This study examined the stress-reducing effect on the endocrine system and the autonomic nervous system of music with a frequency of 528 Hz, which has recently attracted attention as a "healing" type of music. Nine healthy participants (one man and eight women, aged 26 -37 years) listened to 528 Hz and standard 440 Hz music on separate days. We measured salivary biomarkers of stress (cortisol, chromogranin A, and oxytocin) before and after exposure to music, and continuously recorded the activity of the autonomic nervous system. The Profile of Mood State, 2 nd edition, was also administered as a subjective indicator of stress. In the 528 Hz condition, mean levels of cortisol significantly decreased, chromogranin A tended to decrease, and oxytocin significantly increased after music exposure. However, no significant change was observed in any salivary biomarkers in the 440 Hz condition. The ratio of low frequency to high frequency autonomic nervous system activity significantly decreased after exposure to both types of music, and the coefficient of variation of R-R intervals also significantly decreased, but only after exposure to 528 Hz music. Tension-anxiety and Total Mood Disturbance scores were significantly reduced after exposure to 528 Hz music, while there was no significant difference following 440 Hz music. These results suggest that the influence of music on the autonomic nervous system and endocrine system varies depending on the frequency of the music, and furthermore, that 528 Hz music has an especially strong stress-reducing effect, even following only five minutes of exposure.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers. Aberrant expression of genes plays important role in the procession of PDAC. The analysis of gene expression profile will contribute to the research of carcinoma mechanism. Objective: This present study is focused to investigate the differentially expressed genes (DEGs) from 3 PDAC microarray datasets, which would provide candidate genes for putative biomarkers to understand the mechanism of PDAC and potential targets of treatment. Method: Based on the overlap genes obtained from 3 GEO datasets, the hub genes were identified using STRING and Cytoscape plugin MCODE. The enrichment and function analysis were applied using DAVID. The proteinprotein interaction network was performed using cBioPortal and UCSC Xena. The Oncomine was finally used to determine the candidate gene by analyzing their expression between pancreas sample and PDAC sample. Results: 25 hub genes were selected from a total of 1006 DEGs from 3 GEO datasets, consisting of 14 upregulated genes and 11 downregulated genes. The overall decline of hub gene expression enriched in G1 phase of cell cycle in other subtypes of pancreatic cancer. Oncomine database was ultimately performed to determine the 8 candidate genes, including CXCL5, CCL20, NMU, F2R, ANXA1, EDNRA, LPAR6, and GNA15. Conclusions: Conclusively, 8 candidate genes would become the potential PDAC combined biomarkers for diagnosis and therapeutic strategies.

Objectives:To examine the effect of hydrogen water (HW) on the severity of atopic dermatitis (AD) and elucidate the underlying pathophysiological mechanisms.Methods:For this experimental study between March 2015 and December 2015, NC/Nga mice characterized by mild AD severity were given either HW (n=11) or purified water (PW) (n=9) ad libitum; specific-pathogen-free mice (n=9) were used as AD-free control. Atopic dermatitis severity score and transepidermal water loss (TEWL) were examined at baseline (0 week), and after 4 weeks of HW/PW treatment. Levels of serum thymus and activation-regulated chemokine (TARC) and cytokines in the AD lesion were measured by ELISA; and mRNA expression of TARC and aquaporin (AQP-3) genes in the skin was examined by real-time polymerase chain reaction.Results:Mice treated with HW for 4 weeks demonstrated a significant decrease in the AD severity score compared with PW-treated mice (p<0.01). Hydrogen water administration also significantly reduced TEWL and serum TARC levels (p<0.01), infiltration of mast cells (p<0.05), and secretion of the proinflammatory cytokines interleukin (IL)-1β and IL-33 (p<0.05) in skin lesions compared with PW. However, no difference was observed between PW and HW groups in interferon-g secretion and expression of AQP-3 and TARC genes.Conclusion:Hydrogen water suppressed inflammation in AD mice, leading to amelioration of disease severity, which suggests the therapeutic potential of HW in AD treatment.

Inchinkoto (ICKT), a traditional herbal medicine that is often used as a hepatoprotective drug in Japan, has pharmacological properties that include antioxidant, anti-inflammatory, and choleretic actions. Genipin is a metabolite of geniposide and the most abundant ingredient of ICKT; furthermore, it is considered to be the active substance responsible for its pharmacological properties in the liver. Drugs with such pharmacological characteristics are expected to prevent intestinal barrier dysfunction, which causes inflammatory bowel diseases (IBDs). However, no studies have investigated the effects of ICKT on the intestinal epithelial barrier. Therefore, we investigated the activity of ICKT in intestinal tight junctions by using cultured Caco-2 cell monolayers. The action of the compound on tight junctions was examined by measuring transepithelial electrical resistance (TEER) and sodium fluorescein (Na-F) permeability in the presence or absence of lipopolysaccharide (LPS). Moreover, the expression of the tight junction protein claudin-1 was assessed by using immunofluorescent staining. ICKT and genipin increased TEER and decreased Na-F permeability, which was suggestive of enhanced intestinal epithelial barrier function. Moreover, they prevented the LPS-induced destruction of the barrier, i.e., a decrease in TEER and an increase in Na-F permeability. Immunofluorescence staining revealed a high claudin-1 expression level on the cell surface, whereas exposure to LPS downregulated claudin-1. In turn, ICKT and genipin prevented the LPS-mediated reduction of claudin-1. These results suggest that ICKT enhances intestinal epithelial barrier function by upregulating claudin-1. Furthermore, genipin contributed to these effects. ICKT may be a promising medicine for the prevention and treatment of diseases associated with intestinal barrier disruption, such as IBD, obesity, and metabolic disorders.

Aim: Hangekobokuto, a kampo medicine, is considered effective against anxiety neurosis, amnesia, insomnia, and neurotic gastritis. The mechanism of action and verification of effect, however, remain to be confirmed. The aim of this study was therefore to confirm the effect of hangekobokuto for amelioration of aggressiveness and social behavior in a mouse stress model. Methods: Four-week-old male ddY mice were socially stressed by isolated rearing for 4 weeks. The control group was reared in a social group. Hangekobokuto was then given orally in drinking water to the isolation-reared mice at a dose of 0% (purified water), 0.25% and 0.5% for 2 weeks. The socially reared control group was not given any treatment. Aggressiveness and social behavior were evaluated. Blood samples were obtained after the test, and serum corticosterone and interleukin (IL)-6 were measured. The prefrontal region of the brain and the brainstem region were enucleated, and serotonin, dopamine and IL-6 were measured. Results: Hangekobokuto dose-dependently controlled the aggressive behavior induced by isolation stress, and the effect disappeared on 5HT 1A receptor antagonist treatment. Blood corticosterone, increased by isolation stress, decreased with hangekobokuto treatment. Serotonin and dopamine in the prefrontal region, decreased by isolation stress, increased with hangekobokuto treatment. IL-6 in the brainstem, increased by isolation stress, decreased dose dependently on hangekobokuto treatment. Conclusion: Hangekobokuto ameliorates aggressiveness induced by anxiety caused by stress. Furthermore, the mechanism of effect involves the serotonin system.