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Fujii E.Y.,National Center for Child Health and Development | Nakayama M.,Aska Womens Clinic
Fertility and Sterility

Objective: To examine the advanced glycation end products (AGEs), the soluble isoform of the receptor for AGEs (sRAGE), and vascular endothelial growth factor (VEGF) concentrations in plasma and follicular fluid (FF) from reproductive-age women. Design: Clinical preliminary study based on the regulations of the ethical committee at National Center for Child Health and Development (NCCHD). Setting: Women's health clinical office at NCCHD and Aska clinic. Patient(s): Reproductive-age women, young group (<35 yrs) and old group (≥35 yrs), who agreed to let us use plasma or FF samples for the measurements of AGEs, sRAGE, and VEGF. Main Outcome Measure(s): Measurements of AGEs, sRAGE, and VEGF in plasma and FF by ELISA to examine the difference by aging and reproductive dysfunction. Result(s): The plasma concentration of sRAGE was significantly higher in the young group; VEGF in FF was significantly higher in the old group. sRAGE in FF showed a tendency of positive correlation with the number of oocytes. The plasma sRAGE concentration was significantly correlated positively with FF sRAGE and inversely with FF VEGF at the time of egg collection. Conclusion(s): The measurement results suggest a possibility that RAGE-VEGF regulation may be related to reproductive dysfunction in aging women, and that plasma sRAGE might be a biologic marker of reproductive condition. © 2010 American Society for Reproductive Medicine. Source

National Center For Child Health And Development and Nippon Zoki Pharmaceutical Co. | Date: 2013-04-02

An object of the present invention is to provide DNA which regulates the expression of miR-140, a reporter vector which contains the DNA, cells and animals into which the reporter vector is introduced and a screening system for drugs which control the expression of miR-140 and is also to contribute in the development of new therapeutic agents for cartilage diseases such as osteoarthritis and intervertebral disk degeneration using the screening system. The DNA sequence according to the present invention is able to express any gene in a site where miR-140 is expressed and, in addition, it is also able to be utilized for screening a drug which regulates the expression of miR-140. Moreover, the drug that is selected by the screening system of the present invention is expected as a therapeutic agent for cartilage diseases accompanied by abnormality of cartilage.

Mashima R.,Keio University | Mashima R.,National Center for Child Health and Development

miR-155 is involved in non-coding microRNAs found in humans, mice and chickens of which the sequence is conserved. Historically, miR-155 was identified as a B-cell integration cluster (bic), which induces B-cell leucosis in chickens, by its activation through viral promoter insertion. Subsequent studies have shown that transgenic mice expressing miR-155 in B cells generated lymphoma, showing that miR-155 is oncogenic. Biochemical investigation identifies many substrates of miR-155, and one of them in B cells and macrophages is the SH2-domain containing inositol-5′-phosphatase 1. A deficiency of miR-155 in the immune system causes attenuated immune functions. Clinically, several types of malignancy including diffuse large B-cell lymphoma have high miR-155 expression levels. © 2015 John Wiley & Sons Ltd. Source

Sbi Pharmaceuticals Co. and National Center For Child Health And Development | Date: 2013-07-03

An object of the present invention is to provide a regulatory dendritic cell inducing agent applicable to the treatment of immune disease as well as an immune tolerance inducing agent such as a preventive and/or therapeutic agent for allergic disease and a preventive and/or therapeutic agent for autoimmune disease, both of which are safe and have the mechanism of action different from that of conventional drugs. As a means for achieving the above object, an immune tolerance inducing agent comprising 5-aminolevulinic acid (ALA) or a derivative thereof, or a salt of the 5-ALA or the derivative and an iron compound as active ingredients is prepared. Preferable examples of the ALAs can include ALA and various esters such as methyl ester, ethyl ester, propyl ester, butyl ester, and pentyl ester of ALA, and their hydrochlorides, phosphates, and sulfates. Preferable examples of the iron compound can include sodium ferrous citrate.

Mori R.,National Center for Child Health and Development
Cochrane database of systematic reviews (Online)

It has been suggested that low serum zinc levels may be associated with suboptimal outcomes of pregnancy such as prolonged labour, atonic postpartum haemorrhage, pregnancy-induced hypertension, preterm labour and post-term pregnancies, although many of these associations have not yet been established. To assess the effects of zinc supplementation in pregnancy on maternal, fetal, neonatal and infant outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2011) and reference lists of retrieved studies. Randomised trials of zinc supplementation in pregnancy. We excluded quasi-randomised controlled trials. Three review authors applied the study selection criteria, assessed trial quality and extracted data. When necessary, we contacted study authors for additional information. We included 20 randomised controlled trials (RCTs) reported in 51 papers involving over 15,000 women and their babies. Trials were generally at low risk of bias. Zinc supplementation resulted in a small but significant reduction in preterm birth (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.76 to 0.97 in 16 RCTs; 16 trials of 7637 women). This was not accompanied by a similar reduction in numbers of babies with low birthweight (RR 0.93, 95% CI 0.78 to 1.12; 14 trials of 5643 women). No significant differences were seen between the zinc and no zinc groups for any of the other primary maternal or neonatal outcomes, except for induction of labour in a single trial. No differing patterns were evident in the subgroups of women with low versus normal zinc and nutrition levels or in women who complied with their treatment versus those who did not. The evidence for a 14% relative reduction in preterm birth for zinc compared with placebo was primarily represented by trials involving women of low income and this has some relevance in areas of high perinatal mortality. There was no convincing evidence that zinc supplementation during pregnancy results in other useful and important benefits. Since the preterm association could well reflect poor nutrition, studies to address ways of improving the overall nutritional status of populations in impoverished areas, rather than focusing on micronutrient and or zinc supplementation in isolation, should be an urgent priority. Source

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