An Updated Focus on Quadruplex Structures as Potential Therapeutic Targets in Cancer

Non-canonical, four-stranded nucleic acids secondary structures are present within regulatory regions in the human genome and transcriptome. To date, these quadruplex structures include both DNA and RNA G-quadruplexes, formed in guanine-rich sequences, and i-Motifs, found in cytosine-rich sequences, as their counterparts. Quadruplexes have been extensively associated with cancer, playing an important role in telomere maintenance and control of genetic expression of several oncogenes and tumor suppressors. Therefore, quadruplex structures are considered attractive molecular targets for cancer therapeutics with novel mechanisms of action. In this review, we provide a general overview about recent research on the implications of quadruplex structures in cancer, firstly gathering together DNA G-quadruplexes, RNA G-quadruplexes as well as DNA i-Motifs.3TR, IMI2 H2020-JTI538 IMI2-2018Instituto de Salud Carlos III AC18/00008Government of Spain FPU16/0582

Short-term effects of hyaluronic acid on the subgingival microbiome in peri-implantitis: A randomized controlled clinical trial

This study was supported by Ricerfarma srl (Milan, Italy) in collaboration with Research Groups #CTS 583 and #BIO-344 (Junta de Andalucía, Spain) (reference: OTRI-3300). Ana Soriano-Lerma was supported by a fellowship from the Ministry of Education, Culture and Sport (FPU 17/05413). José A. García-Salcedo was supported by “Programa Estatal de Inves-tigación, Desarrollo e Innovación Orientada a los Retos de la Sociedad” (grant SAF-SAF2015-71714-RMINECO/FEDER) and The Network of Tropical Diseases Research—RICET (Instituto de Salud Carlos III).Background: The aim of our study was to evaluate the effects of a hyaluronic acid gel at 45 days on the microbiome of implants with peri-implantitis with at least one year of loading. Methods: A randomized controlled trial was conducted in peri-implantitis patients. Swabs containing the samples were collected both at baseline and after 45 days of treatment. 16S rRNA sequencing techniques were used to investigate the effect of hyaluronic acid gel on the subgingival microbiome. Results: 108 samples of 54 patients were analyzed at baseline and after follow-up at 45 days. Three strata with different microbial composition were obtained in the samples at baseline, representing three main microbial consortia associated with peri-implantitis. Stratum 1 did not show any difference for any variable after treatment with hyaluronic acid, whereas in stratum 2, Streptococcus, Veillonella, Rothia and Granulicatella did decrease (p<0.05). Similarly, Prevotella and Campylobacter (p< 0.05) decreased in stratum 3 after treatment with hyaluronic acid. Microbial diversity was found to be decreased in stratum 3 (p<0.05) after treatment with hyaluronic acid compared to the control group, in which an increase was found (p<0.05). Conclusions: Hyaluronic acid reduced the relative abundance of peri-implantitis-related microorganisms, especially the early colonizing bacteria, suggesting a specific action during the first stages in the development of the disease. Hyaluronic acid did not alter relative abundances of non-oral genera. The use of hyaluronic acid in advanced stages of peri-implantitis resulted in a decrease in microbial alpha diversity, suggesting a protective action of the peri-implant site against bacteria colonization.Ricerfarma srl (Milan, Italy)Junta de Andalucía, Spain Research Groups OTRI-3300: #CTS 583, #BIO-344Ministry of Education, Culture and Sport (FPU 17/05413)SAF-SAF2015-71714-RMINECO/FEDERInstituto de Salud Carlos II

Characterization and engineering of the biosynthesis gene cluster for antitumor macrolides PM100117 and PM100118 from a marine actinobacteria: generation of a novel improved derivative

