Role of Polyamine-Induced Dimerization of Antizyme in Its Cellular Functions

Funding: This work was supported by grants from the Russian Science Foundation (grant # 17-74-20049—synthesis of C-methylated Spd analogues, ITC studies of dimerization of OAZ1, and frameshifting experiments), the Russian Science Foundation (grant # 19-74-10086—isolation of OAZ1, electrophoresis studies of dimerization of OAZ1), and the Academy of Finland (grants # 292574 and # 315487). Acknowledgments: The authors thank A. Karppinen, A. Korhonen, T. Reponen, M. Salminkoski, and S.D. Negrya for their skillful technical assistance.Peer reviewedPublisher PD

Peptidyl transferase centre of bacterial ribosomes: substrate specificity and binding sites.

A detailed scheme of the Peptidyl Transferase Centre of bacterial ribosomes is proposed by summarizing the literature data on the substrate specificity of the acceptor and donor sites. According to the proposed scheme only the elements of the donor and acceptor having a stable structure bind with the ribosome. The present paper proposes such main elements for the donor and acceptor

Anthocyanidin pigments in clinical ophthalmology. Analysis of their profile in eye supplements and food additives containing bilberry extract

Currently, several eye nutritional supplements and food additives with bilberry extract are approved in Russia. Bilberry effects directly depend on anthocyanidin content. Hence, the expertise of nutritional supplements and food additives with bilberry extract is required to determine their qualitative and quantitative composition. Aim. To determine qualitative and quantitative content of bilberry anthocyanidin pigments in food additives. Materials and methods. Anthocyanidins from five samples were extracted with distilled water per anthocyanidin content. The samples were obtained by the dilution of a pill or capsule in 50 mL of water. Extraction was performed under continuous mixing on hot shaker. 1 mL aliquots were taken from the solutions, centrifuged for 10 min at 14,000 rpm, and filtered through syringe filters. Total level (i.e., quantitative and qualitative content) of bilberry anthocyanidin pigments in five samples was evaluated using UV spectroscopy. Experiment was performed twice for each sample. Qualitative content of anthocyanidin pigments was evaluated using reversed-phase HPLC. Results. All examined samples contain anthocyanidin pigments from bilberry extracts but no other natural sources. Their quantity which was measured by pH differential spectrophotometry varies greatly (from 0.168% to 8.30%) and may significantly differ from that of declared by manufacturer. This is due to phytogenic raw material and difficulties in standardization of active component content. Conclusions. The data obtained optimize dosing of food additives with bilberry extract by clinicians and patients considering individual tolerance, needs, and disease severity

Antiretroviral Hydrophobic Core Graft-Copolymer Nanoparticles: The Effectiveness against Mutant HIV-1 Strains and in Vivo Distribution after Topical Application

PURPOSE: Developing and testing of microbicides for pre-exposure prophylaxis and post-exposure protection from HIV are on the list of major HIV/AIDS research priorities. To improve solubility and bioavailability of highly potent anti-retroviral drugs, we explored the use of a nanoparticle (NP) for formulating a combination of two water-insoluble HIV inhibitors. METHODS: The combination of a non-nucleoside HIV reverse transcriptase inhibitor (NNRTI), Efavirenz (EFV), and an inhibitor of HIV integrase, Elvitegravir (ELV) was stabilized with a graft copolymer of methoxypolyethylene glycol-polylysine with a hydrophobic core (HC) composed of fatty acids (HC-PGC). Formulations were tested in TZM-bl cells infected either with wild-type HIV-1IIIB, or drug-resistant HIV-1 strains. In vivo testing of double-labeled NP formulations was performed in female rats after a topical intravaginal administration using SPECT/CT imaging and fluorescence microscopy. RESULTS: We observed a formation of stable 23-30 nm NP with very low cytotoxicity when EFV and ELV were combined with HC-PGC at a 1:10 weight ratio. For NP containing ELV and EFV (at 1:1 by weight) we observed a remarkable improvement of EC50 of EFV by 20 times in the case of A17 strain. In vivo imaging and biodistribution showed in vivo presence of NP components at 24 and 48 h after administration, respectively. CONCLUSIONS: insoluble orthogonal inhibitors of HIV-1 life cycle may be formulated into the non-aggregating ultrasmall NP which are highly efficient against NNRTI-resistant HIV-1 variant