Phenolic-rich extracts from avocado fruit residues as functional food ingredients with antioxidant and antiproliferative properties

In this study, the total phenolic compounds content and profile, the nutritional value, the antioxidant and antiproliferative activities of avocado peel, seed coat, and seed extracts were characterized. Additionally, an in-silico analysis was performed to identify the phenolic compounds with the highest intestinal absorption and Caco-2 permeability. The avocado peel extract possessed the highest content of phenolic compounds (309.95 ± 25.33 mMol GA/100 g of extract) and the lowest effective concentration (EC50) against DPPH and ABTS radicals (72.64 ± 10.70 and 181.68 ± 18.47, respectively). On the other hand, the peel and seed coat extracts had the lowest energy densities (226.06 ± 0.06 kcal/100g and 219.62 ± 0.49 kcal/100g, respectively). Regarding the antiproliferative activity, the avocado peel extract (180 ± 40 µg/mL) showed the lowest inhibitory concentration (IC50), followed by the seed (200 ± 21 µg/mL) and seed coat (340 ± 32 µg/mL) extracts. The IC50 of the extracts induced apoptosis in Caco-2 cells at the early and late stages. According to the in-silico analysis, these results could be related to the higher Caco-2 permeability to hy-droxysalidroside, salidroside, sakuranetin, and luteolin. Therefore, this study provides new insights regarding the potential use of these extracts as functional ingredients with antioxidant and antiproliferative properties and as medicinal agents in diseases related to oxidative stress such as cancer. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Therapeutic molecules for osteoarthritis treatment. role of phloretin, ipriflavone and raloxifene in lipopolysaccharide induced osteoarthritic chondrocytes

Purpose: The search of novel molecules for the treatment of osteoarthritis (OA) is complex as any new therapeutic approach should encompass these requirements: inhibition of cartilage degradation, protection of bone and inhibition of inflammation. In the last years, different drugs have been proposed though most of them did not succeed in fulfil these requirements. Moreover, few of them have been encapsulated in drug delivery systems to improve their therapeutic potential to achieve a sustained or controlled release compared to the administration of equivalent doses of the free compounds. Nanoscience has arisen in the last decades as a potential field of study in drug delivery because nanomaterials may overcome the main current limitations to achieve an efficient and localized drug delivery by improving the targeted delivery and providing a sustained or controlled delivery to prolong the therapeutic effect. On the other hand, different polyphenols and aromatic organic compounds are known to possess anti-inflammatory, antioxidant and bone density-building properties..

First imported case of tick-borne encephalitis in Spain - was it alimentary?

As described by Kerlik, et al, tick-borne encephalitis (TBE) is an emerging infectionin Europe and alimentary transmission is increasingly being reported in some European countries[1,2]. However, this is not the case in Spain where no previous cases have been reported [2,3]. Herein, we describe an imported case of TBE in Spain in a boy who probably acquired the virus by ingestion of contaminated milky products in a trip to Estonia

Generación y caracterización metabólica del ratón carente de la proteína 5 con dominios tiorredoxina (TXNDC5) y su interacción con el escualeno

Actualmente, las herramientas ómicas tienen una potencia sin precedentes, permitiendo encontrar dianas moleculares cuyas funciones no habían sido previamente descritas. Previamente, nuestro grupo describió como la presencia del escualeno en dieta tenía propiedades anti ateroescleróticas y anti esteatósicas. Usando herramientas proteómicas, se encontró la proteína 5 con dominios tiorredoxina (TXNDC5) modulada por el escualeno y asociada con el contenido de grasa hepática. TXNDC5 es una proteína disulfuro isomerasa, encargada de regular el correcto plegamiento de proteínas, actuando como chaperona en el retículo. Sin embargo, las funciones de TXNDC5 y en especial su papel metabólico en el hígado están poco definidas. Esclarecer las funciones de una proteína con potencialmente muchas implicaciones es un proceso fundamental para la ciencia básica, especialmente si pudiera estar implicada en la prevención de enfermedades cardiovasculares o esteatosis.En el presente trabajo, utilizando las nuevas herramientas de edición genética CRISPR/cas9 se generó un modelo animal carente de TXNDC5, y una línea celular hepática que replicase el modelo animal. Para ahondar en el conocimiento de la implicación de TXNDC5, se realizaron varias intervenciones dietéticas. Bajo una dieta occidental se encontró en machos un hígado con un contenido más graso en la ausencia de TXNDC5, por ello se decidió estudiar su transcriptoma, encontrándose una mayor expresión de los genes de fase aguda, amiloide sérico 1 y 2 (Saa1 y Saa2) en ausencia de la tiorredoxina. Debido a la previa implicación en aterosclerosis, se estudió la influencia de TXNDC5 en el perfil plasmático, encontrándose una mayor cantidad de amiloide sérico, APOA1 y actividad PAF-AH, sin embargo, también se encontraron mayores niveles de peroxidación lipídica. La caracterización lipoproteica no reveló diferencias en su perfil, localizándose el amiloide principalmente en las partículas de alta densidad nacientes, curiosamente menos oxidadas en ausencia de TXNDC5. Este hecho ofrece un nuevo punto de vista en la influencia del amiloide, previamente descrito como un marcador aterosclerótico. Aunque se había descrito una posible función de TXNDC5 en el plegamiento de la insulina, los experimentos in vivo de este trabajo resumen una menor glicemia acompañada de un aumento de los ácidos grasos no esterificados en plasma. Se realizó una caracterización metabólica en la que no se observó implicación en la gluconeogénesis, pero una mayor sensibilidad a la insulina en ausencia de TXNDC5. Bajo una dieta más agresiva, se observó un resultado similar: una mayor tolerancia a la glucosa y sensibilidad a la insulina, una menor glicemia acompañada de los mayores niveles de ácidos grasos no esterificados y unos sorprendentes mayores niveles de insulina en plasma. Por último, la ausencia de TXNDC5 impide la acumulación de escualeno en el hígado murino, verificando la implicación previamente observada. Este hecho se reprodujo en las gotas lipídicas, orgánulo propuesto para su acumulación, por lo que se realizó una caracterización del proteoma del orgánulo. Se observó no solo la implicación de TXNDC5 sino como el cambió de un único componente en la dieta es capaz de modular su proteoma. Se encontraron varias proteínas moduladas por el escualeno, como TXNDC5, siendo CALR y APMAP influidas también por la tiorredoxina, pudiendo estar implicadas en el mecanismo de acumulación.Todos estos resultados que se describen en este trabajo, unidos al hecho de que solamente se encontraron cambios en machos, dimorfismo sexual similar al experimento inicial, confirman la gran complejidad de TXNDC5 en su función y en los mecanismos moleculares en los que intervienen como se detalla el este trabajo. <br /

