Theoretical Study of Cyanidin-Resveratrol Copigmentation by the Functional Density Theory.

Anthocyanins are colored water-soluble plant pigments. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood-brain barrier (BBB). Research based on population studies suggests that including anthocyanin-rich sources in the diet lowers the risk of neurodegenerative diseases. The copigmentation caused by copigments is considered an effective way to stabilize anthocyanins against adverse environmental conditions. This is attributed to the covalent and noncovalent interactions between colored forms of anthocyanins (flavylium ions and quinoidal bases) and colorless or pale-yellow organic molecules (copigments). The present work carried out a theoretical study of the copigmentation process between cyanidin and resveratrol (CINRES). We used three levels of density functional theory: M06-2x/6-31g+(d,p) (d3bj); ωB97X-D/6-31+(d,p); APFD/6-31+(d,p), implemented in the Gaussian16W package. In a vacuum, the CINRES was found at a copigmentation distance of 3.54 Å between cyanidin and resveratrol. In water, a binding free energy ∆G was calculated, rendering -3.31, -1.68, and -6.91 kcal/mol, at M06-2x/6-31g+(d,p) (d3bj), ωB97X-D/6-31+(d,p), and APFD/6-31+(d,p) levels of theory, respectively. A time-dependent density functional theory (TD-DFT) was used to calculate the UV spectra of the complexes and then compared to its parent molecules, resulting in a lower energy gap at forming complexes. Excited states' properties were analyzed with the ωB97X-D functional. Finally, Shannon aromaticity indices were calculated and isosurfaces of non-covalent interactions were evaluated.

Impact of chlorogenic acid on surface and phase properties of cholesterol-enriched phosphatidylcholine membranes.

This study analyses the insertion of Chlorogenic acid (CGA) in phosphatidylcholine (PC) membranes enriched with cholesterol (Chol). While cholesterol decreases the area per lipid and increases the dipole potential, CGA increases and decreases these values, respectively. When CGA is inserted into cholesterol-containing DMPC membranes, these effects cancel out, resulting in values that overlap with those of DMPC monolayers without Chol and CGA. The presence of CGA also compensates the increase of dipole potential produced by Chol which can be explain as a consequence of the orientation of CGA molecule at the interphase opposing the cholesterol dipole moieties and water dipoles. This compensatory effect is less effective when lipids lack carbonyl groups (CO). When monolayers are composed by unsaturated PCs the Chol compensation is found at higher concentrations of CGA due to the direct interaction between CGA and Chol. These results suggest that cholesterol modulates the interaction and distribution of CGA in the lipid membrane, which may have implications for its biological activity.

Comparative Analysis of CRISPR-Cas Systems in Pseudomonas Genomes.

Pseudomonas is a bacterial genus with some saprophytic species from land and others associated with opportunistic infections in humans and animals. Factors such as pathogenicity or metabolic aspects have been related to CRISPR-Cas, and in silico studies into it have focused more on the clinical and non-environmental setting. This work aimed to perform an in silico analysis of the CRISPR-Cas systems present in Pseudomonas genomes. It analyzed 275 complete genomic sequences of Pseudomonas taken from the NCBI database. CRISPR loci were obtained from CRISPRdb. The genes associated with CRISPR (cas) and CAS proteins, and the origin and diversity of spacer sequences, were identified and compared by BLAST. The presence of self-targeting sequences, PAMs, and the conservation of DRs were visualized using WebLogo 3.6. The CRISPR-like RNA secondary structure prediction was analyzed using RNAFold and MFold. CRISPR structures were identified in 19.6% of Pseudomonas species. In all, 113 typical CRISPR arrays with 18 putative cas were found, as were 2050 spacers, of which 52% showed homology to bacteriophages, 26% to chromosomes, and 22% to plasmids. No potential self-targeting was detected within the CRISPR array. All the found DRs can form thermodynamically stable secondary RNA structures. The comparison of the CRISPR/Cas system can help understand the environmental adaptability of each evolutionary lineage of clinically and environmentally relevant species, providing data support for bacterial typing, traceability, analysis, and exploration of unconventional CRISPR.

