Presentación de todas las pruebas científicas en la efectividad de ayudas ergonutricionales para mejorar el rendimiento y salud de deportistas: revisión de revisiones sistemática

VIII Congreso Iberoamericano de Nutrición. ¿Nutrición basada en la videncia o en la evidencia

Anteproyecto de un Parque Eólico en la isla de San Andrés, Colombia financiado parcialmente por la comunidad local

Treballs Finals del Màster d’Energies Renovables i Sostenibilitat Energètica, Facultat de Física, Universitat de Barcelona. Curs: 2021-2022. Tutor: Cristian Fàbrega GallegoThis document is a preliminary project for a wind energy generation farm of a single wind turbine, located in the highest and most suitable part of the island of San Andres, Colombia, which will be funded through three financing systems: crowdfunding, a traditional loan and direct investment from the local population. For the selection of the wind turbine, statistical techniques such as the Weibull and Rayleigh probability density distributions and other methods were used to calculate a seasonal yield of 31% and a load factor of 50% at a height of 82 metres for the Vestas V136 wind turbine with a rated power of 3.5 MW. Also, based on the analyses carried out in this preliminary project, it is estimated that the selected wind turbine will produce 15.12 GWh of electrical energy annually, which will save 8% of the CO2 emissions currently emitted by the island as a result of electricity generation. The energy generated by the wind turbine must be sold within the price range of 5.85 to 8.5 cUSD/kWh for the project to be financially viable. In this same range the IRR runs from 7.41% to 17.19% and the payback time can range from 10 to 5 years. The total cost of the investment in the wind farm is estimated at 4.31 million dollars and the annual operating cost is around 400 thousand dollars. The preliminary project concludes with a proposal for a mechanism that allows the local community, beyond just participating as investors, to be part of the decision-making process regarding the project

Importancia del inicio de la terapia hormonal sustitutiva con estrógenos sobre parámetros de estrés oxidativo y consumo de glucosa in vivo

