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Valutazione del ruolo delle cellule progenitrici epatiche e del microambiente cellulare e molecolare nel processo di rigenerazione e carcinogenesi epatica
Full text linkThe liver regeneration, an essential process for physiological homeostasis of the liver, is the final event of a complex process that involves the interaction of different cellular and molecular signals of the hepatic microenvironment. The most important molecular signals are sex steroid hormones and inflammatory molecules.
The aim of this research was to evaluate in a mouse model the molecular and cellular changes in response to acute (induced by CCl4) and chronic (induced by DEN) hepatic injury. We also compared animals treated and not treated with Monocrotaline, an alkaloid that blocks the hepatocyte proliferation. Treated animals showed a significantly higher mortality rate, histology features were more impaired with a greater activation of stellate cells compared to non-treated animals, while there were no significant differences concerning the activation of liver progenitor cells. Regarding the gender difference, a significant dimorphism on the type and degree of the inflammatory response to a damage caused by the same toxic agent was seen in male and female. In female mice it appears to be a predominance of Th1-type cytokines (mainly IFNγ), while in male mice the dominant inflammation was Th2-type (IL-4). Animals of different gender responded by activating two different pathways of inflammation for the same noxa. Moreover, we found the up-regulation of TNFα, according to a recent hypothesis, suggesting to be induced by the stimulation of androgen receptors on Kupffer cells in male livers. The massive production of TNFα could explain in male livers both the slower resolution of liver injury and the high number of Kupffer cells.
This study showed that during liver regeneration, the hepatic microenvironment plays a crucial role and, in particular, highlighted the importance of hormonal and inflammatory components and their interaction throughout the process. The role that sex hormones may play in modulating the inflammatory response and thus the regenerative capacity may be of fundamental importance for the clinical evaluation and therapy of inflammatory diseases with sexual dimorphism.La rigenerazione epatica, processo fisiologico indispensabile per la normale omeostasi del fegato, è l’evento finale di un complesso processo che implica l’interazione di diversi tipi cellulari e segnali molecolari che compongono il microambiente del fegato. Tra i segnali molecolari hanno un ruolo fondamentale gli ormoni steroidei sessuali e le molecole infiammatorie.
Lo scopo di questa ricerca è stato quello di valutare in un modello murino di danno epatico acuto (indotto con CCl4) e cronico (indotto con DEN) le alterazioni molecolari e cellulari in animali di sesso maschile e di sesso femminile. È stata inoltre testata la Monocrotalina, un alcoloide che blocca la proliferazione degli epatociti. Negli animali trattati si è osservato un tasso di mortalità significativamente superiore rispetto ai non trattati, un quadro istologico più compromesso ed una maggiore attivazione delle cellule stellate, mentre non sono state riscontrate differenze significative circa l’attivazione delle cellule progenitrici epatiche. Valutando la differenza della risposta tra sesso maschile e femminile, il presente studio ha rilevato un significativo dimorfismo che riguarda prevalentemente il tipo ed il grado della risposta infiammatoria suscitata dal danno indotto con il medesimo agente tossico. Nei topi di sesso femminile sembra esserci una predominanza di citochine di tipo Th1 (rappresentate dall’IFNγ), mentre nei fegati degli animali di sesso maschile predomina l’infiammazione di tipo Th2 (rappresentata da IL-4). È stato quindi evidenziato che gli animali dei due sessi rispondono attivando due vie di infiammazione diverse per lo stesso stimolo nocivo. Inoltre nei fegati degli animali di sesso maschile è stata riscontrata una sovra-regolazione del TNFα che secondo una recente ipotesi sembra essere indotto dalla stimolazione dei recettori degli androgeni presenti sulle cellule di Kupffer. La produzione massiva di TNFα potrebbe spiegare la risoluzione più lenta del danno epatico negli animali di sesso maschile e al contempo l’elevato numero di cellule macrofagiche presenti nell’animale maschio.
Dal presente studio è quindi emerso che in corso di rigenerazione epatica il microambiente epatico gioca un ruolo fondamentale ed in particolare è emersa l’importanza della componente ormonale e infiammatoria e della loro interazione nell’intero processo. Il ruolo che gli ormoni sessuali possono svolgere nel modulare la risposta infiammatoria e quindi la capacità rigenerativa può essere di fondamentale importanza per la valutazione clinica e terapeutica di diverse patologie infiammatorie che presentano dimorfismo sessuale
Changings and Challenges in Liver Transplantation for Nonalcoholic Fatty Liver Disease/Steatohepatitis
No full textGender as predisposing factor to liver regeneration by hepatic progenitor cells proliferation and stellate cell activation in a murine model of acute liver injury
No full textGender as a predisposing factor to stellate cells activation and oval cells proliferation in a murine model of acute hepatic injury
No full textThe balance between fibrosis and regeneration in chronic liver injury: The role of gender
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Gut-liver axis and liver diseases: the role of the gut microbiota and future implications
No full textreservedIn recent years, substantial study has been conducted on the human gut microbiota, and our understanding of the resident species and their potential functional capacity is quickly expanding. The gut microbiota is a complex community of approximately 100 trillion microbial cells that regulate human physiology, metabolism, nutrition, and immune function. Disruption of the gut microbiota has been related to gastrointestinal diseases like inflammatory bowel disease and obesity, However in this study we concentrate on the importance of the relationship between Gut microbiota and the insurgence of liver diseases, We look at a number of recent research that have focused on improving our understanding of the complexity of intestinal communities, as well as their genetic and metabolic potential, and their effect on determining the pathogenesis on the gut- liver axis, We also discuss newly emerging genetic and other technologies for studying the gut microbiome, as well as the possibility of manipulating the gut microbiota as a therapeutic option for chronic liver diseases by fecal transplant.In recent years, substantial study has been conducted on the human gut microbiota, and our understanding of the resident species and their potential functional capacity is quickly expanding. The gut microbiota is a complex community of approximately 100 trillion microbial cells that regulate human physiology, metabolism, nutrition, and immune function. Disruption of the gut microbiota has been related to gastrointestinal diseases like inflammatory bowel disease and obesity, However in this study we concentrate on the importance of the relationship between Gut microbiota and the insurgence of liver diseases, We look at a number of recent research that have focused on improving our understanding of the complexity of intestinal communities, as well as their genetic and metabolic potential, and their effect on determining the pathogenesis on the gut- liver axis, We also discuss newly emerging genetic and other technologies for studying the gut microbiome, as well as the possibility of manipulating the gut microbiota as a therapeutic option for chronic liver diseases by fecal transplant
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