Medio siglo del inicio de la enseñanza de la Histología en Villa Clara / Half a century since the beginning of the Histology teaching in Villa Clara

Las ideas del Comandante en Jefe Fidel Castro Ruz y la implementación del programa de la Revolución cubana colocaron como principios centrales de la política educacional la universalización de la enseñanza y dentro de ella, la de las ciencias médicas con un amplio acceso en todo el país. La impartición de las Ciencias Básicas Biomédicas en la provincia de Villa Clara comenzó en el curso 1973-1974 con la apertura del primer año de la facultad de Medicina. Al cumplirse en 2024 cincuenta años de este acontecimiento social y docente en la provincia, los autores pretenden socializar algunos elementos históricos sobre el inicio de la docencia médica en esa provincia, haciendo énfasis en la Histología, entre 1974 y 1982, así como reconocer a todos aquellos que contribuyeron al inicio y desarrollo de la docencia de las Ciencias Básicas Biomédicas en la región central de Cuba.

The ideas of Commander in Chief Fidel Castro Ruz and the program implementation of the Cuban Revolution placed the universalization of education as central principles of educational policy and within it, that of medical sciences with wide access throughout the country. The teaching of Basic Biomedical Sciences in the Villa Clara province began in the 1973-1974 academic year with the opening of the first year at the Faculty of Medicine. As 2024 marks the fiftieth anniversary of this social and teaching event in the province, authors intend to socialize some historical elements about the beginning of medical teaching in that province, emphasizing on Histology subject, from 1974 to 1982, as well as give recognition to all those who contributed to the teaching beginning and development of Basic Biomedical Sciences in the Cuban central region.

Iron reducing sludge as a source of electroactive bacteria: assessing iron reduction in biofilm bacteria, planktonic cells and isolates from a microbial fuel cell.

In this study, bacteria from a microbial fuel cell (MFC) and isolates were evaluated on their Fe3+ reduction capability at different concentrations of iron using acetate as the sole source of carbon. The results demonstrated that the planktonic cells can reach an iron reduction up to 60% at 27 mmol Fe3+. Azospira oryzae (µ 0.89 ± 0.27 d-1) and Cupriavidus metallidurans CH34 (µ 2.34 ± 0.81 d-1) presented 55 and 62% of Fe3+ reduction, respectively, at 16 mmol l-1. Enterobacter bugandensis (µ 0.4 ± 0.01 d-1) 40% Fe3+ at 27 mmol l-1, Citrobacter freundii ATCC 8090 (µ 0.23 ± 0.05 d-1) and Citrobacter murliniae CDC2970-59 (µ 0.34 ± 0.02 d-1) reduced Fe3+ in ~ 50%, at 55 mmol l-1. This is the first report on these bacteria on a percentage of iron reduction. These results may be useful for anode design to contribute to a higher energy generation in MFCs.

Cambios en la actividad eléctrica ventricular durante el ejercicio isométrico en adultos jóvenes normorreactivos e hiperreactivos / Changes in ventricular electrical activity during isometric exercise in normoreactive and hyperreactive young adults

RESUMEN Introducción: Los individuos con hiperreación cardiovascular poseen un riesgo cinco veces superior de padecer hipertensión. En el contexto cubano no están descritos los cambios en la actividad eléctrica ventricular del electrocardiograma, durante la prueba isométrica del peso sostenido, y no se conoce si estos pueden estar influenciados por el grado de reactividad cardiovascular. Objetivo: Describir los parámetros de la actividad eléctrica ventricular en condiciones basales y durante el ejercicio isométrico, en adultos jóvenes de ambos sexos con diferente grado de reactividad cardiovascular. Métodos: La muestra estuvo constituida por 130 individuos de ambos sexos, y se dividió en dos grupos: Normorreactivos e hiperreactivos. A todos se les realizó un electrocardiograma digital en derivación DII; se utilizó el programa LabChart 8 en un polígrafo ADInstruments. Se estudiaron las siguientes variables: Complejo QRS, intervalo QT corregido (QTc), intervalo JT, intervalo Tpeak-Tend, amplitud del segmento ST y de la onda T en reposo, en el ejercicio isométrico y durante la recuperación. Resultados: Entre las mujeres normorreactivas e hiperreactivas se encontraron diferencias significativas en la amplitud de la onda T, tanto basales, durante el ejercicio isométrico, como en la recuperación. Entre los hombres de ambos grupos solo se encontraron diferencias significativas en el intervalo JT, durante el ejercicio. Conclusiones: Los cambios producidos en la regulación autonómica de la función cardíaca durante el ejercicio isométrico y la recuperación, se reflejaron en la actividad eléctrica ventricular en los individuos normorreactivos e hiperreactivos de ambos sexos, principalmente en el intervalo JT y la altura de la onda T.

