Cell death in hepatocellular carcinoma: Pathogenesis and therapeutic opportunities

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and the third leading cause of cancer death worldwide. Closely associated with liver inflammation and fibrosis, hepatocyte cell death is a common trigger for acute and chronic liver disease arising from different etiologies, including viral hepatitis, alcohol abuse, and fatty liver. In this review, we discuss the con-tribution of different types of cell death, including apoptosis, necroptosis, pyroptosis, or autophagy, to the progression of liver disease and the development of HCC. Interestingly, inflammasomes have recently emerged as pivotal innate sensors with a highly pathogenic role in various liver diseases. In this regard, an increased inflammatory response would act as a key element promoting a pro-oncogenic microenvironment that may result not only in tumor growth, but also in the formation of a premetastatic niche. Importantly, nonparenchymal hepatic cells, such as liver sinusoidal endothelial cells, hepatic stellate cells, and hepatic macrophages, play an important role in establishing the tumor microenvironment, stimulating tumorigenesis by paracrine communication through cytokines and/or angiocrine factors. Finally, we update the potential therapeutic options to inhibit tumorige-nesis, and we propose different mechanisms to consider in the tumor microenvironment field for HCC resolution. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Local intra-uterine Ang-(1-7) infusion attenuates PGE2 and 6-keto PGF1α in decidualized uterus of pseudopregnant rats

Background: Cyclooxygenase (COX)-derived prostanoids (PGE2, PGI2) are important contributors to the process of decidualization. Previous studies showed the presence of Ang-(1-7) in the primary and secondary decidualized zones of the implantation site at early pregnancy. Decreased concentrations of Ang-(1-7) were found in the decidualized uterus compared to the non-decidualized uterus of pseudopregnant rats, suggesting that low levels of Ang-(1-7) are required for successful decidualization at early pregnancy. Methods: To understand the role of Ang-(1-7) in prostaglandin production in a decidualized uterus, induced by a bolus injection of sesame oil, Ang-(1-7) (24 μg/kg/h) or vehicle was then infused directly into the decidualized uterine horn using an osmotic minipump. The right horns were not injected or infused and served as nondecidualized uterine horns in both groups of animals. Results: Decidualization increased PGE2 concentration in the uterus (0.53±0.05 vs. 12.0±3.2 pmol/mg protein, p\u3c0.001, non-decidualized vs. decidualized horns); Ang-(1-7) infusion attenuated the increase of PGE2 (12.0± 3.2 vs. 5.1±1.3 pmol/mg protein, p\u3c0.01 control vs. Ang-(1-7) treated decidualized horns). The stable metabolite of PGI2 (6-keto PGF1α) was increased with decidualization (0.79±0.17 vs. 3.5±0.82 pmol/mg protein, p\u3c0.001, non-decidualized vs. decidualized horns). Ang-(1-7) infusion attenuated the increase in 6keto PGF1α in the decidualized horn (3.5±0.82 vs 1.8±0.37 pmol/mg protein, p\u3c0.05 control vs. Ang-(1-7) treated decidualized horns). The circulating levels of 6-keto-PGF1a and TXB2 were decreased by Ang-(1-7) infusion, while no difference was observed in circulating PGE2. Although the global assessment of cleaved caspase 3 immunostaining, a marker of apoptosis, was unchanged within the Ang-(1-7) decidualized horn, there were localized decreases in cleaved caspase 3 staining in the luminal region in the decidualized uterus of Ang-(1-7)-treated rats. Conclusions: These studies show that increased local uterine Ang-(1-7) alters the uterine prostaglandin environment, possibly leading to disruptions of early events of decidualization

Artificial light pollution influences behavioral and physiological traits in a keystone predator species, Concholepas concholepas

