Kruppel様ジンクフィンガー型転写因子であるGLI-similar 1は低酸素誘導性転写因子の非古典的機構によって制御されている

GLI-similar 1 (GLIS1) is important for the reprogramming of fibroblasts into induced pluripotent stem cells (iPSCs). However, the molecular mechanisms of regulation of GLIS1 expression remain unclear. We have therefore examined GLIS1 expression in various cancer cell lines and demonstrated that GLIS1 expression was dramatically increased under hypoxic conditions. Importantly, GLIS1 expression was significantly attenuated in VHL-overexpressing renal cell carcinoma cells compared to the VHL-deficient parent control. Moreover, promoter analysis demonstrated that GLIS1 transcription was regulated by hypoxia through a hypoxia-inducible factors (HIFs)-dependent mechanism. Co-transfection experiments revealed that HIF-2a had greater potency on the GLIS1 promoter activation than HIF-1a. Subsequent studies using wild-type and mutant HIF-2a demonstrated that DNA binding activity was not necessary but TADs were critical for GLIS1 induction. Finally, co-transfection experiments indicated that HIF-2a cooperated with AP-1 family members in upregulating GLIS1 transcription. These results suggest that the hypoxic signaling pathway may play a pivotal role in regulating the reprogramming factor GLIS1, via non-canonical mechanisms involving partner transcription factor rather than by direct HIF transactivation.広島大学(Hiroshima University)博士(保健学)Philosophy in Health Sciencedoctora

Comparative Evaluation of the efficacy of Laser Therapy and Fibroblastic Growth Factor Injection on Mucosal Wound Healing in Rat Experimental Model

Introduction: The aim of present study was to compare the effects of laser and bFGF treatment on operative wound healing in a rat model.Methods: 66 male Wistar rats were employed in this study. 10millimeter surgical wound was created on buccal mucosa of each rat ,under anesthesia, and then the rats were divided into 3 groups of 22 each: 1- GF group (received subcutaneous injection of bFGF), 2- laser group (treated with low level laser irradiation) and 3- control group (received no treatment). On day 5 half of rats in each group and on day 10 the other half, were sacrificed. Then, samples were taken from rats' buccal mucosa for histological assay and scoring. The data was analyzed with Mann-Whitney test (α=5%).Results: On day5 there was not any significant difference between GF and control group; however laser group showed delayed wound coverage clinically, compared to other groups(p<0.05). On day 10, histological examination demonstrated marked vascular granulation tissue in GF group. Collagen production was significantly prominent in laser group compared to GF treated samples (p=.004). Inflammation of granulation tissue in GF and laser groups was significantly less than that in control samples (p=.005 and .001, respectively). Conclusion: The components of wound matrix induced by GF and laser treatment were significantly different. Although bFGF or laser treatment of oral wounds, under conditions of present study, did not accelerated wound healing but showed some other notable effects on the quality of healing

Reduction of aflatoxin level in aflatoxin-induced rats by the activity of probiotic Lactobacillus casei strain Shirota.

Aims: Aflatoxin B1 (AFB1) is considered as the most toxic food contaminant, and microorganisms, especially bacteria, have been studied for their potential to reduce the bioavailability of mycotoxins including aflatoxins. Therefore, this research investigated the efficacy of oral administration of Lactobacillus casei Shirota (LcS) in aflatoxin-induced rats. Methods and Results: Sprague Dawley rats were divided into three groups of untreated control, the group induced with AFB1 only, and the group given probiotic in addition to AFB1. In the group induced with AFB1 only, food intake and body weight were reduced significantly. The liver and kidney enzymes were significantly enhanced in both groups induced with AFB1, but they were lower in the group given LcS. AFB1 was detected from all serum samples except for untreated control group's samples. Blood serum level of AFB1 in the group induced with AFB1 only was significantly higher than the group which received probiotic as a treatment (P < 0·05), and there was no significant difference between the control group and the group treated with probiotic. Conclusions: LcS supplementation could improve the adverse effect of AFB1 induction on rats' body weight, plasma biochemical parameters and also could reduce the level of AFB1 in blood serum. Significance and Impact of the Study: This study's outcomes contribute to better understanding of the potential of probiotic to reduce the bioavailability ofAFB1. Moreover, it can open an opportunity for future investigations to study the efficacy of oral supplementation of probiotic LcS in reducing aflatoxin level in human

The Diagnostic Value of Different Sonography Findings and Color Doppler Sonography in Detecting Biliary Atresia in Infants and Neonates

