Kynurenine pathway abnormalities are state-specific but not diagnosis-specific in schizophrenia and bipolar disorder.

Schizophrenia (SCZ) and bipolar disorder (BD) are associated with immunological dysfunctions that have been hypothesized to lead to clinical symptomatology in particular through kynurenine pathway abnormalities. The aim of this study was thus to investigate the impact of serum kynurenine metabolite levels on diagnosis, clinical state, symptom severity and clinical course in a large French transdiagnostic cohort of SCZ and BD patients. Four patient groups (total n = 507) were included in a cross-sectional observational study: 1) hospitalized acute bipolar patients (n = 205); 2) stable bipolar outpatients (n = 116); 3) hospitalized acute schizophrenia patients (n = 111) and 4) stable schizophrenia outpatients (n = 75), in addition to healthy controls (HC) (n = 185).

Kynurenine-3-monooxygenase expression is activated in the pancreatic endocrine cells by diabetes and its blockade improves glucose-stimulated insulin secretion.

Type 2 diabetes is associated with an inflammatory phenotype in the pancreatic islets. We previously demonstrated that proinflammatory cytokines potently activate the tryptophan/kynurenine pathway (TKP) in INS-1 cells and in normal rat islets. Here we examined: (1) the TKP enzymes expression in the diabetic GK islets; (2) the TKP enzymes expression profiles in the GK islets before and after the onset of diabetes; (3) The glucose-stimulated insulin secretion (GSIS) in vitro in GK islets after KMO knockdown using specific morpholino-oligonucleotides against KMO or KMO blockade using the specific inhibitor Ro618048; (4) The glucose tolerance and GSIS after acute in vivo exposure to Ro618048 in GK rats.

20-Hydroxyecdysone activates the protective arm of the RAAS via the MAS receptor.

20-Hydroxyecdysone (20E) is a steroid hormone that plays a key role in insect development through nuclear ecdysteroid receptors (EcR/RXR complex) and at least one membrane GPCR receptor (DopEcR). It also displays numerous pharmacological effects in mammals, where its mechanism of action is still debated, involving either an unidentified GPCR or the estrogen ERβ receptor. The goal of this study was to better understand 20E mechanism of action in mammals.

Intake Estimation of Phytochemicals in a French Well-Balanced Diet.

Phytochemicals contribute to the health benefits of plant-rich diets, notably through their antioxidant and anti-inflammatory effects. However, recommended daily amounts of the main dietary phytochemicals remain undetermined. We aimed to estimate the amounts of phytochemicals in a well-balanced diet.

[Elaboration and psychometric properties of a well-being scale at work. The Serenat study among employees in occupational medicine unit].

Background: Well-being at work is nowadays a major public health challenge. It includes, among others, absence of psychological (anxio-depressive) symptoms, perceived positive work conditions (environment and organization), happiness and good quality of life at work. Many studies have shown that social support and control at work protect mental health while high job demands and effort-reward imbalance are risk factors for anxiety and depression.

Identification of a novel 2-oxindole fluorinated derivative as in vivo antitumor agent for prostate cancer acting via AMPK activation.

The key metabolic sensor adenosine monophosphate-dependent kinase (AMPK) has emerged as a promising therapeutic target for cancer prevention and treatment. Besides its role in energy homeostasis, AMPK blocks cell cycle, regulates autophagy and suppresses the anabolic processes required for rapid cell growth. AMPK is especially relevant in prostate cancer in which activation of lipogenic pathways correlate with tumor progression and aggressiveness.

Use of dynamic light scattering and small-angle X-ray scattering to characterize new surfactants in solution conditions for membrane-protein crystallization.

The structural and interactive properties of two novel hemifluorinated surfactants, F2H9-β-M and F4H5-β-M, the syntheses of which were based on the structure and hydrophobicity of the well known dodecyl-β-maltoside (DD-β-M), are described. The shape of their micellar assemblies was characterized by small-angle X-ray scattering and their intermicellar interactions in crystallizing conditions were measured by dynamic light scattering. Such information is essential for surfactant phase-diagram determination and membrane-protein crystallization.

