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

Ultrasound-assisted extraction of phenolic compounds from blueberry leaves using natural deep eutectic solvents (NADES) for the valorization of agrifood wastes

The food industry demands novel green solvents for the extraction of bioactive compounds, particularly from residues of the agrifood industry. Herein, an ultrasound-assisted method has been developed for the environmentally friendly extraction of phenolic compounds from blueberry leaves using natural deep eutectic solvents (NADES). After the screening of multiple NADES, the best extraction efficiencies in terms of total phenol content and antioxidant activity were provided by NADES composed of lactate, sodium acetate, and water (3:1:2), and of choline chloride and oxalic acid (1:1). Using a Box–Behnken experimental design, the optimal extraction conditions were achieved by sonicating for 45 min at 65 °C and using solvent:sample ratios of 15 and 75 (v/w) for the NADES based on lactic acid and choline, respectively. Compared with conventional organic solvents, the use of these NADES composed of lactic acid and choline provided superior performance for the recovery of phenolic compounds (1.6-fold and 2.2-fold greater efficacy, respectively) and antioxidant compounds (1.6-fold and 2.8-fold greater efficacy, respectively). The chromatographic characterization of the extracts obtained under these optimized conditions evidenced that the lactic-based NADES enabled the extraction of a wide range of hydroxycinnamic acids and flavonol derivatives, whereas the choline-based NADES was selective towards the extraction of anthocyanins. These results indicate that the proposed method could represent an excellent green alternative for the recovery of phenolic compounds from plant materials and agrifood wastes, with improved extraction efficacy and/or selectivity compared to that provided by traditional organic solvents.9 página

Synthesis and Antiviral Activities of Novel Purinyl- and Pyrimidinylcarbanucleosides Derived from Indan

The 12th International Electronic Conference on Synthetic Organic Chemistry session Bioorganic Chemistry and Natural ProductsStarting from (±)-trans- and (±)-cis-3-hydroxymethyl-1-indanol, novel 6-substituted purinylcarbanucleoside derivatives of indan (5, 6, 9, 10, 15 and 17) were synthesized through a key coupling reaction with 6-chloropurine under Mitsunobu conditions. Suzuki–Miyaura reactions of the protected 6-chloropurine derivative with different arylboronic acids afforded the corresponding 6-arylpurinylcarbanucleoside derivatives. Finally, three new 5-halouracilcarbanucleosides (19, 20 and 21) were prepared by reaction of uracilcarbanucleoside 18 with different N-halosuccinimides. All of the new analogues were evaluated for antiviral activity against a wide variety of virusesThe authors thank the Xunta de Galicia for financial support of this work under projects PGIDT05PXIB20301PR and 07CSA008203P

Research facilities and highlights at the Centro Nacional de Aceleradores (CNA)

The Centro Nacional de Aceleradores is a user-oriented accelerator facility in Seville, Spain. Its main facilities are a 3 MV tandem accelerator, an 18 MeV proton Cyclotron, a tandetron used for AMS, a compact accelerator used for radiocarbon measurements, a 60Co irradiator and a PET/CT scanner. The technical specifications and research applications of these facilities are described. A neutron beam line associated to a charged pulsed beam in the tandem allows for time of flight measurements which determine the neutron energy. The use of an adequate stripper gas in the AMS tandetron permits to measure heavy radionuclides with very low detection levels, allowing to perform environmental studies using these radionuclides as tracers. The use of the microbeam in the tandem accelerator allows to apply the ion beam-induced current technique to investigate the spectroscopic properties and radiation hardness of different semiconductor detectors.European Union, H2020-847594, H2020-654002, H2020-847552, H2020-847594Ministry of Science RTI2018-098117-B-C21, RTC-2017-6369-3, EQC2018-004193-P, EQC2018-004095-P, EQC2018-004166- P, PGC2018-094546-B-I00Junta de Andalucía FEDER US-1261006, US-1263369, P18-RT-190

HIV coinfection predicts failure of ledipasvir/sofosbuvir in treatment-naïve noncirrhotic patients with HCV genotype

