The Allium Derivate Propyl Propane Thiosulfinate Exerts Anti-Obesogenic Effects in a Murine Model of Diet-Induced Obesity

Allium species and their organosulfur-derived compounds could prevent obesity and metabolic dysfunction, as they exhibit immunomodulatory and antimicrobial properties. Here, we report the anti-obesogenic potential and dose-dependent effects (0.1 or 1 mg/kg/day) of propyl propane thiosulfinate (PTS) in a murine model of diet-induced obesity. The obesogenic diet increased body weight gain and adipocyte size, and boosted inflammatory marker (Cd11c) expression in the adipose tissue. Conversely, PTS prevented these effects in a dose-dependent manner. Moreover, the higher dose of PTS improved glucose and hepatic homeostasis, modulated lipid metabolism, and raised markers of the thermogenic capacity of brown adipose tissue. In the colon, the obesogenic diet reduced IL-22 levels and increased gut barrier function markers (Cldn3, Muc2, Reg3g, DefaA); however, the highest PTS dose normalized all of these markers to the levels of mice fed a standard diet. Gut microbiota analyses revealed no differences in diversity indexes and only minor taxonomic changes, such as an increase in butyrate producers, Intestimonas and Alistipes, and a decrease in Bifidobacterium in mice receiving the highest PTS dose. In summary, our study provides preclinical evidence for the protective effects of PTS against obesity, which if confirmed in humans, might provide a novel plant-based dietary product to counteract this condition.     

Natural estrogens enhance the engraftment of human hematopoietic stem and progenitor cells in immunodeficient mice

Hematopoietic stem and progenitor cells (HSPC) are crucial in the maintenance of lifelong production of all blood cells. These stem cells are highly regulated to maintain homeostasis through a delicate balance between quiescence, self-renewal and differentiation. However, this balance is altered during the recovery after HSPC transplantation. Transplantation efficacy can be limited by inadequate hematopoietic stem cell number, poor homing, low level of engraftment, or limited self-renewal. As recent evidence indicates that estrogens are involved in regulating hematopoiesis, we sought to examine whether natural estrogens (estrone or E1, estradiol or E2, estriol or E3 and estetrol or E4) modulate human HSPC. Our results show that human HSPC subsets express estrogen receptors, and that signaling is activated by E2 and E4 on these cells. Additionally, these natural estrogens cause different effects on human progenitors in vitro. We found that both E2 and E4 expand human HSPC. However, E4 was the best tolerated estrogen and promoted cell cycling of human hematopoietic progenitors. Furthermore, we found that E2 and, more significantly, E4 doubled human hematopoietic engraftment in immunodeficient mice without altering other HSPC properties. Finally, the impact of E4 on promoting human hematopoietic engraftment in immunodeficient mice might be mediated through the regulation of mesenchymal stromal cells in the bone marrow niche. Collectively, our data demonstrate that E4 is well tolerated and enhances human reconstitution in immunodeficient mice directly, by modulating human hematopoietic progenitor properties, and indirectly, by interacting with the bone marrow niche. This might have particular relevance for improving hematopoietic recovery after myeloablative conditioning, especially when limited numbers of HSPC are available.     

Jugular lymphatic maldevelopment in Turner syndrome and trisomy 21: different anomalies leading to nuchal edema

Increased nuchal translucency (NT), morphologically known as nuchal edema, is an ultrasound marker for aneuploidy. Turner syndrome presents with massive NT, called cystic hygroma. Conflicting data exist as to whether cystic hygroma and increased NT are different entities. Both are associated with jugular lymphatic distension. The authors investigated jugular lymphatics of trisomy 21, Turner syndrome, and normal karyotype fetuses. Fetuses were investigated using immunohistochemistry for blood vascular, lymphatic, and smooth muscle cell markers. Trisomy 21 fetuses showed nuchal cavities within the mesenchymal edema negative for endothelial markers. These were extremely large in Turner fetuses, showing similar characteristics. The skin showed numerous dilated lymphatics in the case of trisomy 21 and scanty small lymphatics in Turner fetuses. A jugular lymphatic sac was present in control and trisomy 21 fetuses and was enlarged in trisomy 21 cases. In Turner fetuses, no jugular lymphatic sac was observed. Nuchal edema in trisomy 21 and Turner syndrome appears to be a similar entity caused by different lymphatic abnormalities.