In breast cancer, lipid metabolic alterations have been recognized as potential oncogenic stimuli that may promote malignancy. To investigate whether the oncogenic nature of lipogenesis closely depends on the overexpression of HER2 protooncogene, the normal breast cell line, HB4a, was transfected with HER2 cDNA to obtain HER2-overexpressing HB4aC5.2 cells. Both cell lines were treated with trastuzumab and docosahexaenoic acid. HER2 overexpression was accompanied by an increase in the expression of lipogenic genes involved in uptake (CD36), transport (FABP4), and storage (DGAT) of exogenous fatty acids (FA), as well as increased activation of “de novo” FA synthesis (FASN). We further investigate whether this lipogenesis reprogramming might be regulated by mTOR/PPARγpathway. Inhibition of the mTORC1 pathway markers, p70S6 K1, SREBP1, and LIPIN1, as well as an increase in DEPTOR expression (the main inhibitor of the mTOR) was detected in HB4aC5.2. Based on these results, a PPARγselective antagonist, GW9662, was used to treat both cells lines, and the lipogenic genes remained overexpressed in the HB4aC5.2 but not HB4a cells. DHA treatment inhibited all lipogenic genes (except for FABP4) in both cell lines yet only induced death in the HB4aC5.2 cells, mainly when associated with trastuzumab. Neither trastuzumab nor GW9662 alone was able to induce cell death. In conclusion, oncogenic transformation of breast cells by HER2 overexpression may require a reprogramming of lipogenic genetic that is independent of mTORC1 pathway and PPARγactivity. This reprogramming was inhibited by DHA.

(1) Purpose: Performing strenuous exercises negatively impacts the immune and gastrointestinal systems. These alterations cause transient immunodepression, increasing the risk of minor infections, especially in the upper respiratory tract. Recent studies have shown that supplementation of probiotics confers benefits to athletes. Therefore, the objective of the current study was to verify the effects of probiotic supplementation on cytokine production by monocytes and infections in the upper respiratory tract after an acute strenuous exercise. (2) Methods: Fourteen healthy male marathon runners received either 5 billion colony forming units (CFU) of a multi-strain probiotic, consisting of 1 billion CFU of each of Lactobacillus acidophilus LB-G80, Lactobacillus paracasei LPc-G110, Lactococcus subp. lactis LLL-G25, Bifidobacterium animalis subp. lactis BL-G101, and Bifidobacterium bifidum BB-G90, or a placebo for 30 days before a marathon. Plasma cytokines, salivary parameters, glucose, and glutamine were measured at baseline, 24 h before, immediately after, and 1 h after the race. Subjects self-reported upper respiratory tract infection (URTI) using the Wisconsin Upper Respiratory Symptom Survey (WURSS—21). The statistical analyses comprised the general linear model (GLM) test followed by the Tukey post hoc and Student’s t-test with p < 0.05. (3) Results: URTI symptoms were significantly lower in the probiotic group compared to placebo. The IL-2 and IL-4 plasma cytokines were lower 24 h before exercise, while the other cytokines showed no significant differences. A lower level of IL-6 produced by monocytes was verified immediately after the race and higher IL-10 at 1 h post. No differences were observed in salivary parameters. Conclusion: Despite the low number of marathoners participating in the study, probiotic supplementation suggests its capability to preserve the functionality of monocytes and mitigate the incidence of URTI.

We evaluated whether the excluded stomach (ES) after Roux-en-Y gastric bypass (RYGB) can represent a premalignant environment. Twenty obese women were prospectively submitted to double-balloon enteroscopy (DBE) with gastric juice and biopsy collection, before and 3 months after RYGB. We then evaluated morphological and molecular changes by combining endoscopic and histopathological analyses with an integrated untargeted metabolomics and transcriptomics multiplatform. Preoperatively, 16 women already presented with gastric histopathological alterations and an increased pH (≥4.0). These gastric abnormalities worsened after RYGB. A 90-fold increase in the concentration of bile acids was found in ES fluid, which also contained other metabolites commonly found in the intestinal environment, urine, and faeces. In addition, 135 genes were differentially expressed in ES tissue. Combined analysis of metabolic and gene expression data suggested that RYGB promoted activation of biological processes involved in local inflammation, bacteria overgrowth, and cell proliferation sustained by genes involved in carcinogenesis. Accumulated fluid in the ES appears to behave as a potential premalignant environment due to worsening inflammation and changing gene expression patterns that are favorable to the development of cancer. Considering that ES may remain for the rest of the patient’s life, long-term ES monitoring is therefore recommended for patients undergoing RYGB.

Background: The gut–brain axis may mediate mood changes due to strenuous exercise. Therefore, probiotic supplementation may mitigate mood worsening. Purpose: The present study aims to evaluate the effect of probiotic supplementation on mood and immunometabolic parameters after a marathon. Materials and methods: Fourteen marathon runners were selected and divided into placebo and probiotic groups that were supplemented for 30 days. Before and after the marathon, mood (POMS) was assessed, and blood was collected for analysis of immunometabolic parameters. Statistical analysis was performed, and p < 0.05 was considered to determine statistically differences. Results: Tension decreased after the marathon in both groups. Vigor decreased only in the placebo group. Fatigue increased after the marathon in both groups. TMD increased after the marathon in placebo. The IL2/IL-4 ratio decreased in the probiotic group after the marathon compared to before and increased compared to the placebo group. The IL-10 increased after the marathon in placebo. TNF-α increased after the marathon in probiotics. The TNF-α/IL-10 ratio decreased after the marathon in both groups. LPS decreased in the probiotic group after the marathon compared to before and in the placebo group. Conclusions: Thirty days of probiotic supplementation attenuated the impact of marathons on mood worsening. The decrease in LPS in the probiotic group mediated the change in the pro/anti-inflammatory balance, indicating an immunometabolic mechanism by which the gut–brain axis impacts mood after strenuous exercise.