Tumor-driven immune suppression is a major barrier to successful immunotherapy in ovarian carcinomas (OvCa). Among various mechanisms responsible for immune suppression, arginase-1 (ARG1)-carrying small extracellular vesicles (EVs) emerge as important contributors to tumor growth and tumor escape from the host immune system. Here, we report that small EVs found in the ascites and plasma of OvCa patients contain ARG1. EVs suppress proliferation of CD4 + and CD8 + T-cells in vitro and in vivo in OvCa mouse models. In mice, ARG1-containing EVs are transported to draining lymph nodes, taken up by dendritic cells and inhibit antigen-specific T-cell proliferation. Increased expression of ARG1 in mouse OvCa cells is associated with accelerated tumor progression that can be blocked by an arginase inhibitor. Altogether, our studies show that tumor cells use EVs as vehicles to carry over long distances and deliver to immune cells a metabolic checkpoint molecule – ARG1, mitigating anti-tumor immune responses.

Lesions made in the anterior medial basal hypothalamus (MBH) in pregnant or lactating ewes caused lack of development of the mammary gland and depressed milk yield, a decrease in plasma prolactin concentration and structural changes in the prolactin cells as manifested by a lack of the expected degranulation (lack of the hormone release) or by atrophic changes and diminished cell granulation (or granule synthesis). Lesions made in the caudal MBH during pregnancy advanced development of the mammary gland, induced a rapid increase in the plasma prolactin concentration and caused extensive degranulation of prolactin cells. These results indicate that at least two functional systems controlling the secretion and production of prolactin exist in the hypothalamus of sheep: an anterior system which is stimulatory and a caudal which is inhibitory.

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance that appears or is for the first time diagnosed during pregnancy. It can lead to many complications in the mother and in the offspring, so diagnostics and management of GDM are important to avoid adverse pregnancy outcomes. Epigenetic studies revealed the different methylation status of genes in pregnancies with GDM compared to pregnancies without GDM. A growing body of evidence shows that the GDM can affect not only the course of the pregnancy, but also the development of the offspring, thus contributing to long-term effects and adverse health outcomes of the progeny. Epigenetic changes occur through histone modification, DNA methylation, and disrupted function of non-coding ribonucleic acid (ncRNA) including microRNAs (miRNAs). In this review, we focus on the recent knowledge about epigenetic changes in GDM. The analysis of this topic may help us to understand pathophysiological mechanisms in GDM and find a solution to prevent their consequences.

Serotonin or melatonin was infused into the 3rd cerebral ventricle (3rd V) or into the medial basal hypothalamus (MBH) of both intact ewes and ewes with lesions of the anterior hypothalamic area (AHA). Prolongation of the estrous cycle and delay of ovulation were obtained after infusions of melatonin or serotonin in both the intact and lesioned ewes. Statistically, serotonin proved to be more effective in this respect than melatonin in the intact ewes. The infusions also blocked the preovulatory peak of LH. Furthermore, the infusion of serotonin blocked estrous behavior, while that of melatonin did not affect this function. The effect of indoleamie infusions in the lesioned ewes, in which the inhibitory action of the AHA over the transmission of gonadotrophic releasing hormones (G-RH) had been eliminated, seems to indicate that the inhibitory action of indoleamines on the release of these neurohormones is being displayed at the level of the MBH.

Hepatocellular carcinoma (HCC) remains a serious oncologic issue with still a dismal prognosis. So far, no key molecular mechanism that underlies its pathogenesis has been identified. Recently, by specific molecular approaches, many genetic and epigenetic changes arising during HCC pathogenesis were detected. Epigenetic studies revealed modified methylation patterns in HCC tumors, dysfunction of enzymes engaged in the DNA methylation process, and a set of histone modifications that influence gene expression. HCC cells are also influenced by the disrupted function of non-coding RNAs, such as micro RNAs and long non-coding RNAs. Moreover, a role of liver cancer stem cells in HCC development is becoming evident. The reversibility of epigenetic changes offers the possibility of influencing them and regulating their undesirable effects. All these data can be used not only to identify new therapeutic targets but also to predict treatment response. This review focuses on epigenetic changes in hepatocellular carcinoma and their possible implications in HCC therapy.