ABSTRACT Introduction: individuals with cardiovascular hyperreaction have a five times higher risk of suffering from hypertension. In the Cuban context, the changes in the ventricular electrical activity of the electrocardiogram during the sustained weight isometric test have not been described, and it is not known whether these may be influenced by the degree of cardiovascular reactivity. Objective: to describe the parameters of ventricular electrical activity in basal conditions and during isometric exercise, in young adults of both genders with different degrees of cardiovascular reactivity. Methods: the sample consisted of 130 individuals of both genders, and was divided into two groups: normoreactive and hyperreactive. All of them underwent a digital electrocardiogram in DII lead; LabChart 8 software on an ADInstruments polygraph was used. The following variables were studied: QRS complex, corrected QT interval (QTc), JT interval, Tpeak-Tend interval, ST segment and T wave amplitude at rest, in isometric exercise and during recovery. Results: significant differences between normoreactive and hyperreactive women were found in the amplitude of the T wave, both at baseline, during isometric exercise, and in recovery. Significant differences were only found between men in both groups in the JT interval, during exercise. Conclusions: the changes produced in the autonomic regulation of cardiac function during isometric exercise and recovery were reflected in the ventricular electrical activity in normoreactive and hyperreactive individuals of both genders, mainly in the JT interval and the height of the T wave.

Self-assembly study of type I collagen extracted from male Wistar Hannover rat tail tendons.

BACKGROUND: Collagen, the most abundant protein in the animal kingdom, represents a promising biomaterial for regenerative medicine applications due to its structural diversity and self-assembling complexity. Despite collagen's widely known structural and functional features, the thermodynamics behind its fibrillogenic self-assembling process is still to be fully understood. In this work we report on a series of spectroscopic, mechanical, morphological and thermodynamic characterizations of high purity type I collagen (with a D-pattern of 65 nm) extracted from Wistar Hannover rat tail. Our herein reported results can be of help to elucidate differences in self-assembly states of proteins using ITC to improve the design of energy responsive and dynamic materials for applications in tissue engineering and regenerative medicine. METHODS: Herein we report the systematic study on the self-assembling fibrillogenesis mechanism of type I collagen, we provide morphological and thermodynamic evidence associated to different self-assembly events using ITC titrations. We provide thorough characterization of the effect of pH, effect of salts and protein conformation on self-assembled collagen samples via several complementary biophysical techniques, including circular dichroism (CD), Fourier Transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), atomic force microscopy (AFM), scanning electron microscopy (SEM), dynamic mechanical thermal analysis (DMTA) and thermogravimetric analysis (TGA). RESULTS: Emphasis was made on the use of isothermal titration calorimetry (ITC) for the thermodynamic monitoring of fibrillogenesis stages of the protein. An overall self-assembly enthalpy value of 3.27 ± 0.85 J/mol was found. Different stages of the self-assembly mechanism were identified, initial stages take place at pH values lower than the protein isoelectric point (pI), however, higher energy release events were recorded at collagen's pI. Denatured collagen employed as a control exhibited higher energy absorption at its pI, suggesting different energy exchange mechanisms as a consequence of different aggregation routes.

Nonirritant and Cytocompatible Tinospora cordifolia Nanoparticles for Topical Antioxidant Treatments.

Tinospora cordifolia extract contains antioxidants such as polyphenols, and thus, it has been used as a natural phytochemical antioxidant therapeutic agent. Many of these compounds are insoluble or only partially soluble in water. In this study, we produced a novel aqueous nanoparticle formulation, with an average particle size of 182.9 ± 3.8 nm, to improve the dispersion of the bioactive compounds in water and to increment its bioavailability. The nanoparticles are composed of polyphenols, alkaloids, and glycosides. We studied the effect of this nanoparticle formulation on mouse 3T3 fibroblast cell viability and New Zealand rabbit dermal irritability tests. Concentrations of 2.5, 25, and 250 µg/mL resulted in similar cell viability to cells in culture media. An intermediate concentration of 12.45 mg/ml was used for the acute dermal irritability test. There were no severe alterations that compromised animal health. These results represent a precedent for application of such nanoparticles derived from plant stems, such as Tinospora cordifolia, in biomedicine and in antiaging cosmetic treatments.

