Supplementation with low molecular weight peptides from fish protein hydrolysate reduces acute mild stress-induced corticosterone secretion and modulates stress responsive gene expression in mice

First evidence started to demonstrate the anxiolytic effects of low molecular weight peptides extracted from natural products, such as fish hydrolysate, but their underlying mechanisms remain to be elucidated. The objective of this study was to evaluate the effect of a chronic administration of fish hydrolysate on stress reactivity and to understand the mechanisms involved. Stress response (corticosterone secretion, expression of stress-responsive genes) was measured in Balb/c mice supplemented with fish hydrolysate (300 mg/kg body weight) or vehicle daily for 7 days before being submitted to an acute mild stress protocol. Our results demonstrated that 30 min after stress induction, fish hydrolysate decreased corticosterone level compared to control mice. Moreover, fish hydrolysate supplementation modulated expression of stress responsive genes involved in hypothalamic pituitary adrenal axis regulation, circadian rhythm and aging process. These findings suggest that fish hydrolysate represents an innovative strategy to prevent stress-induced aversive effects and participate in stress management

Recherche de biomarqueurs tissulaires de la cancerogenèse hépatique par imagerie Maldi

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Benefits of Circulating Human Metabolites from Fish Cartilage Hydrolysate on Primary Human Dermal Fibroblasts, an Ex Vivo Clinical Investigation for Skin Health Applications

International audienceDue to its significant exposure to stressful environmental factors, the skin undergoes a high remodeling rate over time, which alters not only its appearance but also its functionality. This alteration of the skin, namely photoaging, is characterized by dryness and a loss of elasticity that mainly originates from the dysregulation of dermal fibroblast activities. In order to overcome such tissue outcome, cosmetic products have evolved toward nutricosmetics, thus promoting beauty from within. Among bio-actives of interest, bio-peptides deriving from plant or animal sources may exert various biological activities beyond their nutritional value. However, studies remain mostly descriptive and the mode of action at the cellular level in clinic remains a concern. In a recent clinical trial, it was showed that supplementation with a fish cartilage hydrolysate (FCH) improved signs of chronological and photoaging-induced skin changes in healthy women. Here, using an original ex vivo clinical approach adapted to nutricosmetic purpose, we further demonstrated that this fish cartilage hydrolysate was absorbed and that the circulating metabolites produced in humans following FCH intake stimulate human dermal fibroblast growth, promote specific hyaluronan production, up-regulate elastin synthesis and inhibit MMP-1 and 3 expression along with the enhancement of TGF-β release. Altogether, these data provide clues on the mechanisms likely contributing to the beneficial impact of FCH on human skin functionality by supporting hydration, elasticity and limiting the expression of catabolic factors involved in photoaging onset

Tumoral heterogeneity of hepatic cholangiocarcinomas revealed by MALDI imaging mass spectrometry.

International audienceCholangiocarcinoma (CC) is the second most common primary malignancy of the liver. Although all CC derive from biliary epithelial cells, two main subtypes, hilar (H), and peripheral (P) CC are described. The objective of the study was to compare, using MALDI imaging mass spectrometry (MALDI IMS), in situ proteomic profiles of H- and P-CC in order to assess whether these subtypes may express different markers and to describe their respective localizations. Twenty-seven CC (16 P-CC and 11 H-CC) were subjected to MALDI IMS. Proteomic data were submitted to a dedicated cross-classification comparative design, enabling comparison of the entire generated spectra. Immunohistochemistry was performed for validation. Comparative analysis yielded a list of 19 differential protein peaks for the two subtypes, 14 of which were overexpressed in H-CC and five in P-CC. Among H-CC protein markers, most discriminant were human neutrophil peptides 1-3 that were expressed mainly by tumor cells and S100 proteins (A6 and A11) that were restricted to the stromal area. In P-CC, thymosin β4 was diffusely overexpressed. These results highlight the potential of MALDI IMS to discover new relevant biomarkers of CC and to characterize the heterogeneity of the two different subtypes

Fish Hydrolysate Supplementation Prevents Stress-Induced Dysregulation of Hippocampal Proteins Relative to Mitochondrial Metabolism and the Neuronal Network in Mice

