This study is the first to demonstrate that Leytragin reduces the protein expression of several pro-nflammatory cytokines—IL-1β, IL-6, and TNF-α—during the resolution phase of inflammation, indicating its multitarget anti-cytokine action.

[D-Ala²]-dynorphin(1-7)amide is a synthetic opioid heptapeptide (H-Tyr-D-Ala-Gly-Phe-Leu-Arg-Arg-NH₂₎ and a structural analog of natural dynorphin(1-7). While natural dynorphin(1-7) exhibits potent anti-inflammatory activity in the picomolar concentration range, its application is limited by low stability and a short half-life in biological media. Sirtuins are NAD-dependent class III histone deacetylases, represented in mammals by seven isoforms with distinct substrate selectivity and intracellular localization. Nuclear sirtuins 1 (SIRT1) and 6 (SIRT6) play a key role in the resolution of inflammation by deacetylating components of pro-inflammatory signaling pathways. This study aimed to evaluate the effects of inhaled [D-Ala²]-dynorphin(1-7)amide on the transcription of all seven sirtuin isoforms in the lungs of C57BL/6Y mice during simulated acute lung inflammation and acute respiratory distress syndrome. This study is the first to demonstrate that inhalation of the specified heptapeptide significantly increases the transcription of major sirtuins (SIRT1, SIRT6), as well as SIRT2, SIRT5, and SIRT7, in inflamed lungs. Thus, the findings clarify the anti-inflammatory mechanism of [D-Ala²]-dynorphin(1-7)amide, which primarily involves enhancing the transcription of nuclear SIRT1 and SIRT6, established negative regulators of inflammation.

The widespread use of hydrazine derivatives in industry and pharmacy necessitates the development of an effective toxicogenetic model to analyze their N-acetylation and associated toxic effects. Transgenic humanized mice carrying the human NAT2 gene have been shown to model key aspects of hydrazine toxicity in humans. We present these mice as a pharmacogenetic extrapolation platform for assessing and predicting the toxic effects of hydrazine-class compounds during the targeted screening of new nontoxic hydrazine hydrochloride-based pharmaceuticals. The toxicogenetic effects of these compounds can be assessed by analyzing the transcriptional levels of the human NAT2 gene, which encodes the human cytosolic protein NAT2 in a transgenic mouse, as well as those of the genes of nuclear proteins SIRT1 and HMGB1.

This study demonstrates that NAT2-humanized mice are an effective biomodel for the research and screening of promising new drugs in pharmacy and industry. We show that isoniazid induces the transcription of the human NAT2 gene, which encodes N-acetyltransferase 2 (the enzyme responsible for isoniazid inactivation). Isoniazid also induces transcription of the mouse NAT2 gene, which encodes an N-acetyltransferase similar to human NAT1 that inactivates exogenous bioactive amines. Furthermore, isoniazid inhibits the transcription of the SIRT1 gene (encoding a class III nuclear deacetylase) in the brain and kidneys. Notably, Leytragin (SIRT1 transcription activator) only partially mitigates the effect of isoniazid. Finally, isoniazid affects TNF-α gene transcription depending on the type of tissue.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra and a profound dopamine depletion in the striatum. The long preclinical latency period and the inability to directly investigate brain processes impede the analysis of early neurodegeneration and the search for effective therapeutic strategies. In recent years, increasing attention has focused on stem cell-derived exosomes — extracellular vesicles capable of transporting bioactive molecules and penetrating the blood-brain barrier. However, their impact on functional changes in the dopaminergic system in PD remains insufficiently explored. This study evaluated how exosomes isolated from mouse neural (NSC) and mesenchymal stem cell (MSC) conditioned media affect motor activity
and striatal dopamine metabolism in a model of early-stage symptomatic PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Behavior analysis in the open field test revealed that MPTP administration induced motor changes consistent with early Parkinsonian-like impairments. Intranasal administration of exosomes partially normalized these behavioral parameters, with MSC-derived exosomes exhibiting a more pronounced effect on motor activity. Biochemical analysis revealed a depletion of dopamine and its metabolites (dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), homovanillic acid (HVA)) following MPTP administration. Both types of exosomes partially prevented these changes, with NSC-derived exosomes having a stronger effect on dopamine and DOPAC levels. These findings demonstrate that NSC- and MSC-derived exosomes can mitigate early behavioral and biochemical impairments in MPTP-induced PD, highlighting their potential as candidates for neuroprotective therapy.

This article presents a numerical study investigating the direct current flow between two small-scale electrodes placed on the human scalp. The findings reveal spatial  blurring of the electric potential between two closely spaced electrodes.

The conducted experimental studies show that the level of self-regulation during operator activities can be determined by analyzing the mismatch between the cardio-interval duration and the pulse wave duration. 

