Intranasal Administration of Mesenchymal Stem Cell-Derived Exosome Alleviates Hypoxic-Ischemic Brain Injury.

Hypoxic-ischemic brain injury arises from inadequate oxygen delivery to the brain, commonly occurring following cardiac arrest, which lacks effective treatments. Recent studies have demonstrated the therapeutic potential of exosomes released from mesenchymal stem cells. Given the challenge of systemic dilution associated with intravenous administration, intranasal delivery has emerged as a promising approach. In this study, we investigate the effects of intranasally administered exosomes in an animal model. Exosomes were isolated from the cell supernatants using the ultracentrifugation method. Brain injury was induced in Sprague-Dawley rats through a transient four-vessel occlusion model. Intranasal administration was conducted with 3 × 108 exosome particles in 20 µL of PBS or PBS alone, administered daily for 7 days post-injury. Long-term cognitive behavioral assessments, biodistribution of exosomes, and histological evaluations of apoptosis and neuroinflammation were conducted. Exosomes were primarily detected in the olfactory bulb one hour after intranasal administration, subsequently distributing to the striatum and midbrain. Rats treated with exosomes exhibited substantial improvement in cognitive function up to 28 days after the insult, and demonstrated significantly fewer apoptotic cells along with higher neuronal cell survival in the hippocampus. Exosomes were found to be taken up by microglia, leading to a decrease in the expression of cytotoxic inflammatory markers.

Myelocystocele Mimicking Myelomeningocele: A Case Report and Review of the Literature.

BACKGROUND: Myelocystoceles, which are classified as closed neural tube defects, are usually covered by skin and rarely complicated by hydrocephalus. We encountered an unusual case of a terminal myelocystocele with hydrocephalus with clinical characteristics of a myelomeningocele. CASE DESCRIPTION: Severe hydrocephalus and a lumbosacral lesion were detected in the fetus of a gravid 34-year-old woman. Cesarean section was performed at 37 weeks. The neonate presented with a lumbosacral mass with a partial skin defect. As myelomeningocele was suspected, the neonate underwent surgery on the day of birth. The intraoperative findings pointed to a myelocystocele rather than a myelomeningocele. After insertion of a ventriculoperitoneal shunt, the neonate was discharged without any neurologic deficits. CONCLUSIONS: Presence of skin abnormalities, hydrocephalus, and lumbosacral mass strongly suggests a diagnosis of myelomeningocele. However, such cases should be differentiated from myelocystocele, especially when associated with severe hydrocephalus.

Protective role of the HOG pathway against the growth defect caused by impaired biosynthesis of complex sphingolipids in yeast Saccharomyces cerevisiae.

Complex sphingolipids play critical roles in various cellular events in the yeast Saccharomyces cerevisiae. To identify genes that are related to the growth defect caused by disruption of complex sphingolipid biosynthesis, we screened for suppressor mutations and multicopy suppressor genes that confer resistance against repression of AUR1 encoding inositol phosphorylceramide synthase. From the results of this screening, we found that the activation of high-osmolarity glycerol (HOG) pathway is involved in suppression of growth defect caused by impaired biosynthesis of complex sphingolipids. Furthermore, it was found that transcriptional regulation via Msn2, Msn4 and Sko1 is involved in the suppressive effect of the HOG pathway. Lack of the HOG pathway did not enhance the reductions in complex sphingolipid levels or the increase in ceramide level caused by the AUR1 repression, implying that the suppressive effect of the HOG pathway on the growth defect is not attributed to restoration of impaired biosynthesis of complex sphingolipids. On the contrary, the HOG pathway and Msn2/4-mediated transcriptional activation was involved in suppression of aberrant reactive oxygen species accumulation caused by the AUR1 repression. These results indicated that the HOG pathway plays pivotal roles in maintaining cell growth under impaired biosynthesis of complex sphingolipids.

Stereoselective synthesis of the viridiofungin analogue NA808 from a chiral tetrahydrofuran-carboxylic acid.

The viridiofungin analogue NA808 was synthesized by the stereoselective Ireland-Claisen rearrangement of dienylmethyl ester, regioselective bromolactonization of ß-divinylpropanoic acid and retro-bromolactonization.