Adult Stromal Cells Derived from Human Adipose Tissue Provoke Pancreatic Cancer Cell Death both In Vitro and In Vivo

1932-6203 (Electronic) Journal Article Research Support, Non-U.S. Gov'tBACKGROUND: Normal tissue homeostasis is maintained by dynamic interactions between epithelial cells and their microenvironment. Disrupting this homeostasis can induce aberrant cell proliferation, adhesion, function and migration that might promote malignant behavior. Indeed, aberrant stromal-epithelial interactions contribute to pancreatic ductal adenocarcinoma (PDAC) spread and metastasis, and this raises the possibility that novel stroma-targeted therapies represent additional approaches for combating this malignant disease. The aim of the present study was to determine the effect of human stromal cells derived from adipose tissue (ADSC) on pancreatic tumor cell proliferation. PRINCIPAL FINDINGS: Co-culturing pancreatic tumor cells with ADSC and ADSC-conditioned medium sampled from different donors inhibited cancer cell viability and proliferation. ADSC-mediated inhibitory effect was further extended to other epithelial cancer-derived cell lines (liver, colon, prostate). ADSC conditioned medium induced cancer cell necrosis following G1-phase arrest, without evidence of apoptosis. In vivo, a single intra-tumoral injection of ADSC in a model of pancreatic adenocarcinoma induced a strong and long-lasting inhibition of tumor growth. CONCLUSION: These data indicate that ADSC strongly inhibit PDAC proliferation, both in vitro and in vivo and induce tumor cell death by altering cell cycle progression. Therefore, ADSC may constitute a potential cell-based therapeutic alternative for the treatment of PDAC for which no effective cure is available

ACTIVITE REPRODUCTRICE DU LEMUR CORONATUS AGE EN CAPTIVITE

Ces dernières années, la population captive du Lemur coronatus a nettement vu augmenter sa moyenne d'âge, ainsi que diminuer ses effectifs. En parc zoologique, nous assistons donc à l'apparition d'un groupe d'individus âgés de plus de 15 ans ne reproduisant plus. Cette espèce de Lémuriens étant menacée d'extinction dans son milieu naturel, il nous a paru alors nécessaire d'étudier la fonction reproductrice de ces individus âgés, dans le but d'expliquer ce repos sexuel observé en captivité. C'est ainsi que nous avons effectué des observations morphologiques, des mesures testiculaires, des frottis vaginaux, des dosages sériques d'hormones sexuelles et des coupes histologiques de gonades, afin de comparer la physiologie reproductrice des L. coronatus âgés mâles et femelles à celle des L. coronatus dits "reproducteurs ". Au cours de cette étude, nous avons donc mis en évidence la présence d'une activité physiologique reproductrice, chez les mâles comme chez les femelles, au sein de ce groupe d'individus âgés de plus de 15 ans. Cependant, nous ne pouvons conclure concernant une éventuelle altération de la fonction génitrice du L. coronatus au cours de la vieillesse. En effet, il est fort probable que des facteurs environnementaux, comportementaux... influent également sur la vie sexuelle de certains individus.MAISONS-ALFORT-Ecole Vétérin (940462302) / SudocSudocFranceF

Mésusage transgénérationnel d'alcool : Développement des enfants en milieux défavorisés. Étude et revue de la littérature

National audienceL'impact à long terme de l'exposition prénatale à l'alcool sur les composantes du développement des enfants a été montré dans les études longitudinales. Toutefois, les effets transgénérationnels ont été peu évalués et la question reste posée d'effets amplifiés dans les milieux très défavorisés. 22 familles accompagnées pendant plus d'un an avec leur(s) enfant(s) au CAMSP de Roubaix dans un groupe informel de rencontre et les enfants suivis en rééducation ont été revus environ sept ans après. Le mésusage d'alcool (abus) était présent à la génération des grands-mères et de nombreux parents. Le développement cognitif, scolaire et comportemental de leurs enfants a été évalué. L'importance des déficits développementaux reflète à la fois les séquelles du syndrome d'alcoolisation foetale (SAF) et des effets de l'alcool sur le fœtus (EAF), mais aussi les problèmes périnataux, la malnutrition et les dysfonctionnements relationnels parents-enfants. Dans un tiers des familles, les enfants sont placés mais leurs difficultés comportementales sont proportionnellement moins importantes que celles des enfants vivant dans leur famille. L'étude montre que les enfants présentant des troubles du spectre de l'alcoolisation fœtale ont un QI inférieur de 18 points en moyenne par rapport aux autres enfants de la cohorte et que leur cursus scolaire est plus difficile. Des prises en charge doivent être mises en place de façon très précoce pour les enfants porteurs de séquelles d'exposition prénatale à l'alcool

