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Background There are many obvious health benefits to riding, including developing a strong core and legs, but there are also many less obvious benefits, such as increased confidence and introspection. Few studies have addressed the effects of horseback riding on children and the mechanisms underlying how riding affects humans. We examined the effects of horseback riding on the ability to distinguish Go/No-go tasks and solve arithmetic problems in children. Methods The subjects were 34 boys and 72 girls, aged 10–12 years old, which were divided into three groups (horse riding, walking, and resting). They were healthy typical children, who performed the Go/No-go tasks and solved the arithmetic problems. The heart rate and heart rate variability of the children, and the three-dimensional acceleration of the children while walking horses, were examined. Results Riding on a half-breed horse or a pony improved the ability to perform Go/No-go tasks and solve arithmetic problems, possibly through sympathetic activity. Some horses, like the Kiso, might provide a healing effect to children through parasympathetic activity. Statistically significant differences in the three-dimensional acceleration and the autonomic activities were observed among the three horses. The acceleration in the Kiso horse group during walking in hand was significantly different from those involving the other two horses, indicating that the vibrations produced by these horses might modify the autonomic activities. Conclusion The most important beneficial factor of horseback riding for children and for human health appears to be associated with the horse’s vibrations, which may differ among horses. Riding some horses may improve the ability of children to respond with an appropriate action depending on the situation (Go reaction) or use self-control appropriately (No-go reaction), possibly through the activation of the sympathetic nervous system.

Notch signaling plays an essential role in the proliferation and differentiation of intestinal epithelial cells (IECs). We have previously shown that Notch signaling is up-regulated in the inflamed mucosa of ulcerative colitis (UC) and thereby plays an indispensable role in tissue regeneration. Here we show that in addition to Notch signaling, STAT3 signaling is highly activated in the inflamed mucosa of UC. Forced expression of the Notch target gene Hes1 dramatically enhanced the IL-22-mediated STAT3-dependent transcription in human IECs. This enhancement of STAT3-dependent transcription was achieved by the extended phosphorylation of STAT3 by Hes1. Microarray analysis revealed that Hes1-mediated enhancement of IL-22-STAT3 signaling significantly increased the induction of genes encoding antimicrobial peptides, such as REG1A, REG3A and REG3G, in human IECs. Conversely, the reduction of Hes1 protein levels with a γ-secretase inhibitor significantly down-regulated the induction of those genes in IECs, resulting in a markedly poor response to IL-22. Our present findings identify a new role for the molecular function of Hes1 in which the protein can interact with cytokine signals and regulate the immune response of IECs.

Notch signaling has previously been implicated in the regulation of the cell fate of intestinal epithelial cells. However, the expression and function of Notch ligands in the human intestine remain largely unknown. In the present study, we showed that Notch ligands Delta-like 1 (Dll1) and Delta-like 4 (Dll4) are expressed in a goblet cell-specific manner in human colonic tissue. Additionally, we found that Dll1 and Dll4 expression was regulated in-parallel with Atoh1 and MUC2, which are both under the control of the Notch-Hes1 signaling pathway. Because knockdown of Dll1 expression completely abrogated the acquisition of the goblet cell phenotype in Notch-inactivated colonic epithelial cells, we postulate that Dll1 might function as a cis-acting regulatory element that induces undifferentiated cells to become goblet cells. Our results suggest a link between Dll1 expression and human goblet cell differentiation that might be mediated by a function that is distinct from its role as a Notch receptor ligand.

The acoustic mode is the most reasonable means for social animals such as dolphins to maintain contact in the underwater habitat, and has been developed since they moved to the sea. This study investigates variations in dolphin vocalizations under the following conditions in a captive environment: 1) before feeding (Pre-feeding), 2) during feeding (Feeding), 3) during free time without the presence of people (Free), 4) during interaction with people located upon a float (Float), 5) during interaction with people in the water (Water). During the experiments, a total of 2642 whistles were extracted from sonogram data using a spectrogram. About 44% of the total whistles were observed during Pre-feeding (1171/2642), and the number recorded during Free, when people were absent, was the smallest. The acoustic contours of dolphin whistles differed in different situations: convex, wave, and trill whistles were made repeatedly during Pre-feeding, thereby being more common at this time than at other times. The situation of Feeding saw an increased number of Upsweeps, which might be related to the use of echolocation. The lower frequencies were recorded during Pre-feeding, reflecting the emotion related to the dolphin's hunger. The results of this study indicate that dolphins increase their vocalization during interaction with people, suggesting that interactions with dolphins provide an effective treatment for human health problems, which is discussed with a reference article in this study. Vocal data obtained during contact with humans might serve as an important index for the dolphin-assisted therapy.