Increased Fibroblast Metabolic Activity of Collagen Scaffolds via the Addition of Propolis Nanoparticles.

Propolis natural extracts have been used since ancient times due to their antioxidant, anti-inflammatory, antiviral, and antimicrobial activities. In this study, we produced scaffolds of type I collagen, extracted from Wistar Hanover rat tail tendons, and impregnated them with propolis nanoparticles (NPs) for applications in regenerative medicine. Our results show that the impregnation of propolis NPs to collagen scaffolds affected the collagen denaturation temperature and tensile strength. The changes in structural collagen self-assembly due to contact with organic nanoparticles were shown for the first time. The fibril collagen secondary structure was preserved, and the D-pattern gap increased to 135 ± 28 nm, without losing the microfiber structure. We also show that the properties of the collagen scaffolds depended on the concentration of propolis NPs. A concentration of 100 µg/mL of propolis NPs with 1 mg of collagen, with a hydrodynamic diameter of 173 nm, was found to be an optimal concentration to enhance 3T3 fibroblast cell metabolic activity and cell proliferation. The expected outcome from this research is both scientifically and socially relevant since the home scaffold using natural nanoparticles can be produced using a simple method and could be widely used for local medical care in developing communities.

Introducción de la asignatura Sangre y Sistema Inmune: satisfacción y desempeño de los estudiantes / Introduction to the Blood and Immune System subject: satisfaction and student´s performance

RESUMEN Fundamento: en el curso 2017-2018 se introdujo la asignatura Sangre y Sistema Inmune en el tercer semestre de la carrera de Medicina, según el nuevo plan de estudio. Objetivos: identificar el grado de satisfacción y desempeño de los estudiantes en la asignatura Sangre y Sistema Inmune de recién incorporación en el Plan de Estudios D. Método: se realizó un estudio descriptivo en la Universidad de Ciencias Médicas de Villa Clara en el curso académico 2017-2018. Se utilizaron métodos teóricos: análisis-síntesis e inducción-deducción, empíricos: la encuesta en forma de cuestionario en dos momentos concretos del semestre (cuarta y decimoquinta semanas), y matemático-estadísticos para el procesamiento de los datos. Resultados: en sentido general la introducción de la asignatura Sangre y Sistema Inmune en el currículo tuvo un nivel adecuado de aceptación por los alumnos y este evolucionó de forma positiva en la medida en que transcurrió el curso. En los casos de insatisfacción, la principal causa estuvo vinculada a la dificultad de los temas impartidos. Existe preferencia por las clases talleres y prácticas de laboratorio, y el trabajo de curso como evaluación final, y no con un examen teórico. Conclusiones: el nivel de satisfacción expresado por los alumnos con la asignatura fue adecuado, no así el desempeño ya que la mayoría reconocieron no poseer los conocimientos básicos sobre su contenido, aspectos que se tuvieron en cuenta en su posterior impartición.

ABSTRACT Background: in the 2017-2018 academic year, the Blood and Immune System subject was introduced in the third semester of the Medicine degree, according to the new study plan. Objectives: to identify the degree of satisfaction and performance of students in the Blood and Immune System subject of recent incorporation in the Study Plan D. Methods: a descriptive study was carried out at Villa Clara University of Medical Sciences in the academic year 2017-2018. Theoretical methods were used: analysis-synthesis and induction-deduction, empirical ones: the survey in the form of a questionnaire in two specific moments of the semester (fourth and fifteenth weeks), and mathematical-statistics for data processing. Results: in general, the introduction of the Blood and Immune System subject in the curriculum had an adequate level of acceptance by the students and this evolved in a positive way to the extent that the course lasted. In cases of dissatisfaction, the main cause was linked to the difficulty of the subjects taught. There is a preference for workshops and laboratory practices, and a course project work as a final evaluation, and not with a theoretical exam. Conclusions: the level of satisfaction expressed by the students with the subject was adequate, not so the performance since most acknowledged not having the basic knowledge about its content, aspects that were taken into account in its subsequent teaching.