ERK5 Inhibition Induces Autophagy-Mediated Cancer Cell Death by Activating ER Stress

ERK5 kinase; Antitumor drug; ApoptosisKinasa ERK5; Medicament antitumoral; ApoptosiQuinasa ERK5; Medicamento antitumoral; ApoptosisAutophagy is a highly conserved intracellular process that preserves cellular homeostasis by mediating the lysosomal degradation of virtually any component of the cytoplasm. Autophagy is a key instrument of cellular response to several stresses, including endoplasmic reticulum (ER) stress. Cancer cells have developed high dependency on autophagy to overcome the hostile tumor microenvironment. Thus, pharmacological activation or inhibition of autophagy is emerging as a novel antitumor strategy. ERK5 is a novel member of the MAP kinase family that is activated in response to growth factors and different forms of stress. Recent work has pointed ERK5 as a major player controlling cancer cell proliferation and survival. Therefore small-molecule inhibitors of ERK5 have shown promising therapeutic potential in different cancer models. Here, we report for the first time ERK5 as a negative regulator of autophagy. Thus, ERK5 inhibition or silencing induced autophagy in a panel of human cancer cell lines with different mutation patterns. As reported previously, ERK5 inhibitors (ERK5i) induced apoptotic cancer cell death. Importantly, we found that autophagy mediates the cytotoxic effect of ERK5i, since ATG5ˉ/ˉ autophagy-deficient cells viability was not affected by these compounds. Mechanistically, ERK5i stimulated autophagic flux independently of the canonical regulators AMPK or mTORC1. Moreover, ERK5 inhibition resulted in ER stress and activation of the Unfolded Protein Response (UPR) pathways. Specifically, ERK5i induced expression of the ER luminal chaperone BiP (a hallmark of ER stress), the UPR markers CHOP and ATF4, and the spliced form of XBP1. Pharmacological inhibition of UPR with chemical chaperone TUDC, or ATF4 silencing, resulted in impaired ERK5i-mediated UPR, autophagy and cytotoxicity. Overall, our results suggest that ERK5 inhibition induces autophagy-mediated cancer cell death by activating ER stress. Since ERK5 inhibition sensitizes cancer cells and tumors to chemotherapy, future work will determine the relevance of UPR and autophagy in the combined use of chemotherapy and ERK5i to tackle Cancer.This work was supported by the Spanish Ministry of Economy and Competitiveness (MINECO, grant SAF2015-64237-R), the Spanish Ministry of Science and Innovation (Grant PID2019-107561RB-I00), and cofounded by the European Regional Development Fund (ERDF)

Oxidation of End-Capped Pentathienoacenes and Characterization of Their Radical Cations

A detailed investigation of the optical and electrochemical properties of two pentathienoacene derivatives, 2,6-bis(trimethylsilyl)-Α-pentathienoacene ( TMS-T5-TMS ) and 2,6-bis(triisopropylsilyl)-Α-pentathienoacene ( TIPS-T5-TIPS ), as the neutral and oxidized species was performed in the temperature range of 80–300 14K. The experimental solution UV/Vis and solid-state Raman spectra were interpreted by using time-dependent DFT and DFT quantum chemical calculations at the B3LYP/6-31G** level. Bond lengths, HOMO–LUMO positions, and charge distribution were also predicted by computational methods for both the neutral and oxidized states of each thienoacene. As evidenced by ESR and spectroelectrochemical data, upon oxidation the pentathienoacene derivative with the less sterically hindering trimethylsilyl solubilizing groups, TMS-T5-TMS , undergoes Π 14dimerization to form [ TMS-T5-TMS ] 2 2+ . In contrast, TIPS-T5-TIPS , with the more bulky triisopropylsilyl solubilizing groups, was oxidized to the radical cation but dimerization was prevented due to steric interactions. These experimental observations are supported by DFT calculations, which were used to investigate [ TMS-T5-TMS ] 2 2+ and [ TIPS-T5-TIPS ] 2 2+ Π 14dimers in the solid state and in solution. The redox potentials and absorption peak locations corresponding to the radical cations and Π 14dimer of TMS-T5-TMS were identified experimentally.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/64441/1/chem_200900246_sm_miscellaneous_information.pd