Additional file 1: Figure S1. Sequence alignment of the cluster PKS domains active sites. LD, loading domain; M1-M20, extension modules. Polyketide synthase domains are as follows: KS, ketosynthase; AT, acyltransferase; KR, ketoreductase; DH, dehydratase; ER, enoilreductase; ACP, acyl carrier protein; CAL, CoA-ligase. Figure S2. Genetic complementation of mutant strains. UPLC analysis of PM100117 (1) and PM100118 (2) production in strains GUA-pS, CPgonP8, CPgonM4, CPgonMT, CPgonSL, CPgonS1, CPgonS2, CPgonCP, CPgonMR and CPgonL1. Figure S3. Antibiotic activity test of compound 5. Diffusion disc assay against Saccharomyces cerevisiae and Micrococcus luteus. The length (cm) of the inhibition-growth halo is indicated by numbers and yellow lines. Methods S2. Antibiotic activity assay. Format: PDF

Adaptation of targeted nanocarriers to changing requirements in antimalarial drug delivery.

The adaptation of existing antimalarial nanocarriers to new Plasmodium stages, drugs, targeting molecules, or encapsulating structures is a strategy that can provide new nanotechnology-based, cost-efficient therapies against malaria. We have explored the modification of different liposome prototypes that had been developed in our group for the targeted delivery of antimalarial drugs to Plasmodium-infected red blood cells (pRBCs). These new models include: (i) immunoliposome-mediated release of new lipid-based antimalarials; (ii) liposomes targeted to pRBCs with covalently linked heparin to reduce anticoagulation risks; (iii) adaptation of heparin to pRBC targeting of chitosan nanoparticles; (iv) use of heparin for the targeting of Plasmodium stages in the mosquito vector; and (v) use of the non-anticoagulant glycosaminoglycan chondroitin 4-sulfate as a heparin surrogate for pRBC targeting. The results presented indicate that the tuning of existing nanovessels to new malaria-related targets is a valid low-cost alternative to the de novo development of targeted nanosystems

Targeting ribosomal G-quadruplexes with naphthalene-diimides as RNA polymerase I inhibitors for colorectal cancer treatment

17 pags., 6 figs., 2 tabs.Sanchez-Martin et al. report a mode of action for naphthalene-diimides, a well-known class of G-quadruplexes ligands. Their work provides evidence of naphthalene-diimides targeting G-quadruplexes in ribosomal DNA, inducing a blockade of RNA polymerase I-mediated transcription and cell death. These compounds could be exploited in colorectal cancer treatment.This work was supported by the European Commission (TAR- BRAINFECT to J.A.G.-S.) and the National Institutes of Health (GM084946 to D.A.S.). The Government of Spain granted with PhD fellowships FPU16/ 05822 to V.S.-M. and FPU17/05413 to A.S.-L. The University of Almeria granted with PhD fellowship to M.O.-G. Funding for open access charge: Eu- ropean Commissio

Adaptation of targeted nanocarriers to changing requirements in antimalarial drug delivery

The adaptation of existing antimalarial nanocarriers to new Plasmodium stages, drugs, targeting molecules, or encapsulating structures is a strategy that can provide new nanotechnology-based, cost-efficient therapies against malaria. We have explored the modification of different liposome prototypes that had been developed in our group for the targeted delivery of antimalarial drugs to Plasmodium-infected red blood cells (pRBCs). These new models include: (i) immunoliposome-mediated release of new lipid-based antimalarials; (ii) liposomes targeted to pRBCs with covalently linked heparin to reduce anticoagulation risks; (iii) adaptation of heparin to pRBC targeting of chitosan nanoparticles; (iv) use of heparin for the targeting of Plasmodium stages in the mosquito vector; and (v) use of the non-anticoagulant glycosaminoglycan chondroitin 4-sulfate as a heparin surrogate for pRBC targeting. The results presented indicate that the tuning of existing nanovessels to new malaria-related targets is a valid low-cost alternative to the de novo development of targeted nanosystems

Diseño de estrategias conjuntas UA-centros de secundaria para el fomento del conocimiento de disciplinas científico-técnicas

