Cell Expansion-Dependent Inflammatory and Metabolic Profile of Human Bone Marrow Mesenchymal Stem Cells

Stem cell therapy has emerged as a promising new area in regenerative medicine allowing the recovery of viable tissues. Among the many sources of adult stem cells, bone marrow-derived are easy to expand in culture via plastic adherence and their multipotentiality for differentiation make them ideal for clinical applications. Interestingly, several studies have indicated that MSCs expansion in vitro may be limited mainly due to cell aging related to the number of cell divisions in culture. We have determined that MSCs exhibit a progressive decline across successive passages in the expression of stem cell markers, in plasticity and in the inflammatory response, presenting low immunogenicity. We have exposed human MSCs after several passages to TLRs ligands and analyzed their inflammatory response. These cells responded to pro-inflammatory stimuli (i.e., NOS-2 expression) and to anti-inflammatory cytokines (i.e., HO1 and Arg1) until two expansions, rapidly declining upon subculture. Moreover, in the first passages, MSCs were capable to release IL1β, IL6 and IL8, as well as to produce active MMPs allowing them to migrate. Interestingly enough, after two passages, anaerobic glycolysis was enhanced releasing high levels of lactate to the extracellular medium. All these results may have important implications for the safety and efficacy of MSCs-based cell therapies

Continuous Packed Bed Reactor with Immobilized β-Galactosidase for Production of Galactooligosaccharides (GOS)

The β-galactosidase from Bacillus circulans was covalently attached to aldehyde-activated (glyoxal) agarose beads and assayed for the continuous production of galactooligosaccharides (GOS) in a packed-bed reactor (PBR). The immobilization was fast (1 h) and the activity of the resulting biocatalyst was 97.4 U/g measured with o-nitrophenyl-β-d-galactopyranoside (ONPG). The biocatalyst showed excellent operational stability in 14 successive 20 min reaction cycles at 45 °C in a batch reactor. A continuous process for GOS synthesis was operated for 213 h at 0.2 mL/min and 45 °C using 100 g/L of lactose as a feed solution. The efficiency of the PBR slightly decreased with time; however, the maximum GOS concentration (24.2 g/L) was obtained after 48 h of operation, which corresponded to 48.6% lactose conversion and thus to maximum transgalactosylation activity. HPAEC-PAD analysis showed that the two major GOS were the trisaccharide Gal-β(1→4)-Gal-β(1→4)-Glc and the tetrasaccharide Gal-β(1→4)-Gal-β(1→4)-Gal-β(1→4)-Glc. The PBR was also assessed in the production of GOS from milk as a feed solution. The stability of the bioreactor was satisfactory during the first 8 h of operation; after that, a decrease in the flow rate was observed, probably due to partial clogging of the column. This work represents a step forward in the continuous production of GOS employing fixed-bed reactors with immobilized β-galactosidases.This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (BIO2013-48779-C4-1-R and BIO2016-76601-C3-1-R). We thank the support of COST-Action CM1303 on Systems Biocatalysis. P.S.-M. thanks the Spanish Ministry of Education for FPU Grant (FPU13/01185). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)

Regioselective synthesis of neo-erlose by the beta-fructofuranosidase from Xanthophyllomyces dendrorhous

The beta-fructofuranosidase from the yeast Xanthophyllomyces dendrorhous (Xd-INV) catalyzes the synthesis of neo-fructooligosaccharides (neo-FOS of the 6G-series), which contain a beta(2-6) linkage between a fructose and the glucosyl moiety of sucrose. In this work we demonstrate that the enzyme is also able to fructosylate other carbohydrates that contain glucose, in particular disaccharides (maltose, isomaltulose, isomaltose, trehalose) and higher oligosaccharides (maltotriose, raffinose, maltotetraose), but not monosaccharides (glucose, fructose, galactose). With maltose as acceptor, the reaction in the presence of Xd-INV proceeded with high regioselectivity; the product was purified and chemically characterized, and turned out to be 6’-O--fructosylmaltose (neo-erlose). Using 100 g/L sucrose as fructosyl donor and 300 g/L maltose as acceptor, the maximum concentration of neo-erlose was 38.3 g/L. Thus, novel hetero-fructooligosaccharides with potential applications in the functional food and pharmaceutical industries can be obtained with Xd-INV.Projects BIO2010-20508-C04-01 and BIO2010-20508-C04-04 from Spanish Ministry of Science and Innovation supported this research. We thank Fundación Ramon Areces for an institutional grant to the Centro de Biología Molecular Severo Ochoa.Peer reviewe