Bacillus circulans strain YUS-2 was isolated as the strongest antioxidant-producer in fermentation of sesame oil cake (SOC, defatted residue yielded from sesame seed oil production). Two major strong antioxidants from fermented SOC were purified and identified as known sesaminol triglucoside and sesaminol diglucoside, however, our results demonstrated that the fermentation process with B. circulans YUS-2 was highly effective to gain the extraction efficiency of the sesaminol glucosides.

Notch signaling regulates cell differentiation and proliferation, contributing to the maintenance of diverse tissues including the intestinal epithelia. However, its role in tissue regeneration is less understood. Here, we show that Notch signaling is activated in a greater number of intestinal epithelial cells in the inflamed mucosa of colitis. Inhibition of Notch activation in vivo using a γ-secretase inhibitor resulted in a severe exacerbation of the colitis attributable to the loss of the regenerative response within the epithelial layer. Activation of Notch supported epithelial regeneration by suppressing goblet cell differentiation, but it also promoted cell proliferation, as shown in in vivo and in vitro studies. By utilizing tetracycline-dependent gene expression and microarray analysis, we identified a novel group of genes that are regulated downstream of Notch1 within intestinal epithelial cells, including PLA2G2A, an antimicrobial peptide secreted by Paneth cells. Finally, we show that these functions of activated Notch1 are present in the mucosa of ulcerative colitis, mediating cell proliferation, goblet cell depletion, and ectopic expression of PLA2G2A, thereby contributing to the regeneration of the damaged epithelia. This study showed the critical involvement of Notch signaling during intestinal tissue regeneration, regulating differentiation, proliferation, and antimicrobial response of the epithelial cells. Thus Notch signaling is a key intracellular molecular pathway for the proper reconstruction of the intestinal epithelia.

Musashi-1 (Msi-1) is a RNA-binding protein, known as a putative marker of intestinal stem cells (ISCs). However, little is known about the function of Msi-1 within human intestinal epithelial cells (IECs). Thus, the present study aimed to clarify the role of Msi-1 in differentiation and proliferation of IECs.A human intestinal epithelial cell line stably expressing Msi-1 was established. Proliferation of the established cell lines was measured by bromodeoxyuridine incorporation, whereas differentiation were assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of lineage-specific genes. Activities of the Notch and Wnt pathways were examined either by reporter assays or expression of downstream target genes. The distribution of Msi-1 and PLA2G2A expression in vivo was determined by immunohistochemistry.Constitutive expression of Msi-1 in IECs had no significant effect on cell proliferation, but suppressed expression of Paneth cell-specific genes, including PLA2G2A. Msi-1 appeared to suppress expression of the PLA2G2A gene at the mRNA level. Analysis of Notch and Wnt pathway activity, however, revealed no significant change upon Msi-1 expression. The expression of Msi-1 and PLA2G2A in vivo was restricted to IECs residing at the lowest part of the human intestinal crypt, but was clearly separated to within basal columnar cells or mature Paneth cells, respectively.Msi-1 suppresses expression of Paneth cell-specific genes in IECs, presumably through a pathway independent from Notch or Wnt. These findings suggest Msi-1 is a negative regulator of Paneth cell differentiation, an may contribute to maintain the undifferentiated phenotype of ISCs.

IL-7 is a cytokine, which regulates development, maintenance and proliferation of T lymphocytes within the human immune system. Production of IL-7 is observed in a sterile environment such as thymus or bone marrow. However, it is also known that intestinal epithelial cells (IECs) residing in close contact with numerous bacterial stimuli also produce IL-7. Here we show that secretion of IL-7 by IECs is significantly suppressed upon stimulation by various bacterial components, including flagellin. Analysis of the intracellular mechanism by which flagellin regulates IL-7 production revealed that flagellin down-regulates expression of the two major transcripts encoding IL-7. Surprisingly, such function of flagellin was independent from the known transcriptional regulation of the IL-7 gene, as no significant change was observed in the transcriptional activity regulated by the previously identified promoter region. As the stability of IL-7 mRNA also remained unchanged upon flagellin stimulation, results suggested the possible involvement of a yet unknown transcriptional regulation of the IL-7 gene. These results describe a novel regulation of IL-7 production by bacterial stimuli, presumably mediated via Toll-like receptors. The present system might contribute to regulate the local lymphocyte pool, in response to the gut luminal or sub-mucosal bacterial abundance.

