The ability of the human immune system to protect against infectious disease declines with age and efficacy of vaccination reduces significantly in the elderly. Aging of the immune system, also termed as immunosenescence, involves many changes in human T cell immunity that is characterized by a loss in naïve T cell population and an increase in highly differentiated CD28- memory T cell subset. There is extensive data showing that latent persistent human cytomegalovirus (HCMV) infection is also associated with age-related immune dysfunction in the T cells, which might enhance immunosenescence. Understanding the molecular mechanisms underlying age-related and HCMV-related immunosenescence is critical for the development of effective age-targeted vaccines and immunotherapies. In this review, we will address the role of both aging and HCMV infection that contribute to the T cell senescence and discuss the potential molecular mechanisms in aged T cells.

The therapeutic potential of umbilical cord blood mesenchymal stem cells has been studied in several diseases. However, the possibility that human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hUCMSCs) can be used to treat neonatal hypoxic-ischemic encephalopathy (HIE) has not yet been investigated. This study focuses on the potential therapeutic effect of hUCMSC transplantation in a rat model of HIE. Dermal fibroblasts served as cell controls. HIE was induced in neonatal rats aged 7 days. hUCMSCs labeled with Dil were then transplanted into the models 24 hr or 72 hr post-HIE through the peritoneal cavity or the jugular vein. Behavioral testing revealed that hUCMSC transplantation but not the dermal fibroblast improved significantly the locomotor function vs. vehicle controls. Animals receiving cell grafts 24 hr after surgery showed a more significant improvement than at 72 hr. More hUCMSCs homed to the ischemic frontal cortex following intravenous administration than after intraperitoneal injection. Differentiation of engrafted cells into neurons was observed in and around the infarct region. Gliosis in ischemic regions was significantly reduced after hUCMSC transplantation. Administration of ganglioside (GM1) enhanced the behavioral recovery on the base of hUCMSC treatment. These results demonstrate that intravenous transplantation of hUCMSCs at an early stage after HIE can improve the behavior of hypoxic-ischemic rats and decrease gliosis. Ganglioside treatment further enhanced the recovery of neurological function following hUCMSC transplantation.

Dual-specificity phosphatases (DUSPs) dephosphorylate threonine/serine and tyrosine residues on their substrates. Here we show that DUSP1, DUSP4, and DUSP6 are involved in epithelial-to-mesenchymal transition (EMT) and breast cancer stem cell (CSC) regulation. DUSP1, DUSP4, and DUSP6 are induced during EMT in a PKC pathway signal-mediated EMT model. We show for the first time that the key chromatin-associated kinase PKC-θ directly regulates a subset of DUSP family members. DUSP1, DUSP4, and DUSP6 globally but differentially co-exist with enhancer and permissive active histone post-translational modifications, suggesting that they play distinct roles in gene regulation in EMT/CSCs. We show that nuclear DUSP4 associates with the key acetyltransferase p300 in the context of the chromatin template and dynamically regulates the interplay between two key phosphorylation marks: the 1834 (active) and 89 (inhibitory) residues central to p300’s acetyltransferase activity. Furthermore, knockdown with small-interfering RNAs (siRNAs) shows that DUSP4 is required for maintaining H3K27ac, a mark mediated by p300. DUSP1, DUSP4, and DUSP6 knockdown with siRNAs shows that they participate in the formation of CD44hi/CD24lo/EpCAM+ breast CSCs: DUSP1 knockdown reduces CSC formation, while DUSP4 and DUSP6 knockdown enhance CSC formation. Moreover, DUSP6 is overexpressed in patient-derived HER2+ breast carcinomas compared to benign mammary tissue. Taken together, these findings illustrate novel pleiotropic roles for DUSP family members in EMT and CSC regulation in breast cancer.

Objectives: To explore the clinical value of circulating long non-coding RNAs (lncRNAs) as biomarkers to predict fetal congenital heart defects (CHD) in pregnant women. Methods: Differential expression of lncRNAs isolated from the plasma of pregnant women with typical fetal CHD or healthy controls was analyzed by microarray. Gene ontology (GO), pathway and network analysis were performed to study the function of the lncRNAs. Differentially expressed lncRNAs were validated in plasma samples from 62 pregnant women with typical CHD and 62 matched controls by RT-PCR. The sensitivity and specificity of each lncRNA in the diagnosis of fetal CHD was determined by ROC curve analysis. Results: Microarray analysis identified 3694 up-regulated and 3919 down-regulated (fold change ≥2.0) lncRNAs. The top ten significantly differentially expressed, CHD-associated lncRNAs were validated by RT-PCR. Five significantly up-regulated or down-regulated lncRNAs were identified: ENST00000436681, ENST00000422826, AA584040, AA709223 and BX478947 with the AUC of ROC curves calculated as 0.892, 0.817, 0.755, 0.882 and 0.886, respectively. Conclusions: Specific lncRNAs aberrantly expressed in the plasma of pregnant women with typical fetal CHD may play a key role in the development of CHD and may be used as novel biomarkers for prenatal diagnosis of fetal CHD.

Event-related potentials (ERPs) were recorded during a hybrid Simon-spatial Stroop task. We compared interference control and conflict monitoring in children with and without attention-deficit/hyperactivity disorder (ADHD), to examine developmental functional patterns. We found that children with ADHD exhibited lower accuracy rates and longer and more variable reaction time (RT) in both tasks, especially in the incongruent condition. In both controls and ADHD children, the accuracy rate increased and RT decreased with age. Major development in interference control occurred from 6-7 to 8 years in ADHD children and controls, yet only occurred from 9 to 10-11 years in normal children. The ERP results revealed that the N2 potentials were not significantly different from age-matched controls in the two tasks and that the development pattern of conflict monitoring was not different in school age children with and without ADHD. Children with ADHD had normal conflict monitoring ability.