La esperanza de vida se dobló en Europa en el siglo XX. En cualquier etapa de la historia reciente, las mujeres superan en longevidad media a los hombres (hasta un 9.9%). Aunque la base es desconocida, no es atribuible exclusivamente a diferencias sociales, ya que por ejemplo las ratas Wistar hembras viven un 16% más que los machos y en este caso ambos están sometidos a las mismas “condiciones sociales”. Este hecho ha interesado desde hace años a la comunidad científica, publicándose numerosos artículos que han demostrado que estas diferencias de longevidad se fundamentan en parte en diferencias de estrés oxidativo. Los machos poseen un mayor estrés oxidativo que las hembras, pues éstas están protegidas frente al mismo por los estrógenos. Además, se han utilizado los estrógenos como prevención y tratamiento ante diversas patologías (cardiovasculares, neurodegenerativas, etc.) y por su efecto antioxidante, tanto in vivo como in vitro, pero que, en las mujeres, se pierde al aparecer la menopausia. Estudiar las bases moleculares de estas diferencias en relación con la teoría del envejecimiento de los radicales libres y los efectos positivos de la reposición de estrógenos en distintos períodos post-menopausia ha sido el objetivo de la investigación realizada. Para realizar el estudio se planificaron varios protocolos y métodos que se explican a continuación. Se utilizaron ratas hembras Wistar jóvenes (3-4 meses) y viejas (24 meses). Se realizó la ovariectomía de 39 ratas (jóvenes) con un grupo control incluido (SHAM operated) siguiendo un diseño que consistió en: grupo Operación SHAM (n=5) de 3 semanas. OVX 3, 6 ó 9 (semanas tras Ovariectomía), OVX 3E, 3+3E ó 6+3E (semanas tras Ovariectomía más semanas de administración diaria de Estradiol disuelto en vehículo) y OVX 3V, 3+3V ó 6+3V (semanas tras Ovariectomía más semanas de administración diaria de vehículo). Posteriormente, se estudiaron mediante tomografía por emisión de positrones (PET) su metabolismo cerebral de glucosa (diferenciando, además entre un grupo de animales jóvenes y viejos para ver el efecto del envejecimiento) y se sacrificaron, tras los periodos anteriores, los distintos grupos. Entre las medidas realizadas están la determinación de parámetros de estrés oxidativo en diferentes órganos y en mitocondrias aisladas de hígado (MDA, GPx, producción de peróxidos) mediante técnicas de Western Blotting, espectrofotometría y HPLC. Con el plasma sanguíneo se realizó un estudio de los metabolitos presentes por Resonancia Magnética Nuclear (RMN) y obtuvimos el perfil metabólico. En ratas ovariectomizadas disminuye significativamente la actividad de la enzima Glutatión Peroxidasa (GPx) a las 3 semanas, mientras que se revierte con la reposición con estrógenos y no al administrar el vehículo solo (control). Este hecho se repite también cuando el periodo de reposición con estrógenos es más grande (6 y 9 semanas) aunque la disminución en la actividad de la enzima no disminuye tanto como en las semanas siguientes a la ovariectomía (3 semanas primeras) y su recuperación hasta niveles normales también decrece, obteniendo valores similares en la oxidación a lípidos (MDA) y en la producción de peróxido de hidrógeno. En cuanto al consumo de glucosa mediante PET, los resultados indican una disminución con el envejecimiento y ponen de manifiesto el beneficio del tratamiento con estrógenos, solamente si se inicia el tratamiento inmediatamente tras instaurarse la menopausia (ovariectomía). Igualmente ocurre en el perfil metabólico analizado mediante metabolómica (RMN). El tratamiento con estradiol parece ser sólo efectivo si la reposición se produce inmediatamente tras la instauración de la menopausia, y deja de serlo si esperamos varias semanas para comenzarlo. Se hacen necesarios más estudios con animales de laboratorio para extrapolar sus resultados correctamente a los tratamientos en humanos y, así, poder extraerse conclusiones de aplicación clínica.Females live longer than males in many mammalian species, including humans. This natural phenomenon can be explained on the basis of the mitochondrial theory of aging. Mitochondria are a major source of free radicals in cells. Mitochondria from female rats generate half the amount of hydrogen peroxide than those of males and have higher levels of mitochondrial reduced glutathione. The results of this thesis show that the mitochondria from ovariectomized rats (sacrificed at 3, 6, and 9 weeks -OVX 3, 6 and 9- after surgery) generate higher hydrogen peroxide levels than controls (Sham) but are diminished only if estrogen replacement therapy (ERT) is initiated immediately after induced menopause [there were groups which were given 1 μg/kg/day subcutaneously of 17β-estradiol for three weeks, starting the day after surgery (OVX 3E) or three or six weeks later, for the same period of three weeks (OVX 3+3E and OVX 6+3E)]. The same pattern occurs with glutathione peroxidase (GPx) enzymatic activity in mitochondria showing an increase in this antioxidant enzyme and a recovery of oxidative damage to lipids in heart and plasma after the negative effects produced by ovariectomy. Aging and induced menopause decrease the brain glucose uptake in vivo measured by Positron Emission Tomography (PET) and ERT is only relatively beneficial in the immediate treatment group. This “critical time” to initiate the treatment after ovariectomy reflects similar metabolomic profiles (by Nuclear Magnetic Resonance, NMR) compared with control and young rat groups. The challenge for the future is to find a molecular mechanism that can explain the beneficial effects of ERT and to discover if there are molecules which mimic these effects too

Regulación redox del proteoma, el metabolismo y la señalización en células tumorales de hepatocarcinoma

