Novel therapeutic avenues for the study of chronic liver disease and regeneration: The foundation of the Iberoamerican Consortium for the study of liver Cirrhosis / Nuevas dianas terapéuticas para el estudio de la enfermedad hepática crónica: la creación del Consorcio Iberoamericano para el estudio de la cirrosis hepática

Unfortunately, there is a gap of understanding in the pathophysiology of chronic liver disease due to the lack of experimental models that exactly mimic the human disease. Additionally, the diagnosis of patients is very poor due to the lack of biomarkers than can detect the disease in early stages. Thus, it is of utmost interest the generation of a multidisciplinary consortium from different countries with a direct translation. The present reports the meeting of the 2021 Iberoamerican Consortium for the study of liver Cirrhosis, held online, in October 2021. The meeting, was focused on the recent advancements in the field of chronic liver disease and cirrhosis with a specific focus on cell pathobiology and liver regeneration, molecular and cellular targets involved in non-alcoholic hepatic steatohepatitis, alcoholic liver disease (ALD), both ALD and western diet, and end-stage liver cirrhosis and hepatocellular carcinoma. In addition, the meeting highlighted recent advances in targeted novel technology (-omics) and opening therapeutic avenues in this field of research.(AU)

Desafortunadamente, existe una brecha sobre la comprensión en la fisiopatología de la enfermedad hepática crónica debido a la falta de modelos experimentales que recapitulan con exactitud la enfermedad humana. Además, el diagnóstico de los pacientes es muy pobre debido a la falta de biomarcadores que puedan detectar la enfermedad en etapas tempranas. Por ello, es de sumo interés la generación de un consorcio multidisciplinar de diferentes países con una traducción directa. El presente artículo informa sobre la reunión del Consorcio Iberoamericano para el estudio de la cirrosis hepática 2021, celebrado de manera virtual en octubre del 2021. La reunión se centró en los avances recientes en el campo de la enfermedad hepática crónica y la cirrosis, con un enfoque específico en la patobiología celular y regeneración hepática, dianas moleculares y celulares involucradas en la esteatohepatitis hepática no alcohólica, la enfermedad hepática alcohólica (ALD), tanto la ALD como la dieta occidental, y la cirrosis hepática en etapa terminal y el carcinoma hepatocelular. Además, la reunión destacó los avances recientes en tecnología (ómica) y la apertura de vías terapéuticas en este campo de investigación.(AU)

Novel therapeutic avenues for the study of chronic liver disease and regeneration: The foundation of the Iberoamerican Consortium for the study of liver Cirrhosis.

Unfortunately, there is a gap of understanding in the pathophysiology of chronic liver disease due to the lack of experimental models that exactly mimic the human disease. Additionally, the diagnosis of patients is very poor due to the lack of biomarkers than can detect the disease in early stages. Thus, it is of utmost interest the generation of a multidisciplinary consortium from different countries with a direct translation. The present reports the meeting of the 2021 Iberoamerican Consortium for the study of liver Cirrhosis, held online, in October 2021. The meeting, was focused on the recent advancements in the field of chronic liver disease and cirrhosis with a specific focus on cell pathobiology and liver regeneration, molecular and cellular targets involved in non-alcoholic hepatic steatohepatitis, alcoholic liver disease (ALD), both ALD and western diet, and end-stage liver cirrhosis and hepatocellular carcinoma. In addition, the meeting highlighted recent advances in targeted novel technology (-omics) and opening therapeutic avenues in this field of research.

Identification of proteins that allow to distinguish subjects with and without Recurrent Aphthous Stomatitis / IDENTIFICACIÓN DE PROTEÍNAS QUE PERMITAN DISTINGUIR SUJETOS CON Y SIN ESTOMATITIS AFTOSA RECURRENTE

Recurrent aphthous stomatitis (RAS) is the most common ulcerative disease of the oral mucosa. Currently, the therapeutic alternatives are only palliative and limited, due to a poor understanding of the etiopathogenic process. The objective of this study is to identify proteins that allow distinguishing between groups of subjects with and without Recurrent Aphthous Stomatitis, to understand the processes that control health and disease states. In this case-control study, we evaluated by means of proteomics based on mass spectrometry the saliva of healthy controls and patients with recurrent aphthous stomatitis during the presence and absence of lesions. We quantified the proteins, using the spectral counts reported by PEAKS Studio X+, and we prepared a database using SPSS statistics. We determined the differentially expressed proteins between the conditions with Perseus software using ANOVA analysis and hierarchical clustering. The salivary cyclic AMP-dependent transcription factor protein ATF-6 beta (ATF6B), stands out with a better classification profile. Hence, its presence allows us to distinguish between the presence and absence of ulcerative lesions in patients with and without recurrent aphthous stomatitis. Our analysis revealed that ATF6B is related to the endoplasmic reticulum stress response in oral keratinocytes. From a clinical perspective, we suggest that this protein is connected to several biological processes, mainly related to an anti-cell death response, determined by the stress of the endoplasmic reticulum, which could cause the damage that results in the release of this marker into the oral environment.