Background: Biliary atresia (BA) is one of the most common etiologies of cholestasis in infants and toddlers. The most important factor in case of patients’ prognosis is its early diagnosis. There are many diagnostic tools in this field, sonography seems to be the most appropriate and fastest tool in early detecting and differentiating BA from other causes of neonatal cholestasis. The aim of this study was to evaluate the diagnostic value of new ultrasound and Doppler ultrasound methods in BA in infants and toddlers.Methods: This cross-sectional study was performed during a one-year period on 35 infants and toddlers admitted to the gastrointestinal department of Akbar Children's Hospital with suspicion of cholestasis. These children underwent sonography by a radiologist to diagnose BA. All required information was extracted from the hospital records of these children and analyzed after entering the checklist. Data were analyzed using SPSS software version 26.Results: Totally, 35 patients including 18 boys (51.4%) and 17 girls (6.48%) with a mean age of 4/29±4/17 months were enrolled. According to the findings of the analysis, 21 patients (60%) had bile duct atresia and 14 patients (40%) had other diseases. Ultrasound sensitivity in the diagnosis of bile duct atresia was 90%, with an accuracy of 74%, specificity of 50% and positive and negative predictive value of 73% and 77%, respectively. The highest diagnostic value was related to the former hepatic capsular flow.Conclusion: Biliary atresia can be accurately diagnosed by ultrasonography. The high sensitivity and accuracy of ultrasound indicate the appropriateness of this method in diagnosing this diseas

第50期(2010年4月-2010年9月)日本語研修コース成果発表会スピーチ作文集

1. 私の国カンボジア...クン・ラトヴィサル...1 2. 私の日本のせいかつ...クリスティン・ディワ...5 3. 私の国マレーシア...ヨン・ケリー・タウ・レン...9 4. わたしのくにミャンマー...ウェイ・イー・リン...13 5. 情...路明...17 6. カンボジアのまつり...オン・アカラ...20 7. ルーマニアのしょうかいと日本でのけいけん...キル・リア・アレクサンドラ...23 8. わたしの日本のせいかつ...エルハム・カレスィー...26 9. 「日本に来ました」...ラコトマナナ・エリオット...29 10. 日本のびじゅつ...オマル・ロサレス...32 11. 日本の生活...トウ・ギョクメイ...35 12. 私の研究の志望動機...アーネスト・ヘンリー・ナイ...38 13. 遠くて近い...フーリヤ・ギョクデェミル...40 14. 子供の時の思い出...マ・ロン...44 15. 故郷の春...パク・チョンイル...4

Oral administration of Lactobacillus casei Shirota can ameliorate the adverse effect of an acute aflatoxin exposure in sprague dawley rats

Aflatoxin B₁(AFB₁) is a toxic compound commonly found in some crops with an adverse health effect on human and animals. Some beneficial microorganisms (or probiotics) such as lactic acid bacteria have shown the ability to reduce the bioavailability of aflatoxins and its intestinal absorption. However, the dose and duration of aflatoxins exposure and probiotic treatment can influence the ability of probiotics to remove aflatoxins. Therefore, this research aimed to investigate the efficacy of oral probiotic Lactobacillus casei Shirota strain (LcS) induction in an acute exposure to AFB₁ in rats. Experimentally, Sprague Dawley rats were divided into three groups: AFB₁ only (n = 9); AFB₁ treated with LcS (n = 9); and control (no AFB₁ exposure) (n = 6) groups. The blood AFB₁ level of rats treated with LcS was slightly lower than the untreated AFB₁ induced rats (11.12 ± 0.71 vs 10.93 ± 0.69 ng g-1). Also, LcS treatment slightly moderated the liver and kidney biomarkers in AFB₁ induced rats. However, a trend for a significant difference was only observed in ALT of AFB₁ induced rats treated with LcS compared to their counterparts (126.11 ± 36.90 vs 157.36 ± 15.46, p = 0.06). Rats' body weight decreased in all animals force-fed with AFB₁ with no significant difference between LcS treatment compared to the counterpart. In conclusion, this experiment indicated that probiotic LsC was able to slightly ameliorate the adverse effect of an acute exposure to AFB₁ in rats. However, future studies with longer probiotics treatment or higher probiotics dose is required to confirm these findings

Oral administration of Lactobacillus casei Shirota can ameliorate the adverse effect of an acute aflatoxin exposure in Sprague Dawley rats.

