CXCR4 inhibitors: tumor vasculature and therapeutic challenges

CXCL12, also known as SDF-1, is the single natural ligand for chemokine receptors CXCR4 and CXCR7. CXCL12 has angiogenic properties in normal endothelial tissue and is involved in the outgrowth and metastasis of CXCR4 expressing tumors. Recent investigations have indicated that CXCL12 levels increase after chemo- and anti- VEGF therapy, favouring recurrences. The blockade of CXCL12/CXCR4 axis has emerged as a potential additional or alternative target for neo-adjuvant treatments. We have reviewed recent patent applications between 2008 and 2011 in tumor angiogenesis and the most clinical data supporting the potential use of anti-CXCR4 agents in this field. Among these, AMD3100, also known as Plerixaform (Mozobil® by Genzyme), is approved for stem cell mobilisation in patients with leukaemia, while BKT140 (Emory University), POL6326 (Polyphor Ag) and TG-0054 (ChemoCentryx) are currently in clinical trials in combination with chemotherapy for multiple myeloma and leukaemia. The aptamer Nox-A12 (Noxxon) is in trials for chronic lymphatic leukaemia treatment. MSX-122 (Metastatix) is in Phase I trials for solid tumor treatment, while CXCR7-specific inhibitor CCX2066 (ChemoCentryx) is still in preclinical studies. We have also considered other strategies, such RNA interference and miRNA, which could be tested for solid tumor adjuvant therapy

Potential benefits of cell therapy in coronary heart disease

AbstractCardiovascular disease is the leading cause of morbidity and mortality in the world. In recent years, there has been an increasing interest both in basic and clinical research regarding the field of cell therapy for coronary heart disease (CHD). Several preclinical models of CHD have suggested that regenerative properties of stem and progenitor cells might help restoring myocardial functions in the event of cardiac diseases. Here, we summarize different types of stem/progenitor cells that have been tested in experimental and clinical settings of cardiac regeneration, from embryonic stem cells to induced pluripotent stem cells. Then, we provide a comprehensive description of the most common cell delivery strategies with their major pros and cons and underline the potential of tissue engineering and injectable matrices to address the crucial issue of restoring the three-dimensional structure of the injured myocardial region. Due to the encouraging results from preclinical models, the number of clinical trials with cell therapy is continuously increasing and includes patients with CHD and congestive heart failure. Most of the already published trials have demonstrated safety and feasibility of cell therapies in these clinical conditions. Several studies have also suggested that cell therapy results in improved clinical outcomes. Numerous ongoing clinical trials utilizing this therapy for CHD will address fundamental issues concerning cell source and population utilized, as well as the use of imaging techniques to assess cell homing and survival, all factors that affect the efficacy of different cell therapy strategies

Calidad sensorial de albaricoques frescos sometidos a poscosecha prolongada

La calidad sensorial de la fruta fresca es cada vez un aspecto más importante que debe considerarse, particularmente cuando ésta es sometida a periodos de postcosecha muy extensos, como es el caso de la fruta de hueso chilena de exportación. Mantener la calidad sensorial de albaricoques frescos en postcosecha prolongada es un desafío tecnológico, dada la corta vida en almacenamiento y la sensibilidad al trasporte de esta fruta. Para esto, además de las evaluaciones convencionales para determinar el desempeño de la fruta en almacenamiento, es necesario el apoyo del análisis sensorial como una herramienta de evaluación de calidad del producto final. El objetivo del trabajo fue evaluar la calidad sensorial de variedades de albaricoque sometidas a poscosecha prolongada. Se evaluaron las variedades ‘Goldrich’, ‘Castelbrite’ y ‘Orange red’, mantenidas en cámara de frío convencional a 0ºC y 90% de humedad relativa por 0, 14 y 28 días más un periodo variable a 20ºC, hasta que la pulpa alcanzó la firmeza de consumo (4,9 - 14,7 N). Se utilizó un panel entrenado de 12 evaluadores que determinó la intensidad del aroma, dulzor, gusto ácido, textura, jugosidad y sabor. ‘Orange red’ no sometida a almacenaje, obtuvo altas puntaciones en los atributos medidos, que disminuyeron drásticamente a los 28 días de almacenaje refrigerado. ‘Goldrich’ obtuvo un mejor desempeño en postcosecha después de 28 días de almacenamiento, destacando su dulzor y aceptabilidad. Todas las variedades diminuyeron de forma diferencial en aceptabilidad después de 28 días de almacenamiento, lo que indica la existencia de un efecto varietal importante en la respuesta.Este trabajo fue financiado por el proyecto D03 I 10 70 “Mejoramiento de la competitividad del damasco de exportación, mediante la diferenciación del producto y la organización de la industria” de FONDEF

