Epigenetics in Canine Mammary Tumors: Upregulation of miR-18a and miR-18b Oncogenes Is Associated with Decreased ERS1 Target mRNA Expression and ERα Immunoexpression in Highly Proliferating Carcinomas

The expression of miRNAs is one of the main epigenetic mechanisms responsible for the regulation of gene expression in mammals, and in cancer, miRNAs participate by regulating the expression of protein-coding cancer-associated genes. In canine mammary tumors (CMTs), the ESR1 gene encodes for ERa, and represents a major target gene for miR-18a and miR-18b, previously found to be overexpressed in mammary carcinomas. A loss in ERa expression in CMTs is commonly associated with poor prognosis, and it is noteworthy that the downregulation of the ESR1 would appear to be more epigenetic than genetic in nature. In this study, the expression of ESR1 mRNA in formalin-fixed, paraffin-embedded (FFPE) canine mammary tumors (CMTs) was evaluated and compared with the expression levels of miR18a and miR18b, both assessed via RT-qPCR. Furthermore, the possible correlation between the miRNA expression data and the immunohistochemical prognostic factors (ERa immunoexpression; Ki67 proliferative index) was explored. A total of twenty-six FFPE mammary samples were used, including 22 CMTs (7 benign; 15 malignant) and four control samples (three normal mammary glands and one case of lobular hyperplasia). The obtained results demonstrate that miR-18a and miR-18b are upregulated in malignant CMTs, negatively correlating with the expression of target ESR1 mRNA. Of note, the upregulation of miRNAs strictly reflects the progressive loss of ERa immunoexpression and increased tumor cell proliferation as measured using the Ki67 index. The results suggest a central role of miR-18a and miR-18b in the pathophysiology of canine mammary tumors as potential epigenetic mechanisms involved in ERa downregulation. Moreover, as miRNA expression reflects ERa protein status and a high proliferative index, miR-18a and miR-18b may represent promising biomarkers with prognostic value. More detailed investigations on a larger number of cases are needed to better understand the influence of these miRNAs in canine mammary tumors

Administration of protein hydrolysates from anchovy (Engraulis encrasicolus) waste for twelve weeks decreases metabolic dysfunction‐associated fatty liver disease severity in ApoE–/–mice

Metabolic dysfunction‐associated fatty liver disease (MAFLD) includes several diseases, ranging from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Fish‐rich diets are considered helpful in the prevention of MAFLD, and the enzymatic hydrolysis of fish waste has been explored as a means of obtaining high‐value protein hydrolysates, which have been proven to exert beneficial bioactivities including anti‐obesity and hypocholesterol effects. This study aimed to assess the effect of the administration of protein hydrolysates from anchovy waste (APH) for 12 weeks on attenuated high‐fat diet‐induced MAFLD in apolipoprotein E‐knockout mice (ApoE–/–). Thirty ApoE–/– mice were divided into two groups (n = 15/group) and fed a high‐fat diet (HFD), with and without the addition of 10% (w/w) APH. After 12 weeks, serum and hepatic lipid profiles, hepatic enzyme activities, liver histology and immunohistochemistry were analyzed to assess hepatic steatosis, inflammation and fibrosis. Twelve‐weeks on a 10% (w/w) APH diet reduces total cholesterol and triglyceride serum levels, hepatic enzyme activity and hepatic triacylglycerol content (p < 0.0001), and results in a reduction in hepatic fat accumulation and macrophage recruitment (p < 0.0001). The results suggest that a 10% APH diet has an anti‐obesity effect, with an improvement in lipid metabolism, hepatic steatosis and liver injury as a result of a high‐fat diet. Protein hydrolysates from fish waste may represent an efficient nutritional strategy in several diseases, and their use as nutraceuticals is worthy of future investigation

Evaluating CCTs from a Gender Perspective: The Impact of Chile Solidario on Women's Employment Prospect

This paper examines the effects of the Chile Solidario programme on labour market outcomes from a gender perspective. Chile Solidario was implemented as the main anti-poverty programme in Chile in 2002. The purpose of this conditional cash transfer is to provide poor families with auxiliary social services, including support for employment. We compare the gender impact of Chile Solidario using difference-in-differences and regression discontinuity design estimations based on data from the Chile Solidario Panel Survey. We find that the programme has a strong impact on labour market outcomes. However, the positive effects are particularly important for women subjects in the beneficiary families only after the achievement of the conditionalities imposed by the programme. This analysis suggests that cash transfers should be targeted more specifically to women's needs to contribute to their empowerment