Bulletin of Experimental Biology and Medicine最新文献

Alloxan has been proposed as a diabetogenic agent due to its ability to destroy pancreatic β cells through the formation of free radicals, leading to oxidative stress, which has a significant role in the etiology and pathogenesis of diabetes and its complications. In Wistar rats with alloxan-induced diabetes, the levels of liver glycogen in the liver and the levels of total lipids and triglycerides in the liver, adipose tissue, and muscles were assessed over two months. Experimental diabetes was accompanied by a decrease in the levels of liver glycogen and an increase in the levels of triglycerides and total lipids in the liver, muscles, and adipose tissue. Treatment with insulin and metformin led to improvements in these parameters, with insulin having a more pronounced effect. The glycogen levels in the liver in rats receiving insulin was significantly higher than in animals treated with metformin (2767.86 and 1075.40 mg/100 g of tissue, respectively). The total lipid content in the liver significantly decreased against the background of insulin treatment compared to metformin (5730.90 and 8486.87 mg/100 g of tissue, respectively). Metformin administration led to an 11.9% reduction in liver triglycerides, while insulin reduced them by 25%. Oral administration of metformin for two months did not affect liver glycogen levels in alloxan-induced diabetic rats. Insulin injections increased liver glycogen levels and reduced total lipid and triglyceride levels in the liver. The hypolipidemic effect of these drugs appears to be due to the regulation of metabolism at the liver and adipose tissue levels.

The anti-parkinsonian activity of benzolsulfonamide selective MAO-B inhibitors was evaluated in a model of experimental parkinsonism in white mice (systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; MPTP). Six candidate compounds (laboratory codes S6-S8 and S11-S13) were analyzed. Rasagiline was used as the reference drug. Only compound S13 was comparable to rasagiline in preventing the development of rigidity and hypokinesia in animals and surpassed the reference drug in correcting emotional and behavioral activity.

Class III antiarrhythmic drugs used for the treatment of supraventricular tachyarrhythmias can induce polymorphic ventricular tachycardia known as "torsade de pointes" (TdP). This adverse side effect of antiarrhythmic drugs is more pronounced in impaired ventricular perfusion and limits the use of the drugs. In this work, the effects of the antiarrhythmic drug cavutilide were studied in a model of phenylephrine-induced potentiation of TdP. Cavutilide was administered acutely in combination with phenylephrine in non-anesthetized rabbits under continuous ECG monitoring. Cavutilide in the presence of phenylephrine induced pronounced ventricular extrasystoles almost without episodes of ventricular tachycardia or TdP paroxysms. The reference antiarrhythmic drug dofetilide under the same model conditions caused prolonged, multiple episodes of monomorphic ventricular tachycardia and frequent, repetitive paroxysms of high-frequency TdP. Thus, cavutilide demonstrates very low tendency to induce TdP under conditions of impaired myocardial perfusion, which can be explained by direct type of the dependence of its effect on the frequency of myocardium activation.

In modern biotechnological and biomedical research, it is often necessary to activate mammalian cells to obtain a specific response, such as changes in membrane potential or generation of action potential in excitable cells and tissues. Thermogenetics provides a rapid and controlled cellular response and is a promising tool for such tasks. In order to explore the potential of thermogenetic approaches, we generated the HEK293 cell line stably expressing the thermosensitive human TRPV1 ion channel. This cell line exhibited an increase in intracellular Ca²⁺ ion concentration upon exposure to temperatures above 39°C and/or addition of capsaicin. The developed model can be used to further study the functional characteristics of exogenously expressed TRPV1 channels in mammalian cells.

The release of cytochrome C into the cytoplasm after formation of a complex with mitochondrial phospholipids underlays the mitochondrial pathway of apoptosis. Changes in the structure of cytochrome C complex active center depending on phosphatidic acid concentration and at different temperatures (25, 37, and 45°C) were studied. Changes in the active center structure were assessed by optical absorption at 695 nm and compared with the intensity of luminol-dependent chemiluminescence which is proportional to the peroxidase activity of cytochrome C-phosphatidic acid complex. It was found that increasing the temperature from 25 to 45°C leads to comparable changes in the conformation of cytochrome C active center and an increase in its peroxidase activity.

We have shown that changes in the phospholipid and fatty acid composition of atherosclerotic plaques in the carotid arteries of patients who underwent carotid endarterectomy in combination with coronary artery bypass surgery are linked with the development of the pathological process and highlight the importance of cytochrome C-mediated induction of oxidation of membrane phospholipids. An increase of the steady-state equilibrium constant of cytochrome C with atherosclerotic membranes to 10^-5 M and simultaneously a more than three-fold enhancement of LPO process are demonstrated.

The analysis included 3,800 cases of breast cancer. Next-generation sequencing (NGS) of DNA extracted from peripheral blood leukocytes revealed mutations in the gPALB2 gene in 39 (1.03%) patients. The most frequent mutations were c.509_510del (25.64%), c.1592del (20.51%), and c.172_175del (10.26%). The predominant histological variant was invasive ductal carcinoma (84.62%) with moderate differentiation (G2) (48.72%). In most cases, luminal HER2^- subtype (69.23%) was revealed, HER2⁺ and triple-negative were less frequent (12.82 and 17.95%, respectively). Neoadjuvant chemotherapy was administered to 9 patients; a clinical response observed in 100% of cases. RCB-0 (pCR) was noted in 33.3%; RCB-I in 11.1%, RCB-II in 44.4%, and RCB-III in 11.1% of observations. All recorded cases of contralateral breast cancer (10.26%) were metachronous and presented as estrogen receptor-positive HER2^- tumors.

Stabilized trimers of the HIV-1 Env surface glycoprotein are considered as one of the main directions in the design of an HIV-1 vaccine, both individually and in prime-boost immunization strategies. The article presents the results of a study of the immunogenicity of the Env trimer of the recombinant HIV-1 CRF63_02A6 in the form of a recombinant protein and a DNA vaccine, as well as in the prime-boost immunization scheme. The Env trimer in the form of a protein and a DNA vaccine induced the formation of specific antibodies with virus-neutralizing activity against HIV-1 Env-pseudoviruses.

Mouse spleen natural killer (NK) cells were incubated ex vivo in the presence of interleukins (IL)-15 and -18 with or without IL-12 in order to study NK cell proliferation, cluster formation, and expression of gap junction protein connexin 43 (Cx43). While all applied cytokine combinations stimulated all of these functions in treated cells in comparison with control cells incubated without cytokines, IL-12 was found to increase cluster formation and decrease proliferation. Western blotting studies revealed upregulation of Cx43 expression in NK cells treated with IL-12. These results suggest that Cx43 is a marker of cluster formation of NK cells, forming contacts between them after activation of its expression by IL-12. The observed inhibition of proliferation might also be mediated by Cx43, though another possibility is that it could be an independent effect of IL-12 on NK cells.

The nucleocapsid (N) protein of the severe acute respiratory syndrome coronavirus (SARSCoV) is the most abundant structural protein in virus-infected cells. Its primary function is to pack ~30 kb positive-sense viral RNA genome that includes a 5' cap into a ribonucleoprotein (RNP) complex known as capsid. Among the 4 major structural proteins of SARS-CoV, the N protein exhibits the highest expression levels in the host cells. We produced a recombinant SARS-CoV N protein (SARSN1) and used it to detect specific antibodies in mice vaccinated with a live probiotic vaccine containing the coronavirus nucleocapsid protein.