Effects of Royal Jelly Administration on Lipid Profile, Satiety, Inflammation, and Antioxidant Capacity in Asymptomatic Overweight Adults.

OBJECTIVES: Obesity and overweight are chronic disorders of multifactorial origin that are characterized by high oxidative status and by chronic activation of macrophages in peripheral tissues. Effective therapeutic approaches to lower inflammation and oxidative stress are currently of general interest. Royal jelly (RJ) is a functional food with a broad range of pharmacological activities, mainly used by healthy individuals or borderline patients to protect themselves against disease onset. The objective of this randomized, double-blind, placebo-controlled trial was to investigate the effects of RJ supplementation on metabolic profile and oxidative and inflammatory parameters in asymptomatic overweight adults, considered at an early stage of developing metabolic syndrome. MATERIAL AND METHODS: The experimental group (n=30) was given RJ and the control group (n=30) was provided with a placebo for eight weeks. Anthropometric, biochemical parameters, biomarkers of oxidative stress, and inflammation were assessed at baseline, after 4 and 8 weeks of the intervention, and after additional 2 weeks of follow up. RESULTS AND CONCLUSION: Compared with the placebo, RJ supplementation demonstrated a statistically significant decrease in total cholesterol (6.7%; p=0.041) and inflammatory marker C-reactive protein (19%; p=0.027), whereas significant increases were observed in anti-inflammatory marker adiponectin (34%; p=0.011), endogenous antioxidants bilirubin (35%; p=0.002) and uric acid (5%; p=0.018), total antioxidant capacity in serum (54%; p=0.005), and leptin (17%; p=0.025). The present study demonstrated positive effects of RJ administration on lipid profile, satiety, inflammation, and antioxidant capacity in overweight adults. Therefore, our study supports the benefits of RJ supplementation for the improvement of human health.

A Prospective Pharmacogenomic Study of Crohn's Disease Patients during Routine Therapy with Anti-TNF-α Drug Adalimumab: Contribution of ATG5, NFKB1, and CRP Genes to Pharmacodynamic Variability.

Crohn's disease is often treated with the anti-tumor necrosis factor-α drug adalimumab. However, about 20%-40% of patients do not display adequate therapeutic response. We prospectively evaluated, during a routine therapy of Crohn's disease patients, the candidate autophagy-related genes ATG12 and ATG5 and the inflammation-related genes NFKB1, NFKBIA, and CRP as potential predictors of adalimumab treatment response (pharmacodynamics). The associations of haplotypes and SNPs in these genes with response to drug therapy, biochemical parameters, and body mass were determined at baseline and after 4, 12, 20, and 30 weeks of therapy. Association analysis showed that haplotypes defined with the SNPs rs9373839 and rs510432 in ATG5 gene were significantly associated with positive response to therapy (p < 0.002). In addition, allele C and genotypes CC and CT of the rs1130864 in the CRP gene were positively associated with therapeutic response (p < 0.002). To the best of our knowledge, this is the first report that supports the association of SNPs in ATG5 and CRP genes with response to adalimumab therapy in Crohn's disease. Further study of these biological pathways in larger and independent clinical samples is warranted as novel streams of research on precision medicine and diagnostics for Crohn's disease.

The influence of serial repitching of Saccharomyces pastorianus on its karyotype and protein profile during the fermentation of gluten-free buckwheat and quinoa wort.

Gluten-free beer-like beverages from malted buckwheat and quinoa are somehow close to their commercial production, but rather high expenses are expected due to the relatively high price of grain, some technological adaptations of process and the need for external enzyme supplementation during mashing. One of the common and efficient cost reduction measures in the industrial scale is serial repitching of the yeast biomass, which has not been studied for the buckwheat and quinoa wort fermentation before. In that manner we have monitored possible changes in yeast's proteins and chromosomal DNA during eleven serial repitchings of the yeast Saccharomyces pastorianus strain TUM 34/70 for fermentation of the barley, buckwheat and quinoa wort. Karyotypes showed changes in regard to the raw materials used and many responsible candidate proteins are suggested which could cause these differences. Different relative expressions of some protein bands were also linked to the proteins involved in yeast stress response and proteins involved in fermentation performance. Results suggest that serial repitching of the strain TUM 34/70 seems suitable for the production of gluten-free beer-like beverages from buckwheat and quinoa.

Glucagon like-peptide-1 receptor is covalently modified by endogenous mono-ADP-ribosyltransferase.

Our previous study revealed a mono-ADP-ribosyltransferase mediated in vitro mono-ADP-ribosylation of IC(3) peptide, a peptide with sequence corresponded to third intracellular loop of glucagon like-peptide-1 (GLP-1) receptor. Furthermore, Arg(348) was shown to be modified amino acid residue although its mutation did not eliminate mono-ADP-ribosylation completely. In order to further study the signaling mechanisms of GLP-1 receptor, we took on lease a possibility that an alternative site of enzymatic modification exist so mono-ADP-ribosylation of Cys(341) was hypothesized. The results confirmed both Arg(348) and Cys(341) as a site of mono-ADP-ribosylation where Arg(348) is modified predominantly. Sum of mono-ADP-ribosylation rate of both single IC(3) mutants coincided with IC(3) rate. What is in vivo role of Cys(341) mono-ADP-ribosylation is entirely speculative but our study represents an important step toward a complete understanding of signaling via GLP-1 receptor.

Third intracellular loop of glucagon like-peptide-1 receptor is coupled with endogenous mono-ADP-ribosyltransferase - novel type of receptor regulation?

Our previous studies revealed the main role of the third intracellular loop (IC(3)) of glucagon-like peptide-1 receptor (GLP-1 receptor), in G-protein activation, where the presence or absence of agonist and the receptor phosphorylation seemed to be the only regulatory mechanisms. In order to further study the signaling mechanisms of GLP-1 receptor, we investigated the effect of the third intracellular loop-derived peptide on endogenous mono-ADP-ribosyltransferase mediated mono-ADP-ribosylation of G-proteins ß subunit in CHO cells. Results showed an inhibitory effect of IC(3) peptide on mono-ADP-ribosylation of ß subunit, obviously via the mechanism of competitive inhibition. Excluding the activity of this inhibitory mechanism via pertussis toxin-sensitive G proteins, the direct functional coupling of IC(3) of GLP-1 receptor and endogenous mono-ADP-ribosyltransferase was confirmed. We suggest that this arginine specific enzymatic posttranslational modification of third intracellular loop of GLP-1 receptor might represent a possible novel mechanism of receptor activity regulation and the pharmacological potential in treatment of diabetes mellitus type 2.