Balance autonómico basal y durante el ejercicio isométrico en jóvenes con diferente reactividad cardiovascular / Basal autonomic balance and during the isometric exercise in young people with different cardiovascular reactivity

RESUMEN Introducción: El sistema nervioso autónomo desempeña un papel importante en los reajustes cardiovasculares al ejercicio. En la hiperreactividad cardiovascular existe una mayor sensibilidad del sistema simpático ante diferentes estímulos estresantes. Objetivo: Determinar las características del control autonómico cardíaco en adultos jóvenes con diferentes grados de reactividad cardiovascular en condiciones basales y durante el ejercicio isométrico. Método: La muestra estuvo constituida por 97 individuos de ambos sexos, y se dividió en tres grupos: normorreactivos, hiperreactivos y con respuesta hipertensiva, de acuerdo a la respuesta presora a la prueba del peso sostenido. A todos los individuos se les realizó un estudio de variabilidad de la frecuencia cardíaca en reposo y durante la prueba isométrica. Se estudiaron las variables en el dominio de la frecuencia: baja, alta, relación baja/alta en reposo, y los parámetros del diagrama de Poincaré en reposo y durante el ejercicio (valores de desviación estándar 1 [SD1], 2 [SD2], y la razón entre ambos). Resultados: En estado basal los individuos hiperreactivos y con respuesta hipertensiva presentaron un predominio simpático sobre la función cardíaca y una menor variabilidad de la frecuencia cardíaca. Durante el ejercicio isométrico disminuyeron los valores de los ejes SD1 y SD2 en todos los grupos y la razón SD1/SD2 decreció en individuos normorreactivos y con respuesta hipertensiva; pero apenas se modificó en los hiperreactivos. Conclusiones: En los individuos con hiperreactividad cardiovascular ya está presente un desbalance autonómico en estado basal y existe una reducción de la modulación autonómica vagal durante el ejercicio, que puede favorecer el desarrollo de la hipertensión arterial.

ABSTRACT Introduction: The autonomic nervous system plays an important role in cardiovascular readjustments to exercise. In cardiovascular hyperreactivity there is a greater sensitivity of the sympathetic system to different stressors. Objective: To determine the characteristics of cardiac autonomic control in young adults with different degrees of cardiovascular reactivity under basal conditions and during isometric exercise. Method: The sample consisted of 97 individuals of both sexes, and was divided into three groups: normoreactive, hyperreactive and with hypertensive response, according to the pressor response to weight-bearing tests. The individuals underwent a complete study of heart rate variability at rest and during isometric test. The frequency domain for the variables was: low, high, low/high resting ratio, and the parameters of Poincaré plots at rest and during exercise (values of standard deviation 1 [SD1], 2 [SD2], and the reason between them). Results: Under basal conditions, hyperreactive individuals with a hypertensive response had a sympathetic predominance over cardiac function and lower heart rate variability. During the isometric exercise SD1 and SD2 axes values decreased in all groups and SD1/SD2 ratio decreased in normoreactive individuals with hypertensive response; but it was hardly modified in those hyper-reactive. Conclusions: Individuals with cardiovascular hyperreactivity have a prior autonomic imbalance under basal conditions and a reduction of autonomic vagal modulation during exercise that may favor the development of arterial hypertension.

Stem cell exosomes inhibit angiogenesis and tumor growth of oral squamous cell carcinoma.

Recently, exosomes secreted by menstrual mesenchymal stem cells have been identified as inhibitory agents of tumor angiogenesis and modulators of the tumor cell secretome in prostate and breast cancer. However, their direct effect on endothelial cells and paracrine mediators have not yet been investigated. Using a carrier-based cell culture system to test the scalability for exosome production, we showed that different types of endothelial cells present specific kinetics for exosomes internalization. Exosome-treatment of endothelial cells increased cytotoxicity and reduced VEGF secretion and angiogenesis in a dose-dependent manner. Using the hamster buccal pouch carcinoma as a preclinical model for human oral squamous cell carcinoma, we demonstrated a significant antitumor effect of intra-tumoral injection of exosomes associated with a loss of tumor vasculature. These results address up-scaling of exosome production, a relevant issue for their clinical application, and also assess menstrual stem cell exosomes as potential anti-angiogenic agents for the treatment of neoplastic conditions.

Umbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial.

Knee osteoarthritis (OA) is a leading cause of pain and disability. Although conventional treatments show modest benefits, pilot and phase I/II trials with bone marrow (BM) and adipose-derived (AD) mesenchymal stromal cells (MSCs) point to the feasibility, safety, and occurrence of clinical and structural improvement in focal or diffuse disease. This study aimed to assess the safety and efficacy of the intra-articular injection of single or repeated umbilical cord-derived (UC) MSCs in knee OA. UC-MSCs were cultured in an International Organization for Standardization 9001:2015 certified Good Manufacturing Practice-type Laboratory. Patients with symptomatic knee OA were randomized to receive hyaluronic acid at baseline and 6 months (HA, n = 8), single-dose (20 × 106 ) UC-MSC at baseline (MSC-1, n = 9), or repeated UC-MSC doses at baseline and 6 months (20 × 106 × 2; MSC-2, n = 9). Clinical scores and magnetic resonance images (MRIs) were assessed throughout the 12 months follow-up. No severe adverse events were reported. Only MSC-treated patients experienced significant pain and function improvements from baseline (p = .001). At 12 months, Western Ontario and Mc Master Universities Arthritis Index (WOMAC-A; pain subscale) reached significantly lower levels of pain in the MSC-2-treated group (1.1 ± 1.3) as compared with the HA group (4.3 ± 3.5; p = .04). Pain Visual Analog scale was significantly lower in the MSC-2 group versus the HA group (2.4 ± 2.1 vs. 22.1 ± 9.8, p = .03) at 12 months. For total WOMAC, MSC-2 had lower scores than HA at 12 months (4.2 ± 3.9 vs. 15.2 ± 11, p = .05). No differences in MRI scores were detected. In a phase I/II trial (NCT02580695), repeated UC-MSC treatment is safe and superior to active comparator in knee OA at 1-year follow-up. Stem Cells Translational Medicine 2019;8:215&224.

The Reparative Abilities of Menstrual Stem Cells Modulate the Wound Matrix Signals and Improve Cutaneous Regeneration.

Considerable advances have been made toward understanding the cellular and molecular mechanism of wound healing, however, treatments for chronic wounds remain elusive. Emerging concepts utilizing mesenchymal stem cells (MSCs) from umbilical cord, adipose tissue and bone marrow have shown therapeutical advantages for wound healing. Based on this positive outcome, efforts to determine the optimal sources for MSCs are required in order to improve their migratory, angiogenic, immunomodulatory, and reparative abilities. An alternative source suitable for repetitive, non-invasive collection of MSCs is from the menstrual fluid (MenSCs), displaying a major practical advantage over other sources. This study aims to compare the biological functions and the transcriptomic pattern of MenSCs with umbilical cord MSCs in conditions resembling the wound microenvironment. Consequently, we correlate the specific gene expression signature from MenSCs with changes of the wound matrix signals in vivo. The direct comparison revealed a superior clonogenic and migratory potential of MenSCs as well as a beneficial effect of their secretome on human dermal fibroblast migration in vitro. Furthermore, MenSCs showed increased immunomodulatory properties, inhibiting T-cell proliferation in co-culture. We further, investigated the expression of selected genes involved in wound repair (growth factors, cytokines, chemokines, AMPs, MMPs) and found considerably higher expression levels in MenSCs (ANGPT1 1.5-fold; PDGFA 1.8-fold; PDGFB 791-fold; MMP3 21.6-fold; ELN 13.4-fold; and MMP10 9.2-fold). This difference became more pronounced under a pro-inflammatory stimulation, resembling wound bed conditions. Locally applied in a murine excisional wound splinting model, MenSCs showed a significantly improved wound closure after 14 days, as well as enhanced neovascularization, compared to the untreated group. Interestingly, analysis of excised wound tissue revealed a significantly higher expression of VEGF (1.42-fold) among other factors, translating an important conversion of the matrix signals in the wound site. Furthermore, histological analysis of the wound tissue from MenSCs-treated group displayed a more mature robust vascular network and a genuinely higher collagen content confirming the pro-angiogenic and reparative effect of MenSCs treatment. In conclusion, the superior clonogenicity, immunosuppressive and migration potential in combination with specific paracrine signature of MenSCs, resulted in an enhanced wound healing and cutaneous regeneration process.