Continuando con la línea emprendida por el Instituto Universitario de Ingeniería de Procesos Químicos, para desarrollar actividades de fomento del conocimiento de disciplinas de ciencia y tecnología, se ha convocado el “VI Certamen de Proyectos Educativos de Ingeniería Química” durante el curso 2013-2014. Con dicha actividad se pretende promover el interés por estudios relacionados con las disciplinas científico-técnicas, entre los alumnos de ESO, con una mejor conceptualización, comprensión y caracterización de los temas. Para ello, se diseñan, planifican y desarrollan acciones entre profesorado de la UA y centros de secundaria, sobre el papel de la Química en la industria para mejorar la calidad de vida. En la presente edición del certamen se han inscrito 13 centros, que han presentado un total de 20 proyectos, relacionados con los siguientes temas: la Ingeniería Química y el medio ambiente, la Ingeniería Química y la industria alimentaria, la Ingeniería Química y el mundo de los plásticos, la Ingeniería Química y la energía y la Ingeniería Química «Verde» sostenible

Uso de la tomografía corporal total en pacientes con heridas de arma de fuego y hemodinámicamente inestables: ¿rompiendo paradigmas de atención inicial?

Introducción. El objetivo del estudio fue analizar el impacto del uso de la tomografía corporal total en la evaluación de los pacientes con trauma penetrante por proyectil de arma de fuego y hemodinámicamente inestables atendidos en un centro de referencia de trauma. Métodos. Se realizó un estudio analítico, retrospectivo, con base en un subanálisis del registro de la Sociedad Panamericana de Trauma – Fundación Valle del Lili. Se incluyeron los pacientes con trauma penetrante por proyectil de arma de fuego atendidos entre 2018 y 2021. Se excluyeron los pacientes con trauma craneoencefálico severo, trauma leve y en condición in extremis. Resultados. Doscientos pacientes cumplieron los criterios de elegibilidad, 115 fueron estudiados con tomografía corporal total y se compararon con 85 controles. La mortalidad intrahospitalaria en el grupo de tomografía fue de 4/115 (3,5 %) vs 10/85 (12 %) en el grupo control. En el análisis multivariado se identificó que la tomografía no tenía asociación significativa con la mortalidad (aOR=0,46; IC95% 0,10-1,94). El grupo de tomografía tuvo una reducción relativa del 39 % en la frecuencia de cirugías mayores, con un efecto asociado en la disminución de la necesidad de cirugía (aOR=0,47; IC95% 0,22-0,98). Conclusiones. La tomografía corporal total fue empleada en el abordaje inicial de los pacientes con trauma penetrante por proyectil de arma de fuego y hemodinámicamente inestables. Su uso no se asoció con una mayor mortalidad, pero sí con una menor frecuencia de cirugías mayores

Targeting ribosomal G-quadruplexes with naphthalene-diimides as RNA polymerase I inhibitors for colorectal cancer treatment

Guanine quadruplexes (G4s) are non-canonical nucleic acid structures commonly found in regulatory genomic regions. G4 targeting has emerged as a therapeutic approach in cancer. We have screened naph thalene-diimides (NDIs), a class of G4 ligands, in a cellular model of colorectal cancer (CRC). Here, we identify the leading compound T5 with a potent and selective inhibition of cell growth by high-affinity binding to G4s in ribosomal DNA, impairing RNA polymerase I (Pol I) elongation. Consequently, T5 induces a rapid inhibition of Pol I transcription, nucleolus disruption, proteasome-dependent Pol I catalytic subunit A degradation and autophagy. Moreover, we attribute the higher selectivity of carbohydrate-conjugated T5 for tumoral cells to its preferential uptake through the overexpressed glucose transporter 1. Finally, we succinctly demon strate that T5 could be explored as a therapeutic agent in a patient cohort with CRC. Therefore, we report a mode of action for these NDIs involving ribosomal G4 targeting