Vol 22, No 1 (2022)

BACKGROUND: Neuroinflammation is a significant component of the pathogenesis of cerebral ischemia. The JNK and NF-κB signaling pathways play a leading role in the progression of brain tissue inflammation, which may represent a promising target for therapeutic effects.

AIM: To evaluate the effect of new derivatives of 3-formylchromone on the course of neuroinflammation reactions and the activity of JNK and NF-κB translational pathways in brain tissue in rats with cerebral ischemia.

MATERIALS AND METHODS: Cerebral ischemia was modeled in Wistar rats by irreversible right-sided occlusion of the middle cerebral artery. The studied compounds and the reference (ethylmethylhydroxypyridine succinate) were administered per os at doses of 30 and 100 mg/kg, respectively. After 72 hours of ischemia, changes in the concentration of proinflammatory cytokines were evaluated in the cerebrospinal fluid: IL-6, IL-1β, IL-8 and TNF-α. The content of JNK and NF-κB in brain tissue was determined by enzyme immunoassay.

RESULTS: The use of the test compounds 3FC1, 3FC2, 3FC4 and 3FC5, as well as the reference medicine, contributed to a decrease in the content of proinflammatory markers in the liquor. At the same time, the most significant decrease was noted when the compound 3FC5 was administered to animals, namely, the concentration of IL-1β, IL-6, IL-8 and TNF-α was lower relative to similar indicators of the group of animals without treatment by 30.0% (p < 0.05); 64.5% (p < 0.05); 48.5% (p < 0.05) and 56.6% (p < 0.05), respectively. The use of the fluorine-containing compound 3FC3 did not significantly affect the course of brain tissue inflammation reactions in rats. Evaluation of changes in the activity of JNK and NF-κB showed that the studied substances inhibit the NF-κB translational pathway and do not affect JNK, which is probably due to the activation of these signaling pathways and the antioxidant potential of the studied molecules.

CONCLUSIONS: The use of compounds that are derivatives of 3-formylchromone in conditions of experimental cerebral ischemia contributes to the reduction of neuroinflammation reactions by inhibiting the NF-κB pathway, without affecting the activity of the JNK-dependent signaling system. The substance with the highest pharmacological effects is the compound 3FC5, which contains a spatially hindered phenolic hydroxyl in its structure.

BACKGROUND: The use of statins in cardiovascular pathologies in some cases is associated with the risk of developing statin-induced myopathy, the mechanisms of which are not fully understood. Only a few studies of molecular changes in the myocardium in statin myopathy are presented in the literature. However, the myocardium, as a type of muscle tissue, can also be involved in the pathological process. In this regard, in our opinion, it is advisable to analyze the biochemical changes in the rat myocardium against the background of the use of simvastatin.

AIM: To analysis of the dynamics of changes in the end products of glycolysis and the isoform composition of the giant protein titin in the heart muscle in animals with experimental hypercholesterolemia on the background of long-term administration of simvastatin.

MATERIALS AND METHODS: The study was carried out on outbred male rats divided into 3 groups: control group (35 individuals) — intact animals; comparison group (35 animals) — intact animals treated with simvastatin for two months; experimental group — divided into: subgroup 1 (35 individuals) — animals with induced alimentary hypercholesterolemia, subgroup 2 (35 individuals) — animals with induced alimentary hypercholesterolemia, which were administered simvastatin for two months. During the experiment, the content of the giant sarcomere protein titin, as well as changes in the concentration of pyruvate and lactic acid in the myocardium of the animals of the studied groups were studied.

RESULTS: In animals with a physiological course of metabolic processes, the administration of simvastatin caused the accumulation of lactic acid in the myocardium. Under conditions of alimentary hypercholesterolemia under the influence of simvastatin, a decrease in the elevated level of pyruvate and lactic acid was revealed, which is obviously due to a decrease in pathobiochemical shifts in energy metabolism. The determination of the isoform composition of titin made it possible to establish that the administration of simvastatin under conditions of alimentary hypercholesterolemia contributed to the appearance of early dystrophic changes in the myocardium, which is consistent with the results of earlier studies of impaired myocardial contractile activity under the influence of statins.

CONCLUSIONS: The results obtained indicate the need for a more thorough study of statins in terms of their safe use in patients with cardiovascular pathology.

BACKGROUND: Identification of possible biomarkers that assess the severity of post-traumatic stress symptoms is an urgent task for the early diagnosis of post-traumatic stress disorders. The manifestation of emotional states, both human and animal, is reflected in altered behavior and in the violation of the ratio of basic rhythms and cross-correlation connections in the brain electroencephalogram, which indicates the development of pathological processes.

AIM: The aim of the study was to analyze the behavior and electrocorticogram indicators of rats in the delayed period (on day 7) after life-threatening stress, as a way to predict the formation of post-traumatic stress disorder.

MATERIALS AND METHODS: The study was performed on mature female Wistar rats weighing 180–200 g (n = 40). Mental trauma was modeled by the circumstances of experiencing the situation of the death of a partner from the action of a predator and the threat to their own life when placing rats in a terrarium with a tiger python. In rats, the behavior in the “Open Field” test and the bioelectric activity of the brain in the frontal and occipital regions on the left and right were analyzed before and on the 7^th day after stress exposure.

RESULTS: It is shown that in the delayed period after vital stress in female rats, there is a decrease in motor and research activity and altered emotional behavior in the “Open Field” test. Reduction of interhemispheric asymmetry in the index of theta and delta activity and changes in cross-correlation connections in the right hemisphere, as well as changes in the ratio of the main rhythms and cross-correlation connections of the electroencephalography. The revealed changes in the delayed period indicate a pronounced aversive nature of the psychotraumatic effect.

CONCLUSIONS: Life-threatening stress is caused by changes in electrophysiological and behavioral parameters in experimental animals not only at the time of exposure, but also in the long-term period.

Sleep deficit disrupts the normal function of systems and organs in humans and becomes ”epidemic” in nature. Knowledge of the physiology of sleep and the impact of sleep deprivation on the body has expanded in recent years and allows a new assessment of the scale and depth of the problem. In the review summarizes current ideas about the effect of lack of sleep on chronic diseases and pathological processes, taking into account various body systems. Different reviews and studies over the past years have been analyzed, related to lack of sleep which contributes to the development of various diseases, have been analyzed. The use of new information about the impact of sleep on human health and the consequences of its lack opens up additional perspectives in understanding experimental and clinical work. This information can be actively used in diagnostics and therapy within the framework of integrative medicine.

The main reason for the low efficiency of glioblastoma therapy is its resistance to therapeutic procedures. The development of multidrug resistance occurs as a result of the selection of tumor clones during therapy. The resistant cell clones to radiotherapy and chemotherapy can proliferate, leading to tumor growth, in which its own vascular network is formed (angiogenesis), which promotes cell migration, invasion and the appearance of metastases and recurrent glioblastoma. The review examines the relationship at the molecular level of multidrug resistance with proliferation, angiogenesis, migration, metastasis, and the formation of glioblastoma relapses, with an emphasis on identifying new targets among proteins, microRNAs, signal transduction kinases, transcription factors, tumor-supressor genes and oncogenes.