Leptin Reverts Pro-Apoptotic and Antiproliferative Effects of α-Linolenic Acids in BCR-ABL Positive Leukemic Cells: Involvement of PI3K Pathway

It is suspected that bone marrow (BM) microenvironmental factors may influence the evolution of chronic myeloid leukaemia (CML). In this study, we postulated that adipocytes and lipids could be involved in the progression of CML. To test this hypothesis, adipocytes were co-cultured with two BCR-ABL positive cell lines (PCMDS and K562). T cell (Jurkat) and stroma cell (HS-5) lines were used as controls. In the second set of experiments, leukemic cell lines were treated with stearic, oleic, linoleic or α-linolenic acids in presence or absence of leptin. Survival, proliferation, leptin production, OB-R isoforms (OB-Ra and OB-Rb), phosphoinositide 3-kinase (PI3k) and BCL-2 expression have been tested after 24h, 48h and 72h of treatment. Our results showed that adipocytes induced a decrease of CML proliferation and an increase in lipid accumulation in leukemic cells. In addition, CML cell lines induced adipocytes cell death. Chromatography analysis showed that BM microenvironment cells were full of saturated (SFA) and monounsaturated (MUFA) fatty acids, fatty acids that protect tumor cells against external agents. Stearic acid increased Bcl-2 expression in PCMDS, whereas oleic and linoleic acids had no effects. In contrast, α-linolenic acid decreased the proliferation and the survival of CML cell lines as well as BCL-2 and OB-R expression. The effect of α-linolenic acids seemed to be due to PI3K pathway and Bcl-2 inhibition. Leptin production was detected in the co-culture medium. In the presence of leptin, the effect of α-linolenic acid on proliferation, survival, OB-R and BCl-2 expression was reduced

Characterization of Spontaneous Bone Marrow Recovery after Sublethal Total Body Irradiation: Importance of the Osteoblastic/Adipocytic Balance

Many studies have already examined the hematopoietic recovery after irradiation but paid with very little attention to the bone marrow microenvironment. Nonetheless previous studies in a murine model of reversible radio-induced bone marrow aplasia have shown a significant increase in alkaline phosphatase activity (ALP) prior to hematopoietic regeneration. This increase in ALP activity was not due to cell proliferation but could be attributed to modifications of the properties of mesenchymal stem cells (MSC). We thus undertook a study to assess the kinetics of the evolution of MSC correlated to their hematopoietic supportive capacities in mice treated with sub lethal total body irradiation. In our study, colony-forming units – fibroblasts (CFU-Fs) assay showed a significant MSC rate increase in irradiated bone marrows. CFU-Fs colonies still possessed differentiation capacities of MSC but colonies from mice sacrificed 3 days after irradiation displayed high rates of ALP activity and a transient increase in osteoblastic markers expression while pparγ and neuropilin-1 decreased. Hematopoietic supportive capacities of CFU-Fs were also modified: as compared to controls, irradiated CFU-Fs significantly increased the proliferation rate of hematopoietic precursors and accelerated the differentiation toward the granulocytic lineage. Our data provide the first evidence of the key role exerted by the balance between osteoblasts and adipocytes in spontaneous bone marrow regeneration. First, (pre)osteoblast differentiation from MSC stimulated hematopoietic precursor's proliferation and granulopoietic regeneration. Then, in a second time (pre)osteoblasts progressively disappeared in favour of adipocytic cells which down regulated the proliferation and granulocytic differentiation and then contributed to a return to pre-irradiation conditions

Entre Etat et acteurs locaux. Les enjeux communicationnels de la sécurité routière

International audienc

Entre Etat et acteurs locaux. Les enjeux communicationnels de la sécurité routière

