A nontoxic dose of chrysotile can malignantly transform Met-5A cells, in which microRNA-28 has inhibitory effects.

Chrysotile, which is classified as a class I carcinogen by the International Agency for Research on Cancer (IARC), has extensive application in the industry and can lead to lung or other cancers. However, whether chrysotile causes malignant mesothelioma and its molecular mechanism remain debatable. Thus, this study aimed to demonstrate the mesothelioma-inducing potential of chrysotile at the mesothelial cellular level and the function of microRNA-28 in malignantly transformed mesothelial MeT-5A cells. MeT-5A cells malignantly transformed by a nontoxic dose of chrysotile were named Asb-T, and miR-28 expression was downregulated in Asb-T cells. Restoration of miR-28 expression inhibited the proliferation, migration and invasion of Asb-T cells. We verified that IMPDH is a putative target of miR-28. The expression of IMPDH was significantly higher in Asb-T MeT-5A cells than in control cells, whereas the opposite trend was observed with miR-28 overexpression. Additionally, inhibition of IMPDH had similar effects as miR-28 overexpression. After miR-28 was elevated or IMPDH was inhibited, Ras activation was reduced, and its downstream pathways (the Erk and Akt signalling pathways) were inhibited. Surprisingly, the content of miR-28 in the blood of mesothelioma patients was higher than that in control subjects. Overall, nontoxic doses of chrysotile can cause malignant transformation of MeT-5A cells. Moreover, miR-28 inhibits the proliferation, migration and invasion of Asb-T MeT-5A cells, negatively regulates the expression of IMPDH through the Ras signalling pathway and may be an important therapeutic target.

Effects of Fish Oil Combined with Selenium and Zinc on Learning and Memory Impairment in Aging Mice and Amyloid Precursor Protein Processing.

Alzheimer's disease is characterized by the aggregation of amyloid-beta (Aß) peptide into plaques and neurofibrillary tangles. Aß peptide is generated by the cleavage of the ß-amyloid precursor protein (APP) by ß- and γ-secretase. The present study was conducted to investigate the effects of fish oil (or eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)), selenium, and zinc on learning and memory impairment in an aging mouse model and on APP. We performed the Morris water maze and platform recorder tests on male Kunming mice (10/group) grouped as control and D-galactose-induced aging model mice treated with vehicle, fish oil, fish oil + selenium, fish oil + selenium + zinc, and positive control (red ginseng extract). Fish oil + zinc + selenium for 7 weeks significantly improved learning and memory impairments in aging model animals in the Morris water maze and platform recorder tests, as evidenced by shortened incubation periods and number of errors. In vitro analysis of Aß1-40 content in APP695-transfected CHO cells revealed a decrease after treatment with EPA, DHA, and their combinations with selenium or selenium and zinc. Assaying ß- and γ-secretase activities revealed a decrease in PC12 cells and mouse serum as well as a decrease in ß-site APP-cleaving enzyme 1 and presenilin 1 protein levels in the PC12 cells and mouse serum. Taken together, our results show that fish oil combined with selenium and zinc inhibited APP processing and alleviated learning and memory impairment in a mouse model of aging.