La estomatitis aftosa recurrente es la enfermedad más común de la mucosa oral. Actualmente las alternativas terapéuticas son sólo paliativas y limitadas, debido a la escasa comprensión del proceso etiopatogénico. El objetivo de este estudio es identificar proteínas que permitan distinguir entre grupos de sujetos con y sin estomatitis aftosa recurrente, para comprender los procesos que controlan los estados de salud y enfermedad. En este estudio de casos y controles, evaluamos mediante proteómica basada en espectrometría de masas la saliva de controles sanos y pacientes con estomatitis aftosa recurrente durante la presencia y ausencia de lesiones. Cuantificamos las proteínas, utilizando los recuentos espectrales informados por PEAKS Studio X+, y preparamos una base de datos utilizando SPSS. Determinamos las proteínas expresadas diferencialmente entre los grupos con el software Perseus mediante un análisis de ANOVA y un agrupamiento jerárquico. La proteína factor de transcripción dependiente de AMP cíclico salival ATF-6 beta (ATF6B), destaca con un mejor perfil de clasificación, por lo que su presencia permite distinguir entre la presencia y ausencia de lesiones ulcerosas en pacientes con y sin estomatitis aftosa recurrente. Nuestro análisis reveló que ATF6B está relacionada con la respuesta al estrés del retículo endoplásmico en los queratinocitos orales. Desde una perspectiva clínica, sugerimos que esta proteína está relacionada con varios procesos biológicos principalmente referentes con una respuesta anti-muerte celular, determinada por el estrés del retículo endoplásmico que podría ser la causa del daño que resulta en la liberación de este marcador al medio oral.

Inflammatory stress and altered angiogenesis evoked by very high-fat diets in mouse liver.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), a condition that leads to fibrosis, is caused by intake of very high-fat diets (HFDs). However, while the negative impact on the liver of these diets has been an issue of interest, systematic research on the effect of HFDs are lacking. OBJECTIVE: To characterize the overall impact of HFDs on both molecular and morphological signs of liver remodeling. METHODS: A study was conducted on male C57BL/6J mice to assess the effect of 4- and 8-week HFDs (60% kcal from fat) on (i) liver steatosis and fibrosis, and (ii) expression of factors involved in inflammation and angiogenesis. RESULTS: After an 8-week HFD, vascular endothelial growth factor type-2 receptor (VEGF-R2) and fatty acid translocase/trombospondin-1 receptor (CD36) were overexpressed in liver tissue of mice given HFDs. These changes suggest impaired liver angiogenesis and occurred together with (i) increased GPR78-BiP and EIF2α phosphorylation, suggesting endoplasmic reticulum stress, (ii) induction of Col1a1 gene expression, a marker of fibrosis, and (iii) increased CD31 immunolabeling, consistent with active angiogenesis and fibrosis. CONCLUSION: Our data show that very HFDs promote a rapid inflammatory response, as well as deregulation of angiogenesis, both consistent with development of liver fibrosis.

Actualización en la fisiopatología de la preeclampsia: update

La preeclampsia constituye una de las complicaciones más frecuentes y a la vez más serias de la gestación y contribuye de manera significativa a la mortalidad materna y perinatal. No obstante los avances en el estudio de la preeclampsia, aún no está del todo esclarecido su mecanismo fisiopatológico. En este capítulo, intentamos revisar nuevas teorías propuestas acerca de su fisiopatología. Los aspectos genéticos y angiogénicos serán revisados en otros capítulos de este simposio.

Preeclampsia is one of the most frequent and serious disorders of pregnancy. It is a significant contributor of maternal and perinatal mortality worldwide. An important amount of research has been devoted in the research of preeclampsia in the recent years; nonetheless, its pathophysiology is yet to be completely understood. In this review, we will discuss new proposed theories on the pathophysiology of preeclampsia. Genetic and angiogenic aspects of preeclampsia will be reviewed elsewhere in this issue.