Expression of the kynurenine pathway enzymes in the pancreatic islet cells. Activation by cytokines and glucolipotoxicity.

The tryptophan/kynurenine pathway (TKP) is the main route of tryptophan degradation and generates several neuroactive and immunomodulatory metabolites. Experimental and clinical data have clearly established that besides fat, muscle and liver, pancreatic islet tissue itself is a site of inflammation during obesity and type 2 diabetes. Therefore it is conceivable that pancreatic islet exposure to increased levels of cytokines may induce upregulation of islet kynurenine metabolism in a way resembling that seen in the brain in many neurodegenerative disorders.

Influence of hydrophobic micelle structure on crystallization of the photosynthetic RC-LH1-PufX complex from Rhodobacter blasticus.

Small angle X-ray scattering (SAXS) experiments are performed on two non-ionic surfactants, the dodecyl β-maltoside (DDβM) and the propyl(bi)cyclohexyl α-maltoside (PCCαM), a maltoside derivative containing a rigid bicyclohexyl group as hydrophobic chain, in order to compare the influence of both hydrophobic moiety structure and anomeric form on micelle form factors and intermicellar interactions relevant for membrane protein crystallization. Density and refractive index measurements were performed in order to determine volumetric and optical properties of surfactants, essential for determination of micelle molar masses by both SAXS and SEC-MALLS. SAXS form factors were analyzed by Guinier approximation and inverse Fourier transformation, to obtain the radius of gyration (RG) and the pair distribution function (P(r)) of each surfactant.

A class of mild surfactants that keep integral membrane proteins water-soluble for functional studies and crystallization.

Mixed protein-surfactant micelles are used for in vitro studies and 3D crystallization when solutions of pure, monodisperse integral membrane proteins are required. However, many membrane proteins undergo inactivation when transferred from the biomembrane into micelles of conventional surfactants with alkyl chains as hydrophobic moieties. Here we describe the development of surfactants with rigid, saturated or aromatic hydrocarbon groups as hydrophobic parts.

Fine-tuning the amphiphilicity: a crucial parameter in the design of potent alpha-phenyl-N-tert-butylnitrone analogues.

A new series of hydrophilic, lipophilic, and amphiphilic alpha-phenyl-N-tert-butylnitrone (PBN) derivatives were synthesized to explore the relationship between their hydrophilic-lipophilic properties and antioxidant potency. Very potent protective effects of amphiphilic lactobionamide and tris(hydroxymethyl)aminomethane PBN derivatives were observed in mitochondrial preparations, in cell cultures, and in rotifers exposed to unspecific and mitochondria targeted oxidotoxins.

Evidence for control of nitric oxide synthesis by intracellular transforming growth factor-beta1 in tumor cells. Implications for tumor development.

Transforming growth factor-beta1 (TGF-beta1) has been shown to down-regulate NO synthesis in a variety of normal cells. In the present study, we investigated the influence of TGF-beta1 upon NO production in tumor cells and its consequences for tumor development. During the growth of PROb colon carcinoma cells intraperitoneally injected in syngeneic BDIX rats, intratumoral concentration of TGF-beta1 increases while NO concentration stays very low.

Altered complex formation between p21waf, p27kip and their partner G1 cyclins determines the stimulatory or inhibitory transforming growth factor-beta1 growth response of human fibroblasts.

TGF-beta1 stimulates proliferation of WI38 human embryo fibroblasts but inhibits that of their SV40-transformed counterparts, VA13 cells. Protein expression levels of cyclins A, D1, E and that of cdk2 and cdk4 were not affected by TGF-beta1 in either of these cells. However, TGF-beta1-treatment increases cdk2 kinase activity in WI38 cells and reduces it in VA13 cells.

Growth stimulation of murine fibroblasts by TGF-beta1 depends on the expression of a functional p53 protein.