De novo DNA methylation induced by circulating extracellular vesicles from acute coronary syndrome patients

DNA methylation is associated with gene silencing, but its clinical role in cardiovascular diseases (CVDs) remains to be elucidated. We hypothesized that extracellular vesicles (EVs) may carry epigenetic changes, showing themselves as a potentially valuable non-invasive diagnostic liquid biopsy. We isolated and characterized circulating EVs of acute coronary syndrome (ACS) patients and assessed their role on DNA methylation in epigenetic modifications

Skeletal status in children and adolescents with new-onset type 1 diabetes: a preliminary study based on bone densitometry and quantitative ultrasound

Type 1 diabetes (T1D) represents a risk factor for bone loss and impaired bone quality

Consultoría integral en una empresa comercializadora de toallitas húmedas en el municipio de Zapopan

Este documento describe el desarrollo del proceso de consultoría en el período de enero a mayo del año 2019. Se incluye un análisis del entorno, se describen los resultados del diagnóstico hecho a la empresa, así como el planteamiento estratégico que se formuló en conjunto con los empresarios y las propuestas de mejora para cada área funcional. Las propuestas se encuentran descritas por orden de prioridad y se detalla el uso y beneficio que se observó sobre las mismas. Las mediciones finales de uso y beneficio son monitoreadas a través de un plan de acción, o Tablero de Indicadores, que muestra los avances parciales y finales de cada una de las propuestas y como éstas abonan a los objetivos operativos y estratégicos definidos por la empresa. Posteriormente se describe el proceso de implementación de las propuestas, que principalmente fueron dirigidas a la formalización y sistematización de los procesos de la empresa, para colaborar en la obtención de un permiso de producción que requiere el seguimiento de Normas Oficiales Mexicanas, así como analizar segmentos de mercado no explorados y competidores en su área de influencia, que les permita planear y reenfocar su empresa. Durante este proceso se realizaron resúmenes de visita a la empresa, derivados de organización de planes de trabajo previos. Estos resúmenes detallan las actividades realizadas en la empresa y el avance generado sobre las propuestas iniciales. También se mencionan los obstáculos y retos, ajustes al plan de acción inicial, y los resultados logrados. Por último, se describen las recomendaciones que el equipo de consultoría hizo para la empresa en el corto, mediano y largo plazo para cada área de la empresa. Concluimos que la gestión empresarial incide en todas las áreas de la empresa y por tal, es importante fortalecerla.ITESO, A.C

Transcriptome analysis and postharvest behavior of the kiwifruit `Actinidia deliciosa¿ reveal the role of ethylene-related phytohormones during fruit ripening