The efficacy of licensed direct-acting antiviral (DAA) regimens is assumed to be the same for hepatitis C virus (HCV)–monoinfected patients (HCV-Mono) and HIV/HCV-coinfected patients (HCV-Co). However, the high sustained viral response (SVR) rates of DAA regimens and the small number of HIV-infected patients included in registration trials have made it difficult to identify predictors of treatment failure, including the presence of HIV. Methods. We compared treatment outcomes for ledipasvir/sofosbuvir (LDV/SOF) against HCV G1 in treatment-naïve HCV-Mono and HCV-Co without cirrhosis in a prospective registry of individuals receiving DAAs for HCV. Results. Up to September 2017, a total of 17 269 patients were registered, and 1358 patients (1055 HCV-Mono/303 HCV-Co) met the inclusion criteria. Significant differences between HCV-Mono and HCV-Co were observed for age, gender, and G1 subtype distribution. Among HCV-Co, 99.0% were receiving antiretroviral therapy. SVR rates for LDV/SOF at 8 weeks did not differ significantly between HCV-Mono and HCV-Co (96.9% vs 94.0%; P = .199). However, the SVR rate for LDV/SOF at 12 weeks was significantly higher for HCV-Mono than HCV-Co (97.2% vs 91.8%; P = .001). A multivariable logistic regression model including age, sex, liver stiffness, G1 subtype, HCV-RNA, HIV, and treatment duration showed the factors associated with treatment failure to be male sex (adjusted odds ratio [aOR], 2.49; 95% confidence interval [CI], 1.27–4.91; P = .008) and HIV infection (aOR, 2.23; 95% CI, 1.13–4.38; P = .020). Conclusions. The results of this large prospective study analyzing outcomes for LDV/SOF against HCV G1 in treatment-naïve noncirrhotic patients suggest that HIV infection is a predictor of treatment failure in patients with chronic hepatitis C.This work was supported by the Spanish AIDS Research Network (RD16/0025/0017), which is included in the Spanish I+D+I Plan and is co-financed by ISCIII-Subdirección General de Evaluacion and European Funding for Regional Development (FEDER), and the Fondo de Investigación de Sanidad en España (FIS)/Instituto de Salud Carlos III (Spanish Health Research Funds; PI17/00657)

Invirtiendo para mejorar: aprendizaje activo de Teoría de Estructuras.

Se ha desarrollado una metodología de aula invertida para una asignatura obligatoria de 3º curso de Ingeniería. El material docente por diseñar para que los estudiantes afronten con éxito la materia es: lecciones de video de corta duración con el uso de secciones de YouTube, y con preguntas incorporadas sobre el video con la herramienta H5P. Este material será tanto de carácter teórico como resolución de ejercicios tipo. Además, los alumnos dispondrán del material clásico de presentaciones de Power Point, el libro de texto y repositorio de exámenes pasados. La actividad enlace serán las preguntas sobre H5P y cuestionarios en Moodle. Estas actividades se integran en el aula con la explicación por parte del profesor de los errores detectados, además de la realización de ejercicios en clase y en grupo. A la luz de casos similares, se espera una mejora en los resultados de aprendizaje y motivación de los alumnos

Gamificación combinada con aula invertida, aplicación en un grado de ingeniería.

Se ha desarrollado la metodología de aula invertida y gamificación en la asignatura obligatoria “Transferencia de Calor y Materia” de 2º curso del grado de Ingeniero de la Energía en la ETSIME de la Universidad Politécnica de Madrid. Esta experiencia se realiza durante el curso 2018-19 en las dos clases en que se divide esta materia, considerados ambos como grupo experimental. El contraste de resultados se realiza con los grupos que cursaron la misma materia durante el 2017-18, donde “sólo” se tenía aula invertida y que se toman como el grupo de control. El material del que dispone el alumno en ambos casos es el mismo. A pesar de notarse un ligero descenso en la asistencia a clase, los resultados obtenidos por ambos grupos muestran que la inclusión de estas actividades supone un aumento de las notas de casi un punto en cada bloque. Asimismo, se analizan los resultados de los exámenes entre los alumnos que han tenido gamificación activa y los que no. En este caso la diferencia es aún mayor (en torno a 2 puntos en cada bloque). La dispersión en las notas se mantiene constante, estando ambos grupos igualmente nivelados

RIPK3 acts as a lipid metabolism regulator contributing to inflammation and carcinogenesis in non-alcoholic fatty liver disease

