Towards Retinoid Therapy for Alzheimer’s Disease

Alzheimer’s disease(AD) is associated with a variety of pathophysiological features, including amyloid plaques, inflammation, immunological changes, cell death and regeneration processes, altered neurotransmission, and age-related changes. Retinoic acid receptors (RARs) and retinoids are relevant to all of these. Here we review the pathology, pharmacology, and biochemistry of AD in relation to RARs and retinoids, and we suggest that retinoids are candidate drugs for treatment of AD

Unusual Assortment of Segments in 2 Rare Human Rotavirus Genomes

Using full-length genome sequence analysis, we investigated 2 rare G3P[9] human rotavirus strains isolated from children with diarrhea. The genomes were recognized as assortments of genes closely related to rotaviruses originating from cats, ruminants, and humans. Results suggest multiple transmissions of genes from animal to human strains of rotaviruses

Tumor Suppressor p53 Functions as a Negative Regulator in IgE-Mediated Mast Cell Activation

Mast cells are known to play a pivotal role in allergic diseases such as allergic rhinitis, asthma, and atopic dermatitis by releasing granules containing histamine, LTC4, and other preformed chemical mediators. Previous reports have demonstrated that IKK2 (also called IKKβ), a central intracellular component of NF-κB activation pathways, plays a critical role in IgE-mediated degranulation of mast cells and anaphylaxis in mice. In this study, we show that protein levels of tumor suppressor p53 are up-regulated upon IgE-mediated activation in mast cells and lack of p53 results in enhanced responses in both early and late phase anaphylaxis. p53 inhibits not only the catalytic activity of IKK2 presumably through the modulation of glycosylation but also p65 (RelA)-mediated transactivation. Our findings are the first to demonstrate that p53 functions as a negative regulator in mast cells

Glucocorticoid-induced TNF receptor-triggered T cells are key modulators for survival/death of neural stem/progenitor cells induced by ischemic stroke

Increasing evidences show that immune response affects the reparative mechanisms in injured brain. Recently, we have demonstrated that CD4+T cells serve as negative modulators in neurogenesis after stroke, but the mechanistic detail remains unclear. Glucocorticoid-induced tumor necrosis factor (TNF) receptor (GITR), a multifaceted regulator of immunity belonging to the TNF receptor superfamily, is expressed on activated CD4+T cells. Herein, we show, by using a murine model of cortical infarction, that GITR triggering on CD4+T cells increases poststroke inflammation and decreases the number of neural stem/progenitor cells induced by ischemia (iNSPCs). CD4+GITR+T cells were preferentially accumulated at the postischemic cortex, and mice treated with GITR-stimulating antibody augmented poststroke inflammatory responses with enhanced apoptosis of iNSPCs. In contrast, blocking the GITR–GITR ligand (GITRL) interaction by GITR–Fc fusion protein abrogated inflammation and suppressed apoptosis of iNSPCs. Moreover, GITR-stimulated T cells caused apoptosis of the iNSPCs, and administration of GITR-stimulated T cells to poststroke severe combined immunodeficient mice significantly reduced iNSPC number compared with that of non-stimulated T cells. These observations indicate that among the CD4+T cells, GITR+CD4+T cells are major deteriorating modulators of poststroke neurogenesis. This suggests that blockade of the GITR–GITRL interaction may be a novel immune-based therapy in stroke

Molecular Characterization of Rotavirus Gastroenteritis Strains, Iraqi Kurdistan

Of 260 children with acute diarrhea in Erbil, Iraqi Kurdistan, 96 (37%) were infected with rotavirus. Reverse transcription–polymerase chain reaction identified G1, G4, G2, G9, P[8], P[6], and P[4] as the most common genotypes. Eight G/P combinations were found, but P[8]G1 and P[4]G2 accounted for >50% of the strains