Profiles of MicroRNAs in Interleukin-27-Induced HIV-Resistant T Cells: Identification of a Novel Antiviral MicroRNA.

Objectives: Interleukin-27 (IL-27) is known as an anti-HIV cytokine. We have recently demonstrated that IL-27-pretreatment promotes phytohemagglutinin-stimulated CD4(+) T cells into HIV-1-resistant cells by inhibiting an uncoating step.

Purpose: To further characterize the function of the HIV resistant T cells, we investigated profiles of microRNA in the cells using microRNA sequencing (miRNA-seq) and assessed anti-HIV effect of the microRNAs.

Panaxynol, a bioactive component of American ginseng, targets macrophages and suppresses colitis in mice.

Ulcerative colitis has a significant impact on the quality of life for the patients, and can substantially increase the risk of colon cancer in patients suffering long-term. Conventional treatments provide only modest relief paired with a high risk of side effects, while complementary and alternative medicines can offer safe and effective options. Over the past decade, we have shown that both American ginseng and its hexane fraction (HAG) have anti-oxidant and anti-inflammatory properties that can suppress mouse colitis and prevent colitis-associated colon cancer.

IL-27 posttranslationally regulates Y-box binding protein-1 to inhibit HIV-1 replication in human CD4+ T cells.

Objectives: IL-27 is known as an antiviral cytokine that inhibits HIV, hepatitis C virus, and other viruses. We have previously demonstrated that, IL-27 posttreatment after HIV-infection inhibits viral replication in primary CD4 T cells.

Design: Here, we evaluated the anti-HIV effect of IL-27 pretreatment in CD4 T cells from healthy donors prior to HIV infection with HIVNL4.

A novel microRNA, hsa-miR-6852 differentially regulated by Interleukin-27 induces necrosis in cervical cancer cells by downregulating the FoxM1 expression.

We have previously demonstrated that Interleukin-27 differentially regulates the expression of seven novel microRNAs. Here we elucidate the functional significance of these novel microRNAs. Of the seven microRNAs, over expression of miRNA-6852 (miR-SX4) mimic induces cell cycle arrest at G2/M phase and induces necrosis in HEK293 and panel of cervical cancer cells (Human Papilloma Virus (HPV) infected cell lines; HeLa, CaSki and SiHa cells).

Interleukin-27 Enhances the Potential of Reactive Oxygen Species Generation from Monocyte-derived Macrophages and Dendritic cells by Induction of p47.

Interleukin (IL)-27, a member of the IL-12 cytokine family, plays an important and diverse role in the function of the immune system. We have previously demonstrated that IL-27 is an anti-viral cytokine which inhibits HIV-1, HIV-2, Influenza virus and herpes simplex virus infection, and enhances the potential of reactive oxygen species (ROS) generating activity during differentiation of monocytes to macrophages. In this study, we further investigated the mechanism of the enhanced potential for ROS generation by IL-27.

Designing a broad-spectrum integrative approach for cancer prevention and treatment.

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.

A multi-targeted approach to suppress tumor-promoting inflammation.

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity.

A key role of microRNA-29b for the suppression of colon cancer cell migration by American ginseng.

Metastasis of colon cancer cells increases the risk of colon cancer mortality. We have recently shown that American ginseng prevents colon cancer, and a Hexane extract of American Ginseng (HAG) has particularly potent anti-inflammatory and anti-cancer properties. Dysregulated microRNA (miR) expression has been observed in several disease conditions including colon cancer.

The induction of microRNA-16 in colon cancer cells by protein arginine deiminase inhibition causes a p53-dependent cell cycle arrest.

Protein Arginine Deiminases (PADs) catalyze the post-translational conversion of peptidyl-Arginine to peptidyl-Citrulline in a calcium-dependent, irreversible reaction. Evidence is emerging that PADs play a role in carcinogenesis. To determine the cancer-associated functional implications of PADs, we designed a small molecule PAD inhibitor (called Chor-amidine or Cl-amidine), and tested the impact of this drug on the cell cycle.

A limited role of p53 on the ability of a Hexane fraction of American ginseng to suppress mouse colitis.