The effect of chitosan on the efficacy of antimicrobial drugs was studied in vitro. It was established that the enterosorbents Lactofiltrum®, Chitosan Evalar®, and Enterosgel® exert no significant impact on the activity of antibiotics such as ciprofloxacin, amoxiclav, clarithromycin, and cefoperazone. Low-molecularweight crab chitosan (molecular weight (MW): 50 kDa; degree of deacetylation (DD): 85.0%) was found to enhance the efficacy of aminoglycosides (gentamicin and kanamycin), macrolides (clarithromycin), and fluoroquinolones (lomefloxacin and ofloxacin). Medium-molecular-weight crab chitosan (MW: 83.7 kDa; DD: 89.0%) showed a reduction in ofloxacin and lomefloxacin activity by 26.7% and 24.1%, respectively. High-molecular-weight fungal chitosan derived from Rhizopus oryzae F-814 (MW: 400 kDa; DD: 86.8%; ATCC 9363, NRRL 395, IMI 40564) exhibited a 25.4%–57.1% increase in ofloxacin efficacy, highlighting its potential for pharmacological applications. Preliminary sorption of antibiotics onto chitosan for two hours enhanced the antimicrobial effects observed under sequential administration of antibiotic solutions into assay

The study aimed to evaluate the safety of an experimental anti-cholera agent based on bacteriophages, enterosorbents, and specific immunoglobulins. The cytotoxic effects of various formulations of this therapeutic/prophylactic agent and its individual components (immunoglobulins, chinosol, pectin, and Polysorb) was studied using CHO-K1 (Chinese hamster ovary) and HuTu 80 (human duodenal adenocarcinoma) cell line models. Immunoglobulins, pectin, and the preservative chinosol were found to induce cytoplasmic vacuolization, along with cell rounding and death in both cell lines. Conversely, Polysorb MP and cholera bacteriophages did not cause similar changes. Based on the experimental findings, the optimal composition for the new experimental therapeutic/prophylactic agent against cholera was determined: Polysorb-MP, cholera bacteriophages (Rostov-13+Rostov-M3), and specific immunoglobulins, which is a non-toxic and safe formulation.

Literature data indicate that cyclooxygenase-2 (COX-2) expression in tumor cells leads to excessive production of prostaglandin E2 (PGE2), which accelerates carcinogenesis and reduces survival rates by creating an immunosuppressive tumor microenvironment. The present study evaluated the ability of the 5-oxypyrimidine derivative SNK-578 to inhibit COX isoform activity in a cell-free system. The analysis of COX-1 and COX-2 activities revealed that SNK-578 is a non-selective inhibitor of both iso-forms. These results suggest that COX-dependent anti-inflammatory activity is one of the mechanisms underlying the multicomponent antitumor effect of 5-oxypyrimidine derivatives.

Despite the clear successes of chemotherapy in oncology, a significant rise is observed in cognitive impairment during pharmacotherapy and recovery — a phenomenon known as chemobrain. Experimental study of mechanisms underlying chemobrain induction and its modeling provide a critical foundation for developing pharmacological strategies for prevention and correction. The study aimed to evaluate the dosedependent effects of doxorubicin administration on long-term spatial memory and the microscopic morphology of the prefrontal cortex and hippocampus in rats. Doxorubicin was administered intraperitoneally to outbred male white rats (n=40) at doses of 2, 3, and 5 mg/kg on days 1, 7, 14, and 21. Control animals received isotonic saline. Memory function was assessed using the Y-maze test on days 24 and 25, followed by a morphological examination of brain structures on day 32. Rats treated with doxorubicin exhibited a dose-dependent decrease in the time spent in the novel arm of the Y-maze, indicating impaired spatial memory. Microscopic examination revealed disrupted cerebral microcirculation in the prefrontal cortex, as well as in the hippocampal CA1 and CA3 regions (at the maximum dose of 5 mg/kg). These findings suggest that for modeling chemobrain, a doxorubicin dose of 2 mg/kg is optimal, as it induces cognitive impairment with minimal toxicity. Thus, we have experimentally justified the selection of the doxorubicin dose and the behavioral test for assessing spatial memory impairment preferred in chemobrain modeling, facilitating the search for and preclinical study of pharmacological strategies to prevent and correct chemotherapy side effects.

The search for low-toxicity drugs with high therapeutic efficacy remains a critical challenge in cancer therapy. This study aimed to evaluate the effect of bee venom combined with hyperthermia on lipid peroxidation (LPO) product levels and superoxide dismutase (SOD) activity in the liver homogenate of tumor-bearing rats. The experiment used RS-1 tumor-bearing rats. The study examined the effects of bee venom combined with hyperthermia at 42°С and 43°С. Comparison groups included untreated tumor-bearing rats and those subjected to hyperthermia (42°С or 43°С) or bee venom. Intact animals were used to establish the physiological norm. Liver tissue samples were collected on days 1, 7, and 14 post-treatment. The LPO product levels were assessed by measuring diene conjugates (DC), triene (TC) conjugates, and Schiff bases (SB) via spectrophotometry. The status of the antioxidant system was evaluated by analyzing SOD activity, also determined spectrophotometrically. The study demonstrated a reduction in LPO products in the liver homogenates of tumor-bearing rats following the combined application of hyperthermia and bee venom. By day 14, the combination of 43°C hyperthermia and bee venom resulted in a decrease in DC, TC, and SB relative to the control group, reaching the values observed in intact animals. With 42°С hyperthermia and bee venom, the reduction in these markers was less pronounced. Hyperthermia monotherapy proved ineffective, as the levels of the studied parameters continued to rise, consistent with the trends observed in the tumor-bearing control group. Hepatic SOD activity in tumor-bearing rats increased across all observation periods, with the most significant elevation occurring under 43°С hyperthermia. The combined use of hyperthermia and bee venom exerts a beneficial synergistic effect.