Effects of psoriasis and psoralen exposure on the somatic mutation landscape of the skin.

Somatic mutations are hypothesized to play a role in many non-neoplastic diseases. We performed whole-exome sequencing of 1,182 microbiopsies dissected from lesional and nonlesional epidermis from 111 patients with psoriasis to search for evidence that somatic mutations in keratinocytes may influence the disease process. Lesional skin remained highly polyclonal, showing no evidence of large-scale spread of clones carrying potentially pathogenic mutations.

Characterizing Mutational Load and Clonal Composition of Human Blood.

Hematopoietic stem and progenitor cells (HSPCs) gradually accumulate DNA mutations during a lifespan, which can contribute to age-associated diseases such as leukemia. Characterizing mutation accumulation can improve understanding of the etiology of age-associated diseases. Presented here is a method to catalogue somatic mutations in individual HSPCs, which is based on whole-genome sequencing (WGS) of clonal primary cell cultures.

Significantly greater antioxidant anticancer activities of 2,3-dehydrosilybin than silybin.

Silybin or silymarin extract has been used to treat liver diseases, and has now been entered into clinical trials for cancer treatment. Here, we compared antioxidant and anticancer activities between silybin and its oxidized form 2,3-dehydrosilybin (DHS). With IC50 at three-fold lower concentrations than silybin, DHS inhibited reactive oxygen species generation in glucose-glucose oxidase system and HepG2 cells.

Nox1 induces differentiation resistance in immortalized human keratinocytes generating cells that express simple epithelial keratins.

We have shown that superoxide radical-generating NADPH oxidase 1 (Nox1) is increased in intermediate human transformed cells. It was unknown whether Nox1 overexpression could accelerate early transformation steps. We demonstrated that Nox1 rendered human immortalized (GM16) keratinocytes resistant against Ca(2+)/serum-induced differentiation.