Vol 89, No 7 (2024)

Charcot–Marie–Tooth (CMT) neuropathy is a polygenic disorder of peripheral nerves with no effective cure. Thiamine (vitamin B1) is a neurotropic compound improving neuropathies. Our pilot study characterizes therapeutic potential of daily oral administration of thiamine (100 mg) in CMT neuropathy and its molecular mechanisms. The patient hand grip strength is determined before and after the thiamine administration along with the blood levels of the thiamine coenzyme form (thiamine diphosphate, ThDP), activities of endogenous (without ThDP in the assay medium) holo-transketolase and total (with ThDP in the assay medium) transketolase, and the transketolase activation by ThDP [1-(holo-transketolase/total transketolase),%], corresponding to the fraction of the ThDP-free apo-transketolase. Single cases of administration of sulbutiamine (200 mg) or benfotiamine (150 mg) reveal their effects on the assayed parameters within those of thiamine. Administration of thiamine or its pharmacological forms increases the hand grip strength in the CMT patients. Comparison of the thiamin status in patients with varied forms of CMT disease to that of the control subjects without diagnosed pathologies has not found significant differences in the average levels of ThDP, holo-transketolase or transketolase distribution between the holo and apo forms. However, the transketolase regulation by thiamine/ThDP differs in the control and CMT groups. In the assay medium, ThDP does not activate transketolase of CMT patients, while the activation is statistically significant in the control group. Thiamine supplementation in vivo paradoxically decreases endogenous holo-transketolase in CMT patients, the effect not observed in the control group. Correlation analysis reveals sex-specific differences in relationships between the parameters of thiamine status in the control subjects and patients with CMT disease. Thus, our findings link physiological benefits of thiamine supplementation in CMT patients to the changes in their thiamine status, characterized by the blood levels of ThDP and transketolase regulation.

The long-term, over several millennia, adaptation of the ancestors of the indigenous peoples of the Far North of Asia and America to the extreme natural and climatic environments of the Arctic resulted in changes in genes controlling various metabolic processes. However, most of the genetic variability in Eskimos and Paleoasians (Chukchis and Koryaks) is related to adaptation to the traditional “Arctic” diet, which is rich in lipids and proteins but extremely poor in plant carbohydrates. The results of population genetic studies have shown that specific polymorphism variants in genes related to lipid metabolism (CPT1A, FADS1, FADS2, and CYB5R2 genes) and carbohydrate metabolism (AMY1, AMY2A, and SI genes) are common in Eskimos and Paleoasian peoples. When deviating from the traditional diet, these polymorphism variants lead to metabolic disorders. American Eskimo-specific polymorphism variants in genes related to glucose metabolism (TBC1D and ADCY genes) significantly increase the risk of developing type 2 diabetes. All these circumstances indicate the need for large-scale genetic testing of indigenous populations of the Far North and the need to study the biochemical and physiological consequences of genetically determined changes in the activity of enzymes of lipid and carbohydrate metabolism.

Snow (cryotolerant) algae often form red (pink) spots in mountain ecosystems on snowfields around the world, but little is known about their physiology and chemical composition. The content and composition of pigments in the cells of the cryotolerant green microalgae Chloromonas reticulata have been studied. An analysis of the carotenoids content in green (vegetative) cells grown in laboratory conditions and in red resting cells collected from the snow surface in the Subpolar Urals was carried out. There were photosynthetic pigments − carotenoids such as neoxanthin, violaxanthin, anteraxanthin, zeaxanthin, lutein and β-carotene. Among the carotenoids, the ketocarotenoid astaxanthin, which has a high biological activity, was also found. It was established that the cultivation of algae at low positive temperature (+6 °C) and moderate illumination (250 μmol quanta/(m2⋅s) contributed to the accumulation of all identified carotenoids, including extraplastidic astaxanthin. In addition to the pigments, fatty acids accumulated in the algae cells. The data obtained allow us to consider the studied microalgae as a potentially promising species for the production of carotenoids.

Multigene TRIM family is an important component of the innate immune system. For a long time, it was believed that the main function of the genes of this family is the antiviral defense of the host organism. The question of their participation in the response of the immune system to bacterial invasion remained less studied. This review represents the first comprehensive analysis of the mechanisms of action of TRIM family genes in response to bacterial infections, which expands the existing understanding of the role of TRIM in the functioning of the innate immune system. Upon the infection with different types of bacteria, individual TRIM proteins regulate inflammatory, interferon and other immune system responses in cells and influence the processes of autophagy and apoptosis. The mechanisms of action of TRIM proteins in response to bacterial infection, as well as during viral infection, often include one of the main properties of these proteins -ubiquitination, as well as various protein-protein interactions with both bacterial proteins and host cell proteins. Moreover, along with the antibacterial effect, some TRIM proteins, on the contrary, can contribute to the development of infection. While the mechanisms used by different members of the TRIM family in response to viral and bacterial infections are generally similar, the final outcome of the action of these proteins sometimes differs significantly. New data on the effect of TRIM proteins on bacterial infections make an important contribution to a more detailed understanding of the functioning of the innate immune system of animals and humans when interacting with pathogens. These data can also be used to search for new targets for antibacterial protection.

Femtosecond transient absorption spectroscopy spectroscopy was used to study the dynamics of the excited primary electron donor in the reaction centers of the purple bacterium Rhodobacter sphaeroides. Using global analysis and the interval method, a correlation was found between the vibrational coherence damping of the excited primary electron donor and the lifetime of the charge-separated state P+B_A–, indicating the reversibility of electron transfer to the primary electron acceptor, the B_A molecule. In the reaction centers, signs of superposition of two electronic states of P were found for a delay time of less than 200 fs. It is suggested that the admixture value of charge transfer state P_A+P_B– with the excited primary electron donor P* is about 24%. The results obtained are discussed in terms of the two-step electron transfer mechanism.

One of the therapeutic approaches to age-related diseases is to affect the metabolism of the body’s cells through certain diets or their pharmacological mimetics. The ketogenic diet significantly affects the energy metabolism of cells and the functioning of mitochondria, which is being actively studied in various age-related pathologies. In this study, we investigated the effect of the ketogenic diet mimetic beta-hydroxybutyrate (BHB) on the gene expression of proteins regulating mitochondrial biogenesis (Ppargc1a, Nrf1, Tfam), quality control (Sqstm1), the work of the antioxidant system (Nfe2l2, Gpx1, Gpx3, Srxn1, Txnrd2, Slc6a9, Slc7a11), and the inflammatory response (Il1b, Tnf, Ptgs2, Gfap) in the brain, lungs, heart, liver, kidneys, and muscles of young and old rats. In addition, we analyzed mitochondrial DNA (mtDNA) copy number, the accumulation of mtDNA damage, and the level of oxidative stress by the concentration of thiobarbituric acid-reactive substances (TBARS), and reduced glutathione level. We showed that aging in a number of organs disrupts mitochondrial biogenesis and the functioning of the cell’s antioxidant system, which was accompanied by increased oxidative stress and inflammation. Administration of BHB for 2 weeks had different effects on organs of young and old rats. In particular, BHB increased the expression of genes of proteins associated with mitochondrial biogenesis and the antioxidant system, especially in the liver tissue and muscles of the young but not the old rats. At the same time, BHB contributed to the reduction of TBARS in the kidneys of the old rats. Thus, our study has shown that the administration of ketone bodies can significantly affect gene expression in organs, especially in young rats, by increasing mitochondrial biogenesis, improving the antioxidant system and partially reducing the level of oxidative stress. However, these changes were much less pronounced in old animals.