International audienc

Les symptômes thymiques liés à l’usage d’alcool

Si l’existence de liens entre consommation éthylique et symptômes thymiques paraît évidente, la nature et les mécanismes qui sous-tendent ces interactions s’avèrent en revanche très complexes et moins bien connus. Cet article, qui s’appuie essentiellement sur des données empiriques et destinées aux cliniciens, vise à décrire de quelle manière la compréhension de ces symptômes thymiques permet de dégager des pistes de travail ou leviers pour le travail clinique avec les patients alcoolo-dépendants. Nous développons en particulier la manière dont la consommation aiguë entraîne des réactions émotionnelles, hors contexte d’abus ou de dépendance (caractère syntone par rapport au cadre social de consommation, « binge-drinking »). Les consommations chroniques, menant à l’abus ou à la dépendance, sont par la suite abordées en détaillant de quelle manière leur interaction biologique avec le circuit de récompense cérébrale modifie notablement l’humeur, en fonction d’un principe d’allostasie. Nous mettons aussi en évidence le rôle de facteurs de personnalité tels que la conscience de Soi dans la relation qui peut exister entre dépression et « craving ». Nous insistons également sur des manifestations annexes aux symptômes thymiques que sont les troubles de cognition sociale fréquents chez les patients alcooliques, menant souvent à un isolement social ainsi qu’à des relations interpersonnelles conflictuelles qui peuvent à leur tour être des facteurs d’accentuation du vécu dépressif.[Thymic symptoms related to the use of alcohol] Although the existence of links between alcohol consumption and thymic symptoms seems obvious, the nature and mechanisms underlying these interactions are, on the other hand, very complex and less well-known. This article, which relies mainly on empirical data and is intended for clinicians, aims to describe how understanding these thymic symptoms can identify avenues of work or levers for clinical work with alcohol-dependent patients. In particular, we develop the way in which acute consumption leads to emotional reactions, outside the context of abuse or dependence (symptom with the social framework of consumption, “binge-drinking”). Chronic consumption leading to abuse or dependence is then discussed, detailing how their biological interaction with the brain reward circuit significantly changes mood, based on a principle of allostasis. We also highlight the role of personality factors such as self-consciousness in the relationship between depression and craving. Furthermore we emphasize manifestations related to thymic symptoms such as social cognition disorders common in alcoholic patients, often leading to social isolation as well as conflicting interpersonal relationships which can in turn be factors of accentuation as far as depression symptoms are concerned

Links between psychopathological symptoms and cortical thickness in men with severe alcohol use disorder: A Magnetic Resonance Imaging study

Background: Anxiety and depression are psychopathological states frequently co-occurring with severe alcohol use disorder (SAUD). These symptoms generally disappear with abstinence but may persist in some patients, increasing the relapse risk. Methods: The cerebral cortex thickness of 94 male patients with SAUD was correlated with symptoms of depression and anxiety, both measured at the end (2–3 weeks)of the detoxification treatment. Cortical measures were obtained using surface-based morphometry implemented with Freesurfer. Results: Depressive symptoms were associated with reduced cortical thickness in the superior temporal gyrus of the right hemisphere. Anxiety level was correlated with lower cortical thickness in the rostral middle frontal region, inferior temporal region, and supramarginal, postcentral, superior temporal, and transverse temporal regions of the left hemisphere, as well as with a large cluster in the middle temporal region of the right hemisphere. Conclusions: At the end of the detoxification stage, the intensity of depressive and anxiety symptoms is inversely associated with the cortical thickness of regions involved in emotions-related processes, and the persistence of the symptoms could be explained by these brain deficits

SDF-1 expression in irradiated bone marrows and CFU-Fs.

<p><b>A:</b> Labelling with anti-sdf1 antibodies is more intense in bone marrows from day-1 irradiated mice (<b>Ab</b>) compared to control ones (<b>Aa</b>) (original magnification ×200). <b>B:</b> Elisa quantification of sdf-1 in the supernatant of irradiated CFU-Fs showed an increase in sdf-1 until 4 hours after irradiation. <b>C:</b> The level of mRNA expression is not significantly different in control and irradiated CFU-Fs. Data are presented as mean values ± SEM of at least three independent experiments. ***, p<.001 as assessed by one way analysis of variance (ANOVA).</p