[EN]Objective Receptor-interacting protein kinase 3 (RIPK3) is a key player in necroptosis execution and an emerging metabolic regulator, whose contribution to non-alcoholic fatty liver disease (NAFLD) is controversial. We aimed to clarify the impact of RIPK3 signalling in the pathogenesis of human and experimental NAFLD. Design RIPK3 levels were evaluated in two large independent cohorts of patients with biopsy proven NAFLD diagnosis and correlated with clinical and biochemical parameters. Wild-type (WT) or Ripk3-deficient (Ripk3(-/-)) mice were fed a choline-deficient L-amino acid-defined diet (CDAA) or an isocaloric control diet for 32 and 66 weeks. Results RIPK3 increased in patients with non-alcoholic steatohepatitis (NASH) in both cohorts, correlating with hepatic inflammation and fibrosis. Accordingly, Ripk3 deficiency ameliorated CDAA-induced inflammation and fibrosis in mice at both 32 and 66 weeks. WT mice on the CDAA diet for 66 weeks developed preneoplastic nodules and displayed increased hepatocellular proliferation, which were reduced in Ripk3(-/-) mice. Furthermore, Ripk3 deficiency hampered tumourigenesis. Intriguingly, Ripk3(-/-) mice displayed increased body weight gain, while lipidomics showed that deletion of Ripk3 shifted hepatic lipid profiles. Peroxisome proliferator-activated receptor. (PPAR.) was increased in Ripk3(-/-) mice and negatively correlated with hepatic RIPK3 in patients with NAFLD. Mechanistic studies established a functional link between RIPK3 and PPAR. in controlling fat deposition and fibrosis. Conclusion Hepatic RIPK3 correlates with NAFLD severity in humans and mice, playing a key role in managing liver metabolism, damage, inflammation, fibrosis and carcinogenesis. Targeting RIPK3 and its intricate signalling arises as a novel promising approach to treat NASH and arrest disease progression.Main funding is provided by FEDER funds through the COMPETE programme and by national funds through Fundacao para a Ciencia e a Tecnologia to CMPR (grants SAICTPAC/0019/2015-LISBOA-01-0145--FEDER-016405 and PTDC/MED-FAR/29097/2017 -LISBOA-01-0145-FEDER-029097). Additional funding comes from research grant APEF (Portuguese Association for the Study of Liver)/BAYER 2020 to MBA. JG is funded by the Fondation pour la Recherche Medicale (ARF20170938613), the Institute of Cardiometabolism and Nutrition (PAP17NECJG), the Societe Francophone du Diabete (R19114DD) and the Mairie de Paris (Emergences -R18139DD). MBA, PMR, MMP and ALS were investigators or students funded by Fundacao para a Ciencia e a Tecnologia

A comparison of Covid-19 early detection between convolutional neural networks and radiologists

[EN] Background The role of chest radiography in COVID-19 disease has changed since the beginning of the pandemic from a diagnostic tool when microbiological resources were scarce to a different one focused on detecting and monitoring COVID-19 lung involvement. Using chest radiographs, early detection of the disease is still helpful in resource-poor environments. However, the sensitivity of a chest radiograph for diagnosing COVID-19 is modest, even for expert radiologists. In this paper, the performance of a deep learning algorithm on the first clinical encounter is evaluated and compared with a group of radiologists with different years of experience. Methods The algorithm uses an ensemble of four deep convolutional networks, Ensemble4Covid, trained to detect COVID-19 on frontal chest radiographs. The algorithm was tested using images from the first clinical encounter of positive and negative cases. Its performance was compared with five radiologists on a smaller test subset of patients. The algorithm's performance was also validated using the public dataset COVIDx. Results Compared to the consensus of five radiologists, the Ensemble4Covid model achieved an AUC of 0.85, whereas the radiologists achieved an AUC of 0.71. Compared with other state-of-the-art models, the performance of a single model of our ensemble achieved nonsignificant differences in the public dataset COVIDx. Conclusion The results show that the use of images from the first clinical encounter significantly drops the detection performance of COVID-19. The performance of our Ensemble4Covid under these challenging conditions is considerably higher compared to a consensus of five radiologists. Artificial intelligence can be used for the fast diagnosis of COVID-19.Project Chest screening for patients with COVID 19 (COV2000750 Special COVID19 resolution) funded by Instituto de Salud Carlos III. Project DIRAC (INNVA1/2020/42) funded by the Agencia Valenciana de la Innovacion, Generalitat Valenciana.Albiol Colomer, A.; Albiol, F.; Paredes Palacios, R.; Plasencia-Martínez, JM.; Blanco Barrio, A.; García Santos, JM.; Tortajada, S.... (2022). A comparison of Covid-19 early detection between convolutional neural networks and radiologists. Insights into Imaging. 13(1):1-12. https://doi.org/10.1186/s13244-022-01250-311213