This book explains how to use standards like MDA and UML for ontology development. It provides the first detailed description of OMG's upcoming ODM (Ontology Definition Metamodel) standard and fills ...a gap by covering the subject of MDA application for ontology development on the Semantic Web.
Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical ...practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activity and might present multiple non–lipid-lowering actions, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and antioxidative properties. The aim of this expert opinion paper is to provide the first attempt at recommendation on the management of statin intolerance through the use of nutraceuticals with particular attention on those with effective low-density lipoprotein cholesterol reduction.
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Defining a formal domain ontology is generally considered a useful, not to say necessary step in almost every software project. This is because software deals with ideas rather than with self-evident ...physical artefacts. However, this development step is hardly ever done, as ontologies rely on well-defined and semantically powerful AI concepts such as description logics or rule-based systems, and most software engineers are largely unfamiliar with these. Ga#353evic and his co-authors try to fill this gap by detailing how to use model-driven engineering for ontology development on the Semantic Web. Part I of their book describes existing technologies, tools, and standards like XML, RDF, OWL, MDA, and UML. Part II presents the first detailed description of OMG's new ODM (Ontology Definition Metamodel) initiative, a specification which is expected to be in the form of an OMG language like UML. Finally, Part III is dedicated to applications and practical aspects of developing ontologies using MDA-based languages. For this second edition, the descriptions of the related standards (like MOF, ODM, OCL, and OWL) have been revised and updated, new chapters introducing the basic principles of model-driven engineering, recent research results on metamodeling Semantic Web rule languages, an introduction to the Atlas Transformation Language (ATL) and its tool support, and, last but not least, many new examples have been added.
Abstract
In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, ...nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is largely variable and, for many of the nutraceuticals, the evidence is very limited and, therefore, often debatable. The purpose of this position paper is to provide consensus-based recommendations for the optimal use of lipid-lowering nutraceuticals to manage dyslipidemia in patients who are still not on statin therapy, patients who are on statin or combination therapy but have not achieved lipid goals, and patients with statin intolerance. This statement is intended for physicians and other healthcare professionals engaged in the diagnosis and management of patients with lipid disorders, especially in the primary care setting.
The interaction of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain with the host-cell ACE2 receptor is a well-known step in virus infection. Neuropilin-1 (NRP-1) is another host factor ...involved in virus internalization. The interaction between S-glycoprotein and NRP-1 has been identified as a potential COVID-19 treatment target. Herein, the effectiveness of folic acid and leucovorin in preventing contact between S-glycoprotein and NRP-1 receptors was investigated using in silico studies and then confirmed in vitro. The results of a molecular docking study showed that leucovorin and folic acid had lower binding energies than EG01377, a well-known NRP-1 inhibitor, and lopinavir. Two hydrogen bonds with Asp 320 and Asn 300 residues stabilized the leucovorin, while interactions with Gly 318, Thr 349, and Tyr 353 residues stabilized the folic acid. The molecular dynamic simulation revealed that the folic acid and leucovorin created very stable complexes with the NRP-1. The in vitro studies showed that the leucovorin was the most active inhibitor of the S1-glycoprotein/NRP-1 complex formation, with an IC
value of 185.95 µg/mL. The results of this study suggest that folic acid and leucovorin could be considered as potential inhibitors of the S-glycoprotein/NRP-1 complex and, thus, could prevent the SARS-CoV-2 virus' entry into host cells.
The search for effective coronavirus disease (COVID-19) therapy has attracted a great deal of scientific interest due to its unprecedented health care system overload worldwide. We have carried out a ...study to investigate the in silico effects of the most abundant pomegranate peel extract constituents on the multi-step process of serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) internalization in the host cells. Binding affinities and interactions of ellagic acid, gallic acid, punicalagin and punicalin were studied on four selected protein targets with a significant and confirmed role in the process of the entry of virus into a host cell. The protein targets used in this study were: SARS-CoV-2 spike glycoprotein, angiotensin-converting enzyme 2, furin and transmembrane serine protease 2. The results showed that the constituents of pomegranate peel extracts, namely punicalagin and punicalin had very promising potential for significant interactions with the selected protein targets and were therefore deemed good candidates for further in vitro and in vivo evaluation.
New Findings
What is the central question of this study?
What are the biggest challenges in performing in vitro studies on isolated human umbilical arteries?
What is the main finding and its ...importance?
The protocols presented in this study indicate some potential outcomes important for interpretation of the vascular responsivities of human umbilical arteries and could be useful for planning future in vitro studies with human umbilical arteries.
Human umbilical artery (HUA) preparations are of particular importance for in vitro studies on isolated blood vessels because their sampling is not risky for the patient, and they can provide the closest possible impression of changes related to the uteroplacental circulation during pre‐eclampsia. Using organ bath techniques, useful experimental protocols are provided for measuring some pathophysiological phenomena in the vascular responses of HUAs. Several vasoconstrictors (serotonin, prostaglandin F and phenylephrine) and vasodilators (acetylcholine and minoxidil) were seleted for determination of their vasoactivity in HUAs. The role of L‐type voltage‐operated calcium channels and different types of potassium channels (KATP, BKCa and KV) were assessed, as was the impact of homocysteine. Serotonin was confirmed to be the most potent vasoconstrictor, while acetylcholine and phenylephrine caused variability in the relaxation and contraction response of HUA, respectively. The observed increase in serotonin‐induced contraction and a decrease in minoxidil‐induced relaxation in the presence of homocysteine suggested its procontractile effect on HUA preparations. Using selective blockers, it was determined that KATP and KV channels participate in the minoxidil‐induced relaxation, while L‐type voltage‐dependent Ca2+ channels play an important role in the serotonin‐induced contraction. The presented protocols reveal some of the methodological challenges related to HUA preparations and indicate potential outcomes in interpreting the vascular effects of the investigated substances, both in physiological conditions and in the homocysteine‐induced pre‐eclampsia model.
The aim of this study was to assess the oxidative stress status in rheumatoid arthritis (RA) by measuring markers of free radical production, systemic activity of disease, and levels of antioxidant. ...52 RA patients and 30 healthy controls were included in the study, and clinical examination and investigations were performed and disease activity was assessed. Peripheral blood samples were used for all the assays. We assessed the markers of oxidative stress, including plasma levels of index of lipid peroxidation-thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H
2
O
2
), superoxide anion radical (O
2
−
), nitric oxide (NO), and superoxide dismutase activity (SOD), catalase activity (CAT) and glutathione levels in erythrocytes. In the RA group, levels of H
2
O
2
, O
2
−
, and TBARS were significantly higher than in controls (4.08 ± 0.31 vs. 2.39 ± 0.13 nmol/l,
p
< 0.01; 8.90 ± 1.28 vs. 3.04 ± 0.38 nmol/l,
p
< 0.01, 3.65 ± 0.55 vs. 1.06 ± 0.17 μmol/l,
p
< 0.01). RA patients had significantly increased SOD activity compared with healthy controls (2,918.24 ± 477.14 vs. 643.46 ± 200.63UgHbx103,
p
< 0.001). Patients had significantly higher levels of pro-oxidants (O
2
−
, H
2
O
2
, and TBARS) compared to controls, despite significantly higher levels of SOD. Significant differences were also observed in serum levels of NO in patients with high-diseases activity. Our findings support an association between oxidative/nitrosative stress and RA. Stronger response in samples with higher diseases activity suggests that oxidative/nitrosative stress markers may be useful in evaluating the progression of RA as well as in elucidating the mechanisms of disease pathogenesis.
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