Serum soluble mediator waves and networks along healthy ageing.

The ageing process is a complex phenomenon that impacts the immune system, leading to changes in the pattern of serum soluble mediators. In the present study, the serum levels of several chemokines, pro-inflammatory/regulatory cytokines and growth factors were quantified by high-throughput microbeads array in serum samples from 541 healthy subjects at distinct age ranges (3Yrs to >70Yrs). A broad increase in serum soluble mediators was observed at 6-10Yrs with subsequent decline at 11-20Yrs and 21-30Yrs followed by a second round of upregulation starting at 31-40Yrs, with a large increase at 51-60Yrs and a marked decline at age >70Yrs. Heatmap and signatures of serum soluble mediators demonstrated a bimodal profile with one peak at 6-10Yrs and a second wave around 61-70Yrs. A universal decline was observed later at age >70Yrs. In males, the second wave started earlier at 31-40Yrs with a peak at 51-60Yrs and a further smooth decline towards >70Yrs. Conversely, in females, the first peak extended from 3-5Yrs to 6-10Yrs and the second wave starting around 41-50Yrs with a peak at 61-70Yrs followed by a sharp decline at >70Yrs. Overall, CCL11, CXCL8, IL-1ß, IL-6 were underscored as universal age-related biomarkers with higher levels observed at later age ranges (after 31-40Yrs) and TNF with increased levels starting at early age ranges. Data analysis demonstrated that the highest neighborhood connectivity amongst soluble mediators occurred at 3-5Yrs, with distinct declining and strengthening rhythm in males and females. Notably, rebuilding re-arrangements were usually earlier and more frequent in females (at 11-20Yrs, 51-60Yrs and >70Yrs) than in males (at 21-30Yrs, 61-70Yrs). Overall, this study provided a comprehensive landscape of evidence portrayed by distinct waves, rhythms and dynamic network connectivity along healthy ageing with differences in magnitude and timing reported for sexes.

Effects of Holder Pasteurization on Immune Composition of Human Milk.

Background: Human milk (HM) is the ideal food for newborn (NB) nutrition, it provides all macro and micronutrients for human growth and development and also contains bioactive compounds, which influence the development of the neonatal digestive and immune systems. The holder pasteurization process is essential to prevent NB infection from donated milk. Therefore, the aim of this study was to check whether or not holder pasteurization could impact the concentration of immune components in HM and the capacity to induce epithelial cell growth. Materials and Methods: The study was performed on raw and holder pasteurized (62.5°C/30 minutes) paired milk samples after submission to the freezing process in both phases. For cytokine and adipokine measurements, ELISA was performed on 40 individual samples of HM from single donors. For analyzes of epithelial cell growth, HuTu-80 cells were cultivated in Minimum Essential Eagle medium with 15% of raw or pasteurized milk, eight pairs of milk were used. Results: The results showed that no alteration was observed in the concentration of cytokine after milk holder pasteurization, and leptin concentration was reduced in holder pasteurized milk. The heat treatment also did not impact the capacity of breast milk to promote intestinal epithelial cell growth. Conclusions: The results showed that donated breast milk pasteurization has a small impact on the HM bioactive concentration compounds. This technique is important to avoid NB infection.

Host dysbiosis negatively impacts IL-9-producing T-cell differentiation and antitumour immunity.

BACKGROUND: Host-microbiota interactions shape T-cell differentiation and promote tumour immunity. Although IL-9-producing T cells have been described as potent antitumour effectors, their role in microbiota-mediated tumour control remains unclear. METHODS: We analysed the impact of the intestinal microbiota on the differentiation of colonic lamina propria IL-9-producing T cells in germ-free and dysbiotic mice. Systemic effects of the intestinal microbiota on IL-9-producing T cells and the antitumour role of IL-9 were analysed in a model of melanoma-challenged dysbiotic mice. RESULTS: We show that germ-free mice have lower frequency of colonic lamina propria IL-9-producing T cells when compared with conventional mice, and that intestinal microbiota reconstitution restores cell frequencies. Long-term antibiotic treatment promotes host dysbiosis, diminishes intestinal IL-4 and TGF-ß gene expression, decreases the frequency of colonic lamina propria IL-9-producing T cells, increases the susceptibility to tumour development and reduces the frequency of IL-9-producing T cells in the tumour microenvironment. Faecal transplant restores intestinal microbiota diversity, and the frequency of IL-9-producing T cells in the lungs of dysbiotic animals, restraining tumour burden. Finally, recombinant IL-9 injection enhances tumour control in dysbiotic mice. CONCLUSIONS: Host-microbiota interactions are required for adequate differentiation and antitumour function of IL-9-producing T cells.

High-fat diet withdrawal modifies alcohol preference and transcription of dopaminergic and GABAergic receptors.

The bidirectional and positive relation between the ingestion of fat and alcohol has become the subject of extensive discussion. However, this relation is more studied in animal models of binge eating with intermittent access of high-fat diet or in a model of short period of this diet consumption. Here, we developed a model to elucidate how chronic high-fat diet and its withdrawal influence alcohol intake (two-bottle choice) and anxiety behavior (marble burying test). In the first experimental stage, animals were fed on standard (AIN93G) or high sugar and butter (HSB) diet for 8 weeks. Then, a protocol of free-choice between water and a 10% alcohol solution was introduced, and the HSB diet was replaced with AIN93G in two experimental groups. The result obtained with this model point out that the relation among high-fat diet consumption and alcohol intake appears to depend on the presence or absence of the diet when alcohol intake is evaluated, and that an imbalance in the mesocorticolimbic dopaminergic pathway, observed by the transcriptional regulation of the dopamine receptors (Drd1/Drd2) and GABAB receptors subunit (Gabbr1/Gabbr2), can be driving the alcohol intake.

Obesity induction in hamster that mimics the human clinical condition.

Although obesity is well established in hamsters, studies using diets with high levels of simple carbohydrate associated with lipids are necessary to assess the impact of this type of food in the body. In this study a high sugar and butter diet (HSB) and high temperature were employed towards this end. Obesity was successfully induced at a temperature of 30.3°C to 30.9°C after 38 days feeding the animals an HSB diet. It was shown that although diet is important for the induction of obesity, temperature is also essential because at a temperature slightly below the one required, obesity was not induced, even when the animals were fed for a longer period (150 days).The obese clinical condition was accompanied by biochemical and hematological changes, as increased cholesterol and triglyceride levels and increased leukocyte numbers, similar to alterations observed in obese humans. Furthermore, it was demonstrated that increasing the intake of simple carbohydrates associated with lipids provided evidence of inflammation in obese animals.