BackgroundTo clarify the role of the POU domain transcription factor Oct4 in Adipose Tissue Stromal Cells (ATSCs), we investigated the regulation of Oct4 expression and other embryonic genes in fully differentiated cells, in addition to identifying expression at the gene and protein levels. The ATSCs and several immature cells were routinely expressing Oct4 protein before and after differentiating into specific lineages.Methodology/Principal Findings and ConclusionsHere, we demonstrated the role of Oct4 in ATSCs on cell proliferation and differentiation. Exogenous Oct4 improves adult ATSCs cell proliferation and differentiation potencies through epigenetic reprogramming of stemness genes such as Oct4, Nanog, Sox2, and Rex1. Oct4 directly or indirectly induces ATSCs reprogramming along with the activation of JAK/STAT3 and ERK1/2. Exogenic Oct4 introduced a transdifferentiation priority into the neural lineage than mesodermal lineage. Global gene expression analysis results showed that Oct4 regulated target genes which could be characterized as differentially regulated genes such as pluripotency markers NANOG, SOX2, and KLF4 and markers of undifferentiated stem cells FOXD1, CDC2, and EPHB1. The negatively regulated genes included FAS, TNFR, COL6A1, JAM2, FOXQ1, FOXO1, NESTIN, SMAD3, SLIT3, DKK1, WNT5A, BMP1, and GLIS3 which are implicated in differentiation processes as well as a number of novel genes. Finally we have demonstrated the therapeutic utility of Oct4/ATSCs were introduced into the mouse traumatic brain, engrafted cells was more effectively induces regeneration activity with high therapeutic modality than that of control ATSCs. Engrafted Oct4/ATSCs efficiently migrated and transdifferentiated into action potential carrying, functionally neurons in the hippocampus and promoting the amelioration of lesion cavities.

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SummaryArgonaute 2 (Ago2) has a leading function in miRNAinduced RNA silencing, a conserved gene regulatory mechanism in cells and organisms. miRNAs are critical for stem cell self-renewal, development, and other functions. Here, we report that nuclear Ago2, by binding to a specific region of functional genes, directly controls adipose tissue-derived stem cell (ATSC) survival in response to a critical dose of reactive oxygen species (ROS)-mediated oxidative cell damage or senescence. The role of nuclear Ago2 has not been previously reported. Here, we show that human ATSCs in which Ago2 was downregulated underwent apoptosis. Silencing of Ago2 in ATSCs significantly induces upregulation of miR10b and miR23b expression. These miRNAs directly interfere with ROSscavenging gene expression, such as TXNL1 and GPX3. Upregulation of miR10b and miR23b is sufficient to induce ATSC cell apoptosis via p38 MAPK phosphorylation and caspase 3 activation. In addition, Ago2 overexpression or interference by miR10b and miR23b expression in ATSCs partially rescued H 2 O 2 ⁄ ROS-mediated apoptotic cell death by upregulating the expression of TXNL2, JUNK, caspase-3, and cytochrome C. Nuclear Ago2-mediated miR10b and miR23b downregulation also allows cells to escape senescence, which results in telomerase reverse transcriptase, stemness overexpression, and improved self-renewal and differentiation through Wnt5a ⁄ b-catenin activation. Argonaute 2 expression is critical for stem cells to escape senescence by downregulating miR10b and miR23b. The Ago2-binding gene selenoprotein N1 (SEPN1) was also effectively involved in ATSC survival and self-renewal through ROS-mediated p38 MAPK inactivation.

PurposeAllergic rhinitis (AR) is a common and increasing disease in which Dermatophagoides (D.) farinae is one of the most common causative allergens. The aims of this study were to confirm the presence of locally produced antibodies to D. farinae in nasal secretions between nasal provocation test (NPT)-positive and -negative groups of AR patients, to evaluate their relationships with the levels of inflammatory mediators, and to determine adaptive and innate immune responses in nasal mucosa.MethodsSixty AR patients sensitive to house dust mites confirmed by skin prick test or serum specific IgE to D. farinae underwent NPT for D. farinae. Nasal packs were placed in both nasal cavities of the patients for 5 minutes to obtain nasal secretions after NPT. The levels of total IgE, specific IgE to D. farinae, eosinophil cationic protein (ECP), and tryptase in nasal secretions were detected by using ImmunoCAP. The levels of specific IgE, IgA, and secretory IgA antibodies to D. farinae in nasal secretions were measured by using ELISA. The levels of IL-8, VEGF, IL-25, and IL-33 were also measured by using ELISA.ResultsHigh levels of total IgE, specific IgE, specific IgA, and secretory IgA to D. farinae, as well as inflammatory mediators, such as ECP, IL-8, VEGF and tryptase, were detected in nasal secretions, although the differences were not statistically significant between the NPT-positive and NPT-negative groups. Levels of all immunoglobulins measured in this study significantly correlated with ECP, IL-8, and VEGF (P<0.05), but not with tryptase (P>0.05). IL-33 and IL-25 were also detected, and IL-25 level significantly correlated with IL-8 (r=0.625, P<0.001).ConclusionsThese findings confirmed the presence of locally produced specific antibodies, including D. farinae-specific IgE and IgA, in nasal secretions collected from D. farinae-sensitive AR patients in both the NPT-positive and NPT-negative groups, and close correlations were noted between antibodies and nasal inflammatory mediators, including such as ECP, IL-8 and VEGF, indicating that locally produced antibodies may be involved in the nasal inflammation of AR.