The redoxins Thioredoxin (Trx), Glutaredoxin (Grx) and Peroxiredoxins (Prdx) play a very important role both in the maintenance of redox homeostasis and in signaling through reversible oxidation/reduction reactions in cysteine residues key to the regulation of protein function. The main objective of this project is to demonstrate that redoxins exert a role in the control of metabolic flux of tumor cells by regulating the redox state of metabolic enzymes and proteins involved in cell signaling. To study the functions of human Trx1 and Grx1, we have used the hepatocarcinomaderived HepG2 cell line as an experimental model under both normal and oxidative/nitrosative conditions. We have shown that silencing of Trx1 or Grx1 causes major changes in the redox proteome reflected in significant changes in the reduced/oxidized ratio of enzyme cysteines such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH) Cys247 and triosephosphate isomerase (TPI) Cys255 that affect their activity. Trx1 silencing increases glycolytic flux and induces membrane remodelling as indicated by the increase in sphingomyelins and ceramides. On the other hand, Grx1 silencing decreases the glycolytic fluxand increases the synthesis of fatty acids and phospholipids stimulating lipogenesis. These results indicate that, although both redoxins have some common target cysteines, their down-regulation causes different metabolic changes. Among the redox targets of Grx1 is the “extra” non-peroxidatic Cys91, of Prdx6, the only member of the 1-Cys peroxiredoxin family in humans, which in addition to having characteristic peroxidase activity is the only one that also has phospholipase A2 activity calcium independent (iPLA2). Prdx6 silencing in HepG2 cells decreases proliferation and increases cell volume without changing the number of cells; decreases the rate of glucose entry and nucleotide biosynthesis while the levels of amino acids, polyamines, phospholipids and most glycolipids increase. Changes in the global proteome reflect an increase in vesicle traffic while the redox proteome shows changes in various enzymes among which are hexokinase 2 (HK2) Cys368, phosphoenolpyruvate carboxykinase 2 (PCK2) Cys55-63, and 3-phosphoglycerate dehydrogenase (PHGDH) Cys18-19 and Cys281. These results indicate that Prdx6 silencing induces both a predominant metabolic remodelling towards a glyconeogenic flow from amino acids with diversion at the synthesis of serine and other biosynthetic pathways, as well as cell cycle arrest at G1/S transition. It remains to be determined which Prdx6 activity is responsible for these effects, whether its peroxidase or PLA2 or both and what are the detailed mechanisms that lead to these effects The next step has been to verify whether these actions of the studied redoxins also take place in advanced states of hepatocarcinoma in which resistance to the standard treatment with Sorafenib is frequent. In line with this, a study has been carried out in three hepatocarcinoma cell lines with different degrees of epithelialmesenchymal transition and therefore with increasing invasive potential and malignancy (HepG2, SNU423 and SNU475), treated with Sorafenib and/or silenced for Trx1. This drug is jnown as a tyrosine kinase inhibitor and we have observed that treatment with Sorafenib induces reductive changes in key tumor signaling proteins, such as STAT3, MAPK and Akt, in the three cell lines but large changes in the global proteome have only been seen in cells of intermediate dedifferentiation state (SNU423). Silencing of Trx1 does not have a great effect on the overall proteome of the three cell lines but it does counteract the reducing effect of Sorafenib on a thiol group at STAT3 and sensitizes the more mesenchymal hepatocarcinoma cell line (SNU475) against Sorafenib, inactivating TGFß1 pathway and stimulating HIPPO signaling. Therefore, these results support the idea that the combined treatment of Sorafenib with Trx1 inhibitors could help to design more effective therapies against advanced hepatocarcinoma resistant to Sorafenib.Las redoxinas Tiorredoxina (Trx), Glutarredoxina (Grx) y Peroxirredoxina (Prdx) juegan un papel muy importante tanto en el mantenimiento de la homeostais redox como en señalización a través de reacciones de oxido/reducción reversibles en residuos de cisteína claves para la regulación de la función de la proteína. El objetivo principal de este proyecto es estudiar las funciones de las redoxinas en señalización celular y metabolismo en líneas celulares derivadas de hepatocarcinoma sometidas o no a altos niveles de óxido nítrico. Para el estudio de las funciones de la Trx1 y Grx1 hemos empleado como modelo experimental la línea celular derivada de hepatoblastoma (HepG2) bajo condiciones normales y de estrés oxidativo/nitrosativo. Hemos demostrado que el silenciamiento de Trx1 o Grx1 provoca grandes cambios en el proteoma redox tiólico reflejado en cambios significativos en la ratio reducido/oxidado de cisteínas de enzimas como la Cys247 de la gliceraldehido-3-fosfato deshidrogenasa (GAPDH) y Cys255 de la triosafosfato isomerasa (TPI) los cuales afectan a la actividad de dichas enzimas. El silenciamiento de Trx1 aumenta el flujo glucolítico e induce remodelamiento de la membrana lipídica como indica el incremento de esfingomielinas y ceramidas. Por otro lado, el silenciamiento de Grx1 disminuye el flujo glucolítico y aumenta la síntesis de ácidos grasos y fosfolípidos estimulando lipogenesis. Los resultados indican que, a pesar de que ambas redoxinas tengan algunas cisteínas diana comunes, su silenciamiento provoca cambios metabólicos diferentes. Entre las dianas redox de la Grx1 se encuentra la Cys91, no peroxidática, de la Prdx6, el único miembro de la familia de las peroxiredoxinas de 1-Cys en humanos, que además de poseer la actividad peroxidasa característica, es la única que presenta actividad actividad fosfolipasa A2 independiente de calcio (iPLA2). El silenciamiento de Prdx6 en HepG2 disminuye la proliferación y el número de células mientras que el volumen celular aumenta. Además la entrada de glucosa y la biosíntesis de nucleótidos disminuyen mientras que los niveles de amino ácidos, poliaminas, fosfolípidos y la mayoría de glicolípidos aumentan. El efecto del silenciamiento de Prdx6 sobre el proteoma global muestra un aumento en el tráfico de vesículas mientras que el proteoma redox muestra cambios en diversas enzimas de rutas metabólicas entre las que se encuentran la Cys368 de la hexoquinasa 2 (HK2), la Cys55-63 de la fosfoenolpiruvato carboxiquinasa 2 (PCK2), y las Cys18-19 y Cys281 de la 3-fosfoglicerato deshidrogenasa (PHGDH). Los resultados indican que el silenciamiento de Prdx6 induce tanto un remodelamiento metabólico predominante hacia gluconeogénesis desde amino ácidos con desviación hacia la síntesis de serina y otras vías biosintéticas, así como detención del ciclo celular en la transición G1/S. Está por determinar qué actividad de la Prdx6 es responsable de estos efectos, si su peroxidasa o la PLA2 o ambas y cuáles son los mecanismos detallados que conducen a esos efectos. El siguiente paso ha sido comprobar si estas acciones de las redoxinas estudiadas tienen lugar igualmente en estados avanzados de hepatocarcinoma en los que se suele dar una resistencia al tratamiento estándar con Sorafenib. En línea con esto, se ha llevado a cabo un estudio en tres líneas celulares de hepatocarcinoma con distinto grado de transición epitelio-mesenquimal y por tanto, con mayor potencial de invasividad y malignicidad (HepG2, SNU423 y SNU475), tratadas con Sorafenib y/o silenciando la Trx1. El Sorafenib es un medicamento conocido por su actividad como un inhibidor de tirosinas quinasas y nosotros hemos observado que el tratamiento con Sorafenib induce cambios reductores en proteínas clave de señalización tumoral, tales como STAT3, MAPK y Akt, en las tres líneas celulares pero los grandes cambios en el proteoma global se han visto únicamente en células en estado intermedio de desdiferenciación (SNU423). El silenciamiento de Trx1 no tiene un gran efecto en el proteoma global de las tres líneas pero sí contrarresta el efecto reductor del Sorafenib sobre un grupo tiol de STAT3 y sensibiliza a las células de hepatocarcinoma más mesenquimales (SNU475) frente al Sorafenib, inactivando la vía de TGFß1 y estimulando la vía de señalización HIPPO. Por lo tanto, los resultados apoyan la idea de que el tratamiento combinado de Sorafenib con inhibidores de la Trx1 podría ayudar al diseño de terapias más efectivas contra el hepatocarcinoma en estado avanzado resistente a Sorafenib