Artificial Light At Night (ALAN) is an increasing global problem that, despite being widely recognized in terrestrial systems, has been studied much less in marine habitats. In this study we investigated the effect of ALAN on behavioral and physiological traits of Concholepas concholepas, an important keystone species of the south-eastern Pacific coast. We used juveniles collected in intertidal habitats that had not previously been exposed to ALAN. In the laboratory we exposed them to two treatments: darkness and white LED (Lighting Emitting Diodes) to test for the impacts of ALAN on prey-searching behavior, self-righting time and metabolism. In the field, the distribution of juveniles was observed during daylight-hours to determine whether C. concholepas preferred shaded or illuminated microhabitats. Moreover, we compared the abundance of juveniles collected during day- and night-time hours. The laboratory experiments demonstrated that juveniles of C. concholepas seek out and choose their prey more efficiently in darkened areas. White LED illuminated conditions increased righting times and metabolism. Field surveys indicated that, during daylight hours, juveniles were more abundant in shaded micro-habitats than in illuminated ones. However, during darkness hours, individuals were not seen to aggregate in any particular microhabitats. We conclude that the exposure to ALAN might disrupt important behavioral and physiological traits of small juveniles in this species which, as a mechanism to avoid visual predators, are mainly active at night. It follows that ALAN in coastal areas might modify the entire community structure of intertidal habitats by altering the behavior of this keystone species

The estrogenicity of bisphenol A-related diphenylalkanes with various substituents at the central carbon and the hydroxy groups

This work was reported in part at the meeting Estrogens in the Environment IV: Linking Fundamental Knowledge, Risk Assessment, and Public Policy held in Washington, DC, 19-21 July 1997.The chemical structure of hydroxylated diphenylalkanes or bisphenols consists of two phenolic rings joined together through a bridging carbon. This class of endocrine disruptors that mimic estrogens is widely used in industry, particularly in plastics. Bisphenol F, bisphenol A, fluorine-containing bisphenol A (bisphenol AF), and other diphenylalkanes were found to be estrogenic in a bioassay with MCF7 human breast cancer cells in culture (E-SCREEN assay). Bisphenols promoted cell proliferation and increased the synthesis and secretion of cell type-specific proteins. When ranked by proliferative potency, the longer the alkyl substituent at the bridging carbon, the lower the concentration needed for maximal cell yield; the most active compound contained two propyl chains at the bridging carbon. Bisphenols with two hydroxyl groups in the para position and an angular configuration are suitable for appropriate hydrogen bonding to the acceptor site of the estrogen receptor. Our data suggest that estrogenicity is influenced not only by the length of the substituents at the bridging carbon but also by their nature. Because diphenylalkane derivatives are widespread and their production and use are increasing, potential exposure of humans to estrogenic bisphenols is becoming a significant issue. The hazardous effects of inadvertent exposure to bisphenol-releasing chemicals in professional workers and the general populations therefore deserve investigation.This research was supported by grants from the Spanish Ministry of Health (FIS, 95/1959) and the Andalusian Regional Government Department of Health (Consejerla de Salud, 96/159)

Libro segundo de la historia secular y eclesiástica de la ciudad de Palencia : contiene la restauración de la ciudad, reedificación de el templo de San Antonino ...

Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2009-2010Texto a dos col.Errores de pag.: de p. 175 pasa a 178 y de la p. 360 a la 36

Protection from inflammatory disease in insulin resistance: the role of mannan-binding lectin

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Evaluating the function of wildcat faecal marks in relation to the defence of favourable hunting areas

This is an Accepted Manuscript of an article published by Taylor & Francis in Ethology Ecology and Evolution on 2015, available online: http://www.tandfonline.com/10.1080/03949370.2014.905499To date, there have been no studies of carnivores that have been specifically designed to examine the function of scent marks in trophic resource defence, although several chemical communication studies have discussed other functions of these marks. The aim of this study was to test the hypothesis that faecal marks deposited by wildcats (Felis silvestris) serve to defend their primary trophic resource, small mammals. Field data were collected over a 2-year period in a protected area in northwestern Spain. To determine the small mammal abundance in different habitat types, a seasonal live trapping campaign was undertaken in deciduous forests, mature pine forests and scrublands. In each habitat, we trapped in three widely separated Universal Transverse Mercator (UTM) cells. At the same time that the trapping was being performed, transects were conducted on foot along forest roads in each trapping cell and in one adjacent cell to detect fresh wildcat scats that did or did not have a scent-marking function. A scat was considered to have a presumed marking function when it was located on a conspicuous substrate, above ground level, at a crossroad or in a latrine. The number of faecal marks and the small mammal abundance varied by habitat type but not by seasons. The results of the analysis of covariance (ANCOVA) indicated that small mammal abundance and habitat type were the factors that explained the largest degrees of variation in the faecal marking index (number of faecal marks in each cell/number of kilometres surveyed in each cell). This result suggests that wildcats defended favourable hunting areas. They mark most often where their main prey lives and so where they spend the most time hunting (in areas where their main prey is more abundant). This practice would allow wildcats to protect their main trophic resource and would reduce intraspecific trophic competitio