Tuning optical properties of cellulose nanofibrils-based multilayered thin films

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Multi- and transgenerational effects following early-life exposure of zebrafish to permethrin and coumarin 47: Impact on growth, fertility, behavior and lipid metabolism

International audienceTransgenerational effects induced by environmental stressors are a threat to ecosystems and human health. However, there is still limited observation and understanding of the potential of chemicals to influence life outcomes over several generations. In the present study, we investigated the effects of two environmental contaminants, coumarin 47 and permethrin, on exposed zebrafish (FO) and their progeny (F1-F3). Coumarin 47 is commonly found in personal care products and dyes, whereas permethrin is used as a domestic and agricultural pyrethroid insecticide/insect repellent. Zebrafish (F0) were exposed during early development until 28 days post-fertilization and their progeny (F1-F3) were bred unexposed. On one hand, the effects induced by coumarin 47 suggest no multigenerational toxicity. On the other hand, we found that behavior of zebrafish larvae was significantly affected by exposure to permethrin in F1 to F3 generations with some differences depending on the concentration. This suggests persistent alteration of the neural or neuromuscular function. In addition, lipidomic analyses showed that permethrin treatment was partially correlated with lysophosphatidylcholine levels in zebrafish, an important lipid for neurodevelopment. Overall, these results stress out one of the most widely used pyrethroids can trigger long-term, multi- and possibly transgenerational changes in the nervous system of zebrafish. These neurobehavioral changes echo the effects observed under direct exposure to high concentrations of permethrin and therefore call for more research on mechanisms underlying effect inheritance

The insecticide permethrin induces transgenerational behavioral changes linked to transcriptomic and epigenetic alterations in zebrafish (Danio rerio)

International audienceThe pyrethroid insecticide permethrin is widely used for agricultural and domestic purposes. Previous data indicated that it acts as a developmental neurotoxicant and can induce transgenerational effects in non-target organisms. However, associated underlying mechanisms remain unclear. The aim of this study was to investigate permethrin-related transgenerational effects in the zebrafish model, and to identify possible molecular mechanisms underlying inheritance. Zebrafish (F0) were exposed to permethrin during early-life (2 hours postfertilization up to 28 days). The F1 and F2 offspring generations were obtained by pairing exposed F0 males and females, and were bred unexposed. Locomotor and anxiety behavior were investigated, together with transcriptomic and epigenomic (DNA methylation) changes in brains. Permethrin exposed F0 fish were hypoactive at adulthood, while males from the F1 and F2 generations showed a specific decrease in anxiety-like behavior. In F0, transcriptomic data showed enrichment in pathways related to glutamatergic synapse activity, which may partly underlie the behavioral effects. In F1 and F2 males, dysregulation of similar pathways was observed, including a subset of differentially methylated regions that were inherited from the F0 to the F2 generation and indicated stable dysregulation of glutamatergic signaling. Altogether, the present results provide novel evidence on the transgenerational neurotoxic effects of permethrin, as well as mechanistic insight: a transient exposure induces persistent transcriptional and DNA methylation changes that may translate into transgenerational alteration of glutamatergic signaling and, thus, into behavioral alterations

An environmentally relevant mixture of polychlorinated biphenyls (PCBs) and polybrominated diphenylethers (PBDEs) disrupts mitochondrial function, lipid metabolism and neurotransmission in the brain of exposed zebrafish and their unexposed F2 offspring

International audiencePolychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants still present in aquatic environments despite their total or partial ban. Previously, we observed that an environmentally realistic mixture of these compounds affects energy balance, growth, and reproduction in exposed zebrafish (F0), and behavior in their unexposed offspring (F1-F4). In the present work, we performed lipidomic and transcriptomic analyses on brains of zebrafish (F0-F2) from exposed and control lineages to identify molecular changes that could explain the observed phenotypes. The use of both technologies highlighted that F0 zebrafish displayed impaired mitochondrial function and lipid metabolism regulation (depletion in triacylglycerols and phospholipids) which can explain disruption of energy homeostasis. A subset of the regulated biological pathways related to energetic metabolism and neurotransmission were inherited in F2. In addition, there were increasing effects on epigenetic pathways from the F0 to the F2 generation. Altogether, we show that the effects of an environmental exposure to PCBs and PBDEs on energetic metabolism as well as neurotransmission extend over 2 generations of zebrafish, possibly due to transgenerational epigenetic inheritance

The progestin norethindrone affects the glucocorticoid signalling pathway in zebrafish

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Environmental microplastics disrupt swimming activity in acute exposure in Danio rerio larvae and reduce growth and reproduction success in chronic exposure in D. rerio and Oryzias melastigma

International audienceMicroplastics (MPs), widely present in aquatic ecosystems, can be ingested by numerous organisms, but their toxicity remains poorly understood. Toxicity of environmental MPs from 2 beaches located on the Guadeloupe archipelago, Marie Galante (MG) and Petit-Bourg (PB) located near the North Atlantic gyre, was evaluated. A first experiment consisted in exposing early life stages of zebrafish (Danio rerio) to MPs at 1 or 10 mg/L. The exposure of early life stages to particles in water induced no toxic effects except a decrease in larval swimming activity for both MPs exposures (MG or PB). Then, a second experiment was performed as a chronic feeding exposure over 4 months, using a freshwater fish species, zebrafish, and a marine fish species, marine medaka (Oryzias melastigma). Fish were fed with food supplemented with environmentally relevant concentrations (1% wet weight of MPs in food) of environmental MPs from both sites. Chronic feeding exposure led to growth alterations in both species exposed to either MG or PB MPs but were more pronounced in marine medaka. Ethoxyresorufin-O-deethylase (EROD) and acetylcholinesterase (AChE) activities were only altered for marine medaka. Reproductive outputs were modified following PB exposure with a 70 and 42% decrease for zebrafish and marine medaka, respectively. Offspring of both species (F1 generation) were reared to evaluate toxicity following parental exposure on unexposed larvae. For zebrafish offspring, it revealed premature mortality after parental MG exposure and parental PB exposure produced behavioural disruptions with hyperactivity of F1 unexposed larvae. This was not observed in marine medaka offspring. This study highlights the ecotoxicological consequences of short and long-term exposures to environmental microplastics relevant to coastal marine areas, which represent essential habitats for a wide range of aquatic organisms

Chronic feeding exposure to virgin and spiked microplastics disrupts essential biological functions in teleost fish

International audienceToxicity of polyethylene (PE) and polyvinyl chloride (PVC) microplastics (MPs), either virgin or spiked with chemicals, was evaluated in two short-lived fish using a freshwater species, zebrafish, and a marine species, marine medaka. Exposures were performed through diet using environmentally relevant concentrations of MPs over 4 months. No modification of classical biomarkers, lipid peroxidation, genotoxicity or F0 behaviour was observed. A significant decrease in growth was reported after at least two months of exposure. This decrease was similar between species, independent from the type of MPs polymer and the presence or not of spiked chemicals, but was much stronger in females. The reproduction was evaluated and it revealed a significant decrease in the reproductive output for both species and in far more serious numbers in medaka. PVC appeared more reprotoxic than PE as were MPs spiked with PFOS and benzophenone-3 compared to MPs spiked with benzo[a]pyrene. Further, PVC-benzophenone-3 produced behavioural disruption in offspring larvae. These results obtained with two species representing different aquatic environments suggest that microplastics exert toxic effects, slightly different according to polymers and the presence or not of sorbed chemicals, which may lead in all cases to serious ecological disruptions