Intestinal epithelial cells (IECs) regulate the absorption and secretion of anions, such as HCO3(-) or Cl(-). Bestrophin genes represent a newly identified group of calcium-activated Cl(-) channels (CaCCs). Studies have suggested that, among the four human bestrophin-family genes, bestrophin-2 (BEST2) and bestrophin-4 (BEST4) might be expressed within the intestinal tissue. Consistently, a study showed that BEST2 is expressed by human colonic goblet cells. However, their precise expression pattern along the gastrointestinal tract, or the lineage specificity of the cells expressing these genes, remains largely unknown. Here, we show that BEST2 and BEST4 are expressed in vivo, each in a distinct, lineage-specific manner, in human IECs. While BEST2 was expressed exclusively in colonic goblet cells, BEST4 was expressed in the absorptive cells of both the small intestine and the colon. In addition, we found that BEST2 expression is significantly down-regulated in the active lesions of ulcerative colitis, where goblet cells were depleted, suggesting that BEST2 expression is restricted to goblet cells under both normal and pathologic conditions. Consistently, the induction of goblet cell differentiation by a Notch inhibitor, LY411575, significantly up-regulated the expression of not BEST4 but BEST2 in MUC2-positive HT-29 cells. Conversely, the induction of absorptive cell differentiation up-regulated the expression of BEST4 in villin-positive Caco-2 cells. In addition, we found that the up- or down-regulation of Notch activity leads to the preferential expression of either BEST4 or BEST2, respectively, in LS174T cells. These results collectively confirmed that BEST2 and BEST4 could be added to the lineage-specific genes of humans IECs due to their abilities to clearly identify goblet cells of colonic origin and a distinct subset of absorptive cells, respectively.

Background: Transcription factor pancreatic and duodenal homeobox 1 (Pdx1) is essential for pancreatic development and maintaining proper islet function. Null mutant mice lacking Pdx1 are apancreatic and survive only a few days after birth. The role of Pdx1 in modulating intestinal gene expression has therefore yet to be determined in viable mice with normal pancreatic development. Objective: We aimed to identify genes differentially regulated by Pdx1 in response to Pdx1 inactivation restricted to intestinal epithelium. Methods: To conditionally inactivate Pdx1 in the intestine of Pdx1;VilCremice, mutant mice homozygous for loxP site-flanked Pdx1 alleles were crossed with transgenic mice expressing Cre recombinase under the control of mouse villin 1 gene promoter. Total RNA was isolated from the first five centimeters of the small intestine from adult Pdx1;VilCre and littermate control mice. Microarray analysis was then performed to compare genome-wide transcriptional profiles of the proximal small intestine between Pdx1;VilCre and littermate control mice. Differentially expressed genes identified by the microarray analysis were validated by real-time RT-PCR. Results: Among more than thirty-nine thousand mouse transcripts screened by microarray analysis, expression of twenty genes decreased while that of six genes increased more than 2-fold in the proximal small intestine of Pdx1;VilCre mice, as compared to that of control mice (p

Summary With an avidin-biotin-peroxidase (or glucose oxidase) complex method using anti-epidermal growth factor receptor monoclonal antibody (528 IgG), the tissue and cellular distribution of the receptors for epidermal growth factor (EGF) in normal human placental villi, from 6 to 42 weeks of gestation, were studied. EGF receptors were mainly localized on the free surface of the syncytiotrophoblast that directly faced to intervillous space of the maternal circulation. The cell surface of cytotrophoblasts, except for the region that was adjacent to the basal lamina, was also positive for EGF receptors. The receptors were in close contact to the fetal vessels in the villous stroma. The EGF receptors on the syncytiotrophoblast were thought to be involved in the production and secretion of human chorionic gonadotropin and placental lactogen, probably under the control of maternal EGF. The receptors on cytotrophoblasts may play a role in trophoblastic proliferation, possibly mediated by EGF in the fertal circulatory system.