CAT25 defines microsatellite instability in colorectal cancer by high-resolution melting PCR

Background: CAT25 (T25mononucleotide repeat of the Caspase 2 gene), is a promising DNA marker for detecting microsatellite instability (MSI) in colorectal cancer. CAT25 has the potential to be incorporated into the Bethesda panel, a commonly used panel of DNA microsatellites, or replace it in its entirety. We aimed to develop and validate a high-resolution melting-PCR (HRM-PCR) method for CAT25 instability detection in clinical samples. Methods: The instability of CAT25, BAT25 (a poly(A) tract occurring in c‐kit) and BAT26 (a poly(A) tract localized in hMSH2) microsatellites were assessed in DNA from tumour and peripheral blood obtained from 110 patients with colorectal cancer using HRM-PCR and capillary electrophoresis. Immunohistochemistry (IHC) staining for MSH2, MSH6, MLH1, and PMS2 enzymes was performed on tumours with jigj MSI. Allelic size variation of CAT25 was analysed on peripheral blood DNA from 208 healthy volunteers. Results: The HRM-PCR for CAT25 was validated in clinical samples. CAT25 showed a tight range of 64–66 base pairs. Of 110 tumours, 11 had High MSI, later confirmed by IHC. CAT25 defines MSI alone as well as when used together with BAT25 and BAT26. CAT25 results provided 100% predictive values and p < 0.0001 to classify a tumour as having high MSI. Conclusions: We developed and validated a new HRM-PCR assay to detect CAT25 instability. Our findings showed a limited allelic size variation of CAT25 and highlighted to CAT25 as a promising marker for MSI analysis.Fil: Sánchez, A.G.. Hospital Privado Universitario de Córdoba; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; ArgentinaFil: Juaneda, I.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Eynard, H.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Basquiera, Ana Lisa. Hospital Privado Universitario de Córdoba; ArgentinaFil: Palazzo, E.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Calafat, P.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Palla, V.. Hospital Privado Universitario de Córdoba; ArgentinaFil: Romagnoli, Pablo Alberto. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa | Instituto de Investigación Médica Mercedes y Martín Ferreyra. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Grupo Vinculado Centro de Investigación en Medicina Traslacional Severo R. Amuchástegui - Cimetsa; ArgentinaFil: Alvarellos, T.. Hospital Privado Universitario de Córdoba; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentin

Omega-3 Fatty Acids from Fish Oil Lower Anxiety, Improve Cognitive Functions and Reduce Spontaneous Locomotor Activity in a Non-Human Primate

Omega-3 (ω3) polyunsaturated fatty acids (PUFA) are major components of brain cells membranes. ω3 PUFA-deficient rodents exhibit severe cognitive impairments (learning, memory) that have been linked to alteration of brain glucose utilization or to changes in neurotransmission processes. ω3 PUFA supplementation has been shown to lower anxiety and to improve several cognitive parameters in rodents, while very few data are available in primates. In humans, little is known about the association between anxiety and ω3 fatty acids supplementation and data are divergent about their impact on cognitive functions. Therefore, the development of nutritional studies in non-human primates is needed to disclose whether a long-term supplementation with long-chain ω3 PUFA has an impact on behavioural and cognitive parameters, differently or not from rodents. We address the hypothesis that ω3 PUFA supplementation could lower anxiety and improve cognitive performances of the Grey Mouse Lemur (Microcebus murinus), a nocturnal Malagasy prosimian primate. Adult male mouse lemurs were fed for 5 months on a control diet or on a diet supplemented with long-chain ω3 PUFA (n = 6 per group). Behavioural, cognitive and motor performances were measured using an open field test to evaluate anxiety, a circular platform test to evaluate reference spatial memory, a spontaneous locomotor activity monitoring and a sensory-motor test. ω3-supplemented animals exhibited lower anxiety level compared to control animals, what was accompanied by better performances in a reference spatial memory task (80% of successful trials vs 35% in controls, p<0.05), while the spontaneous locomotor activity was reduced by 31% in ω3-supplemented animals (p<0.001), a parameter that can be linked with lowered anxiety. The long-term dietary ω3 PUFA supplementation positively impacts on anxiety and cognitive performances in the adult mouse lemur. The supplementation of human food with ω3 fatty acids may represent a valuable dietary strategy to improve behavioural and cognitive functions

