Vhl-1

HIF-1-mediated adaptation to changes in oxygen availability is a critical aspect of healthy physiology. HIF is regulated by a conserved mechanism whereby EGLN/PHD family members hydroxylate HIF in an oxygen-dependent manner, targeting it for ubiquitination by Von-Hippel-Lindau (VHL) family members, leading to its proteasomal degradation. The activity of the only C. elegans PHD family member, EGL-9, is also regulated by a hydrogen sulfide sensing cysteine-synthetase-like protein, CYSL-1, which is, in turn, regulated by RHY-1/acyltransferase. Over the last decade, multiple seminal studies have established a role for the hypoxic response in regulating longevity, with mutations in vhl-1 substantially extending C. elegans lifespan through a HIF-1-dependent mechanism. However, studies on other components of the hypoxic signaling pathway that similarly stabilize HIF-1 have shown more mixed results, suggesting that mutations in egl-9 and rhy-1 frequently fail to extend lifespan. Here, we show that egl-9 and rhy-1 mutants suppress the long-lived phenotype of vhl-1 mutants. We also show that RNAi of rhy-1 extends lifespan of wild-type worms while decreasing lifespan of vhl-1 mutant worms. We further identify VHL-1-independent gene expression changes mediated by EGL-9 and RHY-1 and find that a subset of these genes contributes to longevity regulation. The resulting data suggest that changes in HIF-1 activity derived by interactions with EGL-9 likely contribute greatly to its role in regulation of longevity.

The minimally invasive procedures (mips) for the treatment of symptoms of benign prostatic hyperplasia (bph) are presented as attractive techniques due to their ease of accomplishment and the possibility of outpatient treatment. This guideline aims to present recommendations that may assist in decision making in patients with benign prostatic hyperplasia and indication of the different minimally invasive therapies. For this, a systematic review of the literature was performed, with the descriptors according to the pico: patient with benign prostatic hyperplasia, minimally invasive therapy, clinical outcome and adverse events. With no time restriction, in medline, cochrane central and lilacs databases via vhl, 1,007 papers were retrieved, of which 16 were selected to respond to clinical doubt. Details of the methodology and results of this guideline are set out in annex I.