Could inhibition of metalloproteinases be used to block the process of metastasis?

Metastasis is a multisequential process that allows tumor cells to migrate to tissues distant from the primary tumor. Only a small number of cells escape from the primary tumor; however, the metastases generated are responsible for more than 90% of cancer deaths. Many metastatic processes initially require the total or partial start-up of a program for the transformation of tumor epithelial cells into mesenchymal cells (EMT). The launching of the EMT program is stimulated by cytokines and other elements produced by the diverse types of cells composing the tumor stroma. In parallel, a process of destabilization of the extracellular matrix (ECM) takes place by means of the synthesis of proteases of the matrix metalloproteinases (MMPs) family. EMC degradation allows the exportation of some tumor cells as mesenchymal cells to the circulatory system and their subsequent implantation in a tissue distant from the primary tumor. The blocking of these both processes appears as a hypothetical stop point in the metastatic mechanism. The present review deals with the different options to achieve the inhibition of MMPs, focusing on MMP7 as a target given its involvement in the metastatic processes of a wide variety of tumorsS

Spectroscopic characterization of mitochondrial G-quadruplexes

Guanine quadruplexes (G4s) are highly polymorphic four-stranded structures formed within guanine-rich DNA and RNA sequences that play a crucial role in biological processes. The recent discovery of the first G4 structures within mitochondrial DNA has led to a small revolution in the field. In particular, the G-rich conserved sequence block II (CSB II) can form different types of G4s that are thought to play a crucial role in replication. In this study, we decipher the most relevant G4 structures that can be formed within CSB II: RNA G4 at the RNA transcript, DNA G4 within the non-transcribed strand and DNA:RNA hybrid between the RNA transcript and the non-transcribed strand. We show that the more abundant, but unexplored, G6AG7 (37%) and G6AG8 (35%) sequences in CSB II yield more stable G4s than the less profuse G5AG7 sequence. Moreover, the existence of a guanine located 1 bp upstream promotes G4 formation. In all cases, parallel G4s are formed, but their topology changes from a less ordered to a highly ordered G4 when adding small amounts of potassium or sodium cations. Circular dichroism was used due to discriminate different conformations and topologies of nucleic acids and was complemented with gel electrophoresis and fluorescence spectroscopy studiesThis research was funded by the Gobierno de España—Ministerio de Economía y Competitividad, grant number CTQ2014-59020-R, the Xunta de Galicia, grant numbers ED431B 2019/18, ED431G 2019/03 Centro singular de investigación de Galicia accreditation 2019–2022, and Ph.D. fellowship to S.I. and the European Union (European Regional Development Fund—ERDF)S

Dinamika roda Acartia (Calanoida: Copepoda) u temperiranom plitkom estuariju (ušće rijeke Mondego) na zapadnoj obali Portugala

The purpose of this work was to review the dynamics of the Acartia species in the Mondego estuary (a temperate North-Atlantic shallow estuary in Western Portugal) in a genus integrated perspective. The Acartia genus is represented in the system by the species Acartia clausi and Acartia tonsa; the samples were taken between July 1999 and June 2000, with 63 and 125 µm mesh size nets, and between January 2003 and January 2004, with a 335 µm mesh size net, in the downstream and upstream areas of the estuary. Significant differences in abundance were found between months and sampling stations for the two species (ANOVA, P < 0.05). A. clausi dominated in the downstream estuary, registering peaks in June (156 ind. m-3) and September (73 ind. m-3); in the upstream estuary this species showed a maximum of density in September (35 ind. m-3). A. tonsa dominated in the upstream estuary with peaks of abundance occurring in December (2372 ind. m-3) and October (1056 ind. m-3) in the downstream estuary this species exhibited higher abundance in August (52 ind. m-3). The two species of the genus coexist in time exhibiting a strong spatial segregation behavior in the estuary.Cilj ovog rada je dati pregled dinamike vrsta Acartia u estuariju Mondego (temperirani sjevernoatlantski plitki estuarij u zapadnom Portugalu) za sve nađene vrste toga roda. Rod Acartia je prisutan s tri vrste: Acartia clausi, Acartia bifilosa var. inermis i Acartia tonsa; uzorci uzeti od srpnja 1999 do lipnja 2000 su dobiveni pomoću mreže veličine oka 63 i 125 µm, a od siječnja 2003 do siječnja 2004 pomoću mreže veličine oka 335 µm, u nizvodnom i uzvodnom dijelu estuarija. Nađene su znatne razlike u abundanciji dviju vrsta (ANOVA, P < 0.05). A. clausi je bila dominantna u nizvodnom estuariju s maksimumom u lipnju (156 ind. m -3) i rujnu (73 ind. m-3); u uzvodnom estuariju ova vrsta je imala maksimum gustoće u rujnu (35 ind. m-3). A. tonsa je bila dominantna u uzvodnom estuariju s makmimumom gustoće u prosincu (2372 ind. m-3) i listopadu (1056 ind. m-3). U nizvodnom estuariju ova je vrsta bila obilatije zastupljena u rujnu (52 ind. m-3). Dvije vrste se u estuariju javljaju istovremeno, ali su prostorno izrazito odijeljen

