The use of cochlear-enhancement imaging to predict hearing preservation following vestibular schwannoma removal.

BACKGROUND: Hearing preservation is challenging for patients after the removal of large vestibular schwannomas (VSs). Here, using preoperative magnetic resonance (MR) imaging, we investigated the significance of cochlear enhancement (CE) for predicting postoperative hearing preservation. METHODS: Between January 2014 and December 2019, 34 VS-patients with serviceable hearing underwent tumor-removal surgery using a retrosigmoid approach. The presence or absence of CE using both T2-weighted and gadolinium-enhanced T1-weighted MR images was assessed in VS patients using the pixel-analysis method. Segmented volumetric analyses were also performed using GrowCut 3D slicer software. RESULTS: There were 17 patients (50%) without CE and 17 (50%) with CE. Ten of the 17 non-CE patients (58.8%) had postoperative hearing preservation. In contrast, only 3 of the 17 patients with CE (17.6%) had postoperative hearing preservation. There were no significant tumor-characteristic differences between the two groups. The presence of CE on both the T2-weighted and the gadolinium-enhanced T1-weighted MR images correlated significantly with postoperative hearing outcomes (p = 0.032). Only pure-tone averages were significantly different between the two groups (p = 0.049). CONCLUSIONS: Preoperative serviceable hearing is likely to be preserved after surgery in non-CE VS patients. Preoperative CE assessment using MR imaging may be a useful predictor for postoperative hearing outcomes in VS patients.

Functional characterization of a glycine-rich RNA-binding protein 2 in Arabidopsis thaliana under abiotic stress conditions.

Although glycine-rich RNA-binding protein 2 (GRP2) has been implicated in plant responses to environmental stresses, the function and importance of GRP2 in stress responses are largely unknown. Here, we examined the functional roles of GRP2 in Arabidopsis thaliana under high-salinity, cold or osmotic stress. GRP2 affects seed germination of Arabidopsis plants under salt stress, but does not influence seed germination and seedling growth of Arabidopsis plants under osmotic stress. GRP2 accelerates seed germination and seedling growth in Arabidopsis plants under cold stress, and contributes to enhancement of cold and freezing tolerance in Arabidopsis plants. No differences in germination between the wild-type and transgenic plants were observed following addition of abscisic acid (ABA) or glucose, implying that GRP2 affects germination through an ABA-independent pathway. GRP2 complements the cold sensitivity of an Escherichia coli BX04 mutant and exhibits transcription anti-termination activity, suggesting that it has an RNA chaperone activity during the cold adaptation process. Mitochondrial respiration and catalase and peroxidase activities were affected by expression of mitochondrial-localized GRP2 in Arabidopsis plants under cold stress. Proteome analysis revealed that expression of several mitochondrial-encoded genes was modulated by GRP2 under cold stress. These results provide new evidence indicating that GRP2 plays important roles in seed germination, seedling growth and freezing tolerance of Arabidopsis under stress conditions, and that GRP2 exerts its function by modulating the expression and activity of various classes of genes.

Regulation of urokinase plasminogen activator by epigallocatechin-3-gallate in human fibrosarcoma cells.

(-)-Epigallocatechin-3-gallate (EGCG), a main flavanol of green tea, potently suppressed the urokinase-type plasminogen activator (uPA) expression in human fibrosarcoma HT 1080 cells. EGCG induced not only the suppression of the uPA promoter activity but also the destabilization of uPA mRNA. EGCG inhibited the phosphorylation of extracellular signal-regulated kinases 1 and 2 (Erk-1/2) and P38 mitogen-activated protein kinase (MAPK), but not the phosphorylation of c-jun N-terminal kinase (JNK) and Akt. Specific inhibitors of Erk-1/2 (2'-amino-3'-methoxyflavone, PD98059) and P38 MAPK (pyridinylimidazole, SB203580) were found to suppress the uPA expression and the uPA promoter activity. However, the specific inhibitors did not affect the uPA mRNA stability. These results suggest that EGCG could regulate the uPA expression by at least two different mechanisms: EGCG may inhibit the Erk-1/2 and P38 MAPK, leading to suppression of the uPA promoter activity, and EGCG may destabilize the uPA mRNA in an Erk-1/2- and p38 MAPK-independent way.

Involvement of NF-kappaB and caspases in silibinin-induced apoptosis of endothelial cells.

Silibinin, the flavonoid found in the milk thistle, has been shown to suppress cell growth and exhibit anti-cancer effects. Some flavonoids were reported to inhibit angiogenesis which is essential for tumor growth and metastasis. In this study, to clarify the underlying mechanisms for the anti-cancer effect of silibinin, we examined the effects of silibinin on human endothelial ECV304 cells. Silibinin was found to suppress the growth and induce the apoptosis of ECV304 cells. The induction of apoptosis by silibinin was confirmed by ladder-patterned DNA fragmentation, cleaved and condensed nuclear chromatin and DNA hypoploidy. Silibinin could effectively inhibit constitutive NF-kappaB activation as revealed by electrophoretic mobility shift assay and NF-kappaB-dependent luciferase reporter study. Consistent with this, silibinin treatment resulted in a significant decrease in the nuclear level of p65 subunit of NF-kappaB. In addition, silibinin treatment caused a change in the ratio of Bax/Bcl-2 in a manner that favors apoptosis. Silibinin also induced the cytochrome c release, activation of caspase-3 and caspase-9 and cleavage of PARP. These results suggest that silibinin may exert, at least partly, its anti-cancer effect by inhibiting angiogenesis through induction of endothelial apoptosis via modulation of NF-kappaB, Bcl-2 family and caspases.