A cDNA encoding a double-stranded-RNA (dsRNA)-binding protein was isolated by screening a HeLa cell cDNA expression library for proteins that bind the HIV-1 Rev-responsive-element RNA. The cDNA encoded a protein that was identical to TRBP, the previously reported cellular protein that binds the transactivation response element (TAR) RNA ofhuman immunodeficiency virus type 1. TRBP inhibited phosphorylation ofthe interferon-induced ribosome-asted protein kinase PKR and of the eukaryotic transtion initiation factor eIF-2a in a transient-expression system in which the translation of a reporter gene was inhibited by the localized activation of PKR. TRBP expression in HeLa cells complemented the growth and protein-synthesis defect of a vaccinia virus mutant laking the expression of the dsRNA-binding protein E3L. These results implicate RBP as a cellular regulatory protein that binds RNAs containing specific secondary structure(s) to mediate the hnhibition ofPKR activation and stimulate translation in a llized manner.

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Oncomirs are microRNAs (miRNA) associated with carcinogenesis and malignant transformation. They have emerged as potential molecular targets for anti-cancer therapy. We hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic effects through modulations of oncomirs and their downstream targets. We found that GSE significantly down-regulated oncomirs miR-19a and -19b in a variety of lung neoplastic cells. GSE also increased mRNA and protein levels of insulin-like growth factor II receptor (IGF-2R) and phosphatase and tensin homolog (PTEN), both predicted targets of miR-19a and -19b. Furthermore, GSE significantly increased PTEN activity and decreased AKT phosphorylation in A549 cells. Transfection of miR-19a and -19b mimics reversed the up-regulations of IGF2R and PTEN gene expression and abrogated the GSE induced anti-proliferative response. Additionally, oral administration of leucoselect phytosome, comprised of standardized grape seed oligomeric procyanidins complexed with soy phospholipids, to athymic nude mice via gavage, significantly down-regulated miR-19a, -19b and the miR-17-92 cluster host gene (MIR17HG) expressions, increased IGF-2R, PTEN, decreased phosphorylated-AKT in A549 xenograft tumors, and markedly inhibited tumor growth. To confirm the absorption of orally administered GSE, plasma procyanidin B1 levels, between 60 and 90 min after gavage of leucoselect phytosome (400 mg/kg), were measured by LC/MS at week 2 and 8 of treatment; the estimated concentration that was associated with 50% growth inhibition (IC50) (1.3 μg/mL) in vitro was much higher than the IC50 (0.032-0.13 μg/ml) observed in vivo. Our findings reveal novel antineoplastic mechanisms by GSE and support the clinical translation of leucoselect phytosome as an anti-neoplastic and chemopreventive agent for lung cancer.

This study evaluated the clinical effectiveness of wireless contralateral routing of offside signals hearing aids (CROS) in patients with severe to profound unilateral sensorineural hearing loss (USNHL). Twenty-one patients with USNHL were enrolled in this prospective study. The change of subjective satisfaction was evaluated using three questionnaires (K-HHIE, K-IOI-HA, K-SSQ). Changes in objective measurements were evaluated with sound localization test (SLT) and hearing in noise test (HINT). These tests were performed at pre-CROS fitting, 2 and 4 weeks after use of CROS. Subjects were grouped according to the age: young (<40 years) vs. old (≥40 years) group. The average K-HHIE and K-SSQ scores significantly improved with the use of CROS. SLT result revealed that hit rate and error degree improved in the young group and lateralization ability improved in both groups. In quiet environments, the reception threshold for speech also indicated a significant benefit in the young group. When the noise was presented to the normal ear, HINT revealed benefit of CROS, while loss of performance with CROS use was significant when noise was presented to the impaired ear. Wireless CROS provided increased satisfaction and overall improvement of localization and hearing. Although true binaural hearing cannot be obtained, CROS is a practical option for rehabilitation of USNHL.

The aim of this study was to investigate the effects of intracochlear bleeding during cochleostomy on cochlear inflammatory response and residual hearing in a guinea pig animal model. Auditory brainstem response threshold shifts were greater in blood injected ears (p<0.05). Interleukin-1β, interleukin-10, tumor necrosis factor-α and nitric oxide synthase 2, cytokines that are related to early stage inflammation, were significantly increased in blood injected ears compared to normal and cochleostomy only ears at 1 day after surgery; with the increased IL-1β being sustained until 3 days after the surgery (p<0.05). Hair cells were more severely damaged in blood injected ears than in cochleostomy only ears. Histopathologic examination revealed more extensive fibrosis and ossification in blood injected ears than cochleostomy only ears. These results show that intracochlear bleeding enhanced cochlear inflammation resulting in increased fibrosis and ossification in an experimental animal model.