Transforming Growth Factor-beta1 (TGF-beta1) inhibits the proliferation of most cells, but stimulates some mesenchymal cell types, including murine NIH3T3 fibroblasts. We show here that TGF-beta1 growth stimulation of NIH3T3 fibroblasts is reversed when these cells are transformed by SV40 or are transfected with a plasmid encoding the SV40 Large T antigen. Inversion of the TGF-beta1 growth stimulation of NIH3T3 cells is not observed when these cells are transfected with plasmids expressing either a mutant Large T, unable to bind P53, or the E1A adenovirus oncoprotein which binds the retinoblastoma protein pRB but not P53.

Transforming growth factor-beta1 enhances the lethal effects of DNA-damaging agents in a human lung-cancer cell line.

In tissue culture conditions, exogeneous active transforming growth factor-beta1 (TGF-beta1) enhances the lethal effect of DNA-damaging agents (UV-C, gamma rays, cisplatin, methotrexate and 5-fluorouracil) toward human A549 cells and mink Mv1Lu cells, as detected by the loss of their capacity to give rise to colonies; both these cell lines harbor a wild-type p53, as determined by immunoprecipitation. Contrastingly, the sole effect of the cytokine used alone is to inhibit reversibly the multiplication of the same cells without further impairing, once withdrawn from their environment, their capacity to divide and give rise to colonies. The lethal synergy between TGF-beta1 and UV-C was studied on mink and human cell lines, and the biomodulation by TGF-beta1 of cell killing by cisplatin, gamma rays, 5-fluorouracil or methotrexate was tested only on human cells.

Differential-effects of transforming growth-factor-Beta-1 on protein-levels of p21 waf and cdk-2 and on cdk-2 kinase-activity in human rd and ccl64 mink lung-cells.

Currently, the cyclin-dependent kinase inhibitor p21 WAF-1 is considered to be a crucial downstream effector in the p53-specific pathway of negative growth control in mammalian cells. Wild-type p53, but not mutant forms of this protein, transactivate the WAF-1 gene. We show a correlation between growth-inhibition and induction of WAF-1 protein expression following transforming growth factor-beta 1 (TGF-beta 1) treatment of two human tumour cell lines devoid of wild-type p53 protein and in SV40-transformed WI38 fibroblasts.

Synergism between growth-factors in the control of glioma cell-proliferation, migration and invasion in-vitro.

Gliomas constitute more than 50% of primary brain tumours in man. Perhaps the most important hallmark of these tumours is their diffuse invasion of the normal brain structures. The biological factors involved in the control of both their proliferation and invasion are, however, not well known.

Human wild type p53 inhibits cell proliferation and elicits dramatic morphological changes in human glioma cell lines in vitro.

A human pilocytic astrocytoma-derived cell line, a grade III astrocytoma-derived cell line, and a glioblastoma-derived cell line were transfected with the human wild-type p53 gene, in order to demonstrate the possible suppressor role of this gene in low grade as well as in high grade human astrocytomas. p53 exhibited a strong growth suppressor effect on the three cell lines studied, irrespective of the grade of malignancy of the tumours from which they originate. Furthermore, the p53 gene elicited important morphological changes in these cell lines.

Transforming growth factor-beta 1 enhances serum-induced dephosphorylation of the P53 protein in cell lines growth-inhibited by this factor.

A 24 hr TGF-beta 1 treatment (4 ng/ml) of SV40-transformed WI38 embryonic fibroblasts (VA13 cells) causes a moderate but reproducible inhibition of their serum-stimulated growth. By immunoprecipitation with the PAb122 antibody, we show that serum stimulation of previously serum-deprived cells causes a dephosphorylation of the wild type P53 protein, which is accentuated by the TGF-beta 1 treatment. The TGF-beta 1-enhanced dephosphorylation effect is also observed in two other cell lines growth-inhibited by TGF-beta 1, but which do not contain Large T (mink lung CCL64 and human KHOS cells).