Relaxin/insulin-like-family peptide receptor-4 (RXFP4), the cognate receptor for insulin-like peptide 5 (INSL5), has previously been implicated in feeding behaviour. To explore Rxfp4 expression and physiology, we generated Rxfp4-Cre mice. Whole body chemogenetic activation (Dq) or inhibition (Di) of Rxfp4-expressing cells using designer receptors exclusively activated by designer drugs (DREADDs) altered food intake and preference. Potentially underlying this effect, Rxfp4-expressing neurons were identified in nodose and dorsal root ganglia and the central nervous system, including the ventromedial hypothalamus (VMH). Single-cell RNA-sequencing defined a cluster of VMH Rxfp4-labelled cells expressing Esr1, Tac1 and Oxtr. VMH-restricted activation of Rxfp4-expressing (RXFP4VMH) cells using AAV-Dq recapitulated the whole body Dq feeding phenotype. Viral tracing demonstrated RXFP4VMH neural projections to the bed nucleus of the stria terminalis, paraventricular hypothalamus, paraventricular thalamus, central nucleus of the amygdala and parabrachial nucleus. These findings identify hypothalamic RXFP4 signalling as a key regulator of food intake and preference.

Background: Anthraquinones are a possible treatment option for oncological patients due to their anti-cancer properties. Cancer patients often exhaust a plethora of resources that ultimately fail to provide fully curative measures. Alternative treatments are subsequently sought in the hope of finding a therapeutic remedy. Potential regimens include aloe-emodin and its related derivatives. This review therefore summarizes the effects of aloe-emodin and other aloe components in light of their anti-proliferative and anti-carcinogenic properties. Methods: A systematic search was performed in PubMed for aloe-emodin and cancer in humans. Sixty abstracts of in vitro studies were selected and reviewed with subsequent screening of the full text. Thirty-eight articles were summarized. Results: Aloe-emodin possesses multiple anti-proliferative and anti-carcinogenic properties in a host of human cancer cell lines, with often multiple vital pathways affected by the same molecule. The most notable effects include inhibition of cell proliferation, migration, and invasion; cycle arrest; induction of cell death; mitochondrial membrane and redox perturbations; and modulation of immune signaling. The effects of aloe-emodin are not ubiquitous across all cell lines but depend on cell type. Conclusions: On the basis of this systematic review, the multiple consistent effects of aloe-emodin in human-derived cancer cell lines suggest that aloe-emodin is a potential anti-cancer agent that acts on cancer cells in a pleiotropic manner. Relevance for patients: Cancer patients often utilize alternative therapies as a result of suboptimal efficacy of conventional treatments. Aloe-emodin might become a therapeutic option for cancer patients if the basic research is confirmed in clinical trials.

An RCT of short-term HRT after BC may be feasible among Canadian physicians.