Kiwifruit are climacteric fruit, so they must be harvested before they are fully ripe, allowing for the extension of their shelf-life via cold storage. Therefore, an adequate knowledge about how ethylene-induced fruit senescence is required to avoid significant economic losses. The main goal of the present study was to investigate the kiwifruit ripening process at the physiological and molecular levels by RNA-seq after 1-methylcyclopropene (1-MCP, ethylene inhibitor) and Ethrel® (ethylene stimulator) treatments. The results showed that Ethrel® (ethephon) treatment induced more accelerated fruit ripening, leading to rapid fruit senescence, meanwhile 1-MCP caused a slowing flesh softening, and thus a longer shelf-life period. The RNA-seq was carried out on the fruit after 4 and 13 days, considering day 4 as the most determinant in terms of differentially expressed genes (DEGs). The sequencing achieved 70.7% alignment with the `Hongyang¿ genome, obtaining 18,036 DEGs. The protein-protein interaction (PPI) network shows the interaction between different pathways in two main clusters: (1) pentose and glucoronate interconversions, citrate cycle, glycolysis and gluconeogenesis or starch, and sucrose metabolism and (2) porphyrin and chlorophyll metabolism. The first cluster is mainly interconnected by G6PD1 (pentose pathway); E1 ALPHA and ACLB-2 (citrate cycle); Achn209711 (pentose and glucoronate); LOS2 (glycolysis); HKL1 and HXK1 (glycolysis¿starch and sucrose); and PHS2 (starch and sucrose). In the second cluster, GUN5 through PORA is interacting with CRD1 and NYC1 which were overexpressed by 1-MCP in the porphyrin and chlorophyll metabolism. In addition, genes linked to PSBY and PSBP photosynthesis-linked proteins in photosystem 2 were overexpressed by 1-MCP which is undoubtedly related to chlorophyll degradation and fruit senescence. These results suggest that in kiwifruit, the main pathways that are regulated by ethylene-induced senescence comprise sugar catabolism and chlorophyll degradation.The authors would like to thank the National Commission for Scientific and Technological Research (CONICYT) of Chile government through the project FONDEF N° D09i-1136. Additionally, we thank the Seneca Foundation in the region of Murcia (Spain) through the Regional subprogram “Saavedra Fajardo” (20397/ SF/17) and Ministry of Science and Innovation through the project “Juan de la Cierva Incorporación” N° IJC2018-0366-

The impacts of agricultural and urban land-use changes on plant and bird biodiversity in Costa Rica (1986-2014)

Costa Rica is recognized worldwide for its nature conservation policy following the traditional land-sparing approach. However, concerns have been raised about the opposite trends of the agricultural land cover changes driven by the option to expand old and new export crops after the country's external debt crisis of the 1980s. We study what happened during the last 20 years by applying landscape ecology metrics to the REDD+ land cover maps of 1986, 2001, and 2014, and statistically testing these indicators with the locations of species richness of plants and birds recorded by INBio. Our results confirm that deforestation has been reversed and most of the biodiversity considered is housed in forestland, but also that the expansion of export monocultures and urban sprawl have fragmented and isolated these tropical forests. Ecological connectivity values decreased 13% across the territory, all crops are negatively correlated with bird and plant locations, and the metropolitan expansion caused a detrimental impact on coffee agroforestry. All these outcomes are consistent with the growing deficit of the Costa Rican physical trade balance due to a faster increase of tropical exports than the growing imports of staple food, with a loss of soil organic matter filled by high doses of agrochemicals imported. Overcoming these environmental problems require a new land-sharing approach to nature conservation aimed at improving ecological connectivity through an agroecology approach combined with land-use planning to preserve the remaining green belt of the shade coffee plantations as a buffer green infrastructure in the metropolitan area

Detection of Quantitative Trait Loci Controlling the Content of Phenolic Compounds in an Asian Plum (Prunus salicina L.) F1 Population

