Dietary phytochemicals, HDAC inhibition, and DNA damage/repair defects in cancer cells

Genomic instability is a common feature of cancer etiology. This provides an avenue for therapeutic intervention, since cancer cells are more susceptible than normal cells to DNA damaging agents. However, there is growing evidence that the epigenetic mechanisms that impact DNA methylation and histone status also contribute to genomic instability. The DNA damage response, for example, is modulated by the acetylation status of histone and non-histone proteins, and by the opposing activities of histone acetyltransferase and histone deacetylase (HDAC) enzymes. Many HDACs overexpressed in cancer cells have been implicated in protecting such cells from genotoxic insults. Thus, HDAC inhibitors, in addition to unsilencing tumor suppressor genes, also can silence DNA repair pathways, inactivate non-histone proteins that are required for DNA stability, and induce reactive oxygen species and DNA double-strand breaks. This review summarizes how dietary phytochemicals that affect the epigenome also can trigger DNA damage and repair mechanisms. Where such data is available, examples are cited from studies in vitro and in vivo of polyphenols, organosulfur/organoselenium compounds, indoles, sesquiterpene lactones, and miscellaneous agents such as anacardic acid. Finally, by virtue of their genetic and epigenetic mechanisms, cancer chemopreventive agents are being redefined as chemo- or radio-sensitizers. A sustained DNA damage response coupled with insufficient repair may be a pivotal mechanism for apoptosis induction in cancer cells exposed to dietary phytochemicals. Future research, including appropriate clinical investigation, should clarify these emerging concepts in the context of both genetic and epigenetic mechanisms dysregulated in cancer, and the pros and cons of specific dietary intervention strategies

Effect of Radiofrequency Thermal Ablation Treatment on Nasal Ciliary Motility

OBJECTIVE: To investigate the efficacy of nasal ciliary motility after radiofrequency ablation treatment in patients with isolated inferior turbinate hypertrophy and to clarify how long until normal ciliary function is restored. STUDY DESIGN: Prospective, single-group, pretest-posttest design. SETTING: Academic tertiary care medical center. SUBJECTS AND METHODS: This study involved 34 adult patients affected by nasal obstruction due to inferior turbinate hypertrophy who underwent radiofrequency ablation treatment between June and December 2014. Diagnosis was assessed according to clinical history, nasal endoscopy, and active anterior rhinomanometry. Cytologic samples were collected by nasal scraping before surgery and 1, 2, and 3 months after surgery. Ciliary motility was evaluated by nasal cytology with phase-contrast microscopy. Functional aspects of nasal mucosa were studied, with a focus on 3 parameters: (1) nasal mucociliary clearance, assessed by saccharin nasal transit time test; (2) percentage of ciliated cell motility, measured as the ratio between cells with motility and cells without motility; and (3) efficacy of ciliary motility, measured as the ratio between cells with valid motility and cells with hypovalid motility. RESULTS: Ciliary motility and ciliary efficacy showed a significant reduction after 1 and 2 months from surgery, returning to normal values within 3 months. No significant changes in saccharin nasal transit time were recorded during the follow-up. CONCLUSIONS: The outcomes of this study suggest that radiofrequency ablation treatment causes ciliary motility changes of nasal mucosa that are completely restored after at least 3 months after surgery. These cytologic abnormalities do not affect nasal functionality

Proanthocyanidin-Rich Date Seed Extract Protects Against Chemically Induced Hepatorenal Toxicity

A hydroacetone extract was prepared from seeds of Phoenix dactylifera L. var. Khalas, which is an industrial by-product of date processing. The proanthocyanidin nature of the extract (coded as DTX) was characterized by phytochemical and nuclear magnetic resonance (NMR) analyses. The total phenol/proanthocyanidin content and antioxidant activity of DTX were estimated by Folin–Ciocalteu, vanillin-sulfuric acid, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays, respectively. The hepatorenal protective activity of DTX was evaluated using CCl(4)-induced toxicity model in rats, in comparison with silymarin (SYL). Results of the histopathological examination and measurements of various hepatorenal serum indices and tissue biochemical markers demonstrated that DTX displayed marked protective potential against CCl(4)-induced liver and kidney injury at 100 mg/kg/rat. Relative to the control CCl(4)-intoxicated group, pretreatment with DTX significantly (P<.001) suppressed the elevated serum levels of alanine aminotransferase and aspartate aminotransferase (ALT and AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), bilirubin, creatinine, and calcium, whereas it significantly (P<.001) increased the diminished serum levels of high-density lipoprotein cholesterol (HDL-C) and total protein (TP). Moreover, DTX significantly decreased malondialdehyde (MDA) formation and increased TP synthesis in hepatorenal tissues compared with the intoxicated control. The improvement in biochemical parameters by DTX was observed in a dose-dependent manner and confirmed by restoration of normal histological features. The acute toxicity test of DTX in rats revealed safety of the extract. This study reveals that DTX enhances the recovery from xenobiotics-induced toxicity initiated by free radicals

Being Native American in business: Culture, identity, and authentic leadership in modern American Indian enterprises

Tribally-owned American Indian enterprises provide a unique cross-cultural setting for emerging Native American business leaders. This paper examines the manner in which American Indian leaders negotiate the boundaries between their indigenous organizations and the non-indigenous communities in which they do business. Through a series of qualitative interviews, we find that American Indian business leaders fall back on a strong sense of “self”, which allows them to maintain effective leadership across boundaries. This is highly consistent with theories of authentic leadership. Furthermore, we find that leaders define self through their collective identity, which is heavily influenced by tribal affiliation and tribal culture. We add to the literature on authentic leadership by showing the role that culture and collective identity have in creating leader authenticity within the indigenous community