a 3-part series, outlines current best practices in patient evaluation and selection for minimally invasive mitral valve procedures, and discusses preoperative planning for cannulation and myocardial protection

Minimally Invasive Mitral Valve Surgery II: Surgical Technique and Postoperative Management.

Techniques for minimally invasive mitral valve repair and replacement continue to evolve. This expert opinion, the second of a 3-part series, outlines current best practices for nonrobotic, minimally invasive mitral valve procedures, and for postoperative care after minimally invasive mitral valve surgery

Paradoxical Changes: EMMPRIN Tissue and Plasma Levels in Marfan Syndrome-Related Thoracic Aortic Aneurysms

Background: Thoracic aortic aneurysms (TAAs) associated with Marfan syndrome (MFS) are unique in that extracellular matrix metalloproteinase inducer (EMMPRIN) levels do not behave the way they do in other cardiovascular pathologies. EMMPRIN is shed into the circulation through the secretion of extracellular vesicles. This has been demonstrated to be dependent upon the Membrane Type-1 MMP (MT1-MMP). We investigated this relationship in MFS TAA tissue and plasma to discern why unique profiles may exist. Methods: Protein targets were measured in aortic tissue and plasma from MFS patients with TAAs and were compared to healthy controls. The abundance and location of MT1-MMP was modified in aortic fibroblasts and secreted EMMPRIN was measured in conditioned culture media. Results: EMMPRIN levels were elevated in MFS TAA tissue but reduced in plasma, compared to the controls. Tissue EMMPRIN elevation did not induce MMP-3, MMP-8, or TIMP-1 expression, while MT1-MMP and TIMP-2 were elevated. MMP-2 and MMP-9 were reduced in TAA tissue but increased in plasma. In aortic fibroblasts, EMMPRIN secretion required the internalization of MT1-MMP. Conclusions: In MFS, impaired EMMPRIN secretion likely contributes to higher tissue levels, influenced by MT1-MMP cellular localization. Low EMMPRIN levels, in conjunction with other MMP analytes, distinguished MFS TAAs from controls, suggesting diagnostic potential

Modelling Visual Neglect: Computational Insights into Conscious Perception

Background: Visual neglect is an attentional deficit typically resulting from parietal cortex lesion and sometimes frontal lesion. Patients fail to attend to objects and events in the visual hemifield contralateral to their lesion during visual search. Methodology/Principal Finding: The aim of this work was to examine the effects of parietal and frontal lesion in an existing computational model of visual attention and search and simulate visual search behaviour under lesion conditions. We find that unilateral parietal lesion in this model leads to symptoms of visual neglect in simulated search scan paths, including an inhibition of return (IOR) deficit, while frontal lesion leads to milder neglect and to more severe deficits in IOR and perseveration in the scan path. During simulations of search under unilateral parietal lesion, the model’s extrastriate ventral stream area exhibits lower activity for stimuli in the neglected hemifield compared to that for stimuli in the normally perceived hemifield. This could represent a computational correlate of differences observed in neuroimaging for unconscious versus conscious perception following parietal lesion. Conclusions/Significance: Our results lead to the prediction, supported by effective connectivity evidence, that connections between the dorsal and ventral visual streams may be an important factor in the explanation of perceptua

Evolution and Optimality of Similar Neural Mechanisms for Perception and Action during Search

A prevailing theory proposes that the brain's two visual pathways, the ventral and dorsal, lead to differing visual processing and world representations for conscious perception than those for action. Others have claimed that perception and action share much of their visual processing. But which of these two neural architectures is favored by evolution? Successful visual search is life-critical and here we investigate the evolution and optimality of neural mechanisms mediating perception and eye movement actions for visual search in natural images. We implement an approximation to the ideal Bayesian searcher with two separate processing streams, one controlling the eye movements and the other stream determining the perceptual search decisions. We virtually evolved the neural mechanisms of the searchers' two separate pathways built from linear combinations of primary visual cortex receptive fields (V1) by making the simulated individuals' probability of survival depend on the perceptual accuracy finding targets in cluttered backgrounds. We find that for a variety of targets, backgrounds, and dependence of target detectability on retinal eccentricity, the mechanisms of the searchers' two processing streams converge to similar representations showing that mismatches in the mechanisms for perception and eye movements lead to suboptimal search. Three exceptions which resulted in partial or no convergence were a case of an organism for which the targets are equally detectable across the retina, an organism with sufficient time to foveate all possible target locations, and a strict two-pathway model with no interconnections and differential pre-filtering based on parvocellular and magnocellular lateral geniculate cell properties. Thus, similar neural mechanisms for perception and eye movement actions during search are optimal and should be expected from the effects of natural selection on an organism with limited time to search for food that is not equi-detectable across its retina and interconnected perception and action neural pathways

Top-Down Modulations from Dorsal Stream in Lexical Recognition: An Effective Connectivity fMRI Study

Both the ventral and dorsal visual streams in the human brain are known to be involved in reading. However, the interaction of these two pathways and their responses to different cognitive demands remains unclear. In this study, activation of neural pathways during Chinese character reading was acquired by using a functional magnetic resonance imaging (fMRI) technique. Visual-spatial analysis (mediated by the dorsal pathway) was disassociated from lexical recognition (mediated by the ventral pathway) via a spatial-based lexical decision task and effective connectivity analysis. Connectivity results revealed that, during spatial processing, the left superior parietal lobule (SPL) positively modulated the left fusiform gyrus (FG), while during lexical processing, the left SPL received positive modulatory input from the left inferior frontal gyrus (IFG) and sent negative modulatory output to the left FG. These findings suggest that the dorsal stream is highly involved in lexical recognition and acts as a top-down modulator for lexical processing