Corporate Social Responsibility and Peacebuilding: Analysis of a multinational company from Colombia

Resumen La presente investigación busca comprender de qué manera una multinacional 1 colombiana contribuye a la construcción de paz, a través del desarrollo de prácticas de Responsabilidad Social Empresarial -RSE- y conocer cuáles son los retos que enfrenta para que este ejercicio adopte un énfasis en construcción de paz. Para tal efecto, el estudio revisa los informes de sostenibilidad correspondientes al período 2010-2015 publicados por una multinacional que opera en Colombia y los analiza mediante el diseño de teoría fundamentada. Los resultados obtenidos muestran que la multinacional ha contribuido a la construcción de paz en el país, a través de su ejercicio de RSE, por medio de: la orientación hacia el desarrollo de sus stakeholders, la implementación de alianzas estratégicas, el enfoque de derechos humanos en las relaciones que establece con sus grupos de interés, el apoyo al emprendimiento, el impulso al desarrollo local y el impacto en el desarrollo económico y social del país. Con relación a los retos que enfrenta la multinacional analizada para alcanzar un ejercicio de RSE con énfasis en la construcción de paz se encuentra que esta requiere fortalecer la participación en acciones de reconciliación, el análisis del contexto en el que opera, la participación en procesos de negociación de paz, la vinculación laboral de excombatientes irregulares, así como, ampliar la visión de gestión de la diversidad y trascender de la perspectiva de prevención a la de promoción de la salud.Abstract The present research seeks to comprehend in what manner a Colombian multinational1 contributes to peacebuilding through Corporate Social Responsibility-CSR- practices development, and to know what challenges it faces in order for this exercise to adopt a peacebuilding emphasis. To that end, this study reviews sustainability reports corresponding to the 2010-2015 period published by a multinational operating in Colombia and analyses them by means of grounded theory design. The results obtained show that the multinational has contributed to our country’s peacebuilding through the exercise of its CSR by means of: orientation towards its stakeholders’ development, implementing strategic alliances, human right focus on the relationships established with its groups of interest, supporting entrepreneurship, boosting local development and the impact on our country’s economic and social development. With regards to the challenges faced by the analyzed multinational in order to reach a CSR exercise with emphasis on peacebuilding, it was found that it needs to strengthen its participation in reconciliation acts, analysis of the context in which it operates, participation in peace negotiation processes, work incorporation of irregular ex-combatants, as well as to widen its managerial vision of diversity and transcend from a perspective of prevention to health promoting