Trabectedin plus radiotherapy for advanced soft-tissue sarcoma: experience in forty patients treated at a sarcoma reference center

Symptomatic control and tumoral shrinkage is an unmet need in advanced soft-tissue sarcoma (STS) patients beyond first-line. The combination of trabectedin and radiotherapy showed activity in a recently reported clinical trial in this setting. This retrospective series aims to analyze our experience with the same regimen in the real-life setting. We retrospectively reviewed advanced sarcoma patients treated with trabectedin concomitantly with radiotherapy with palliative intent. Growth-modulation index (GMI) was calculated as a surrogate of efficacy. Forty metastatic patients were analyzed. According to RECIST, there was one (2.5%) complete response, 12 (30%) partial responses, 18 (45%) disease stabilizations, and nine (22.5%) progressions. After a median follow-up of 15 months (range 2–38), median progression-free survival (PFS) and overall survival (OS) were 7.5 months (95% CI 2.8–12.2) and 23.5 months (95% CI 1.1–45.8), respectively. Median GMI was 1.42 (range 0.19–23.76), and in 16 (53%) patients, it was >1.33. In patients with GMI >1.33, median OS was significantly longer than in those with GMI 0–1.33 (median OS 52.1 months (95% CI not reached) vs. 8.9 months (95% CI 6.3–11.6), p = 0.028). The combination of trabectedin plus radiotherapy is an active therapeutic option in patients with advanced STS, especially when tumor shrinkage for symptomatic relief is neede

Lean-green improvement opportunities for sustainable manufacturing using water telemetry in agri-food industry.

Water has become a critical resource due to increased manufacturing activities. However, there is a lack of detailed information on water management and consumption by industries. In the recent bibliography, lean–green was established as a good approach for achieving sustainability in manufacturing industries, but few studies have aimed to achieve both operational and environmental improvements in water consumption. In this paper, we present a multi-case study in the agri-food industry in which water consumption in company activities is monitored, allowing them to improve their industrial processes based on lean–green practices, leading to a zero-waste strategy for this critical resource. The aim of this paper is to demonstrate the importance of having detailed knowledge regarding water consumption in order to discover, in a lean–green context, new improvement opportunities which could remain hidden by the current way of analysing consumption

Study of Cr2O3 nanoparticles supported on carbonaceous materials as catalysts for O2 reduction reaction

A series of chromium oxides (Cr2O3) nanoparticles supported on different carbonaceous material, namely: graphene, graphene oxide (GO) and graphite, were synthetized by precipitation of the salt precursors with precipitant (ammonia) and the subsequent thermal treatment. The catalytic activity of these composites and the Cr2O3 nanoparticles have been analysed by Koutecky-Levich (KL) and rotating ring-disc electrode methods and the results have been discussed following a model proposed here, which considers the O2 electrosorption as the rate determining step. Among them, graphite and graphene based composites have better catalytic activities and their behaviours agree with the proposed treatment: logarithm dependent of the intercept and nondependent slopes values of the KL plots with the potential. Cr2O3-graphite shows a mechanism interchanging 4 e-, which has been attributed to a graphite- Cr2O3 nanoparticles interaction. Besides, Cr2O3-graphite-based electrodes have been tested as cathode in a Zn/PVA-KOH/air battery, confirming its good properties to be applied as positive electrode in metal-air batteries.The authors thank the financial support from Fundación Séneca (Región de Murcia, Spain; Ref: 20985/PI/18), Spanish Agencia Estatal de Investigación (PID2019-104272RB-C55/AEI/10.13039/501100011033, CTQ2017-90659-REDT and PID2019-106097 GB/AEI/10.13039/501100011033), MINECO (projects MAT2017-84118-C2-2-R and MAT2017-82252-R) and Banco Santander-UCM (project PR87/19-22613). The authors also acknowledge Victor Galindo Garre for providing R-Studio scripts for data analysis

Utilización de antimicrobianos en los hospitales públicos de Andalucía: 1995-1996

