Heme oxygenase (HO), the rate-limiting enzyme in heme degradation, plays a role in neonatal jaundice. Understanding the regulation of the developmental expression patterns of the two HO isozymes, HO-1 and HO-2, is essential for targeting HO to control pathologic jaundice, and uncovering the fundamental role that they play in mammalian development. Here we characterized the ontogeny of HO-1 and HO-2 expression in the developing mouse cortex by in vivo bioluminescence imaging, quantitative RT-PCR, and Western blot. HO-2, the predominant isoform in the adult cortex, was relatively stable throughout all ages. HO-1 was observed to be progressively down-regulated in an age-related manner. HO-1 expression in the adult cortex was also the lowest among the eight adult tissues analyzed. Because there is a 283-bp CpG island region in the HO-1 promoter, we hypothesized that methylation of the island is responsible for the age-related HO-1 down-regulation in the cortex. Methylation status was assessed using regular and quantitative methylation-specific PCR and the CpG island was found to be hypomethylated at all ages. Therefore, we conclude that HO-1 gene expression in the cortex is developmentally-regulated and that methylation of the HO-1 CpG island is not associated with the downregulation of the gene. H eme oxygenase (HO) is the rate-limiting enzyme for the degradation of heme derived from senescent red blood cells and other hemoproteins (1). In this pathway, HO cleaves the heme ring via oxidation at the ␣-methene bridge to yield equimolar quantities of biliverdin, carbon monoxide (CO), and free iron. Biliverdin is subsequently converted to bilirubin by biliverdin reductase. Among the many implications of HO in development, it is the controlling step in bilirubin production and has been identified as a target for prevention of pathologic jaundice.HO has many physiologic functions (2,3) and plays a key role during development. It not only regulates cellular heme and hemoprotein levels (e.g. cytochrome P450), but also all of its heme degradation products are biologically active: the bile pigments biliverdin and bilirubin are potent antioxidants (4); CO generates cGMP and MAP kinase, and is shown to be a potential vasodilator and smooth muscle relaxant (5); and free iron regulates expression of various genes and hematopoiesis (6,7). To date, two primary isoforms of HO have been identified in the human and rodent: the inducible HO-1, also known as Hsp32, and the constitutive HO-2 (8,9). HO-3, a third isoform cloned only from rats, has been reported to be a processed pseudogene derived from HO-2 transcripts (10). HO-1 and HO-2 have some protein similarities, but are encoded from different genes.Expression of HO-1 is transcriptionally regulated by a 15-kb regulatory region, consisting of a basal promoter and three enhancer regions (11). Several regulatory elements and transcriptional factor binding sites have been reported to play important roles in up-regulating HO-1, including metal response elements (MREs), stress...

N-terminal pro-brain natriuretic peptide levels at birth are elevated in monochorionic diamniotic twins with selective intrauterine growth restriction.

Mesenchymal stem cells (MSCs) are a heterogeneous cell population that is isolated initially from the bone marrow (BM) and subsequently almost all tissues including umbilical cord (UC). UC-derived MSCs (UC-MSCs) have attracted an increasing attention as a source for cell therapy against various degenerative diseases due to their vigorous proliferation and differentiation. Although the cell proliferation and differentiation of BM-derived MSCs is known to decline with age, the functional difference between preterm and term UC-MSCs is poorly characterized. In the present study, we isolated UC-MSCs from 23 infants delivered at 22–40 weeks of gestation and analyzed their gene expression and cell proliferation. Microarray analysis revealed that global gene expression in preterm UC-MSCs was distinct from term UC-MSCs. WNT signaling impacts on a variety of tissue stem cell proliferation and differentiation, and its pathway genes were enriched in differentially expressed genes between preterm and term UC-MSCs. Cell proliferation of preterm UC-MSCs was significantly enhanced compared to term UC-MSCs and counteracted by WNT signaling inhibitor XAV939. Furthermore, WNT2B expression in UC-MSCs showed a significant negative correlation with gestational age (GA). These results suggest that WNT signaling is involved in the regulation of GA-dependent UC-MSC proliferation.

Association of congenital cytomegalovirus (CMV) infection with autism spectral disorder (ASD) has been suggested since 1980s. Despite the observed association, its role as a risk factor for ASD remains to be defined. In the present review, we systematically evaluated the available evidence associating congenital CMV infection with ASD using PubMed, Web of Science, Cochrane Library, and Embase databases. Any studies on children with CMV infection and ASD were evaluated for eligibility and three observational studies were included in meta-analysis. Although a high prevalence of congenital CMV infection in ASD cases (OR 11.31, 95% CI 3.07-41.66) was indicated, too few events (0-2 events) in all included studies imposed serious limitations. There is urgent need for further studies to clarify this issue.

A combined elevation in serum IL-6 and CRP levels at birth was associated with the development of WMI in preterm infants with FIR.