Intracellular virion traffic to the endosome driven by cell type specific sialic acid receptors determines parvovirus tropism

Parvoviruses are promising anticancer and gene therapy agents, but a deep knowledge of the entry process is crucial to exploit their therapeutic potential. We addressed this issue while attempting to retarget the oncolytic parvovirus minute virus of mice (MVMp) to the tumor vasculature. Residues at three functional domains of the icosahedral capsid were substituted by rational design with peptides competing with the vascular endothelial growth factor. Most substitutions impaired virus maturation, though some yielded infectious chimeric virions, and substitutions in a dimple at the twofold axis that allocates sialic acid (SIA) receptors altered viral tropism. One dimple-modified chimeric virion was efficiently attached as MVMp to α2-linked SIA moieties, but the infection was impaired by the binding to some inhibitory α2-3,-6,-8 SIA pseudoreceptors, which hampers intracellular virus traffic to the endosome in a cell type-dependent manner. Infectious from nonproductive traffic could be mechanistically discriminated by an endosomal drastic capsid structural transition comprising the cleavage of some VP2-Nt sequences and its associated VP1-Nt exposure. Correspondingly, neuraminidase removal of inhibitory SIA moieties enhanced the infection quantitatively, correlating to the restored virus traffic to the endosome and the extent of VP2-Nt cleavage/VP1-Nt exposure. This study illustrates (i) structural constraints to retarget parvoviruses with evolutionary adopted narrow grooves allocating small SIA receptors, (ii) the possibility to enhance parvovirus oncolysis by relaxing the glycan network on the cancer cell surface, and (iii) the major role played by the attachment to cell type-specific SIAs in the intracellular virus traffic to the endosome, which may determine parvovirus tropism and host rang

Deficiency of Parkinson’s Related Protein DJ-1 Alters Cdk5 Signalling and Induces Neuronal Death by Aberrant Cell Cycle Re-entry

DJ-1 is a multifunctional protein involved in Parkinson disease (PD) that can act as antioxidant, molecular chaperone, protease, glyoxalase, and transcriptional regulator. However, the exact mechanism by which DJ-1 dysfunction contributes to development of Parkinson’s disease remains elusive. Here, using a comparative proteomic analysis between wild-type cortical neurons and neurons lacking DJ-1 (data available via ProteomeXchange, identifier PXD029351), we show that this protein is involved in cell cycle checkpoints disruption. We detect increased amount of p-tau and α-synuclein proteins, altered phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signalling pathways, and deregulation of cyclin-dependent kinase 5 (Cdk5). Cdk5 is normally involved in dendritic growth, axon formation, and the establishment of synapses, but can also contribute to cell cycle progression in pathological conditions. In addition, we observed a decrease in proteasomal activity, probably due to tau phosphorylation that can also lead to activation of mitogenic signalling pathways. Taken together, our findings indicate, for the first time, that aborted cell cycle re-entry could be at the onset of DJ-1-associated PD. Therefore, new approaches targeting cell cycle re-entry can be envisaged to improve current therapeutic strategies

Influence of Training Load on Mood Disturbance at Sea Level and 3900 m Altitude: A Case Study of a Wheelchair Athlete

