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(1) Morroniside belongs to an extensive group of natural iridorid glycosides. In the present study, using human neuroblastoma SH-SY5Y cells, we have investigated the protective effects of this compound on modifications in endogenous reduced glutathione (GSH), intracellular oxygen species (ROS) and apoptotic death on H(2)O(2)-mediated cytoxicity. (2) Incubation of cells with morroniside led to a significant dose-dependent elevation of cellular GSH accompanied by a marked protection against H(2)O(2)-mediated toxicity. Morroniside at 1-100 microM inhibited the formation of ROS and the activation of caspase-3 and 9, and the upregulation of Bcl-2, whereas no significant change occurred in Bax levels. (3) The results indicated that the anti-oxidative and anti-apoptotic properties render this natural compound potentially protective against H(2)O(2)-induced cytotoxicity. (4) This study suggested that intracellular GSH appeared to be an important factor in morroniside-mediated cytoprotection against H(2)O(2)-toxicity in SH-SY5Y cells.

To study interaction and dose-related effects of mixed cypermethrin and methyl parathion on endocrine and immune functions, 120 Wistar rats were divided randomly into six groups of ten male and ten female rats, respectively, at the age of 2 months. All groups were force-fed every 2 days for 30 days with cypermethrin 0.0, 8.0, 0.0, 8.0, 1.8, 0.4 mg/kg bw and methyl parathion 0.0, 0.0, 0.23, 0.23, 0.0518, 0.0115 mg/kg bw. Controls received vehicle solvent only. Body weight gain and organ weights were measured. Serum or blood were used to test luteinizing hormone, follicle stimulating hormone, estradiol (E(2)), testosterone, thyroid hormones (T(3), T(4), TSH), IgG, IgA, rate of neutrophil phagocytosis and of lymphocyte transformation. The effects on relative weights of ovaries and adrenals, IgA and rate of lymphocyte transformation were antagonistic interaction; the effect on estradiol was synergistic in female, whereas addictive in male rats; and the other indices indicated addictive interaction. Organ weights were similar in exposed and control animals except for adrenal (heavier in exposed rats, P<0.01). Serum levels of FSH and estradiol were higher in exposed groups than in controls (P<0.01). IgG levels were lower in exposed rats than in controls (P<0.01), and IgA levels were higher in exposed females than in controls (P<0.01). Lymphocyte transformation rates were lower (P<0.01) and neutrophil phagocytosis rates were higher (P<0.01) in exposed rats than in controls. Our results showed that exposure to low-dose mixtures of cypermethrin and methyl parathion may affect hormone levels (especially estradiol) and immune function in rats, and the NOAELs of combined compounds were located at 1/600 LD(50).

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The accurate and quantitative analysis of microRNA (miRNA) expression is critical for biomedical research and clinical theranostics. In this study, we report a novel sensor for the sensitive detection of miRNA based on a duplex-specific nuclease (DSN)-assisted dual signal amplification strategy. A chimeric probe (DNA/2-OMe-RNA) that consists of a miRNA recognition DNA sequence and a Taqman probe hybridization RNA sequence (2'-O-methyl RNA) was designed and synthesized. One molecule of target miRNA can trigger cyclical cleavage of the chimeric probes to produce 2'-O-methyl RNA by DSN in the first round of amplification. The 2'-O-methyl RNA molecules can subsequently hybridize with Taqman probes and initiate the second round of cyclical amplification to generate detectable fluorescence by DSN. The proposed strategy exhibits high specificity in discriminating cognate miRNAs, and the dual signal transduction process enables the detection of miRNA concentrations as low as 7.3fM. We further applied this assay to miRNA quantification in cancer cells to confirm its applicability. The present study provides a sensitive, specific and simple method for miRNA detection and holds great potential for further application in biomedical research and in the clinical laboratory.

Long‐term arsenic exposure can promote cancer through epigenetic mechanisms, and arsenite methyltransferase (AS3MT) plays an important role in this process. However, the expression patterns and mechanisms of AS3MT in arsenic carcinogenesis remain unclear. In this study, we found that the AS3MT was overexpressed in arsenic exposed population, non‐small cell lung cancer (NSCLC) tissues, and A549 cells with sodium arsenite (NaAsO2) treatment for 48 hours. Besides, the level of AS3MT expression was positively correlated with the concentrations of urinary total arsenic (tAs), inorganic arsenic (iAs), methanearsonic acid (MMA), and dimethylarsinic acid (DMA) in all subjects. Functional experiments demonstrated that siRNA‐mediated knockdown of AS3MT significantly inhibited proliferation of A549 cells. Mechanism investigation revealed that silencing of AS3MT inhibited proliferation by increasing mRNA expression levels of p21 and E2F1, and inhibiting CDK1, CDK2, CDK4, CDK6, Cyclin A2, Cyclin E1, Cyclin E2, and PCNA mRNA expression. Therefore, arsenic increased AS3MT expression in vivo and in vitro, which could directly act on the cell and affect the progression of NSCLC by regulating cell cycle genes.

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