Embryoid body size-mediated differential endodermal and mesodermal differentiation using polyethylene glycol (PEG) microwell array

Embryoid bodies have a number of similarities with cells in gastrulation, which provides useful biological information about embryonic stem cell differentiation. Extensive research has been done to study the control of embryoid body-mediated embryonic stem cell differentiation in various research fields. Recently, microengineering technology has been used to control the size of embryoid bodies and to direct lineage specific differentiation of embryonic stem cells. However, the underlying biology of developmental events in the embryoid bodies of different sizes has not been well elucidated. In this study, embryoid bodies with different sizes were generated within microfabricated PEG microwell arrays, and a series of gene and molecular expressions related to early developmental events was investigated to further elucidate the size-mediated differentiation. The gene and molecular expression profile suggested preferential visceral endoderm formation in 450 μm embryoid bodies and preferential lateral plate mesoderm formation in 150 μm embryoid bodies. These aggregates resulted in higher cardiac differentiation in 450 μm embryoid bodies and higher endothelial differentiation in 150 μm embryoid bodies, respectively. Our findings may provide further insight for understanding embryoid body size-mediated developmental progress.National Science Foundation (U.S.) (CAREER Award DMR0847287)United States. Office of Naval Research (Naval Research Young National Investigator Award)National Institutes of Health (U.S.) (HL092836, EB02597, AR057837

Percutaneous placement of self-expandable metallic stents in patients with obstructive jaundice secondary to metastatic gastric cancer after gastrectomy

OBJECTIVE: To evaluate the outcomes of patients undergoing percutaneous placements of a biliary stent for obstructive jaundice secondary to metastatic gastric cancer after gastrectomy. MATERIALS AND METHODS: Fifty patients (mean age, 62.4 years; range, 27-86 years) who underwent percutaneous placements of a biliary stent for obstructive jaundice secondary to metastatic gastric cancer after gastrectomy were included. The technical success rate, clinical success rate, complication rate, stent patency, patient survival and factors associated with stent patency were being evaluated. RESULTS: The median interval between the gastrectomy and stent placement was 23.1 months (range, 3.9-94.6 months). The 50 patients received a total of 65 stents without any major procedure-related complications. Technical success was achieved in all patients. The mean total serum bilirubin level, which had been 7.19 mg/dL ± 6.8 before stent insertion, decreased to 4.58 mg/dL ± 5.4 during the first week of follow-up (p < 0.001). Clinical success was achieved in 42 patients (84%). Percutaneous transhepatic biliary drainage catheters were removed from 45 patients (90%). Infectious complications were noted in two patients (4%), and stent malfunction occurred in seven patients (14%). The median stent patency was 233 ± 99 days, and the median patient survival was 179 ± 83 days. Total serum bilirubin level after stenting was an independent factor for stent patency (p = 0.009). CONCLUSION: Percutaneous transhepatic placement of a biliary stent for obstructive jaundice secondary to metastatic gastric cancer after gastrectomy is a technically feasible and clinically effective palliative procedure

Cannabinoids Inhibit Insulin Receptor Signaling in Pancreatic β\beta-Cells

Objective: Optimal glucose homeostasis requires exquisitely precise adaptation of the number of insulin-secreting $\beta$-cells in the islets of Langerhans. Insulin itself positively regulates $\beta$-cell proliferation in an autocrine manner through the insulin receptor (IR) signaling pathway. It is now coming to light that cannabinoid 1 receptor (CB1R) agonism/antagonism influences insulin action in insulin-sensitive tissues. However, the cells on which the CB1Rs are expressed and their function in islets have not been firmly established. We undertook the current study to investigate if intraislet endogenous cannabinoids (ECs) regulate $\beta$-cell proliferation and if they influence insulin action. Research Design and Methods: We measured EC production in isolated human and mouse islets and $\beta$-cell line in response to glucose and KCl. We evaluated human and mouse islets, several $\beta$-cell lines, and CB1R-null (CB1R$^{−/−}$) mice for the presence of a fully functioning EC system. We investigated if ECs influence $\beta$-cell physiology through regulating insulin action and demonstrated the therapeutic potential of manipulation of the EC system in diabetic (db/db) mice. Results: ECs are generated within $\beta$-cells, which also express CB1Rs that are fully functioning when activated by ligands. Genetic and pharmacologic blockade of CB1R results in enhanced IR signaling through the insulin receptor substrate 2-AKT pathway in $\beta$-cells and leads to increased $\beta$-cell proliferation and mass. CB1R antagonism in db/db mice results in reduced blood glucose and increased $\beta$-cell proliferation and mass, coupled with enhanced IR signaling in $\beta$-cells. Furthermore, CB1R activation impedes insulin-stimulated IR autophosphorylation on $\beta$-cells in a G$\alpha_i$-dependent manner. Conclusions: These findings provide direct evidence for a functional interaction between CB1R and IR signaling involved in the regulation of $\beta$-cell proliferation and will serve as a basis for developing new therapeutic interventions to enhance $\beta$-cell function and proliferation in diabetes

Targeted exome sequencing for the identification of a protective variant against Internet gaming disorder at rs2229910 of neurotrophic tyrosine kinase receptor, type 3 (NTRK3): A pilot study

Background and aims Internet gaming disorder (IGD) has gained recognition as a potential new diagnosis in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders, but genetic evidence supporting this disorder remains scarce. Methods In this study, targeted exome sequencing was conducted in 30 IGD patients and 30 control subjects with a focus on genes linked to various neurotransmitters associated with substance and non-substance addictions, depression, and attention deficit hyperactivity disorder. Results rs2229910 of neurotrophic tyrosine kinase receptor, type 3 (NTRK3) was the only single nucleotide polymorphism (SNP) that exhibited a significantly different minor allele frequency in IGD subjects compared to controls (p = .01932), suggesting that this SNP has a protective effect against IGD (odds ratio = 0.1541). The presence of this potentially protective allele was also associated with less time spent on Internet gaming and lower scores on the Young’s Internet Addiction Test and Korean Internet Addiction Proneness Scale for Adults. Conclusions The results of this first targeted exome sequencing study of IGD subjects indicate that rs2229910 of NTRK3 is a genetic variant that is significantly related to IGD. These findings may have significant implications for future research investigating the genetics of IGD and other behavioral addictions

Comparison of Repellency Effect of Mosquito Repellents for DEET, Citronella, and Fennel Oil

To confirm that Korean Food and Drug Administration (KFDA) guidelines are applicable to test the efficacy of mosquito repellents, these guidelines were used to test the efficacy and complete protection times (CPTs) of three representative mosquito repellents: N,N-diethyl-3-methylbenzamide (DEET), citronella, and fennel oil. The repellency of citronella oil decreased over time, from 97.9% at 0 h to 71.4% at 1 h and 57.7% at 2 h, as did the repellency of fennel oil, from 88.6% at 0 h to 61.2% at 1 h and 47.4% at 2 h. In contrast, the repellency of DEET remained over 90% for 6 h. The CPT of DEET (360 min) was much longer than the CPTs of citronella (10.5 min) and fennel oil (8.4 min). These results did not differ significantly from previous findings, and hence confirm that the KFDA guidelines are applicable for testing the efficacy of mosquito repellents