Biglycan Regulates MG63 Osteosarcoma Cell Growth Through a LPR6/β-Catenin/IGFR-IR Signaling Axis

Biglycan, a small leucine rich proteoglycan (SLRP), is an important participant in bone homeostasis and development as well as in bone pathology. In the present study biglycan was identified as a positive regulator of MG63 osteosarcoma cell growth (p ≤ 0.001). IGF-I was shown to increase biglycan expression (p ≤ 0.01), whereas biglycan-deficiency attenuated significantly both basal and IGF-I induced cell proliferation of MG63 cells (p ≤ 0.001; p ≤ 0.01, respectively). These effects were executed through the IGF-IR receptor whose activation was strongly attenuated (p ≤ 0.01) in biglycan-deficient MG63 cells. Biglycan, previously shown to regulate Wnt/β-catenin pathway, was demonstrated to induce a significant increase in β-catenin protein expression evident at cytoplasmic (p ≤ 0.01), membrane (p ≤ 0.01), and nucleus fractions in MG63 cells (p ≤ 0.05). As demonstrated by immunofluorescence, increase in β-catenin expression is attributed to co-localization of biglycan with the Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) resulting in attenuated β-catenin degradation. Furthermore, applying anti-β-catenin and anti-pIGF-IR antibodies to MG-63 cells demonstrated a cytoplasmic and to the membrane interaction between these molecules that increased upon exogenous biglycan treatment. In parallel, the downregulation of biglycan significantly inhibited both basal and IGF-I-dependent ERK1/2 activation, (p ≤ 0.001). In summary, we report a novel mechanism where biglycan through a LRP6/β-catenin/IGF-IR signaling axis enhances osteosarcoma cell growth

Treating dyslipidemias: Is inflammation the missing link?

Low-grade chronic inflammation is now being held as an important process in the development of atherosclerosis, with new links between dyslipidemia and inflammation being constantly found. While most studies aim to discover inflammatory pathways leading from dyslipidemia to atherogenesis, there is evidence that inflammation can also act in reverse, altering lipid metabolism in unfavorable ways, possibly creating a vicious cycle of inflammationdyslipidemia-inflammation. This is highly relevant for the search of novel therapeutic targets. In this review, after a brief account of the inflammatory mechanisms leading from dyslipidemia to atherogenesis, we focus on what is currently known about the ways inflammation can impair lipid metabolism and whether anti-inflammatory therapies could have a role in dyslipidemia management. © 2014 Bentham Science Publishers

Monte carlo computational software and methods in radiation dosimetry

The fast developments and ongoing demands in radiation dosimetry have piqued the attention of many software developers and physicists to create powerful tools to make their experiments more exact, less expensive, more focused, and with a wider range of possibilities. Many software toolkits, packages, and programs have been produced in recent years, with the majority of them available as open source, open access, or closed source. This study is mostly focused to present what are the Monte Carlo software developed over the years, their implementation in radiation treatment, radiation dosimetry, nuclear detector design for diagnostic imaging, radiation shielding design and radiation protection. Ten software toolkits are introduced, a table with main characteristics and information is presented in order to make someone entering the field of computational Physics with Monte Carlo, make a decision of which software to use for their experimental needs. The possibilities that this software can provide us with allow us to design anything from an X-Ray Tube to whole LINAC costly systems with readily changeable features. From basic x-ray and pair detectors to whole PET, SPECT, CT systems which can be evaluated, validated and configured in order to test new ideas. Calculating doses in patients allows us to quickly acquire, from dosimetry estimates with various sources and isotopes, in various materials, to actual radiation therapies such as Brachytherapy and Proton therapy. We can also manage and simulate Treatment Planning Systems with a variety of characteristics and develop a highly exact approach that actual patients will find useful and enlightening. Shielding is an important feature not only to protect people from radiation in places like nuclear power plants, nuclear medical imaging, and CT and X-Ray examination rooms, but also to prepare and safeguard humanity for interstellar travel and space station missions. This research looks at the computational software that has been available in many applications up to now, with an emphasis on Radiation Dosimetry and its relevance in today's environment. © 2021 by the author(s)

Global consequences of liver ischemia/reperfusion injury

Liver ischemia/reperfusion injury has been extensively studied during the last decades and has been implicated in the pathophysiology of many clinical entities following hepatic surgery and transplantation. Apart from its pivotal role in the pathogenesis of the organ's post reperfusion injury, it has also been proposed as an underlying mechanism responsible for the dysfunction and injury of other organs as well. It seems that liver ischemia and reperfusion represent an event with "global" consequences that influence the function of many remote organs including the lung, kidney, intestine, pancreas, adrenals, and myocardium among others. The molecular and clinical manifestation of these remote organs injury may lead to the multiple organ dysfunction syndrome, frequently encountered in these patients. Remote organ injury seems to be in part the result of the oxidative burst and the inflammatory response following reperfusion. The present paper aims to review the existing literature regarding the proposed mechanisms of remote organ injury after liver ischemia and reperfusion. © 2014 Constantinos Nastos et al