Objetivo. Describir el consumo de antiinfecciosos en los hospitales públicos de Andalucía durante los años 1995 y 1996. Establecer las diferencias cuali y cuantitativas en el consumo, cuando se expresa en DDD o DDPs. Método. Se estudió el consumo de antimicrobianos mediante el cálculo de las DDDs y DDPs/100 estancias-día, siguiendo básicamente la clasificación ATC. Se analizó la utilización para el conjunto de los hospitales y por tipo de hospital (regional, de especialidades y comarcal), valorándose los grupos terapéuticos y antimicrobianos más utilizados mediante una clasificación descendente en consumo. Resultados. En ambos años participaron 27 de 31 hospitales (87,1%). El consumo total en DDD/100 Est.-día fue de 73,67 y 75,17 y en DDPs/100 Est.-día fue de 64,61 y 65,39. El 80% de la utilización se concentra en penicilinas, cefalosporinas, quinolonas y aminoglucósidos. Destaca un 24% de aumento interanual en las quinolonas. Amoxicilinaclavulánico es el antibiótico con una mayor utilización en los dos años: 9,84 y 11,93 DDDs/100 Est.-día. La diferencia en el consumo global resultó ser un 12,6% más baja si se expresa en DDP.Objetive. To describe the consumption of anti-infectious agents in public hospitals of Andalucia, Spain, in 1995 and 1996. To establish qualitative and quantitative differences in consumption expressed as DDD and PDD. Method. Antimicrobial consumption was calculated by DDD and PDD/100 hospital days following the ATC classification. An analysis was made of drug use by the overall group of hospitals and by the type of hospital (regional, specialty, and local). Therapeutic groups and the most frequently used antimicrobial agents were analyzed by a descending classification of consumption. Results. In the two years of the study, 27 of 31 (87.1%) hospitals participated. Overall consumption by DDD/100 hospital days was 73.67 and 75.17 and by PDD/100 hospital days, 64.61 and 65.39. Eighty percent of the drugs used were penicillins, cephalosporins, quinolones and aminoglycosides. An interannual increase of 24% in quinolone use was noteworthy. Amoxicillin-clavulanic acid was the antibiotic most often used in both years: 9.84 and 11.93 DDD/100 hospital days. The difference in overall consumption was 12.0%, with a lower PDD

Congenital hyperinsulinism in two siblings with ABCC8 mutation: same genotype, different phenotypes

Congenital hyperinsulinism (CHI) is a heterogenous disease caused by insulin secretion regulatory defects, being ABCC8/KCNJ11 the most commonly affected genes. Therapeutic options include diazoxide, somatostatin analogues and surgery, which is curative in focal CHI. We report the case of two siblings (born two years apart) that presented themselves with hypoketotic hyperinsulinemic persistent hypoglycemias during neonatal period. The diagnosis of diffuse CHI due to an ABCC8 compound mutation (c.3576delG and c.742C>T) was concluded. They did not benefit from diazoxide therapy (or pancreatectomy performed in patient number 1) yet responded to somatostatin analogues. Patient number 1 developed various neurological deficits (including epilepsy), however patient number 2 experienced an entirely normal neurodevelopment. We believe this case shows how previous knowledge of the firstborn sibling's disease contributed to a better and timelier medical care in patient number 2, which could potentially explain her better neurological outcome despite their same genotype.S

Red de investigación en docencia universitaria de la UA: “Universidad, Docencia, Género e Igualdad” (II)

La Red de investigación en docencia universitaria “Universidad, docencia, genero e igualdad” persigue avanzar en la calidad e innovación de las enseñanzas universitarias a partir de la inclusión de la perspectiva de género. Se busca dar cumplimiento a las directrices generales de los nuevos planes de estudio respecto del principio de igualdad de oportunidades entre hombres y mujeres en la formación universitaria (Real Decreto 1393/2007. BOE nº 260, 30 de octubre de 2007). En la tercera edición de la Red, y dada su composición multidisciplinar, se desarrollaron dos líneas de investigación: por un lado, se continuó trabajando en el mantenimiento del “Portal web con recursos docentes con perspectiva de género”, proyecto financiado por el Instituto de la Mujer (PACUI, 2012) e iniciado en el curso 2012-2013, incrementándose en un 36% la colección de recursos; y, por otro, se inició una nueva línea de investigación con la que se busca desarrollar una herramienta informática de ayuda para la redacción de textos con lenguaje inclusivo

Idoneidad y validez de herramientas que fomentan el aprendizaje asociativo a partir de exámenes tipo test

Depto. de Salud Pública y Materno - InfantilFac. de MedicinaFALSEsubmitte