Listening In on the Past: What Can Otolith δ18O Values Really Tell Us about the Environmental History of Fishes?

Oxygen isotope ratios from fish otoliths are used to discriminate marine stocks and reconstruct past climate, assuming that variations in otolith δ18O values closely reflect differences in temperature history of fish when accounting for salinity induced variability in water δ18O. To investigate this, we exploited the environmental and migratory data gathered from a decade using archival tags to study the behaviour of adult plaice (Pleuronectes platessa L.) in the North Sea. Based on the tag-derived monthly distributions of the fish and corresponding temperature and salinity estimates modelled across three consecutive years, we first predicted annual otolith δ18O values for three geographically discrete offshore sub-stocks, using three alternative plausible scenarios for otolith growth. Comparison of predicted vs. measured annual δ18O values demonstrated >96% correct prediction of sub-stock membership, irrespective of the otolith growth scenario. Pronounced inter-stock differences in δ18O values, notably in summer, provide a robust marker for reconstructing broad-scale plaice distribution in the North Sea. However, although largely congruent, measured and predicted annual δ18O values of did not fully match. Small, but consistent, offsets were also observed between individual high-resolution otolith δ18O values measured during tag recording time and corresponding δ18O predictions using concomitant tag-recorded temperatures and location-specific salinity estimates. The nature of the shifts differed among sub-stocks, suggesting specific vital effects linked to variation in physiological response to temperature. Therefore, although otolith δ18O in free-ranging fish largely reflects environmental temperature and salinity, we counsel prudence when interpreting otolith δ18O data for stock discrimination or temperature reconstruction until the mechanisms underpinning otolith δ18O signature acquisition, and associated variation, are clarified

Endogenous cycles, activity patterns and energy expenditure of an intertidal fish is modified by artificial light pollution at night (ALAN)

The increase of global light emissions in recent years has highlighted the need for urgent evaluation of their impacts on the behaviour, ecology and physiology of organisms. Numerous species exhibit daily cycles or strong scototaxic behaviours that could potentially be influenced if natural lighting conditions or cycles are disrupted. Artificial Light Pollution at Night (ALAN) stands for situations where artificial light alters natural light-dark cycles, as well as light intensities and wavelengths. ALAN is increasingly recognized as a potential threat to biodiversity, mainly because a growing number of studies are demonstrating its influence on animal behaviour, migration, reproduction and biological interactions. Most of these studies have focused on terrestrial organisms and ecosystems with studies on the effects of ALAN on marine ecosystems being more occasional. However, with the increasing human use and development of the coastal zone, organisms that inhabit shallow coastal or intertidal systems could be at increasing risk from ALAN. In this study we measured the levels of artificial light intensity in the field and used these levels to conduct experimental trials to determine the impact of ALAN on an intertidal fish. Specifically, we measured ALAN effects on physiological performance (oxygen consumption) and behaviour (activity patterns) of “Baunco” the rockfish Girella laevifrons, one of the most abundant and ecologically important intertidal fish in the Southeastern Pacific littoral. Our results indicated that individuals exposed to ALAN exhibited increased oxygen consumption and activity when compared with control animals. Moreover, those fish exposed to ALAN stopped displaying the natural (circatidal and circadian) activity cycles that were observed in control fish throughout the experiment. These changes in physiological function and behaviour could have serious implications for the long-term sustainability of fish populations and indirect impacts on intertidal communities in areas affected by ALAN