Characterization of the gut microbiota of Kawasaki disease patients by metagenomic analysis

Kawasaki disease (KD) is an acute febrile illness of early childhood. Previous reports have suggested that genetic disease susceptibility factors, together with a triggering infectious agent, could be involved in KD pathogenesis; however, the precise etiology of this disease remains unknown. Additionally, previous culture-based studies have suggested a possible role of intestinal microbiota in KD pathogenesis. In this study, we performed metagenomic analysis to comprehensively assess the longitudinal variation in the intestinal microbiota of twenty-eight KD patients. Several notable bacterial genera were commonly extracted during the acute phase, whereas a relative increase in the number of Ruminococcus bacteria was observed during the non-acute phase of KD. The metagenomic analysis results based on bacterial species classification suggested that the number of sequencing reads with similarity to five Streptococcus spp. (S. pneumonia, pseudopneumoniae, oralis, gordonii, and sanguinis), in addition to patient-derived Streptococcus isolates, markedly increased during the acute phase in most patients. Streptococci include a variety of pathogenic bacteria and probiotic bacteria that promote human health; therefore, this further species discrimination could comprehensively illuminate the KD-associated microbiota. The findings of this study suggest that KD-related Streptococci might be involved in the pathogenesis of this disease

Cell-free Embryonic Stem Cell Extract-mediated Derivation of Multi-potent Stem Cells from NIH3T3 Fibroblasts for Functional and Anatomical Ischemic Tissue Repair

The oocyte-independent generation of multipotent stem cells is one of the goals in regenerative medicine. We report that upon exposure to mouse ES cell (ESC) extracts, reversibly permeabilized NIH3T3 cells undergo de-differentiation followed by stimulus-induced re-differentiation into multiple lineage cell types. Genome-wide expression profiling revealed significant differences between NIH3T3 and ESC-extract treated NIH3T3 cells including re-activation of ESC specific transcripts. Epigenetically, ESC extracts induced CpG de-methylation of Oct4 promoter, hyper-acetylation of histones 3 and 4 and decreased lysine 9 (K-9) dimethylation of histone 3. In mouse models of surgically-induced hind limb ischemia (HLI) or acute myocardial infarction (AMI) transplantation of reprogrammed NIH3T3 cells significantly improved post-injury physiological functions and showed antomical evidence of engraftment and trans-differentiation into skeletal muscle, endothelial cell and cardiomyocytes. These data provide evidence for the generation of functional multi-potent stem like cells from terminally differentiated somatic cells without the introduction of trans-genes or ESC fusion

Gut Cryptopatches Direct Evidence of Extrathymic Anatomical Sites for Intestinal T Lymphopoiesis

AbstractAthymic cytokine receptor γ chain mutant mice that lack the thymus, Peyer's patches, cryptopatches (CP), and intestinal T cells were reconstituted with wild-type bone marrow cells. Bone marrow–derived TCR− intraepithelial lymphocytes (IEL) first appeared within villous epithelia of small intestine overlying the regenerated CP, and these TCR− IEL subsequently emerged throughout the epithelia. Thereafter, TCR+ IEL increased to a comparable number to that in athymic mice and consisted of TCRγδ and TCRαβ IEL. In gut-associated lymphoid tissues of wild-type mice, only CP harbored a large population of c-kithighIL-7R+CD44+Thy-1+/−CD4+/−CD25low/−αEβ7−Lin− (Lin, lineage markers) lymphocytes that included cells expressing germline but not rearranged TCRγ and TCRβ gene transcripts. These findings provide direct evidence that gut CP develop progenitor T cells for extrathymic IEL descendants

Brain structure alterations in girls with central precocious puberty

PurposeCentral precocious puberty (CPP) is puberty that occurs at an unusually early age with several negative psychological outcomes. There is a paucity of data on the morphological characteristics of the brain in CPP. This study aimed to determine the structural differences in the brain of patients with CPP.MethodsWe performed voxel- and surface-based morphometric analyses of 1.5 T T1-weighted brain images scanned from 15 girls with CPP and 13 age-matched non-CPP controls (NC). All patients with CPP were diagnosed by gonadotropin-releasing hormone (GnRH) stimulation test. The magnetic resonance imaging (MRI) data were evaluated using Levene’s test for equality of variances and a two-tailed unpaired t-test for equality of means. False discovery rate correction for multiple comparisons was applied using the Benjamini–Hochberg procedure.ResultsMorphometric analyses of the brain scans identified 33 candidate measurements. Subsequently, increased thickness of the right precuneus was identified in the patients with CPP using general linear models and visualizations of cortical thickness with a t-statistical map and a random field theory map.ConclusionThe brain scans of the patients with CPP showed specific morphological differences to those of the control. The features of brain morphology in CPP identified in this study could contribute to further understanding the association between CPP and detrimental psychological outcomes