Effects of the total replacement of fish-based diet with plant-based diet on the hepatic transcriptome of two European sea bass (Dicentrarchus labrax) half-sibfamilies showing different growth rates with the plant-based diet

Background: Efforts towards utilisation of diets without fish meal (FM) or fish oil (FO) in finfish aquaculture have been being made for more than two decades. Metabolic responses to substitution of fishery products have been shown to impact growth performance and immune system of fish as well as their subsequent nutritional value, particularly in marine fish species, which exhibit low capacity for biosynthesis of long-chain poly-unsaturated fatty acids (LC-PUFA). The main objective of the present study was to analyse the effects of a plant-based diet on the hepatic transcriptome of European sea bass (Dicentrarchus labrax). Results: We report the first results obtained using a transcriptomic approach on the liver of two half-sibfamilies of the European sea bass that exhibit similar growth rates when fed a fish-based diet (FD), but significantly different growth rates when fed an all-plant diet (VD). Overall gene expression was analysed using oligo DNA microarrays (GPL9663). Statistical analysis identified 582 unique annotated genes differentially expressed between groups of fish fed the two diets, 199 genes regulated by genetic factors, and 72 genes that exhibited diet-family interactions. The expression of several genes involved in the LC-PUFA and cholesterol biosynthetic pathways was found to be up-regulated in fish fed VD, suggesting a stimulation of the lipogenic pathways. No significant diet-family interaction for the regulation of LC-PUFA biosynthesis pathways could be detected by microarray analysis. This result was in agreement with LC-PUFA profiles, which were found to be similar in the flesh of the two half-sibfamilies. In addition, the combination of our transcriptomic data with an analysis of plasmatic immune parameters revealed a stimulation of complement activity associated with an immunodeficiency in the fish fed VD, and different inflammatory status between the two half-sibfamilies. Biological processes related to protein catabolism, amino acid transaminations, RNA splicing and blood coagulation were also found to be regulated by diet, while the expression of genes involved in protein and ATP synthesis differed between the half-sibfamilies. Conclusions: Overall, the combined gene expression, compositional and biochemical studies demonstrated a large panel of metabolic and physiological effects induced by total substitution of both FM and FO in the diets of European sea bass and revealed physiological characteristics associated with the two half-sibfamilies

Lipid Composition of the Human Eye: Are Red Blood Cells a Good Mirror of Retinal and Optic Nerve Fatty Acids?

International audienceBACKGROUND: The assessment of blood lipids is very frequent in clinical research as it is assumed to reflect the lipid composition of peripheral tissues. Even well accepted such relationships have never been clearly established. This is particularly true in ophthalmology where the use of blood lipids has become very common following recent data linking lipid intake to ocular health and disease. In the present study, we wanted to determine in humans whether a lipidomic approach based on red blood cells could reveal associations between circulating and tissue lipid profiles. To check if the analytical sensitivity may be of importance in such analyses, we have used a double approach for lipidomics. METHODOLOGY AND PRINCIPAL FINDINGS: Red blood cells, retinas and optic nerves were collected from 9 human donors. The lipidomic analyses on tissues consisted in gas chromatography and liquid chromatography coupled to an electrospray ionization source-mass spectrometer (LC-ESI-MS). Gas chromatography did not reveal any relevant association between circulating and ocular fatty acids except for arachidonic acid whose circulating amounts were positively associated with its levels in the retina and in the optic nerve. In contrast, several significant associations emerged from LC-ESI-MS analyses. Particularly, lipid entities in red blood cells were positively or negatively associated with representative pools of retinal docosahexaenoic acid (DHA), retinal very-long chain polyunsaturated fatty acids (VLC-PUFA) or optic nerve plasmalogens. CONCLUSIONS AND SIGNIFICANCE: LC-ESI-MS is more appropriate than gas chromatography for lipidomics on red blood cells, and further extrapolation to ocular lipids. The several individual lipid species we have identified are good candidates to represent circulating biomarkers of ocular lipids. However, further investigation is needed before considering them as indexes of disease risk and before using them in clinical studies on optic nerve neuropathies or retinal diseases displaying photoreceptors degeneration