La postura influye sobre la respuesta presora al ejercicio isométrico sin modificar la reactividad cardiovascular / Posture has an influence on the pressor response to isometric exercise without modifying cardiovascular reactivity

Este estudio se realizó con el objetivo de determinar si la posición del cuerpo influye sobre la respuesta presora a la prueba isométrica del peso sostenido. La muestra estuvo constituida por 97adultos jóvenes de ambos sexos, a los que se les realizó una prueba isométrica en posición sentada y en decúbito supino. Se obtuvieron los valores de las presiones arteriales sistólica, diastólica y media en reposo y al segundo minuto del ejercicio isométrico, así como las variaciones de las presiones sistólica, diastólica y media en posición sentada y en decúbito. Las medias de las presiones en reposo y durante la prueba isométrica fueron superiores en la posición sentada respecto al decúbito. Los valores delta de las presiones arteriales sistólica, diastólica y media no tuvieron diferencias significativas. Se concluye que la posición del cuerpo influye en la respuesta presora durante el ejercicio isométrico y no en el grado de la reactividad cardiovascular(AU)

Prostate tumor-induced angiogenesis is blocked by exosomes derived from menstrual stem cells through the inhibition of reactive oxygen species.

Mesenchymal stem cells (MSCs) secrete exosomes that are capable of modifying the tumor environment through different mechanisms including changes in the cancer-cell secretome. This activity depends on their cargo content that is largely defined by their cellular origin. Endometrial cells are fine regulators of the angiogenic process during the menstrual cycle that includes an angiostatic condition that is associated with the end of the cycle. Hence, we studied the angiogenic activity of menstrual stem cells (MenSCs)-secreted exosomes on prostate PC3 tumor cells. Our results showed that exosomes induce a reduction in VEGF secretion and NF-κB activity. Lower reactive oxygen species (ROS) production in exosomes-treated cells was detected by the DCF method, suggesting that the inhibition of the intracellular ROS impacts both NF-κB and VEGF pathways. We confirmed using tubule formation and plug transplantation assays that MenSCs-exosomes suppress the secretion of pro-angiogenic factors by the PC3 cells in a ROS-dependent manner. The inhibition of the tumor angiogenesis and, consequently, the tumor growth was also confirmed using a xenograft mouse model. Additionally, the anti-tumoral effect was associated with a reduction of tumor hemoglobin content, vascular density and inhibition of VEGF and HIF-1α expression. Importantly, we demonstrate that the exosomes anti-angiogenic effect is specific to the menstrual cell source, as bone marrow MSCs-derived exosomes showed an opposite effect on the VEGF and bFGF expression in tumor cells. Altogether, our results indicate that MenSCs-derived exosomes acts as blockers of the tumor-induced angiogenesis and therefore could be suitable for anti-cancer therapies.

Toll-like receptor 3 pre-conditioning increases the therapeutic efficacy of umbilical cord mesenchymal stromal cells in a dextran sulfate sodium-induced colitis model.

BACKGROUND AIMS: Immunomodulatory properties of human umbilical cord-derived mesenchymal stromal cells (UCMSCs) can be differentially modulated by toll-like receptors (TLR) agonists. Here, the therapeutic efficacy of short TLR3 and TLR4 pre-conditioning of UCMSCs was evaluated in a dextran sulfate sodium (DSS)-induced colitis in mice. The novelty of this study is that although modulation of human MSCs activity by TLRs is not a new concept, this is the first time that short TLR pre-conditioning has been carried out in a murine inflammatory model of acute colitis. METHODS: C57BL/6 mice were exposed to 2.5% dextran sulfate sodium (DSS) in drinking water ad libitum for 7 days. At days 1 and 3, mice were injected intraperitoneally with 1 × 10(6) UCMSCs untreated or TLR3 and TLR4 pre-conditioned UCMSCs. UCMSCs were pre-conditioned with poly(I:C) for TLR3 and LPS for TLR4 for 1 h at 37°C and 5% CO2. We evaluated clinical signs of disease and body weights daily. At the end of the experiment, colon length and histological changes were assessed. RESULTS: poly(I:C) pre-conditioned UCMSCs significantly ameliorated the clinical and histopathological severity of DSS-induced colitis compared with UCMSCs or LPS pre-conditioned UCMSCs. In contrast, infusion of LPS pre-conditioned UCMSCs significantly increased clinical signs of disease, colon shortening and histological disease index in DSS-induced colitis. CONCLUSIONS: These results show that short in vitro TLR3 pre-conditioning with poly(I:C) enhances the therapeutic efficacy of UCMSCs, which is a major breakthrough for developing improved treatments to patients with inflammatory bowel disease.

