The Efficacy of a Peptide Product from the Pituitary Gland of Rangifer tarandus as an Antioxidant Agent Under the Combined Effects of Light Desynchronosis and Depriming Toxicant

The possibility of using methods for determining the oxidative status of an organism (enzymatic and non-enzymatic links of the cellular antioxidant system) to assess the antioxidant properties of peptides of the pituitary gland of the reindeer (Rangifer tarandus) were investigated in an experimental study conducted with a combined effect of factors of different nature on rats: a physical factor — prolonged light desynchronosis (different light modes) and a chemical factor - acute severe poisoning with depriving toxicant (sodium thiopental, LD50). The pharmacological correction of the oxidative status of cells in the animals of the experimental subgroups was carried out with the peptide product of the pituitary gland, intranasally injecting the surviving rats with the bioproduct at a dose of 100 µg/kg, once in the first half of the objective day for 14 days after poisoning with sodium thiopental. The surviving animals of the control groups were similarly injected with saline. The effectiveness of the correction of the disruptions of the cellular oxidative status with the peptide product of the pituitary gland was tested 30 days after the onset of the combined effect of stress factors on rats. It was found that the use of this bioactive peptide product in experimental animals exposed to different light modes and a chemical factor contributed to a decrease in the initially increased indicators of lipid peroxidation in rat erythrocytes and an increase in the initially reduced indicators of the enzymatic link of antioxidant protection. The activity of superoxide dismutase, glutathione peroxidase, glutathione transferase, as well as glucose-6-phosphate dehydrogenase increased after pharmacological correction. The concentration of reduced glutathione also increased in erythrocytes. The maximum changes were observed in the experimental subgroup of rats exposed to the combined effects of constant illumination and depriming toxicant. It was also found that the revealed positive changes in the indicators of the enzymatic link of antioxidant protection in animals of the experimental subgroups are associated with the maintenance of a sufficient concentration of reduced glutathione in red blood cells, which contributed to the maintenance of the cellular redox balance, when the conditions of the external lighting regime are violated.

Modern Approaches to the Management of Obesity in Children: Novelties

Objective of the Review: To analyse scientific publications in non-drug and drug therapy of paediatric obesity. Key Points. The paramount challenge in obesity management is timely diagnosis of overweight by paediatricians and prompt initiation of efficient non-drug therapy. A tremendous advantage of the life style, nutrition and physical activity correction is their safety. Psychologist engagement boosts non-drug therapy efficiency. Where non-drug therapy is inefficient, medications can be prescribed to children over 12 years old in addition to lifestyle correction. Orlistat possesses an acceptable efficiency profile and is safe, but it is associated with a number of adverse reactions and does not modify the eating habits of the patient. Liraglutide, a glucagon-like peptide product, has proven to be efficient in adolescents of 12 to 18 years old, including visceral adiposopathy management. An extended action with minor adverse enteric reactions makes Liraglutide a promising product for the management of adolescent obesity. Conclusion. Obesity management in children and adolescents is based on a set of non-drug measures possessing proven efficiency and safety. In Russia, Orlistat and Liraglutide are approved for the use in children. Metformin can be considered as an off-label medication. To prove the efficiency and safety of bariatric surgery, further studies are warranted. Keywords: obesity, children, non-drug therapy, drug therapy, Liraglutide.

Rational design of an improved photo-activatable intein for the production of head-to-tail cyclized peptides

Head-to-tail cyclization of genetically encoded peptides and proteins can be achieved with the split intein circular ligation of peptides and proteins (SICLOPPS) method by inserting the desired polypeptide between the C- and N-terminal fragments of a split intein. To prevent the intramolecular protein splicing reaction from spontaneously occurring upon folding of the intein domain, we have previously rendered this process light-dependent in a photo-controllable variant of the M86 intein, using genetically encoded ortho-nitrobenzyltyrosine at a structurally important position. Here, we report improvements on this photo-intein with regard to expression yields and rate of cyclic peptide formation. The temporally defined photo-activation of the purified stable intein precursor enabled a kinetic analysis that identified the final resolution of the branched intermediate as the rate-determining individual reaction of the three steps catalyzed by the intein. With this knowledge, we prepared an R143H mutant with a block F histidine residue. This histidine is conserved in most inteins and helps catalyze the third step of succinimide formation. The engineered intein formed the cyclic peptide product up to 3-fold faster within the first 15 min after irradiation, underlining the potential of protein splicing pathway engineering. The broader utility of the intein was also shown by formation of the 14-mer sunflower trypsin inhibitor 1.

1.2 Å resolution crystal structure of the periplasmic aminotransferase PvdN fromPseudomonas aeruginosa

The Gram-negative pathogenPseudomonas aeruginosauses a nonribosomal peptide synthetase (NRPS) biosynthetic cluster for the production of a peptide siderophore. In addition to four multimodular NRPS proteins, the biosynthetic pathway also requires several additional enzymes involved in the production of nonproteinogenic amino acids and maturation of the peptide product. Among the proteins that are required for the final steps in pyoverdine synthesis is PvdN, a pyridoxal phosphate-dependent enzyme that catalyzes an uncharacterized step in pyoverdine production. This study reports the high-resolution structure of PvdN bound to a PLP cofactor solved by multi-wavelength anomalous dispersion (MAD). The PvdN model shows high structural homology to type I aspartate aminotransferases and also contains positive density that suggests an uncharacterized external aldimine.