Consumption of fresh fruit is known to protect against non-communicable diseases due to the fruit's content in compounds with an antioxidant capacity, among them is polyphenols. Asian plums (Prunus salicina L.) accumulate more than 40 phenolic compounds, with a remarkable diversity in their profiles, depending on the variety and environmental conditions. Although candidate genes have been indicated to control this trait, the loci controlling its phenotypic variation have not yet been defined in this species. The aim of this work was to identify the quantitative trait Loci (QTL) controlling the phenolic compounds content in the Asian plum skin and flesh. Using UHPLC-DAD-Orbitrap-MS, we determined that cyanidin-3-glucoside and cyanidin-3-rutinoside are the main anthocyanins in Asian plums. Other anthocyanins found to a lesser extent were tentatively identified as cyanidin bound to different sugar and procyanidin moieties. Then we phenotyped fruits of 92 and 80 F1 seedlings from the cross (98 Ang) for two harvest seasons. We used HPLC-DAD to quantify single anthocyanin and spectrophotometric techniques to determine the total content of phenols, flavonoids, procyanidins, and antioxidant activity (DPPH and FRAP). To determine the phenotype-genotype association of phenolic compounds content, phenotypic values (adjusted by linear mixed-effects models), genotypic data and linkage maps were analyzed with the multiple QTL model (MQM) approach. We found a total of 21 significant trait-marker associations: 13 QTLs segregating from “98.99” and 8 QTLs from “Angeleno.” From these associations, 8 corresponded to phenolic compound content in the flesh and 13 in the skin. Phenotype variance was explained by the detected loci, ranging from 12.4 to 27.1%. The identified loci are related to the content of cyanidin-3-glucoside (LG4), cyanidin-3-rutinoside (LG4), total flavonoids and procyanidins (LG5 and LG8), and minor anthocyanin compounds (LG3 and LG4). These results will help improve the efficiency of breeding programs for the generation of Asian plum varieties with high phenolic compound content.This work has been funded by the National Agency of Research and Development (ANID), Chile: Fondecyt start into Research No. 11150662, Fondecyt Regular No. 1191446, and FONDEF Project IT17I0069 Sweet Pekeetah: un modelo tecnológico-comercial para una nueva variedad chilena de fruta; BB and CS-A were supported by BECAS DE DOCTORADO NACIONAL/2020 No. 21200330 and 21191605, respectively. The work of JS was supported by the Ministry of Science and Innovation of Spain through Juan de la Cierva incorporation contract (IJC2018-036623-I

CLASH-X: A Comparison of Lensing and X-ray Techniques for Measuring the Mass Profiles of Galaxy Clusters

We present profiles of temperature (Tx), gas mass, and hydrostatic mass estimated from new and archival X-ray observations of CLASH clusters. We compare measurements derived from XMM and Chandra observations with one another and compare both to gravitational lensing mass profiles derived with CLASH HST and ground-based lensing data. Radial profiles of Chandra and XMM electron density and enclosed gas mass are nearly identical, indicating that differences in hydrostatic masses inferred from X-ray observations arise from differences in Tx measurements. Encouragingly, cluster Txs are consistent with one another at ~100-200 kpc radii but XMM Tx systematically decline relative to Chandra Tx at larger radii. The angular dependence of the discrepancy suggests additional investigation on systematics such as the XMM point spread function correction, vignetting and off-axis responses. We present the CLASH-X mass-profile comparisons in the form of cosmology-independent and redshift-independent circular-velocity profiles. Ratios of Chandra HSE mass profiles to CLASH lensing profiles show no obvious radial dependence in the 0.3-0.8 Mpc range. However, the mean mass biases inferred from the WL and SaWLens data are different. e.g., the weighted-mean value at 0.5 Mpc is = 0.12 for the WL comparison and = -0.11 for the SaWLens comparison. The ratios of XMM HSE mass profiles to CLASH lensing profiles show a pronounced radial dependence in the 0.3-1.0 Mpc range, with a weighted mean mass bias of value rising to ~0.3 at ~1 Mpc for the WL comparison and of 0.25 for SaWLens comparison. The enclosed gas mass profiles from both Chandra and XMM rise to a value 1/8 times the total-mass profiles inferred from lensing at 0.5 Mpc and remain constant outside of that radius, suggesting that [8xMgas] profiles may be an excellent proxy for total-mass profiles at >0.5 Mpc in massive galaxy clusters.Comment: Accepted to ApJ; 24 pages; scheduled to appear in the Oct 10, 2014 issue. This version corrects the typographical error in the superscripts for Equation (2) to include the square of (r/r_core). The correct version of this equation was used in the analysi