RESUMEN
BACKGROUND: The Mediterranean diet is considered one of the healthier food habits and olive oil is one of its key components. Olive oil polyphenols are known to induce beneficial effects in several pathological conditions, such as inflammatory bowel disease, and to contrast the proliferation of cancer cells or hypercholesterolemia. Polyphenols are also present in waste products derived from the olive industry: olive mill wastewaters (OMWW) are rich in polyphenols and there is an increasing interest in using OMWW in animal nutrition. OMWW are attributed with positive effects in promoting chicken performance and the quality of food-derived products. However, a tissue-specific transcriptome target analysis of chickens fed with OMWW has never been attempted. RESULTS: We explored the effect of dietary OMWW on the intestinal function in broilers. A morphological analysis of the jejunum revealed that OMWW reduced crypt depth, whereas no significant modifications were observed for villus height and the villus height/crypt depth ratio. An RNA Sequencing analysis was performed on isolated, intestinal, epithelial cells and 280 differentially expressed genes were found using a count-based approach. An enrichment analysis revealed that the majority of up regulated genes in the OMWW group were over-represented by the regulation of viral genome replication-related GO-Terms, whereas down regulated genes were mainly involved in cholesterol and lipid metabolism. CONCLUSIONS: Our study showed how an industrial waste product can be recycled as a feed additive with a positive relapse. OMWW dietary supplementation can be a nutritional strategy to improve chicken performance and health, prevent intestinal damage, enhance innate immunity and regulate cholesterol metabolism and fat deposition.
Asunto(s)
Yeyuno/ultraestructura , Aceite de Oliva/química , Polifenoles/administración & dosificación , Transcriptoma/efectos de los fármacos , Aguas Residuales/química , Alimentación Animal , Animales , Pollos , Células Epiteliales/química , Células Epiteliales/efectos de los fármacos , Células Epiteliales/ultraestructura , Aditivos Alimentarios/química , Aditivos Alimentarios/farmacología , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica/efectos de los fármacos , Yeyuno/química , Yeyuno/efectos de los fármacos , Microscopía Electrónica de Transmisión , Aceite de Oliva/farmacología , Polifenoles/farmacología , Análisis de Secuencia de ARN/métodosRESUMEN
BACKGROUND: Essential oil (EO) dietary supplementation is a new strategy to improve animal health. EO compounds have antiparasitic, antimicrobial, antiviral, antimycotic, antioxidant and anti-inflammatory proprieties. Nutrigenomics investigations represent innovative approaches in understanding the relation between diet effect and gene expression related to the animal performance. Few nutrigenomics studies have used a high-throughput RNA-Sequencing (RNA-Seq) approach, despite great potential of RNA-Seq data in gene expression quantification and in co-expression network analyses. Our aim is to use the potential of RNA-Sequencing data in order to evaluate the effect of an EO supplementary diet on gene expression in both lamb liver and muscle. RESULTS: Using a treatment and sex interaction model, 13 and 4 differentially expressed genes were identified in liver and muscle respectively. Sex-specific differentially expressed (DE) genes were identified in both sexes. Using network based analysis, different clusters of co-expressed genes that were highly correlated to the diet were detected in males vs. females, in agreement with DE analysis. A total of five regulatory genes in liver tissue associated to EO diet were identified: DNAJB9, MANF, UFM1, CTNNLA1 and NFX1. Our study reveals a sex-dependent effect of EO diet in both tissues, and an influence on the expression of genes mainly involved in immune, inflammatory and stress pathway. CONCLUSION: Our analysis suggests a sex-dependent effect of the EO dietary supplementation on the expression profile of both liver and muscle tissues. We hypothesize that the presence of EOs could have beneficial effects on wellness of male lamb and further analyses are needed to understand the biological mechanisms behind the different effect of EO metabolites based on sex. Using lamb as a model for nutrigenomics studies, it could be interesting to investigate the effects of EO diets in other species and in humans.
