RESUMEN
Surfaces contaminated with bacteria and viruses contribute to the transmission of infectious diseases and pose a significant threat to global public health. Modern day disinfection either relies on fast-acting (>3-log reduction within a few minutes), yet impermanent, liquid-, vapor-, or radiation-based disinfection techniques, or long-lasting, but slower-acting, passive antimicrobial surfaces based on heavy metal surfaces, or metallic nanoparticles. There is currently no surface that provides instant and persistent antimicrobial efficacy against a broad spectrum of bacteria and viruses. In this work, we describe a class of extremely durable antimicrobial surfaces incorporating different plant secondary metabolites that are capable of rapid disinfection (>4-log reduction) of current and emerging pathogens within minutes, while maintaining persistent efficacy over several months and under significant environmental duress. We also show that these surfaces can be readily applied onto a variety of desired substrates or devices via simple application techniques such as spray, flow, or brush coating.
RESUMEN
Low H19 and abundant IGF-II expression may have a role in the development of adrenocortical carcinomas. In the mouse, the H19 promoter area has been found to be methylated when transcription of the H19 gene is silent and unmethylated when it is active. We used PCR-based methylation analysis and bisulfite genomic sequencing to study the cytosine methylation status of the H19 promoter region in 16 normal adrenals and 30 pathological adrenocortical samples. PCR-based analysis showed higher methylation status at three HpaII-cutting CpG sites of the H19 promoter in adrenocortical carcinomas and in a virilizing adenoma than in their adjacent normal adrenal tissues. Bisulfite genomic sequencing revealed a significantly higher mean degree of methylation at each of 12 CpG sites of the H19 promoter in adrenocortical carcinomas than in normal adrenals (P < 0.01 for all sites) or adrenocortical adenomas (P < 0.01, except P < 0.05 for site 12 and P > 0.05 for site 11). The mean methylation degree of the 12 CpG sites was significantly higher in the adrenocortical carcinomas (mean +/- SE, 76 +/- 7%) than in normal adrenals (41 +/- 2%) or adrenocortical adenomas (45 +/- 3%; both P < 0.005). RNA analysis indicated that the adrenocortical carcinomas expressed less H19 but more IGF-II RNAs than normal adrenal tissues did. The mean methylation degree of the 12 H19 promoter CpG sites correlated negatively with H19 RNA levels (r = -0.550; P < 0.01), but positively with IGF-II mRNA levels (r = 0.805; P < 0.001). In the adrenocortical carcinoma cell line NCI-H295R, abundant IGF-II, but minimal H19, RNA expression was detected by Northern blotting. Treatment with a cytosine methylation inhibitor, 5-aza-2'-deoxycytidine, increased H19 RNA expression, whereas it decreased IGF-II mRNA accumulation dose- and time-dependently (both P < 0.005) and reduced cell proliferation to 10% in 7 d. Our results suggest that altered DNA methylation of the H19 promoter is involved in the abnormal expression of both H19 and IGF-II genes in human adrenocortical carcinomas.