Soluble carbohydrate content variation in Sanionia uncinata and Polytrichastrum alpinum, two Antarctic mosses with contrasting desiccation capacities.

BACKGROUND: Cryptogamic vegetation dominates the ice-free areas along the Antarctic Peninsula. The two mosses Sanionia uncinata and Polytrichastrum alpinum inhabit soils with contrasting water availability. Sanionia uncinata grows in soil with continuous water supply, while P. alpinum grows in sandy, non-flooded soils. Desiccation and rehydration experiments were carried out to test for differences in the rate of water loss and uptake, with non-structural carbohydrates analysed to test their role in these processes. RESULTS: Individual plants of S. uncinata lost water 60 % faster than P. alpinum; however, clumps of S. uncinata took longer to dry than those of P. alpinum (11 vs. 5 h, respectively). In contrast, rehydration took less than 10 min for both mosses. Total non-structural carbohydrate content was higher in P. alpinum than in S. uncinata, but sugar levels changed more in P. alpinum during desiccation and rehydration (60-50 %) when compared to S. uncinata. We report the presence of galactinol (a precursor of the raffinose family) for the first time in P. alpinum. Galactinol was present at higher amounts than all other non-structural sugars. CONCLUSIONS: Individual plants of S. uncinata were not able to retain water for long periods but by growing and forming carpets, this species can retain water the longest. In contrast individual P. alpinum plants required more time to lose water than S. uncinata, but as moss cushions they suffered desiccation faster than the later. On the other hand, both species rehydrated very quickly. We found that when both mosses lost 50 % of their water, carbohydrates content remained stable and the plants did not accumulate non-structural carbohydrates during the desiccation prosses as usually occurs in vascular plants. The raffinose family oligosaccarides decreased during desiccation, and increased during rehydration, suggesting they function as osmoprotectors.

Soluble carbohydrate content variation in Sanionia uncinata and Polytrichastrum alpinum, two Antarctic mosses with contrasting desiccation capacities

BACKGROUND: Cryptogamic vegetation dominates the ice-free areas along the Antarctic Peninsula. The two mosses Sanionia uncinata and Polytrichastrum alpinum inhabit soils with contrasting water availability. Sanionia uncinata grows in soil with continuous water supply, while P. alpinum grows in sandy, non-flooded soils. Desiccation and rehydration experiments were carried out to test for differences in the rate of water loss and uptake, with non-structural carbohydrates analysed to test their role in these processes. RESULTS: Individual plants of S. uncinata lost water 60 % faster than P. alpinum; however, clumps of S. uncinata took longer to dry than those of P. alpinum (11 vs. 5 h, respectively). In contrast, rehydration took less than 10 min for both mosses. Total non-structural carbohydrate content was higher in P. alpinum than in S. uncinata, but sugar levels changed more in P. alpinum during desiccation and rehydration (60-50 %) when compared to S. uncinata. We report the presence of galactinol (a precursor of the raffinose family) for the first time in P. alpinum. Galactinol was present at higher amounts than all other non-structural sugars. CONCLUSIONS: Individual plants of S. uncinata were not able to retain water for long periods but by growing and forming carpets, this species can retain water the longest. In contrast individual P. alpinum plants required more time to lose water than S. uncinata, but as moss cushions they suffered desiccation faster than the later. On the other hand, both species rehydrated very quickly. We found that when both mosses lost 50 % of their water, carbohydrates content remained stable and the plants did not accumulate non-structural carbohydrates during the desiccation prosses as usually occurs in vascular plants. The raffinose family oligosaccarides decreased during desiccation, and increased during rehydration, suggesting they function as osmoprotectors.