Ulcerative colitis (UC) is debilitating and carries a high colon cancer risk. Apoptosis of inflammatory cells is a key mechanism regulating UC. We have recently shown that American ginseng (AG), and to a greater extent, a Hexane fraction of AG (HAG) can cause apoptosis and suppress mouse colitis through a p53-mediated mechanism.

Suppression of DNA damage in human peripheral blood lymphocytes by a juice concentrate: a randomized, double-blind, placebo-controlled trial.

Chronic inflammation contributes to many prevalent diseases worldwide, and it is widely accepted that inflammatory molecules contribute to DNA damage. In this ancillary study, we investigated the influence of an encapsulated fruit and vegetable juice powder concentrate on peripheral blood lymphocytes (PBL) DNA damage. Using a double-blind, placebo-controlled approach, subjects were randomly assigned capsules containing placebo, or one of two formulations of the juice powder.

A hexane fraction of American ginseng suppresses mouse colitis and associated colon cancer: anti-inflammatory and proapoptotic mechanisms.

Ulcerative colitis is a chronic inflammatory condition associated with a high colon cancer risk. We have previously reported that American ginseng extract significantly reduced the inflammatory parameters of chemically induced colitis. The aim of this study was to further delineate the components of American ginseng that suppress colitis and prevent colon cancer.

Suppression of colitis in mice by Cl-amidine: a novel peptidylarginine deiminase inhibitor.

Inflammatory bowel diseases (IBDs), mainly Crohn's disease and ulcerative colitis, are dynamic, chronic inflammatory conditions that are associated with an increased colon cancer risk. Inflammatory cell apoptosis is a key mechanism for regulating IBD. Peptidylarginine deiminases (PADs) catalyze the posttranslational conversion of peptidylarginine to peptidylcitrulline in a calcium-dependent, irreversible reaction and mediate the effects of proinflammatory cytokines.

Mechanistic insight into the ability of American ginseng to suppress colon cancer associated with colitis.

We have recently shown that American ginseng (AG) prevents and treats mouse colitis. Because both mice and humans with chronic colitis have a high colon cancer risk, we tested the hypothesis that AG can be used to prevent colitis-driven colon cancer. Using the azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of ulcerative colitis, we show that AG can suppress colon cancer associated with colitis.

Suppression of colitis-driven colon cancer in mice by a novel small molecule inhibitor of sphingosine kinase.

Sphingolipid metabolism is driven by inflammatory cytokines. These cascade of events include the activation of sphingosine kinase (SK), and subsequent production of the mitogenic and proinflammatory lipid sphingosine 1-phosphate (S1P). Overall, S1P is one of the crucial components in inflammation, making SK an excellent target for the development of new anti-inflammatory drugs.

Resveratrol suppresses colitis and colon cancer associated with colitis.

Resveratrol is a naturally occurring polyphenol that exhibits pleiotropic health beneficial effects, including anti-inflammatory, cardio-protective, and cancer-protective activities. It is recognized as one of the more promising natural molecules in the prevention and treatment of chronic inflammatory and autoimmune disorders. Ulcerative colitis is an idiopathic, chronic inflammatory disease of the colon associated with a high colon cancer risk.

American ginseng suppresses colitis through p53-mediated apoptosis of inflammatory cells.

Ulcerative colitis is a dynamic, chronic inflammatory condition associated with an increased colon cancer risk. Inflammatory cell apoptosis is a key mechanism regulating ulcerative colitis. American ginseng (AG) is a putative antioxidant that can suppress hyperactive immune cells.

The ERK and PI3K signaling pathways mediate inhibition of insulin-like growth factor-1 receptor mRNA expression by somatostatin.

Somatostatins (SSs) are a structurally diverse family of peptide hormones that regulate various aspects of growth, development, and metabolism in vertebrates. Previously, we showed that SSs inhibit mRNA and functional expression of insulin-like growth factor-1 receptors (IGFR1) in gill filaments of rainbow trout. In this study, we used trout gill filaments, which express in high abundance two distinct IGFR1s, IGFR1A and IGFR1B, to examine the mechanism(s) through which SSs exert their inhibitory effects on IGFR1 expression.