International audienceOver the past several decades, stress has dramatically increased in occidental societies. The use of natural resources, such as fish hydrolysates, may be an attractive strategy to improve stress management. Our previous study demonstrated the anxiolytic effects of fish hydrolysate supplementation in mice exposed to acute mild stress by limiting stress-induced corticosterone release and modulating the expression of a number of stress-responsive genes. Here, we explore hippocampal protein modulation induced by fish hydrolysate supplementation in mice submitted to acute mild stress, with the aim of better elucidating the underlying mechanisms. Hippocampi from the same cohort of Balb/c mice supplemented with fish hydrolysate (300 mg.kg(-1) body weight) or vehicle daily for seven days before being submitted or not to an acute mild stress protocol (four groups, n = 8/group) were subjected to label-free quantitative proteomics analysis combined with gene ontology data mining. Our results show that fish hydrolysate supplementation prevented the observed stress-induced dysregulation of proteins relative to mitochondrial pathways and the neuronal network. These findings suggest that fish hydrolysate represents an innovative strategy to prevent the adverse effects of stress and participate in stress management

Imaging mass spectrometry provides fingerprints for distinguishing hepatocellular carcinoma from cirrhosis.

International audienceMALDI imaging mass spectrometry (MALDI IMS) is a powerful tool for comprehending the spectrum of peptides/proteins expressed in tissue sections. The aim of the present study was to investigate, using MALDI IMS, the proteome of hepatocellular carcinomas (HCC) and to compare it with peritumoral cirrhosis so as to characterize new biomarkers of HCC. Frozen liver tissues corresponding to HCC and background cirrhosis (n = 30) were selected and subjected to MALDI IMS. We found a set of proteins/peptides with a differential intensity level that most accurately delineated cancer from adjacent cirrhotic tissue. Using a support vector machine algorithm, we generated a classification model in the train set that enabled segmenting images from the independent validation set and that in most cases matched histologic analysis. The most discriminating peak (m/z 8565) more intense in HCC was characterized as the monomeric ubiquitin. An immunohistochemical study in a large series of HCC/cirrhosis sampled on tissue microarray supported that ubiquitin was overexpressed in HCC. We demonstrated also that this increase was not related to an upregulation of ubiquitin gene transcription in HCC, thus suggesting a post-transcriptional mechanism. This approach might provide a new tool for diagnosis of difficult HCC cases and an opportunity for identifying candidate biomarkers

Progression from cirrhosis to cancer is associated with early ubiquitin post-translational modifications: identification of new biomarkers of cirrhosis at risk of malignancy

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Proteomic Landscape of Cholangiocarcinomas Reveals 3 Different Subgroups According to their Localization and the Aspect of Non-Tumor Liver

International audiencePURPOSE:Cholangiocarcinomas (CC), tumors derived from epithelial biliary cells, define a heterogeneous entity based upon their anatomic localization (intra- versus extrahepatic) and, for those developing in the liver, depending on the aspect of non-tumor liver (normal versus cirrhosis). The aim of the study was to characterize the molecular heterogeneity of the different types of CC by a global proteomic approach.EXPERIMENTAL DESIGN:Thirty-three tumor samples from 17 intrahepatic CC (iCC) including 9 and 8 developed on normal (iCCN ) and cirrhotic liver (iCCC ), respectively; 5 hilar CC (CCH ), 5 CC developed in the pancreatic portion of the bile duct (CCP ) and 6 hepatocellular carcinoma (HCC), were submitted to label-free quantitative proteomic analysis. Differentially expressed proteins were further analyzed by immunohistochemistry in a validation set of 30 CC.RESULTS:In the overall series, 4590 proteins were quantified. Unsupervised analysis revealed two main clusters: cluster 1 contained most the iCCC while cluster 2 was divided in 2 subgroups, one containing most of the iCCN and the other regrouping CCH and CCP . Compared to iCCN , iCCC displayed upregulation of molecules involved in cell adhesion and motility and in angiogenesis. Epithelial markers associated with secretory pathway (mucins and AGR2) as well as fibroblast markers (S100A4) were overexpressed in CCH compared to iCCN .CONCLUSION AND CLINICAL RELEVANCE:This study demonstrated that among iCC, iCCC is a specific entity, suggesting a major impact of the underlying liver condition on the tumor biology, and confirmed that extrahepatic CCs, including CCP and CCH, define an homogeneous subgroup