A diet rich in fermentable fiber promotes robust changes in the intestinal microbiota, mitigates intestinal permeability, and attenuates autoimmune uveitis.

Therapeutic approaches for noninfectious uveitis have expanded greatly over the past 10 years, but are limited by potential side effects and limited efficacy. Thus, therapeutic approaches that include less toxic, potentially preventative strategies to manage noninfectious uveitis are essential areas of study. Diets rich in fermentable fiber are potentially preventative in various conditions such as metabolic syndrome and type 1 diabetes.

Myostatin regulates pituitary development and hepatic IGF1.

Circulating myostatin-attenuating agents are being developed to treat muscle-wasting disease despite their potential to produce serious off-target effects, as myostatin/activin receptors are widely distributed among many nonmuscle tissues. Our studies suggest that the myokine not only inhibits striated muscle growth but also regulates pituitary development and growth hormone (GH) action in the liver. Using a novel myostatin-null label-retaining model (Jekyll mice), we determined that the heterogeneous pool of pituitary stem, transit-amplifying, and progenitor cells in Jekyll mice depletes more rapidly after birth than the pool in wild-type mice.

Disruption of Intestinal Homeostasis and Intestinal Microbiota During Experimental Autoimmune Uveitis.

Purpose: We determine the changes in intestinal microbiota and/or disruptions in intestinal homeostasis during uveitis.

Methods: Experimental autoimmune uveitis (EAU) was induced in B10.RIII mice with coadministration of interphotoreceptor retinoid-binding protein peptide (IRBP) and killed mycobacterial antigen (MTB) as an adjuvant.

Short chain fatty acids ameliorate immune-mediated uveitis partially by altering migration of lymphocytes from the intestine.

Short chain fatty acids (SCFA) are metabolites of intestinal bacteria resulting from fermentation of dietary fiber. SCFA are protective in various animal models of inflammatory disease. We investigated the effects of exogenous administration of SFCAs, particularly propionate, on uveitis using an inducible model of experimental autoimmune uveitis (EAU).

Gut Microbial Alterations Associated With Protection From Autoimmune Uveitis.

Purpose: To investigate the contribution of the gut microbiota to the pathogenesis of uveitis.

Methods: Experimental autoimmune uveitis (EAU) in B10.RIII mice was induced using interphotoreceptor binding protein peptide.

Metabolic diseases and pro- and prebiotics: Mechanistic insights.

Metabolic diseases, such as obesity and type 2 diabetes, are world-wide health problems. The prevalence of metabolic diseases is associated with dynamic changes in dietary macronutrient intake during the past decades. Based on national statistics and from a public health viewpoint, traditional approaches, such as diet and physical activity, have been unsuccessful in decreasing the prevalence of metabolic diseases.

Modulation of oxidative stress by γ-glutamylcysteine (GGC) and conjugated linoleic acid (CLA) isomer mixture in human umbilical vein endothelial cells.

Individually, γ-glutamylcysteine (GGC), a dipeptide and precursor of glutathione (GSH), and conjugated linoleic acid (CLA), a trans-fatty acid, exhibit antioxidant properties. The objective of this study was to compare effects of co-administration of GGC and CLA to treatment with GGC alone on oxidative stress and GSH synthesis in human endothelial cells. Changes in levels of 8-epi-PGF2α, thiobarbituric acid reactive substances (TBARS), GSH, total antioxidants, GSH synthetase (GSS) expression, and transcription factor DNA binding were assessed in human umbilical vein endothelial cells (HUVEC) treated with GGC alone (100 μmol/L) or combined with CLA isomer mixture (10, 50, 100 μmol/L) for 24h.

γ-Glutamylcysteine inhibits oxidative stress in human endothelial cells.

Aims: γ-Glutamylcysteine (GGC) is a dipeptide and substrate for synthesis of the antioxidant glutathione (GSH), whose health promoting properties include reducing risks of oxidative stress-related injuries and diseases. The objective of this study was to investigate the efficacy of GGC on GSH synthesis and oxidative stress in human endothelial cells.

Main Methods: We assessed oxidative stress, GSH, GSH synthetase (GSS) expression, and transcription factor DNA binding levels in human umbilical vein endothelial cells (HUVEC).

Lipophilic compound-mediated gene expression and implication for intervention in reactive oxygen species (ROS)-related diseases: mini-review.

In addition to exhibiting antioxidant properties, conjugated linoleic acid (CLA) and vitamin E may modulate gene expression of endogenous antioxidant enzymes. Depending on cellular microenvironments, such modulation reflects either antioxidant or prooxidant outcomes. Although epidemiological/experimental studies have indicated that CLA and vitamin E have health promoting properties, recent findings from clinical trials have been inconclusive.

Conjugated linoleic acid isomers' roles in the regulation of PPAR-gamma and NF-kappaB DNA binding and subsequent expression of antioxidant enzymes in human umbilical vein endothelial cells.

Objective: Conjugated linoleic acid (CLA) isomers have shown health benefits. Because CLA isomers may act as activators for peroxisome proliferator-activated receptors and may induce antioxidant enzymes, this study was conducted to examine the effects of CLA isomers on the gene expression of antioxidant enzymes, copper/zinc superoxide dismutase, and catalase in human umbilical vein endothelial cells.

Methods: Human umbilical vein endothelial cells were treated with graded concentrations of the 9-cis, 11-trans or the 10-trans, 12-cis-CLA isomer for 24 h.

Alpha-tocopherol modulates human umbilical vein endothelial cell expression of Cu/Zn superoxide dismutase and catalase and lipid peroxidation.

Recent studies suggest the potential of alpha-tocopherol as a gene regulator, possibly through peroxisome proliferator-activated receptor gamma (PPARgamma) activation due to the structural similarity of alpha-tocopherol to a PPARgamma ligand, troglitazone. Other investigators have suggested that a link exists between induction of the antioxidant enzymes Cu/Zn superoxide dismutase (SOD) and catalase and PPARgamma activation. This study was designed to examine whether alpha-tocopherol modulates expression of Cu/Zn SOD and catalase in human umbilical vein endothelial cells through redox-sensitive transcription factors, PPARgamma, and nuclear factor-kappaB (NF-kappaB).

Conjugated linoleic acid modulation of risk factors associated with atherosclerosis.

Conjugated linoleic acid (CLA) has been the subject of extensive investigation regarding its possible benefits on a variety of human diseases. In some animal studies, CLA has been shown to have a beneficial effect on sclerotic lesions associated with atherosclerosis, be a possible anti-carcinogen, increase feed efficiency, and act as a lean body mass supplement. However, the results have been inconsistent, and the effects of CLA on atherogenesis appear to be dose-, isomer-, tissue-, and species-specific.

Oxidation of serum low-density lipoprotein (LDL) and antioxidant status in young and elderly humans.

The incidence of atherosclerosis increases with age, as do various indices of free-radical mediated damage, e.g., lipid peroxidation.

Age-related changes of serum lipoprotein oxidation in rats.

Oxidation of low-density lipoprotein (LDL) may be a prelude to atherogenesis and directly age related. To assess whether there may be relationship between age and plasma lipoprotein (LP) oxidation, we studied copper-mediated LP oxidation isolated from the blood of 2 months, 7 months, and 15 months old rats. We determined whether the susceptibility of LP to oxidation might be related to vitamin C levels in serum, vitamin E levels in LP, or the total antioxidant capacity (TAC) of serum or LP.