Novel Selective Estrogen Receptor Modulator Ameliorates Murine Colitis

Estrogen-receptor-mediated signaling has been suggested to decrease the inflammatory response in monocyte macrophages. Previously, we showed that a novel selective estrogen receptor modulator (SERM2) promotes anti-inflammatory phenotype of monocytes in vitro. In this study, we demonstrate the potential of SERM2 in amelioration of colitis. We utilized a dextran sodium sulfate (DSS)-induced colitis model in FVB/n mice to demonstrate the effects of orally administered SERM2 on the clinical status of the mice and the histopathological changes in the colon, as well as proportion of Mrc-1 positive macrophages. SERM2 nuclear receptor affinities were measured by radioligand binding assays. Orally administered, this compound significantly alleviated DSS-induced colitis in male mice and induced local estrogen receptor activation in the inflamed colon, as well as promoting anti-inflammatory cytokine expression and infiltration of anti-inflammatory monocytes. We show that this novel drug candidate has an affinity to estrogen receptors alpha and beta and progesterone receptors, but not to glucocorticoid receptor, thus expressing unique binding properties compared to other sex steroid receptor ligands. These results indicate that novel drug candidates to alleviate inflammatory conditions of the colon could be found among sex steroid receptor activating compounds

From efficiency to resilience:systemic change towards sustainability after the COVID-19 pandemic

Abstract The COVID-19 pandemic has revealed the vulnerability of current socio-economic systems and thrown into question the dominant global paradigm geared towards short-term financial efficiency. Although it has been acknowledged for several decades that this paradigm has detrimental impacts on the climate, the environment and global welfare, the pandemic has now offered a grim ‘rehearsal round’ for more serious crises that are to come with the accelerating climate emergency, loss of biodiversity and growing human inequalities. Along with worsening climate change, there are looming risks for mass migrations and armed conflicts as habitats capable of supporting human wellbeing become scarce, such as through the loss of potable water, an increasing lack of suitable land for agriculture, or the rise of unliveable temperatures. Although the COVID-19 pandemic has temporarily decreased some of the climate impacts, e.g. in the energy and transportation sectors, it has at the same time accelerated several global welfare problems. In this chapter, we claim that the way out of the crisis scenario is to replace the dominant efficiency paradigm with a resilience paradigm. Against the backbone of the key societal systems outlined in the Global Sustainable Development Report (GSDR 2019), we show how the pursuit of narrowly-defined efficiency hampers present and future sustainability, and chart some key actions on the path to transforming these systems towards resilience