Review Article MicroRNA in Diabetic Nephropathy: Renin Angiotensin, AGE/RAGE, and Oxidative Stress Pathway

MicroRNAs (miRNA) are a novel class of small, noncoding RNA molecules that have gained the attention of many researchers in recent years due to their ability to posttranscriptionally regulate the expression of families of genes simultaneously. Their role in normal physiology and pathobiology is intriguing and their regulation in normal and disease states is fascinating. That the cells can return to a state of homeostasis when these small molecules are perturbed is truly remarkable given the multiple cellular targets of each miRNA and that many mRNAs are targeted by multiple miRNAs. Several reviews have covered aspects of miRNA function in biology and disease. Here, we review the role of miRNA in regulating the renin-angiotensin system, AGE/RAGE signalling, and under conditions of oxidative stress in the context of diabetic nephropathy

Social communication impairments and restricted, repetitive patterns ("Kodawari") considered from the "Comprehension" section of the WISC-IV in autism spectrum disorder

Background: Many studies have used the Wechsler Intelligence Scale (WISC) to examine the characteristics of autism spectrum disorder (ASD). However, most studies have been based on profile analysis, not on content analysis. Objective: The objective of the present study was to apply the WISC-IV to clinical assessment of ASD and clarify how the characteristics of the disorder were reflected in specific items. Methods: The study participants were 20 patients aged 5-16 years diagnosed with ASD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). We recruited 20 patients with attention-deficit/hyperactivity disorder (ADHD) and 20 patients with other disorders (neurotic disorders) as controls. We then compared the scores of the ninth item of the WISC-IV ("Comprehension") among the three groups. Results: The differences observed between the ASD vs. the other disorders group were not significant by the standard scoring method. Thus, a two-level scoring method of 0 and ≥1 point was adopted. As a result, significantly more participants in the ASD group scored 0 points compared with the ADHD and other disorders grou

Antagonist of sphingosine 1-phosphate receptor 3 reduces cold injury of rat donor hearts for transplantation

Cold storage is widely used to preserve an organ for transplantation; however, a long duration of cold storage negatively impacts graft function. Unfortunately, the mechanisms underlying cold exposure remain unclear. Based on the sphingosine-1-phosphate (S1P) signal involved in cold tolerance in hibernating mammals, we hypothesized that S1P signal blockage reduces damage from cold storage. We used an in vitro cold storage and rewarming model to evaluate cold injury and investigated the relationship between cold injury and S1P signal. Compounds affecting S1P receptors (S1PR) were screened for their protective effect in this model and its inhibitory effect on S1PRs was measured using the NanoLuc Binary Technology (NanoBiT)-β-arrestin recruitment assays. The effects of a potent antagonist were examined via heterotopic abdominal rat heart transplantation. The heart grafts were transplanted after 24-hour preservation and evaluated on day 7 after transplantation. Cold injury increased depending on the cold storage time and was induced by S1P. The most potent antagonist strongly suppressed cold injury consistent with the effect of S1P deprivation in vitro. In vivo, this antagonist enabled 24-hour preservation, and drastically improved the beating score, cardiac size, and serological markers. Pathological analysis revealed that it suppressed the interstitial edema, inflammatory cell infiltration, myocyte lesion, TUNEL-positive cell death, and fibrosis. In conclusion, S1PR3 antagonist reduced cold injury, extended the cold preservation time, and improved graft viability. Cold preservation strategies via S1P signaling may have clinical applications in organ preservation for transplantation and contribute to an increase in the donor pool

Antenatal antiarrhythmic treatment for fetal tachyarrhythmias: a study protocol for a prospective multicentre trial

Introduction Several retrospective or single-centrestudies demonstrated the efficacy of transplacentaltreatment of fetal tachyarrhythmias. Our retrospectivenationwide survey showed that the fetal therapy willbe successful at an overall rate of 90%. For fetuseswith hydrops, the treatment success rate will be 80%.However, standard protocol has not been established.The objective of this study is to evaluate the efficacy andsafety of the protocol-defined transplacental treatment offetal tachyarrhythmias. Participant recruitment began inOctober 2010.Methods and analysis The current study is a multicentre,single-arm interventional study. A total of 50 fetuseswill be enrolled from 15 Japanese institutions. Theprotocol-defined transplacental treatment is performed forsingletons with sustained fetal tachyarrhythmia ≥180 bpm,with a diagnosis of supraventricular tachycardia or atrialflutter. Digoxin, sotalol, flecainide or a combination is usedfor transplacental treatment. The primary endpoint isdisappearance of fetal tachyarrhythmias. The secondaryendpoints are fetal death related to tachyarrhythmia,proportion of preterm birth, rate of caesarean sectionattributable to fetal arrhythmia, improvement in fetalhydrops, neonatal arrhythmia, neonatal central nervoussystem disorders and neonatal survival. Maternal, fetal andneonatal adverse events are evaluated at 1 month afterbirth. Growth and development are also evaluated at 18and 36 months of corrected age.Ethics and dissemination The Institutional Review Boardof the National Cerebral and Cardiovascular Center ofJapan has approved this study. Our findings will be widelydisseminated through conference presentations and peerreviewedpublications

Sensitivity of CT perfusion for the diagnosis of cerebral infarction

We aimed to determine the sensitivity of CT perfusion (CTP) for the diagnosis of cerebral infarction in the acute stage. We retrospectively reviewed patients with ischemic stroke who underwent brain CTP on arrival and MRI-diffusion weighted image (DWI) after hospitalization between October 2008 and October 2011. Final diagnosis was made from MRI-DWI findings and 87 patients were identified. Fifty-five out of 87 patients (63%) could be diagnosed with cerebral infarction by initial CTP. The sensitivity depends on the area size (s) : 29% for S<3 cm2, 83% for S≥3 cm2-<6 cm2, 88% for S≥6 cm2-<9 cm2, 80% for S≥9 cm2-<12 cm2, and 96% for S≥12 cm2 (p<0.001). Sensitivity depends on the type of infarction : 0% for lacunar, 74% for atherothrombotic, and 92% for cardioembolism (p<0.001). Sensitivity is not correlated with hours after onset. CT perfusion is an effective imaging modality for the diagnosis and treatment decisions for acute stroke, particularly more serious strokes