[Semaglutide - effectiveness in weight loss and side effects when used according to studies by SUSTAIN, PIONEER, STEP].

Overweight and obesity are a worldwide common problem and are diagnosed with a body mass index (BMI) value in the range of 25.0-29.9 kg/m2 and ≥30.0 kg/m2, respectively. Obese patients are at high risk of developing concomitant diseases, such as hypertension, type 2 diabetes mellitus (DM2), hyperlipidemia, stroke and even some types of cancer. In the Russian Federation in 2016, the proportion of overweight people was 62.0%, with obesity - 26.2%. The authors performed an electronic search in the PubMed information database. Two search elements were used: «Semaglutide¼ and «Obesity¼. The search included studies published from the date of foundation of the database to August 2022. The search was limited only to the results of clinical trials. The authors obtained 26 results, but only the studies of SUSTAIN, PIONEER (Peptide Innovation for Early Diabetes Treatment) and STEP were considered, since they were original, randomized, controlled clinical trials conducted before the approval of semaglutide for the treatment of DM2 and obesity.

[The mechanism of the pulmoprotective action of carboxytherapy]. / Mekhanizm pul'moprotektornogo deistviia karboksiterapii.

The problem of finding new ways for pharmacological prophylaxis and treatment of respiratory tract diseases is very relevant in public health. To eliminate hypoxia, many European and American clinics use carboxytherapy as an additional or alternative treatment. Carbon dioxide administration eliminates the sequels of oxygen starvation, by producing artificial tissue hypercapnia, which causes an increase in oxygen delivery and carbon dioxide removal from the tissues and then from the body. The main mechanism of action of carboxytherapy is associated with enhanced tissue oxygenation and is due to the Verigo-Bohr effect: the effect of CO2 concentration and pH on the binding of hemoglobin to oxygen and release of the latter from hemoglobin. By affecting the chemoreceptors of the respiratory center, carboxytherapy contributes to increased pulmonary ventilation and reduces bronchial smooth muscle tone and bronchial mucous secretion, as well as inflammation; all this improves breathing. By exerting a direct and reflex effect on the respiratory center, carboxytherapy induces hurried and deeper breathing, which increases pulmonary ventilation, speeds up perfusion and gas exchange in the lung, eliminates dyspnea and bronchospasm; therefore, it is widely used for lung diseases (asthma, pneumosclerosis, and silicosis). Carboxytherapy improves lung function in case of bronchopulmonary diseases, performance, and quality of life and it is used as an additional method in the pharmacotherapy of many diseases in pulmonology.

[Carboxytherapy - an innovative trend in resort medicine]. / Karboksiterapiia - odno iz innovatsionnykh napravlenii v kurortologii.

Carboxytherapy (the treatment based on carbon dioxide injections) is a multipurpose and widely used medical technology. The use of CO2 injections (intracutaneous, subcutaneous, and pneumopuncture) have substantially supplemented and increased the practical relevance of carboxytherapy as a method for the treatment of many diseases. Thanks to it physiological properties, CO2 has antihypoxic, antioxidant, vasodilatory, anti-inflammatory, analgesic, and spasmolytic activities; moreover, it improves blood viscosity, stimulates neoangiogenesis, and regenerative processes. Carbon dioxide is a sort of biochemical 'peacemaker' in tissue oxygenation: when blood cells are exposed to high CO2 concentrations (Bohr effect), the rate of gas exchange (CO2 and O2) increases. The human organism interprets carboxytherapy (local hypercapnia) as oxygen deficiency and responses to it by boosting not only the blood flow, but also the vascular endothelial growth factor which stimulates neoangiogenesis and in the long run improves blood supply and tissue trophism. The multiple mechanisms of action, polymodal efficacy, a tool kit with a wide range of detectors and various modes of treatment make carboxytherapy a popular medical technology all over the world, namely in cosmetology, dermatology, aesthetic medicine, angiology, orthopaedics, cardiology, neurology, pulmonology, gynaecology, urology, proctology, plastic and general surgery, and other areas. Carboxytherapy provides a perfect example of the off-label usage in medicine that made it one of the most extensively applied medical technology for the treatment of various diseases despite the lack of the preclinical data and scarce relevant information available in textbooks, reference books and booklets.

Chronopharmacological Characteristics of the Effect of Hepatoprotectors in Experiment?

We studied circadian rhythms of activity of hepatoprotectors (Antral, Carsil, and glutargin) under conditions of acute paracetamol-induced hepatitis simulated in the morning, afternoon, evening, and at night (09.00, 15.00, 21.00, and 03.00). Antral and Carsil exhibited similar chronoprofiles with the maximum hepatoprotective activity at 09.00 and 21.00, while glutargin exhibited circadian pattern opposite and its activity was maximum at 15.00 and 03.00.

[Thermal denaturation of eukaryotic class 1 translation termination factor eRF1. Relationship between stability of the eRF1 molecule and alteration of functional activity of its mutants].

Thermal denaturation of eukaryotic class-1 translation termination factor eRF1 and its mutants was examined using differential scanning microcalorimetry (DSK). Changes of free energy caused by mutants in the N domain of human eRF1 were calculated. Melting of eRF1 molecule composed of three individual domains is cooperative. Some amino acid substitutions did not affect protein thermostability and in some other cases even slightly stabilize the protein globule. These imply that these amino acid residues are not involved in maintenance of the 3D structure of human eRF1. Thus, in Glu55Asp, Tyr125Phe, Asn61Ser, Glu55Arg, Glu55A1a, Asn61Ser + Ser64Asp, Cys127Ala and Ser64Asp mutants selective inactivation of release activity is not caused by a destabilization of protein 3D structure and, most likely, is associated with local stereochemical changes introduced by substitutions of amino acid side chains in the functionally essential sites of N-domain molecule. Some residues (Asn129, Phe131) as shown by calorimetric measurements are essential for preservation of stable protein structure, but at the same time they affect selective stop codon recognition probably via their neighboring amino acids. Recognition of UAG and UAA stop codons in vitro is more sensitive to preservation of protein stability than the UGA recognition.

[Molecular morphology of eukaryotic class I translation termination factor eRF1 in solution]. / Molekularnaia morfologiia faktora terminatsii transliatsii 1-go klassa éukariot eRF1 v rastvore.

The integral structural parameters and the shape of the molecule of human translation termination factor eRF1 were determined from the small-angle X-ray scattering in solution. The molecular shapes were found by bead modeling with nonlinear minimization of the root-mean-square deviation of the calculated from the experimental scattering curve. Comparisons of the small-angle scattering curves computed for atomic-resolution structures of eRF1 with the experimental data on scattering from solution testified that the crystal and the solution conformations are close. In the ribosome, the distance between the eRF1 motifs GGQ and NIKS must be shorter than in crystal or solution (75 versus 107-112 A). Therefore, like its bacterial counterpart RF2, the eukaryotic eRF1 must change its conformation as it binds to the ribosome. The conformational mobility of eukaryotic and prokaryotic class-1 release factors is another feature making them functionally akin to tRNA.