A survey on supply chain ontologies

[EN] Nowadays, the business area cannot be sustainable and efficient without the presence of the Supply Chain. However, Supply Chain Management is by no means an easy task. Experts, in their effort to achieve the most efficient Supply Chain Management, have turned their attention to the management of knowledge related to supply chains. Thus, they model the concepts and the semantic relationships between them in Supply Chain Networks and create conceptual models and ontologies. In this paper, a survey of the existing ontologies in this field is carried out, with the aim of creating a new ontology of the Supply Chain that will unify its structural elements and lead to the integration of all supply systems. For this purpose, 22 ontological models from different supply systems, from over 90 sources, have been collected, briefly presented and commented on. These models, although being an intersection in the effort to model business operations and delineate a good basis for businesses to engage in Logistics processes, they lack an adequate formulation of appropriate semantics and terminology to describe all the different functions of the Supply Chain. Consequently, this lack inevitably leads to incompatible interpretations and uses of the knowledge that results from intercompany transactions.Samaridi, NE.; Karanikolas, NN.; Papoutsidakis, M.; Papakitsos, EC.; Papakitsos, CE. (2023). A survey on supply chain ontologies. International Journal of Production Management and Engineering. 11(1):89-101. https://doi.org/10.4995/ijpme.2023.187028910111

Colchicine and the heart: Pushing the envelope

Colchicine, a natural and ancient drug still used today, is traditionally considered the staple therapy for gout and a second-line treatment for pericarditis, as well as a basic part of familial Mediterranean fever and Behcet's disease management. It is commonly classified as an anti-inflammatory agent, although its mechanism of action does not involve the arachidonic acid pathway affected by non-steroid anti-inflammatory drugs and glucocorticoids. Colchicine inhibits microtubule polymerization by binding to tubulin, thus affecting any process that requires cytoskeletal changes, including cell mitosis and neutrophil motility. Recent studies suggest that colchicine may prove to be useful in a much wider spectrum of cardiovascular diseases than previously suspected, rekindling the interest in this old drug. In this review we briefly present the biochemical characteristics, mechanism of action and side-effects of colchicine, as well as examine what is currently known about the promising role of colchicine in cardiovascular medicine beyond pericardial disease. © 2013 by the American College of Cardiology Foundation

The role of endothelin system in cardiovascular disease and the potential therapeutic perspectives of its inhibition

Since its identification in 1988 and the recognition of its primary role as a potent vasoconstrictor, endothelin has been extensively studied and is now considered as a ubiquitous protein, involved in important aspects of human homeostasis as well as in several pathophysiological pathways, mostly associated with cardiovascular disease. From an evolutionary point of view, endothelin consists a primitive molecule with the rare characteristic of being exactly the same in all mammals, thus permitting scientists to perform experiments in animals and doing predictions for humans. The understanding of its contribution to the genesis, evolution and maintenance of disease through activation of special receptor subtypes has led to the development of both selective and unselective receptor antagonists. Despite the disappointing results of these antagonists in the field of heart failure, almost from the initial animal trials of bosentan, a dual endothelin receptor antagonist, in pulmonary arterial hypertension, it has been demonstrated that the drug leads at least to hemodynamic and clinical improvement of the patients, thus receiving official approval for the management of this rare but eventually lethal disease. Resistant hypertension is another area where endothelin receptor blockers might potentially play a role, while the pathophysiological role of endothelin in atherosclerotic coronary artery disease is well-established and the relative research goes on. The main goal of this review is to describe the endothelin system and mostly to enlighten its role in pathophysiologic pathways, as well to state the relative research in the various fields of cardiovascular disease and also highlight its prognostic significance wherever there exists one. © 2013 Bentham Science Publishers

MicroRNAs and the heart: Small things do matter

MicroRNAs are small RNA molecules and constitute a relatively novel class of gene expression regulators, found in the great majority of eukaryotic cells. Their role in human physiology and pathology is actively being researched with new exciting discoveries continuously coming to the forefront. MicroRNAs play a crucial role in the biogenesis and function of the cardiovascular system and act as important regulators of various metabolic and signaling pathways in cardiovascular disease. In this review there will be a summary on current knowledge about the expression, regulation and function of microRNAs in the most common diseases of the cardiovascular system as well as a presentation of and discussion about their promising future role as new biomarkers and therapeutic targets. © 2013 Bentham Science Publishers