Khalesi Taharoom, SS ORCiD: 0000-0002-8208-2518Aflatoxin B1(AFB1) is a toxic compound commonly found in some crops with an adverse health effect on human and animals. Some beneficial microorganisms (or probiotics) such as lactic acid bacteria have shown the ability to reduce the bioavailability of aflatoxins and its intestinal absorption. However, the dose and duration of aflatoxins exposure and probiotic treatment can influence the ability of probiotics to remove aflatoxins. Therefore, this research aimed to investigate the efficacy of oral probiotic Lactobacillus casei Shirota strain (LcS) induction in an acute exposure to AFB1 in rats. Experimentally, Sprague Dawley rats were divided into three groups: AFB1 only (n = 9); AFB1 treated with LcS (n = 9); and control (no AFB1 exposure) (n = 6) groups. The blood AFB1 level of rats treated with LcS was slightly lower than the untreated AFB1 induced rats (11.12 ± 0.71 vs 10.93 ± 0.69 ng g-1). Also, LcS treatment slightly moderated the liver and kidney biomarkers in AFB1 induced rats. However, a trend for a significant difference was only observed in ALT of AFB1 induced rats treated with LcS compared to their counterparts (126.11 ± 36.90 vs 157.36 ± 15.46, p = 0.06). Rats' body weight decreased in all animals force-fed with AFB1 with no significant difference between LcS treatment compared to the counterpart. In conclusion, this experiment indicated that probiotic LsC was able to slightly ameliorate the adverse effect of an acute exposure to AFB1 in rats. However, future studies with longer probiotics treatment or higher probiotics dose is required to confirm these findings

Identifying and predicting the pathogenic effects of a novel variant inducing severe early onset MMA: a bioinformatics approach

Abstract Background Methylmalonic acidemia (MMA) is a rare metabolic disorder resulting from functional defects in methylmalonyl-CoA mutase. Mutations in the MMAB gene are responsible for the cblB type of vitamin B12-responsive MMA. Results This study used Whole-exome sequencing (WES), Sanger sequencing, linkage analysis, and in-silico evaluation of the variants’ effect on protein structure and function to confirm their pathogenicity in a 2-day-old neonate presenting an early-onset metabolic crisis and death. WES revealed a homozygous missense variant on chromosome 12, the NM_052845.4 (MMAB):c.557G > A, p.Arg186Gln, in exon 7, a highly conserved and hot spot region for pathogenic variants. After being confirmed by Sanger sequencing, the wild-type and mutant proteins’ structure and function were modeled and examined using in-silico bioinformatics tools and compared to the variant NM_052845.4 (MMAB):c.556C > T, p.Arg186Trp, a known pathogenic variant at the same position. Comprehensive bioinformatics analysis showed a significant reduction in the stability of variants and changes in protein–protein and ligand–protein interactions. Interestingly, the variant c.557G > A, p.Arg186Gln depicted more variations in the secondary structure and less binding to the ATP and B12 ligands compared to the c.556C > T, p.Arg186Trp, the known pathogenic variant. Conclusion This study succeeded in expanding the variant spectra of the MMAB, forasmuch as the variant c.557G > A, p.Arg186Gln is suggested as a pathogenic variant and the cause of severe MMA and neonatal death. These results benefit the prenatal diagnosis of MMA in the subsequent pregnancies and carrier screening of the family members. Furthermore, as an auxiliary technique, homology modeling and protein structure and function evaluations could provide geneticists with a more accurate interpretation of variants’ pathogenicity. Graphical Abstrac

Probiotics for the treatment of asthma: a systematic review and meta-analysis of randomized trials

Background: Asthma is a growing problem worldwide and the limitations of the current therapy for allergic asthma highlight the need for novel therapeutics. We conducted a systematic review and meta-analysis to find out the role of probiotics in the treatment of Asthma.Materials and Methods: In this systematic review, a comprehensive search of the major electronic databases was done till October 2017. Clinical trials comparing the effect of probiotics versus placebo on treating asthma were included. Trials focusing on prevention of asthma were not included. A predefined set of outcome measures was assessed. Continuous data were expressed as standardized mean difference with 95% confidence interval (CI). Dichotomous data were expressed as odds ratio with 95% CI. P-value < 0.05 was considered as significant.Results: 11 studies with 2,027 participants were included. Probiotic intake was associated with a significant improvement in pulmonary function test and slight benefits in asthma control test. Probiotics did not reduce asthma exacerbation and wheezing episodes although there was a high degree of heterogeneity in studies. It also has no significant effect on viral respiratory infection in asthmatics and no improvement in quality of life. Probiotic intake improved the following parameters: longer time free from episodes of asthma. Adverse events were not significant.Conclusion: Although trials showed promising effects of probiotics as an additive on therapy on some parameters of asthma, as this evidence was generated from only a few trials with high degree of heterogeneity, routine use of probiotics as an additive on therapy of asthmatic patients cannot be recommended at this time