Exploring the Biological Properties of Zn(II) Bis thiosemicarbazone Helicates

The design of artificial helicoidal molecules derived from metal ions with biological properties is one of the objectives within metallosupramolecular chemistry. Herein, we report three zinc helicates derived from a family of bis thiosemicarbazone ligands with different terminal groups, Zn(L Me)∙2HO 1, Zn(L Ph)∙2HO 2 and Zn(L PhNO2) 3, obtained by an electrochemical methodology. These helicates have been fully characterized by different techniques, including X-ray diffraction. Biological studies of the zinc(II) helicates such as toxicity assays with erythrocytes and interaction studies with proteins and oligonucleotides were performed, demonstrating in all cases low toxicity and an absence of covalent interaction with the proteins and oligonucleotides. The in vitro cytotoxicity of the helicates was tested against MCF-7 (human breast carcinoma), A2780 (human ovarian carcinoma cells), NCI-H460 (human lung carcinoma cells) and MRC-5 (normal human lung fibroblasts), comparing the IC values with cisplatin. We will try to demonstrate if the terminal substituent of the ligand precursor exerts any effect in toxicity or in the antitumor activity of the zinc helicates

Differential Inhibitor Sensitivity between Human Kinases VRK1 and VRK2

Human vaccinia-related kinases (VRK1 and VRK2) are atypical active Ser-Thr kinases implicated in control of cell cycle entry, apoptosis and autophagy, and affect signalling by mitogen activated protein kinases (MAPK). The specific structural differences in VRK catalytic sites make them suitable candidates for development of specific inhibitors. In this work we have determined the sensitivity of VRK1 and VRK2 to kinase inhibitors, currently used in biological assays or in preclinical studies, in order to discriminate between the two proteins as well as with respect to the vaccinia virus B1R kinase. Both VRK proteins and vaccinia B1R are poorly inhibited by inhibitors of different types targeting Src, MEK1, B-Raf, JNK, p38, CK1, ATM, CHK1/2 and DNA-PK, and most of them have no effect even at 100 µM. Despite their low sensitivity, some of these inhibitors in the low micromolar range are able to discriminate between VRK1, VRK2 and B1R. VRK1 is more sensitive to staurosporine, RO-31-8220 and TDZD8. VRK2 is more sensitive to roscovitine, RO 31–8220, Cdk1 inhibitor, AZD7762, and IC261. Vaccinia virus B1R is more sensitive to staurosporine, KU55933, and RO 31–8220, but not to IC261. Thus, the three kinases present a different pattern of sensitivity to kinase inhibitors. This differential response to known inhibitors can provide a structural framework for VRK1 or VRK2 specific inhibitors with low or no cross-inhibition. The development of highly specific VRK1 inhibitors might be of potential clinical use in those cancers where these kinases identify a clinical subtype with a poorer prognosis, as is the case of VRK1 in breast cancer

5to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

El V Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2019, realizado del 6 al 8 de febrero de 2019 y organizado por la Universidad Politécnica Salesiana, ofreció a la comunidad académica nacional e internacional una plataforma de comunicación unificada, dirigida a cubrir los problemas teóricos y prácticos de mayor impacto en la sociedad moderna desde la ingeniería. En esta edición, dedicada a los 25 años de vida de la UPS, los ejes temáticos estuvieron relacionados con la aplicación de la ciencia, el desarrollo tecnológico y la innovación en cinco pilares fundamentales de nuestra sociedad: la industria, la movilidad, la sostenibilidad ambiental, la información y las telecomunicaciones. El comité científico estuvo conformado formado por 48 investigadores procedentes de diez países: España, Reino Unido, Italia, Bélgica, México, Venezuela, Colombia, Brasil, Estados Unidos y Ecuador. Fueron recibidas un centenar de contribuciones, de las cuales 39 fueron aprobadas en forma de ponencias y 15 en formato poster. Estas contribuciones fueron presentadas de forma oral ante toda la comunidad académica que se dio cita en el Congreso, quienes desde el aula magna, el auditorio y la sala de usos múltiples de la Universidad Politécnica Salesiana, cumplieron respetuosamente la responsabilidad de representar a toda la sociedad en la revisión, aceptación y validación del conocimiento nuevo que fue presentado en cada exposición por los investigadores. Paralelo a las sesiones técnicas, el Congreso contó con espacios de presentación de posters científicos y cinco workshops en temáticas de vanguardia que cautivaron la atención de nuestros docentes y estudiantes. También en el marco del evento se impartieron un total de ocho conferencias magistrales en temas tan actuales como la gestión del conocimiento en la universidad-ecosistema, los retos y oportunidades de la industria 4.0, los avances de la investigación básica y aplicada en mecatrónica para el estudio de robots de nueva generación, la optimización en ingeniería con técnicas multi-objetivo, el desarrollo de las redes avanzadas en Latinoamérica y los mundos, la contaminación del aire debido al tránsito vehicular, el radón y los riesgos que representa este gas radiactivo para la salud humana, entre otros

Fructosa-1,6-bifosfatasa en Mytilus galloprovincialis Lmk

Available from Centro de Informacion y Documentacion Cientifica CINDOC. Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai

El artículo neutro en gallego-asturiano

En la mayor parte del gallego-asturiano, el dialecto gallego-portugués hablado en el extremo occidental de Asturias, el artículo neutro presenta dos variantes formales: el y lo. El alomorfo el del artículo es un buen ejemplo del polimorfismo que se da dentro de este paradigma: el puede funcionar como artículo masculino, como femenino ante palabra que comience por cualquier vocal tónica o /a/ átona inicial y también como neutro. La forma lo se puede emplear en cualquier contexto de uso del artículo neutro; en cambio el tiene algunas restricciones en su combinatoria sintáctica y se trata de una forma en claro retroceso

La frontera lingüística entre el gallego y el asturiano

Anexos de "Revista de Filoloxía Asturiana", I