Maternal separation (MS) has been developed as a model for inducing stress and depression in studies using rodents. The concept of the gut-brain axis suggests that gut health is essential for brain health. Here, we present the effects of administration of a probiotic, Lactobacillus paracasei PS23 (PS23), to MS mice against psychological traits including anxiety and depression. The administration of live and heat-killed PS23 cells showed positive behavioural effects on MS animals, where exploratory tendencies and mobility were increased in behavioural tests, indicating reduced anxiety and depression compared to the negative control mice (P<0.05). Mice administered with both live and heat-killed PS23 cells also showed lower serum corticosterone levels accompanied by higher serum anti-inflammatory interleukin 10 (IL-10) levels, compared to MS separated mice (P<0.05), indicating a stress-elicited response affiliated with increased immunomodulatory properties. Assessment of neurotransmitters in the brain hippocampal region revealed that PS23 affected the concentrations of dopaminergic metabolites differently than the control, suggesting that PS23 may have improved MS-induced stress levels via neurotransmitter pathways, such as dopamine or other mechanisms not addressed in the current study. Our study illustrates the potential of a probiotic in reversing abnormalities induced by early life stress and could be an alternative for brain health along the gut-brain axis.
Pluripotent stem cells may serve as an alternative source of beta-like cells for replacement therapy of type 1 diabetes; however, the beta-like cells generated in many differentiation protocols are immature. The maturation of endogenous beta cells involves an increase in insulin expression starting in late gestation and a gradual acquisition of the abilities to sense glucose and secrete insulin by week 2 after birth in mice; however, what molecules regulate these maturation processes are incompletely known. In this study, we aim to identify small molecules that affect immature beta cells. A cell-based assay, using pancreatic beta-like cells derived from murine embryonic stem (ES) cells harboring a transgene containing an insulin 1-promoter driven enhanced green fluorescent protein reporter, was used to screen a compound library (NIH Clinical Collection-003). Cortisone, a glucocorticoid, was among five positive hit compounds. Quantitative reverse transcription-polymerase chain reaction analysis revealed that glucocorticoids enhance the gene expression of not only insulin 1 but also glucose transporter-2 (Glut2; Slc2a2) and glucokinase (Gck), two molecules important for glucose sensing. Mifepristone, a pharmacological inhibitor of glucocorticoid receptor (GR) signaling, reduced the effects of glucocorticoids on Glut2 and Gck expression. The effects of glucocorticoids on ES-derived cells were further validated in immature primary islets. Isolated islets from 1-week-old mice had an increased Glut2 and Gck expression in response to a 4-day treatment of exogenous hydrocortisone in vitro. Gene deletion of GR in beta cells using rat insulin 2 promoter-driven Cre crossed with GRflox/flox mice resulted in a reduced gene expression of Glut2, but not Gck, and an abrogation of insulin secretion when islets were incubated in 0.5 mM d-glucose and stimulated by 17 mM d-glucose in vitro. These results demonstrate that glucocorticoids positively regulate glucose sensors in immature murine beta-like cells.
Laparotomy incisions provide easy and rapid access to the peritoneal cavity in case of emergency surgery. Incisional hernia (IH) is a late manifestation of the failure of abdominal wall closure and represents frequent complication of any abdominal incision: IHs can cause pain and discomfort to the patients but also clinical serious sequelae like bowel obstruction, incarceration, strangulation, and necessity of reoperation. Previous guidelines and indications in the literature consider elective settings and evidence about laparotomy closure in emergency settings is lacking. This paper aims to present the World Society of Emergency Surgery (WSES) project called ECLAPTE (Effective Closure of LAParoTomy in Emergency): the final manuscript includes guidelines on the closure of emergency laparotomy.