Evaluation of the anti-angiogenic potential of hydroxytyrosol derivatives

Angiogenesis, a process which allows the formation of new vessels from pre-existing ones, is an essential phenomenon for tumor survival since it allows cancer cells to obtain nutrients and oxygen. This explains the increasing interest showed by many groups of research and pharmaceutical companies to find compounds with potential to disrupt at least one of the steps within the angiogenic process. Hydroxytyrosol (3,4-dihydroxyphenyl ethanol) has been identified as the most important health-related phenolic compound of virgin olive oil because of its pleiotropic effects on multiple targets. In 2012, our group identified hydroxytyrosol as an anti-angiogenic compound able to inhibit several key steps in the angiogenic process. In the present study, the potential effects of six hydroxytyrosol derivatives are tested and compared with those exhibited by hydroxytyrosol by making use of several in vitro and in vivo assays. Results indicate that these are candidate new anti-angiogenic compounds with potential utility in anti-tumor and anti-angiogenic therapies.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech [Our experimental work is supported by grants BIO2014-56092-R (MINECO and FEDER) and P12-CTS-1507 (Andalusian Government and FEDER) and funds from group BIO-267 (Andalusian Government). The "CIBER de Enfermedades Raras" is an initiative from the ISCIII (Spain)]. This communication has the support of a travel grant

The London Charter and the Seville Principles as sources of requirements for e-archaeology systems development purposes

[EN] Requirements engineering (RE) is a discipline of critical importance in software development. This paper provides a process and a set of software artefacts to help in the production of e-archaeology systems with emphasis on requirements reuse and standards. In particular, two important guidelines in the field of earchaeology, the London Charter and the Principles of Seville, have been shown as two sources of requirements to be considered as a starting point for developing this type of systems.[ES] La Ingeniería de Requisitos (IR) es una disciplina de importancia crítica en el desarrollo de software. Este artículo proporciona un proceso y un conjunto de artefactos software para ayudar en la producción de sistemas de e-arqueología con énfasis en reutilización de requisitos y estándares. En particular, dos guías relevantes en el campo de la e-arqueología, la Carta de Londres y los Principios de Sevilla, se han mostrado como dos fuentes de requisitos a tener en cuenta como punto de partida para el desarrollo de este tipo de sistemas.This research is part of the project PEGASO-PANGEA (TIN2009-13718-C02-02), financed by the Spanish Ministry of Science and Innovation (Spain).Carrillo Gea, JM.; Toval, A.; Fernández Alemán, JL.; Nicolás, J.; Flores, M. (2013). The London Charter and the Seville Principles as sources of requirements for e-archaeology systems development purposes. Virtual Archaeology Review. 4(9):205-211. https://doi.org/10.4995/var.2013.4275OJS20521149CH'NG, E. et al. (2011): "From sites to landscapes: how computing technology is shaping archaeological practice", en Computer, vol. 44, n. 7, pp. 40-46.COS, J.A. et al. (2012): "Internationalization requirements for e-learning audit purposes", en Proceedings of the 3rd IEEE Global Engineering Education Conference, EDUCON 2012, pp. 90-95. http://dx.doi.org/10.1109/educon.2012.6201027GLASS, R.L. (2002): Software engineering: facts and fallacies. Addison-Wesley. Boston.GREENFIELD, J. and SHORT, K. (2004): Software factories: assembling applications with patterns, models, frameworks, and tools. Wiley. Indianapolis.KÄKÖLÄ, T. and DUEÑAS, J.C. (Eds.) (2006): Software Product Lines. Research issues in engineering and management. Springer. Berlin Heidelberg. http://dx.doi.org/10.1007/978-3-540-33253-4TOVAL, A. et al. (2002): "Requirements reuse for improving information systems security: a practitioner's approach", en REJ Requirements Engineering Journal, vol. 6, n. 4, pp. 205-219.TOVAL, A. et al. (2008): "Eight key issues for an effective reuse-based requirements process", en IJCSSE International Journal of Computer Systems Science and Engineering, vol. 23, n. 6, pp. 373-385.TOVAL, A. et al. (2011): "Learning systems development using reusable standard-based requirements catalogs", en Proceedings of the 2nd IEEE Global Engineering Education Conference, EDUCON 2011, pp. 907- 912. http://dx.doi.org/10.1109/educon.2011.577325

Organocatalytically Generated Donor − Acceptor Cyclopropanes in Domino Reactions. One-Step Enantioselective Synthesis of Pyrrolo[1,2 ‑ a ]quinolines

An easy and straightforward procedure has been developed for the synthesis of highly enantioenriched pyrrolo-[1,2-a]quinolines through a one-pot process that comprises a domino cyclopropane ring opening/aza-Michael/aldol reaction followed by acid-promoted lactamization. The key feature of the synthetic approach relies on the ability of conveniently functionalized cyclopropaneacetaldehydes to undergo organocatalytic activation by a chiral secondary amine that enables the catalytic generation of a donor acceptor cyclopropane. This intermediate has the potential to undergo a ring opening that generates an electrophilic alpha,beta-unsaturated iminium ion that subsequently reacts through the already mentioned domino sequence and in which stereochemical information is very efficiently transferred from the amine catalyst to the final products. Moreover, one of the alkoxycarbonyl moieties can be easily removed by standard hydrolysis/decarboxylation, providing access to the target adducts as single stereoisomers.This research was supported by the Spanish MINECO (FEDER-CTQ2014-52107-P), the Basque Government (Grupos IT328-10), and UPV/EHU (fellowship to E.S. and UFI QOSYC 11/22). Membership in the COST action CM1407 (NatChemDrugs) is also acknowledged

