The healthy prostate is a relatively quiescent tissue. Yet, prostate epithelium overgrowth is a common condition during aging, associated with urinary dysfunction and tumorigenesis. For over thirty years, TGF-b ligands have been known to induce cytostasis in a variety of epithelia, but the intracellular pathway mediating this signal in the prostate, and its relevance for quiescence, have remained elusive. Here, using mouse prostate organoids to model epithelial progenitors, we find that intra-epithelial non-canonical Activin A signaling inhibits cell proliferation in a Smad-independent manner. Mechanistically, Activin A triggers Tak1 and p38 ΜAPK activity, leading to p16 and p21 nuclear import. Spontaneous evasion from this quiescent state occurs upon prolonged culture, due to reduced Activin A secretion, a condition associated with DNA replication stress and aneuploidy. Organoids capable to escape quiescence in vitro are also able to implant with increased frequency into immunocompetent mice. This study demonstrates that non-canonical Activin A signaling safeguards epithelial quiescence in the healthy prostate, with potential implications for the understanding of cancer initiation, and the development of therapies targeting quiescent tumor progenitors.

Background/Aims: Dietary fibers are frequently included in diets to decrease body weight, but their scarce palatability and the occurrence of meteorism prevent a long-term intake. The aim of this study was to test a mixture of dietary fibers expressly chosen to decrease their negative properties and strengthen their positive effects. Methods: In a series of 10 patients with a slight overweight, the effectiveness of a palatable dietary fibers mixture on gastric emptying and intestinal transit was tested with scintigraphic methods. Then, the effects on body weight and digestive sensations and characteristics of defecations, were evaluated for 4 weeks. Results: The intestinal transit was significantly shortened by the fiber intake, while the gastric emptying was delayed, but not significantly. The body mass index significantly and progressively decreased, whereas the sense of satiation significantly increased. No effect on abdominal bloating was referred, whereas a significant increase in number of defecations with stools of normal consistency was observed. The acceptability of the fiber mixture was good. Conclusions: The present research demonstrated that it is possible to prepare a palatable mixture of dietary fibers that maintains the property of decreasing body weight, favors the sense of satiation and accelerates the intestinal transit, with normalization of the stool consistency without the occurrence of meteorism.

The present research demonstrates that it is possible to create at the LES level a dynamic closure of a value considered sufficient to prevent GER, by implanting in the esophageal submucosa of anatomical specimens a magnetic device by means of a special endoluminal probe. Once effectiveness and tolerability of magnets covered by a biocompatible sheath have been demonstrated in vivo, this device could become a simple and effective nonsurgical solution to GER.

This research demonstrated that the implantation of a couple of magnets in the wall of the anal canal is able to create a high pressure zone of a value sufficient to prevent fecal incontinence and that the strength of this "dynamic closure" can be modulated by using magnets of various attraction force, so allowing a "tailored correction" of the anal sphincter hypotension.

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