Retinoic acid-inducible gene-I (RIG-I) is a cytoplasmic protein that recognizes viral double-stranded RNA to induce the type I interferon (IFN) response. In human keratinocytes, RIG-I is induced by IFN-γ and tumor necrosis factor-α stimulation. This study investigated the effects of extraneous stimuli including viral infection and UVB exposure on the RIG-I expression in human keratinocytes. Polyinosinic-polycytidylic acid (poly (I:C) ), which mimics viral infection, significantly induced the RIG-I expression, while UVB inhibited the basal RIG-I expression as well as the poly (I:C)-induced RIG-I overexpression in cultured human keratinocytes. Thus, suppression of the RIG-I expression caused by UVB exposure may partly explain the inhibition of skin-based immune responses, leading to viral infection and recrudescence.
Background and aim: The aim of this study is to investigate the relationship between methane production
and gut microbiota in a general population. Methods: Total of 697 subjects (58 ± 13 years, 261 men and 436 women) have participated in this study. Their breath methane and hydrogen concentration were measured after an overnight fasting using gas chromatography, and their gut bacterial component was analyzed using T-RFLP (Terminal restriction fragment length polymorphism) method. All gut microbiota were divided into 28 operational taxonomic units (OTUs) according to its predominant bacterial groups. The breath methane concentration of above 10 ppm and breath hydrogen concentration of above 20 ppm were considered positive. Subjects were divided into four groups; (1) Both negative: both methane and hydrogen were negative (2) CH₄ only: only methane was positive (3) H₂ only: only hydrogen was positive (4) Both positive: both hydrogen and methane were positive. Results: OTU317 (Prevotella) was significantly higher in CH₄ only than both negative and H₂ only. And OTU940 (Clostridium subcluster XIVa and Enterobacteriales) was significantly lower in CH₄ only than both negative and H₂ only. Conclusions: OTU317 and OTU940 might affect the bacterial metabolism of methanogens.
Background: P38 mitogen-activated protein kinase (MAP kinase) plays on important role for progression
of pathological cardiac hypertrophy. However, the role of p38 MAP kinase in cardiac hypertrophy induced by
pressure overload remains unclear. We investigated the effect of chronic treatment with p38 MAP kinase inhibitor on
the development of heart failure induced by transverse aortic constriction (TAC) in mice. Methods and Results: TAC increased left ventricular septal wall thickness (LVSWT) and cross-sectional area (CSA) of cardiomyocyte, and decreased LV fractional shortening (FS) compared with sham operation after 6 weeks. TAC also increased phosphorylation of p38 MAP kinase, whereas other hypertrophic signals were unchanged. In another experiment, TAC mice and sham operated mice were treated with subcutaneous injection of p38 MAP kinase
inhibitor SB202190 (5mg/kg/day) or placebo five times a week for six weeks. Treatment with p38 MAP kinase
inhibitor attenuated the increase in LVSWT and CSA, and the decrease in FS in mice with TAC. Conclusions: Inhibition of p38 MAP kinase attenuated left ventricular hypertrophy and inhibited progression of
systolic dysfunction in pressure overload-induced cardiac hypertrophy. These results suggest that inhibition of p38
MAP kinase has a protective effect for development of heart failure induced by pressure overload.
Coronary artery spasm plays an important role in the etiology of coronary spastic angina (CSA) and other acute coronary syndromes. Mice with a targeted disruption of the ATP-binding cassette transporter C9‒ABCC9 gene were developed as an animal model of CSA. Thus, the ABCC9 may be involved in the regulation of coronary artery vasomotility. The aim of this study was to investigate whether mutation in the coding region of the ABCC9 gene is detected in Japanese patients with CSA. The study included 9 Japanese patients with CSA (6 men and 3 women with a mean age of 51 ± 13 years). Genomic DNA was extracted from the whole blood, and Mutation analysis of the coding region of ABCC9 was performed by direct sequencing. In one CSA patient, we found a single base substitution (G to A) at nucleotide position 126 in exon 21 of the coding region, which was heterozygous and did not cause amino acid substitution (T878T, silent mutation). In the remaining 8 patients, no base substitution was detected in the coding region of the ABCC9 gene. The results indicate that the mutation of the ABCC9 gene may not be involved in the genetic pathogenesis of CSA in humans.
Sleep is one of important factors relating to the quality of life (QOL) of individuals, thus public programmes which comprehensively educate the need for good sleep status and how to improve it are required. This study revealed the relationship between sleep disorders and lifestyle in the Japanese general population. The subjects were 1,273 volunteers who participated in the Iwaki Health Promotion Project in 2007 to 2009. Self-questionnaires regarding lifestyle were performed and a sleep disorders was diagnosed according to the Pittsburgh Sleep Quality Index (PSQI). The subjects were divided by age into the young, middle-aged and elderly groups. A multiple regression analysis was performed with the global PSQI score as an objective valuable and body mass index, smoking status, drinking status and depression as explanatory valuables. All analyses were carried out in males and females separately. As results, a positive correlation between sleep disorders and depression was shown in all groups and both genders. In conclusions, the implementation of mental support strategies is required for prevention of sleep disorders and development of a good sleep status, which could bring about improvement in the QOL of the general population (low risk population).
