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Period circadian regulator (Per)1 and Per2 genes are involved in the molecular mechanism of the circadian clock, and exhibit tumor suppressor properties. Several studies have reported a decreased expression of Per1, Per2 and Per3 genes in different types of cancer and cancer cell lines. Promoter methylation downregulates Per1, Per2 or Per3 expression in myeloid leukemia, breast, lung, and other cancer cells; whereas histone deacetylase inhibitors (HDACi) upregulate Per1 or Per3 expression in certain cancer cell lines. However, the transcriptional regulation of Per1 and Per2 in cancer cells by chromatin modifications is not fully understood. The present study aimed to determine whether HDACi regulate Per1 and Per2 expression in gastric cancer cell lines, and to investigate changes in chromatin modifications in response to HDACi. Treatment of KATO III and NCI-N87 human gastric cancer cells with sodium butyrate (NaB) or Trichostatin A (TSA) induced Per1 and Per2 mRNA expression in a dose-dependent manner. Chromatin immunoprecipitaion assays revealed that NaB and TSA decreased lysine 9 trimethylation on histone H3 (H3K9me3) at the Per1 promoter. TSA, but not NaB increased H3K9 acetylation at the Per2 promoter. It was also observed that binding of Sp1 and Sp3 to the Per1 promoter decreased following NaB treatment, whereas Sp1 binding increased at the Per2 promoter of NaB- and TSA-treated cells. In addition, Per1 promoter is not methylated in KATO III cells, while Per2 promoter was methylated, although NaB, TSA, and 5-Azacytidine do not change the methylated CpGs analyzed. In conclusion, HDACi induce Per1 and Per2 expression, in part, through mechanisms involving chromatin remodeling at the proximal promoter of these genes; however, other indirect mechanisms triggered by these HDACi cannot be ruled out. These findings reveal a previously unappreciated regulatory pathway between silencing of Per1 gene by H3K9me3 and upregulation of Per2 by HDACi in cancer cells. [ABSTRACT FROM AUTHOR]

Excessive caloric intake and a sedentary life style are factors that promote adipose tissue growth and obesity. Adipose tissue releases several bioactive molecules such as leptin, adiponectin, interleukin6 (IL-6), tumor necrosis factor-α (TNF-α) and plasminogen activator inhibitor-1 (PAI-I). Under the pathological conditions of obesity, the excess of dysfunctional adipose tissue alters the release and balance of these molecules; leptin, IL-6, and TNF-α are increased, whereas adiponectin decreases, leading to the development of the metabolic syndrome and cardiovascular diseases. In this article we review the main metabolic alterations derived from obesity, such as: dyslipidemia, oxidative stress, inflammation, diabetes, endothelial dysfunction, insulin resistance, risk factors that contribute to the development of atherosclerosis, myocardial infarction, and other cardiovascular diseases. [ABSTRACT FROM AUTHOR]

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Saliva is a fluid that can be collected easily and noninvasively. Its functions in the oral cavity are well known. Advances in molecular biology and technology, as well as research conducted by the various disciplines of omics (genomics, transcriptomics, proteomics, metabolomics, and metagenomics) have contributed to the identification and characterization of salivary components, including DNA, RNA, proteins, metabolites, and microorganisms. These biomolecules enter the saliva through extracellular and intracellular routes, providing information from several organs and systems and raising the possibility of their use as disease biomarkers. In recent years, these factors have expanded the potential use of saliva as a diagnostic fluid for oral and systemic diseases. This review integrates information regarding salivary biomolecules studied through omics and explores their utility as biomarkers for the diagnosis of several infectious and noninfectious diseases, and the opportunity they represent for the development of point of care devices for clinical application. We also discuss the advantages, disadvantages, and challenges to be overcome in order to establish saliva as a useful fluid for the accurate diagnosis and monitoring of a wide range of diseases.