The purpose of this case study was to investigate the influence of a training load (TL), oxygen saturation (SO2) and blood pressure (BP) on mood states in a wheelchair marathoner during (7 weeks at sea level (SL), 5 weeks at 3860 m altitude, 1 week returning to SL). TL was obtained with Foster's equation while mood states were obtained with the Profile of Mood States Questionnaire (POMS). Furthermore, SO2 and BP were assessed upon wakening. SO2 (%) decreased at altitude, compared to SL (88.31 ± 2.46 vs. 98.52 ± 0.11) and increased until the last week at altitude (92.64 ± 1.12). Systolic pressure (SP) increased at altitude compared to pre-altitude (126.0 ± 5.1 vs. 107.6 ± 4.4 mmhg), and was not different from the last week at altitude. Controlling for SO2 and SP, differences were also observed in fatigue (97.66 ± 18.92 vs. 17.39 ± 13.71) and vigor (73.23 ± 8.62 vs. 26.48 ± 11.89) as a function of altitude. Upon return to SL, fatigue, vigor, SO2 and SP returned to pre values. This case study demonstrated the POMS was sensitive to worsening patterns in fatigue and vigor at altitude through a practical survey approach combined with daily physiological assessment

Hematological and ventilatory responses to a 3900 m altitude sojourn in an elite wheelchair-marathoner.

This case study aimed to report blood markers and resting respiratory rate (RR) oscillations at sea level, during a 5-wk 3900 m altitude sojourn, and after returning to sea level in a 36-year-old professional wheelchair marathoner. Outcome measures plasma erythropoietin (EPO) concentration, hemoglobin, reticulocytes count, erythrocytes and hematocrit as well as RR were measured upon wakening 7-weeks pre-altitude, 7-days pre-altitude, 35 hours after arrival to altitude, on days 8, 15, 21, 28 and 35 at altitude, 6 and 16 days after returning to sea level. EPO increased up to 259 % (31.6 U l-1) 35 hours upon arrival at altitude and decreased below pre-altitude level (12.2 U l-1) on the 21st day of the camp (8.7 U l-1), reaching the lowest values 16 days after returning from altitude (1.9 U l-1). All blood parameters, except for reticulocytes, increased (range: +17.9 to +23.8%) after 35 days of altitude exposure. Compared to pre-altitude, RR increased during the first week of exposure to hypoxic conditions and remained elevated throughout the camp until the fifth week (5.1±0.4 vs. 9.1±1.6 and 6.6±0.8 breaths min-1; Cohen´s d = +3.4 and +2.4, respectively). A 5-wk high-altitude sojourn triggered polycythemia and elevations in RR (as indicators of effective hypoxic acclimatization) in a professional wheelchair-marathoner

Thioredoxin Downregulation Enhances Sorafenib Effects in Hepatocarcinoma Cells

Sorafenib is the first-line recommended therapy for patients with advanced hepatocarcinoma (HCC) in de-differentiation stage (presenting epithelial–mesenchymal transition, EMT). We studied the role of the thioredoxin system (Trx1/TrxR1) in the sensitivity or resistance of HCC cells to the treatment with Sorafenib. As a model, we used a set of three established HCC cell lines with different degrees of de-differentiation as occurs in metastasis. By quantitative proteomics, we found that the expression levels of Trx1 and TrxR1 followed the same trend as canonical EMT markers in these cell lines. Treatment with Sorafenib induced thiol redox reductive changes in critical elements of oncogenic pathways in all three cell lines but induced drastic proteome reprograming only in HCC cell lines of intermediate stage. Trx1 downregulation counteracted the thiol reductive effect of Sorafenib on Signal Transducer and Activator of Transcription 3 (STAT3) but not on Mitogen-Activated Protein Kinase (MAPK) or Protein Kinase B (Akt) and transformed advanced HCC cells into Sorafenib-sensitive cells. Ten targets of the combined Sorafenib–siRNATrx1 treatment were identified that showed a gradually changing expression trend in parallel to changes in the expression of canonical EMT markers, likely as a result of the activation of Hippo signaling. These findings support the idea that a combination of Sorafenib with thioredoxin inhibitors should be taken into account in the design of therapies against advanced HCC.Ministerio de Economía y Competitividad BFU2016-80006-PInstituto de Salud Carlos III (ISCIII) PI13/00021 y PI16/00090Junta de Andalucía Consejería de Economía, Innovación, Ciencia y Empleo BIO-0216 y CTS-6264Junta de Andalucía Consejería de Igualdad, Salud y Políticas Sociales PI-00025-2013 y PI-0198-201