Genomic and proteomic analyses reveal a relationship between WNT pathway, genes, oxidative stress metabolism and vascular calcification

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Role of Klotho and AGE/RAGE-Wnt/β-catenin signalling pathway on the development of cardiac and renal fibrosis in diabetes

Fibrosis plays an important role in the pathogenesis of long-term diabetic complications and contributes to the development of cardiac and renal dysfunction. The aim of this experimental study, performed in a long-term rat model, which resembles type 1 diabetes mellitus, was to investigate the role of soluble Klotho (sKlotho), advanced glycation end products (AGEs)/receptor for AGEs (RAGE), fibrotic Wnt/β-catenin pathway, and pro-fibrotic pathways in kidney and heart. Diabetes was induced by streptozotocin. Glycaemia was maintained by insulin administration for 24 weeks. Serum and urine sKlotho, AGEs, soluble RAGE (sRAGE) and biochemical markers were studied. The levels of Klotho, RAGEs, ADAM10, markers of fibrosis (collagen deposition, fibronectin, TGF-β1, and Wnt/β-catenin pathway), hypertrophy of the kidney and/or heart were analysed. At the end of study, diabetic rats showed higher levels of urinary sKlotho, AGEs and sRAGE and lower serum sKlotho compared with controls without differences in the renal Klotho expression. A significant positive correlation was found between urinary sKlotho and AGEs and urinary albumin/creatinine ratio (uACR). Fibrosis and RAGE levels were significantly higher in the heart without differences in the kidney of diabetic rats compared to controls. The results also suggest the increase in sKlotho and sRAGE excretion may be due to polyuria in the diabetic rats

Diabetes-related excess mortality in Mexico: a comparative analysis of National Death Registries between 2017-2019 and 2020

OBJECTIVE: To estimate diabetes-related mortality in Mexico in 2020 compared with 2017-2019 after the onset of the coronavirus disease 2019 (COVID-19) pandemic. RESEARCH DESIGN AND METHODS: This retrospective, state-level study used national death registries of Mexican adults aged ≥20 years for the 2017-2020 period. Diabetes-related death was defined using ICD-10 codes listing diabetes as the primary cause of death, excluding certificates with COVID-19 as the primary cause of death. Spatial and negative binomial regression models were used to characterize the geographic distribution and sociodemographic and epidemiologic correlates of diabetes-related excess mortality, estimated as increases in diabetes-related mortality in 2020 compared with average 2017-2019 rates. RESULTS: We identified 148,437 diabetes-related deaths in 2020 (177 per 100,000 inhabitants) vs. an average of 101,496 deaths in 2017-2019 (125 per 100,000 inhabitants). In-hospital diabetes-related deaths decreased by 17.8% in 2020 versus 2017-2019, whereas out-of-hospital deaths increased by 89.4%. Most deaths were attributable to type 2 diabetes (130 per 100,000 inhabitants). Compared with 2018-2019 data, hyperglycemic hyperosmolar state and diabetic ketoacidosis were the two contributing causes with the highest increase in mortality (128% and 116% increase, respectively). Diabetes-related excess mortality clustered in southern Mexico and was highest in states with higher social lag, rates of COVID-19 hospitalization, and prevalence of HbA1c ≥7.5%. CONCLUSIONS: Diabetes-related deaths increased among Mexican adults by 41.6% in 2020 after the onset of the COVID-19 pandemic, occurred disproportionately outside the hospital, and were largely attributable to type 2 diabetes and hyperglycemic emergencies. Disruptions in diabetes care and strained hospital capacity may have contributed to diabetes-related excess mortality in Mexico during 2020

Randomized, double-blind, placebo-controled clinical trial of sublingual immunotherapy in natural rubber latex allergic patients

<p>Abstract</p> <p>Background</p> <p>Natural rubber latex allergy is a common and unsolved health problem. Since the avoidance of exposure is very difficult, immunotherapy is strongly recommended, but before its use in patients, it is essential to prove the efficacy and safety of extracts.</p> <p>The aim of the present randomised, double-blind, placebo-controlled clinical trial was to assess the efficacy and tolerability of latex sublingual immunotherapy in adult patients undergoing permanent latex avoidance.</p> <p>Methods</p> <p>Twenty-eight adult latex-allergic patients (5 males and 23 females), with mean age of 39 years (range 24-57) were randomized to receive a commercial latex-sublingual immunotherapy or placebo during one year, followed by another year of open, active therapy. The following outcomes were measured at baseline and at the end of first and second year of follow-up: skin prick test, gloves-use score, conjunctival challenge test, total and specific IgE, basophil activation test, and adverse reactions monitoring.</p> <p>Results</p> <p>No significant difference in any of the efficacy <it>in vivo </it>variables was observed between active and placebo groups at the end of the placebo-controlled phase, nor when each group was compared with their baseline values at the end of the two year-study. An improvement in the average percentage of basophils activated was observed. During the induction phase, 4 reactions in the active group and 5 in the placebo group were recorded. During the maintenance phase, two patients dropped out due to pruritus and to acute dermatitis respectively.</p> <p>Conclusion</p> <p>Further studies are needed to evaluate latex-sublingual immunotherapy, since efficacy could not be demonstrated in adult patients with avoidance of the allergen.</p> <p>Trial registration number</p> <p><a href="http://www.anzctr.org.au/ACTRN12611000543987.aspx">ACTRN12611000543987</a></p