The aim of this study was to investigate the relationships among nutritional intake, body fat percentage and situation of sexual hormone secretion in female athletes, as well as their effects on the athletes' neutrophil immune function.
A total of 51 female university athletes participated in the present study. Out of 51 athletes, 15 of them were gymnasts, 17 long-distance runners, and 19 judoists. We investigated the body composition, nutritional intake, menstrual situation, blood biochemistry and serum opsonic activity (SOA).
In the present study, % fat and total energy intake was lower in gymnasts than long-distance runners and judoists. Additionally, the prevalence of menstrual abnormality was highest in gymnasts, followed by long-distance runners and judoists, suggesting that lower % fat is a risk factor for menstrual abnormality. On the other hand, body fat percentage, total energy intake and fat intake were found to have a significant positive correlation with SOA.
Hence, the stress arising from training and diet restriction as well as decrease in body fat mass was found to cause reduced immune function through decreased HPG functions. The extent of this decrease was affected by total energy intake especially fat intake and body fat mass of athletes.
Methylone, an analog of 3,4-methylenedioxymethamphetamine (MDMA) is a narcotic drug which is forbidden due to its abusability. However, a detailed behavioral toxicity and rewarding effect of methylone has not yet been reported to this date. The aim of this study is to evaluate the toxicity and addictive effects of methylone. In order to detect the stimulant effect to central nervous system, a mouse behavioral toxicity test and a conditioned place preference (CPP) test were conducted by administering mehtylone, MDMA and methamphetamine (MAP). An immunohistochemical study was also performed to analyze ΔFosB, which is known to accumulate in the nucleus accumbens after chronic administration of the drugs of abuse. For determining the expression levels of ΔfosB mRNA in striatum, quantitative PCR analysis was also conducted by acute administration of methylone. Significant differences appeared in mice that were administered with 50 mg/kg and above of methylone. Methylone causes a similar qualitative behavioral effect as MAP, however not the same stereotyped behavior as MDMA. According to the result from CPP test, methylone of 2.5 mg/kg and above had shown a rewarding action. Chronic administration of methylone causes significant ΔFosB accumulation in the neurons of nucleus accumbens. Methylone and MDMA significantly induce ΔfosB mRNA in striatum. It is therefore suggested that methylone has psychoactive effects and can be considered as an addictive drug.
The relationship between delivery/menopause and arteriosclerosis has received much attention. The authors examined this relationship in the Japanese general female population. The subjects of the study comprised 735 women who participated in the Iwaki Health Promotion Project between 2006 and 2009. Lifestyle, reproduction history, serum parameters (LDL-cholesterol, HbA1c etc.) and brachial-ankle pulse wave velocity (baPWV) were surveyed. baPWV, systolic blood pressure (SBP), LDL-cholesterol and HbA1c were higher in the menopause group than in the non-menopause group. The higher the number of deliveries, the higher was the baPWV, SBP and HbA1c. In the non-delivery group, baPWV, LDL-cholesterol and HbA1c were higher in the menopause group than in the non-menopause group. In the delivery group, in addition to the previous three factors, SBP was higher in the menopause group than in the non-menopause group. In both the menopause and non-menopause groups, baPWV and SBP were higher in the delivery than in the non-delivery group. A positive association was noted between baPWV and smoking habit, and between SBP and BMI/smoking habit/alcohol consumption. In conclusions, menopause and delivery/delivery number promoted arteriosclerosis independently. Therefore, for these groups, long-term health management is required, and improvements in lifestyle need to be promoted.
S-1, an oral prodrug of 5-fluorouracil, has been employed in treatment of solid tumors in Japan. We report two patient cases whose international normalized ratio (INR) increased due to concomitant treatment with warfarin and S-1. In case 1, a 63-year-old man, who had taken 3.5 mg/day warfarin for dilated cardiomyopathy, had a subcutaneous hematoma in a left lower eyelid on the ninth course of combination chemotherapy with S-1 and docetaxel for metastatic gastric cancer. His INR increased to 3.68 despite careful monitoring of coagulation parameters. In case 2, a 68-year-old man, who received combination chemotherapy with S-1 and irinotecan for metastatic colorectal cancer, had to reduce the dose of warfarin twice during the same chemotherapy courses because of repeated prolongation of INR. We speculate that multiple mechanisms of unstable INR are involved in strengthening the anticoagulant effect of warfarin. Frequent monitoring of INR is required to prevent unexpected adverse events of coagulation abnormality induced by the interaction between S-1 and warfarin．