Analysis of serum microRNA expression in male workers with occupational noise-induced hearing loss

Occupational noise-induced hearing loss (ONIHL) is a prevalent occupational disorder that impairs auditory function in workers exposed to prolonged noise. However, serum microRNA expression in ONIHL subjects has not yet been studied. We aimed to compare the serum microRNA expression profiles in male workers of ONIHL subjects and controls. MicroRNA microarray analysis revealed that four serum microRNAs were differentially expressed between controls (n=3) and ONIHL subjects (n=3). Among these microRNAs, three were upregulated (hsa-miR-3162-5p, hsa-miR-4484, hsa-miR-1229-5p) and one was downregulated (hsa-miR-4652-3p) in the ONIHL group (fold change >1.5 and Pbon value <0.05). Real time quantitative PCR was conducted for validation of the microRNA expression. Significantly increased serum levels of miR-1229-5p were found in ONIHL subjects compared to controls (n=10 for each group; P<0.05). A total of 659 (27.0%) genes were predicted as the target genes of miR-1229-5p. These genes were involved in various pathways, such as mitogen-activated protein kinase (MAPK) signaling pathway. Overexpression of miR-1229-5p dramatically inhibited the luciferase activity of 3′ UTR segment of MAPK1 (P<0.01). Compared to the negative control, HEK293T cells expressing miR-1229-5p mimics showed a significant decline in mRNA levels of MAPK1 (P<0.05). This preliminary study indicated that serum miR-1229-5p was significantly elevated in ONIHL subjects. Increased miR-1229-5p may participate in the pathogenesis of ONIHL through repressing MAPK1 signaling.

Genistein prevents cadmium-induced neurotoxic effects through its antioxidant mechanisms.

INTRODUCTION: Cadmium-induced neurotoxic effects are mediated through adverse oxidative stress and calcium signaling. Genistein, a phytoestrogen is a potent antioxidant and exhibits property to cross blood-brain barrier. METHODS: Experimental model of cadmium-induced neurotoxic effects were induced by treatment with cadmium (5 mg/kg) for 28 days in wistar rats. For determining the protective effect, genistein was administered at a dose of (10 mg/kg) for 7 days followed by cadmium treatment for 28 days. Serum and tissues were analyzed for various oxidative stress markers such as total antioxidant capacity, total oxidant levels, non-enzymic antioxidants, enzymic antioxidants, lipid peroxide levels and protein carbonyl content. RESULTS: The results showed significant increase in the oxidative stress markers during cadmium treatment was attenuated in rats treated with genistein followed by cadmium treatment. In addition, cadmium induced alterations and activities of ATPase were significantly restored by genistein treatment. CONCLUSION: The present study observations show promising results of genistein against cadmium-induced neurotoxic effects in wistar rats. Thus its potent antioxidant and cytoprotective effects could act as potent therapeutic agent against various neuro-degenerative diseases involving oxidative stress as primary mechanism.

Synergistic function of Kras mutation and HBx in initiation and progression of hepatocellular carcinoma in mice.

Although the activation of Ras pathway is frequently observed in human hepatocellular carcinoma (HCC), the in vivo role of Ras activation in HCC initiation and progression is underdetermined. To test the consequence of Kras activation in hepatocyte, we generated a hepatocyte-specific Kras(G12D) transgenic mouse strain and observed spontaneous development of HCC in these mice. Remarkably, HBV X protein (HBx) expression significantly promotes the formation and malignant progression of Kras(G12D)-driven HCC as shown with the accelerated tumor onset, the increased tumor burden and the more poorly differentiated lesions. At the cellular level, concomitant expression of Kras(G12D) and HBx results in a robust increase in hepatocellular proliferation. We reveal that the Akt, MAPK, p53 and TGF-ß pathways are deregulated in the Kras(G12D)-driven HCCs. Also, the dysregulation is more pronounced in the HCCs developed in Kras(G12D) and HBx double transgenic mice. In addition, the altered expressions of ß-catenin, CD44 and E-cadherin are only observed in the Kras(G12D) and HBx double transgenic mice. These results demonstrate a crucial role of Ras activation in hepatocellular carcinogenesis and the functional synergy between Kras(G12D) and HBx in HCC initiation and progression. The novel genetic mouse models that closely recapitulate the histopathologic progression and molecular alterations of human HCC may potentially facilitate the future therapeutic studies.