Short sleep duration has been reported to increase the risk of diabetes. However, the influence of sleep duration on glycemic control in diabetic patients has not been clarified. In this study we evaluated the association between sleep duration and glycemic control in diabetic patients. We analyzed the data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2007-2010. Sleep duration was classified into five groups: <6, 6, 7, 8, and ≥9 h/day. Fasting blood glucose and HbA1c showed a U-shaped trend according to sleep duration. Sleep duration of 7 h/day had the lowest HbA1c (7.26%) among the subjects (P=0.026). In the older age group (≥65 yr), a sleep duration of 6 h/day was associated with the lowest HbA1c (7.26%). The adjusted odds ratio (OR) with a 95% confidence interval (CI) of worse glycemic control (HbA1c ≥7.0%) in group of sleep duration of ≥9 h/day was 1.48 (1.04-2.13) compared with the group of 7 h/day. This relationship disappeared after adjusting duration of diabetes (OR, 1.38; 95% CI, 0.93-2.03). Our results suggest that sleep duration and glycemic control in diabetic patients has U-shaped relationship which was mainly affected by duration of diabetes.

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BackgroundRecent studies have shown that men with diabetes have lower testosterone levels than healthy men. However, studies on the correlation between testosterone and diabetes are rare in Korea. We examined the relationship between testosterone deficiency and markers related to diabetes in adult Korean men.MethodsA total 464 men with diabetes who visited an outpatient clinic at Ajou University Hospital and had serum total testosterone and serum insulin levels measured between January 2000 and September 2013 were selected. Blood samples were collected after the subjects had fasted overnight. We divided the participants into testosterone deficient and normal groups. Testosterone deficiency was defined as having a serum total testosterone level <3.5 ng/mL.ResultsOf 464 subjects, 34.9% had a testosterone deficiency. The mean levels of fasting plasma glucose (P=0.007) and glycated hemoglobin (HbA1c; P=0.038) were significantly higher in the testosterone deficiency group than in the normal group. To clarify the relationship between serum total testosterone level and fasting plasma glucose or HbA1c values, Pearson's correlation test was performed. Fasting plasma glucose levels (r=-0.142, P=0.002) and HbA1c values (r=-0.097, P=0.040) showed a significant negative correlation with serum testosterone levels in men with diabetes.ConclusionMajor markers of diabetes that are associated with testosterone deficiency are fasting plasma glucose and HbA1c values. Poor glycemic control appears to be associated with testosterone deficiency in Korean men with diabetes.

Background/AimsProbiotics are expected to modify the composition of gut microbiota. We aimed to investigate the changes in the composition and diversity of gut microbiota by the administration of probiotics in healthy individuals.MethodsTwelve healthy volunteers with age range of 30–42 years provided baseline fecal samples. Subsequently, they took commercially available probiotic capsules (a mixture for Bifidobacterium, Lactobacillus, and Enterococcus) for 4 weeks. Fecal samples were collected at 4 weeks of administration and 2 weeks after the stop of administration. Fecal microbiota was analyzed via 16S ribosomal RNA gene sequencing.ResultsThe mean Shannon index was not significantly altered by the 4-week administration of probiotics (4.365 vs 4.556, P > 0.05). The proportion of Bacteroidetes, Actinobacteria, Firmicutes, and Proteobacteria was not significantly changed by the 4-week administration of probiotics. At the genus level, the proportions of Lactobacillus (2.138% vs 2.773%, P = 0.028) and Enterococcus (0.022% vs 2.758%, P = 0.004) significantly increased 4 weeks after the administration of probiotics, but reduced 2 weeks after the stop of administration (2.773% vs 3.292%, P = 0.064 and 2.758% vs 0.001%, P = 0.001).ConclusionsThe diversity of fecal microbiota is not significantly affected by 4 weeks of probiotics administration. The proportion of fecal microbiota at the genus level is significantly altered by the administration of probiotics. However, this effect does not seem to last long, probably because of homeostasis or dietary influence.