Pulmonary vascular research institute GoDeep: a meta-registry merging deep phenotyping datafrom international PH reference centers

The Pulmonary Vascular Research Institute GoDeep meta-registry is a collaboration of pulmonary hypertension (PH) reference centers across the globe. Merging worldwide PH data in a central meta-registry to allow advanced analysis of the heterogeneity of PH and its groups/subgroups on a worldwide geographical, ethnical, and etiological landscape (ClinTrial. gov NCT05329714). Retrospective and prospective PH patient data (diagnosis based on catheterization; individuals with exclusion of PH are included as a comparator group) are mapped to a common clinical parameter set of more than 350 items, anonymized and electronically exported to a central server. Use and access is decided by the GoDeep steering board, where each center has one vote. As of April 2022, GoDeep comprised 15,742 individuals with 1.9 million data points from eight PH centers. Geographic distribution comprises 3990 enrollees (25%) from America and 11,752 (75%) from Europe. Eighty-nine perecent were diagnosed with PH and 11% were classified as not PH and provided a comparator group. The retrospective observation period is an average of 3.5 years (standard error of the mean 0.04), with 1159 PH patients followed for over 10 years. Pulmonary arterial hypertension represents the largest PH group (42.6%), followed by Group 2 (21.7%), Group 3 (17.3%), Group 4 (15.2%), and Group 5 (3.3%). The age distribution spans several decades, with patients 60 years or older comprising 60%. The majority of patients met an intermediate risk profile upon diagnosis. Data entry from a further six centers is ongoing, and negotiations with >10 centers worldwide have commenced. Using electronic interface-based automated retrospective and prospective data transfer, GoDeep aims to provide in-depth epidemiological and etiological understanding of PH and its various groups/subgroups on a global scale, offering insights for improved management

Adrenomedullin and tumour microenvironment

Adrenomedullin (AM) is a regulatory peptide whose involvement in tumour progression is becoming more relevant with recent studies. AM is produced and secreted by the tumour cells but also by numerous stromal cells including macrophages, mast cells, endothelial cells, and vascular smooth muscle cells. Most cancer patients present high levels of circulating AM and in some cases these higher levels correlate with a worst prognosis. In some cases it has been shown that the high AM levels return to normal following surgical removal of the tumour, thus indicating the tumour as the source of this excessive production of AM. Expression of this peptide is a good investment for the tumour cell since AM acts as an autocrine/paracrine growth factor, prevents apoptosis-mediated cell death, increases tumour cell motility and metastasis, induces angiogenesis, and blocks immunosurveillance by inhibiting the immune system. In addition, AM expression gets rapidly activated by hypoxia through a HIF-1α mediated mechanism, thus characterizing AM as a major survival factor for tumour cells. Accordingly, a number of studies have shown that inhibition of this peptide or its receptors results in a significant reduction in tumour progression. In conclusion, AM is a great target for drug development and new drugs interfering with this system are being developed

Influence d'un entraînement physique prolongé sur la composition en acides gras du tissu adipeux épididymaire et de la carcasse chez le jeune rat soumis à un régime à base d'huile de tournesol, colza ou primor

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EFFETS A TRES COURT TERME DE L'HUILE DE COLZA SUR LES LIPIDES CARDIAQUES ET HÉPATIQUES DU RAT SEVRÉ : INFLUENCE DU RAFFINAGE ET DE L'INTERESTÉRIFICATION

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