Neuroendocrine–immune disequilibrium and endometriosis: an interdisciplinary approach

Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, protein–glycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis

Time- and dose dependent actions of cardiotonic steroids on transcriptome and intracellular content of Na+ and K+: a comparative analysis

Recent studies demonstrated that in addition to Na(+),K(+)-ATPase inhibition cardiotonic steroids (CTSs) affect diverse intracellular signaling pathways. This study examines the relative impact of [Na(+)](i)/[K(+)](i)-mediated and -independent signaling in transcriptomic changes triggered by the endogenous CTSs ouabain and marinobufagenin (MBG) in human umbilical vein endothelial cells (HUVEC). We noted that prolongation of incubation increased the apparent affinity for ouabain estimated by the loss of [K(+)](i) and gain of [Na(+)](i). Six hour exposure of HUVEC to 100 and 3,000 nM ouabain resulted in elevation of the [Na(+)](i)/[K(+)](i) ratio by ~15 and 80-fold and differential expression of 258 and 2185 transcripts, respectively. Neither [Na(+)](i)/[K(+)](i) ratio nor transcriptome were affected by 6-h incubation with 30 nM ouabain. The 96-h incubation with 3 nM ouabain or 30 nM MBG elevated the [Na(+)](i)/[K(+)](i) ratio by ~14 and 3-fold and led to differential expression of 880 and 484 transcripts, respectively. These parameters were not changed after 96-h incubation with 1 nM ouabain or 10 nM MBG. Thus, our results demonstrate that elevation of the [Na(+)](i)/[K(+)](i) ratio is an obligatory step for transcriptomic changes evoked by CTS in HUVEC. The molecular origin of upstream [Na(+)](i)/[K(+)](i) sensors involved in transcription regulation should be identified in forthcoming studies