Novel synthetic analogue of ACTH 4–10 (Semax) but not glycine prevents the enhanced nitric oxide generation in cerebral cortex of rats with incomplete global ischemia

This work investigates whether nitric oxide production and lipid peroxidation contribute to the pathophysiology of ischemia and whether glycine and a novel Russian compound, Semax are neuroprotective via a mechanism involving the regulation nitric oxide (NO) and lipid peroxidation. In brief, nitric oxide and indices of lipid peroxidation were elevated following global ischemia. While glycine proved ineffective in reducing NO levels or ameliorating the neurological deficits following global ischemia, Semax proved to be highly effective in abating the rise in nitric oxide and restoring neurologic functioning.     

Role of silymarin as antioxidant in clinical management of chronic liver diseases: a narrative review

Chronic liver disease (CLD), manifested as hepatic injury, is a major cause of global morbidity and mortality. CLD progresses to fibrosis, cirrhosis, and—ultimately—hepatocellular carcinoma (HCC) if left untreated. The different phenotypes of CLD based on their respective clinical features and causative agents include alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD), and drug-induced liver injury (DILI). The preferred treatment modality for CLD includes lifestyle modification and diet, along with limited pharmacological agents for symptomatic treatment. Moreover, oxidative stress (OS) is an important pathological mechanism underlying all CLD phenotypes; hence, the use of antioxidants to manage the disease is justified. Based on available clinical evidence, silymarin can be utilized as a hepatoprotective agent, given its potent antioxidant, antifibrotic, and anti-inflammatory properties. The role of silymarin in suppressing OS has been well established, and therefore silymarin is recommended for use in ALD and NAFLD in the guidelines approved by the Russian Medical Scientific Society of Therapists and the Gastroenterology Scientific Society of Russia. However, to discuss the positioning of the original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies, an expert panel of international and Russian medical professionals was convened on 11 November 2020. The panel reviewed approaches for the prevention and treatment of OS, existing guidelines for patient management for CLD, and available evidence on the effectiveness of silymarin in reducing OS, fibrosis, and hepatic inflammation and presented in the form of a narrative review.

Key messages

• An expert panel of international and Russian medical professionals reviewed existing guidelines for ALD, NAFLD, MAFLD, and DILI to establish consensus recommendations that oxidative stress is the common pathophysiological mechanism underlying these conditions.
• The panel also discussed the positioning of original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies.
• The panel reviewed the effectiveness of 140 mg original silymarin three times a day in reducing oxidative stress in chronic liver diseases such as ALD, NAFLD, MAFLD, and DILI.

     

Polymorphism in Adiponectin and Adiponectin Receptor Genes in Diabetes Mellitus Pathogenesis

The role played by hereditary factors in the development of diabetes mellitus type 2 (DM2) has not yet been fully established. Therefore, the purpose of our study was to investigate the prevalence of adiponectin and polymorphism in its gene receptors in connection with the primary symptoms of DM2 pathogenesis. Genomic DNA was isolated from the whole blood of 94 patients with an established diagnosis of DM2 using the phenol–chloroform method. Gene polymorphisms were determined using real-time polymerase chain reaction (PCR). The most common polymorphic variants in patients with DM2 were the genotypes AA (rs11061971) and GG (rs16928751) on the ADIPOR2 gene. A strong correlation was found between the rs16928751 polymorphism on the ADIPOR2 gene and increased body mass index (BMI). TG (rs2275737) ADIPOR1 gene genotype carriers were found to have the highest levels of glycosylated hemoglobin (HbA1), whereas TT (rs2275738) caused stable hyperglycemia. In addition, the rs16928751 ADIPOR2 gene polymorphism showed an association with the development of key mechanisms of DM2 in the Russian population, although a number of genomic searches failed to show any association of this gene with DM2. Unique gene variants associated with the risk of developing DM2 in the Crimean population were established.     

SARS-CoV-2 will continue to circulate in the human population: an opinion from the point of view of the virus-host relationship

Inflammation Research - At the population level, the virus-host relationship is not set up to end with the complete elimination of either or both. Pathogen-resistant individuals will always remain...     

Fabrication and Impact of Fouling-Reducing Temperature-Responsive POEGMA Coatings with Embedded CaCO3 Nanoparticles on Different Cell Lines

In the present work, we have successfully prepared and characterized novel nanocomposite material exhibiting temperature-dependent surface wettability changes, based on grafted brush coatings of non-fouling poly(di(ethylene glycol)methyl ether methacrylate) (POEGMA) with the embedded CaCO₃ nanoparticles. Grafted polymer brushes attached to the glass surface were prepared in a three-step process using atom transfer radical polymerization (ATRP). Subsequently, uniform CaCO₃ nanoparticles (NPs) embedded in POEGMA-grafted brush coatings were synthesized using biomineralized precipitation from solutions of CaCl₂ and Na₂CO₃. An impact of the low concentration of the embedded CaCO₃ NPs on cell adhesion and growth depends strongly on the type of studied cell line: keratinocytes (HaCaT), melanoma (WM35) and osteoblastic (MC3T3-e1). Based on the temperature-responsive properties of grafted brush coatings and CaCO₃ NPs acting as biologically active substrate, we hope that our research will lead to a new platform for tissue engineering with modified growth of the cells due to the release of biologically active substances from CaCO₃ NPs and the ability to detach the cells in a controlled manner using temperature-induced changes of the brush.     

The detection of tissue antigens

Summary Sensitivity of the general methods was compared. For that purpose the following determinations were carried out: 1) the minimal dose of the antigen, to which guinea pigs, passively sensitized by various doses of the corresponding immune serum, reacted and 2) the quantity of the antigen which could be determined by the same immune serum in experiments in vitro. Anaphylactic reaction was found to be more advantageous in experiments with low doses of Immune serum. Sensitivity of the serological method could be increased in conducting experiments by the so called. rectangular scheme, which takes the law of optimal ratios into consideration, as well as by using the method of large volume of antibodies. In order to reveal the components of the complex antigen one should study the method of passive anaphylaxis by sensitization of animals by immune sera, in which the antigens of the normal tissues were previously exhausted in vitro.The problems which are next to be investigated are, the methods of differentiation of antigenic components which possess common antigenic groups, the characteristics of the new serological methods, the problem of tumor antigens with consideration of conceptions on autoantigens.     

Computer Modelling of Energy Structure of Yb3+ and Lu3+ Doped LaF3 Crystals

The energy band structure, as well as partial and total densities of states have been calculated for LaF₃:Yb and LaF₃:Lu crystals within density functional theory using the projector augmented wave method and Hubbard corrections (DFT + U). The influence of geometric optimization on the results of energy band calculations of LaF₃:Ln crystals (Ln = Yb, Lu) was analysed and the absence of relaxation procedure is confirmed to negatively influence the energy position of states, and the variability between obtained results of different optimization algorithms are within the calculation accuracy. The top of the valence band of LaF₃ is confirmed to be formed by the 2pF^--states and the bottom of the conduction band is formed by the 5d-states of La³⁺. The positions of the 4f-states and 5d-states of activator ions in LaF₃ were studied. It is shown that the 4f-states of Yb³⁺ are slightly above the top of the valence band and the 4f-states of Lu³⁺ to be 3.5 eV below the top of the valence band. The energy levels of the 5d states of the impurities are energetically close to the bottom of the LaF₃ conduction band. The calculated band gap of 9.6 eV for LaF₃ is in a good agreement with the experimental result and is not affected by impurity ions.