Asunto(s)
Perfilación de la Expresión Génica/veterinaria , Redes Reguladoras de Genes , Hígado/química , Músculos/química , Aceites Volátiles/administración & dosificación , Animales , Suplementos Dietéticos , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Secuenciación de Nucleótidos de Alto Rendimiento/veterinaria , Hígado/efectos de los fármacos , Masculino , Músculos/efectos de los fármacos , Nutrigenómica , Aceites Volátiles/farmacología , Especificidad de Órganos , Análisis de Secuencia de ARN/veterinaria , Factores Sexuales , OvinosRESUMEN
Acute myeloid leukemia (AML) still represents an unmet clinical need for adult and pediatric patients. Adoptive cell therapy by chimeric antigen receptor (CAR)-engineered T cells demonstrated a high therapeutic potential, but further development is required to ensure a safe and durable disease remission in AML, especially in elderly patients. To date, translation of CAR T-cell therapy in AML is limited by the absence of an ideal tumor-specific antigen. CD123 and CD33 are the 2 most widely overexpressed leukemic stem cell biomarkers but their shared expression with endothelial and hematopoietic stem and progenitor cells increases the risk of undesired vascular and hematologic toxicities. To counteract this issue, we established a balanced dual-CAR strategy aimed at reducing off-target toxicities while retaining full functionality against AML. Cytokine-induced killer (CIK) cells, coexpressing a first-generation low affinity anti-CD123 interleukin-3-zetakine (IL-3z) and an anti-CD33 as costimulatory receptor without activation signaling domains (CD33.CCR), demonstrated a powerful antitumor efficacy against AML targets without any relevant toxicity on hematopoietic stem and progenitor cells and endothelial cells. The proposed optimized dual-CAR cytokine-induced killer cell strategy could offer the opportunity to unleash the potential of specifically targeting CD123+/CD33+ leukemic cells while minimizing toxicity against healthy cells.
Asunto(s)
Interleucina-3 , Leucemia Mieloide Aguda , Humanos , Niño , Anciano , Interleucina-3/metabolismo , Células Endoteliales/metabolismo , Linfocitos T , Línea Celular Tumoral , Leucemia Mieloide Aguda/patologíaRESUMEN
Intensive farming systems represent a stressful environment for pigs and negatively influence neuroendocrine functions, behavior, and performance. Outdoor farming is an alternative option, which is thought to imply several beneficial effects for the animal. Dietary essential oils are known to be an innovative strategy to improve pig health and performance, and oregano essential oil (ORE) possesses beneficial effects due to its antimicrobial, anti-fungal, and antioxidant properties. We tested the effect of dietary ORE on peripheral blood mononuclear cells (PBMCs) in 36 growing pigs, either reared under indoor or outdoor conditions. Quantitative real-time PCR (RT-qPCR) assay was used to evaluate the effect of diet (control vs. ORE) and the time of sampling (T1-120 days vs. T2-190 days) on the expression of inflammatory and immune-related genes (TNF, IL1ß, IL8, IL18, IL10, IL1RN, STAT3, HSP90, ICAM-1, and NFKB1). Under outdoor condition, the majority of transcripts were upregulated (p < 0.05), assuming a general inflammatory status (TNF, HSP90, NFKB1, IL1ß, and STAT3). However, an interaction between diet and the farming system was observed: HSP90, NFKB1, and STAT3 were downregulated (p < 0.05) in the outdoor reared pigs when fed the ORE diet. Our study showed that bioactive compounds of ORE exert their activity, especially when the animals are exposed to stressful stimuli. Dietary ORE can be an acceptable strategy to help pigs tolerate the stress related to the harsh, outdoor, rearing conditions.
RESUMEN
Intensive farming of broilers involves stressful conditions that reduce animal welfare and performance. New dietary strategies to improve performance and meat quality include the administration of plant extracts. Oregano (Origanum vulgare L.) is known for its antimicrobial, anti-fungal, insecticidal and antioxidant properties. However, studies on diet supplementation with oregano are mainly focused on the evaluation of animal performance, while partial information is available on transcriptomics and nutrigenomics and, in particular, Next Generation Sequencing (NGS) is not widely applied. In this study we tested the effect of an oregano aqueous extract supplemented diet on gene expression in broiler chickens. Whole liver transcriptome of 10 birds fed with a supplemented diet versus 10 controls was analyzed using the RNA-Seq technique. One hundred and twenty-nine genes were differentially expressed with an absolute log fold change >1. The analysis reveals a massive down-regulation of genes involved in fatty acid metabolism and insulin signaling pathways in broilers fed with the oregano aqueous extract supplementation. Down-regulated genes could be associated to chicken lean line, suggesting the potential beneficial effect of oregano supplementation in reducing both abdominal and visceral fat deposition. Down-regulation of insulin signaling pathway related genes suggest that dietary oregano supplementation might be an option in obesity and diabetes conditions.