E M Malinovskaya, G V Shmarina, E S Ershova, L V Kameneva, N N Veiko, V P Veiko, M S Konkova, P A Bobrovsky, E A Kozhina, P E Umriukhin, V N Lazarev, A Y Asanov, T M Rozhnova, V N Nikolenko, M Y Sinelnikov, S V Kostyuk
{"title":"GC-Reach DNA Fragments Reduce the Expression of Survival Genes in MCF7 Breast Carcinoma Cells: TLR9/MyD88/NF-κB Signaling Pathway as a Potential Target for Cancer Therapy.","authors":"E M Malinovskaya, G V Shmarina, E S Ershova, L V Kameneva, N N Veiko, V P Veiko, M S Konkova, P A Bobrovsky, E A Kozhina, P E Umriukhin, V N Lazarev, A Y Asanov, T M Rozhnova, V N Nikolenko, M Y Sinelnikov, S V Kostyuk","doi":"10.1007/s10517-025-06357-3","DOIUrl":"10.1007/s10517-025-06357-3","url":null,"abstract":"<p><p>Cell-free DNA (cfDNA) attracts increasing attention not only as a diagnostic tool for tumor resistance to cytostatic therapy, but also as an active participant of the tumor process. GC-rich DNA accumulates in the cfDNA pool and stimulates TLR9/MyD88/NF-κB signaling, thereby increasing the expression of genes responsible for viability of cancer cells. We studied the effect of GC-DNA on the transcriptional activity of survival genes in wild-type MCF7 cells (wt MCF7) and TLR9 gene knockout MCF7 cells (TLR9-/- MCF7). It was shown that, in contrast to wt MCF7 cell cultures, TLR9-/- MCF7 cells responded to stimulation with GC-DNA fragments by a decrease in the activity of TLR9/MyD88/NF-κB signaling cascade and a decline in survival gene expression. Our data indicate that TLR9/MyD88/NF-κB signaling cascade components may be considered as potential targets for cancer therapy.</p>","PeriodicalId":9331,"journal":{"name":"Bulletin of Experimental Biology and Medicine","volume":" ","pages":"467-472"},"PeriodicalIF":0.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparison of the Effects of Tetrahydrobiopterine, L-Tryptophan, and Iron Ions on the Thermal Stability of Wild Type and P447R Mutant Tryptophan Hydroxylase 2.","authors":"P D Komleva, R Deeb, E I Terentieva, A V Kulikov","doi":"10.1007/s10517-025-06354-6","DOIUrl":"10.1007/s10517-025-06354-6","url":null,"abstract":"<p><p>The enzyme tryptophan hydroxylase 2 (TPH2) hydroxylates L-tryptophan to L-5-hydroxytryptophan (5-HTP) in the presence of tetrahydrobiopterin (BH<sub>4</sub>), iron ions (Fe<sup>2+</sup>), and molecular oxygen, the first and rate-limiting step in the synthesis of the neurotransmitter serotonin (5-HT) in the mammalian brain. We compared the effect of L-tryptophan and bi- and trivalent iron ions on the thermal stability of the mutant (mt) and wild type (wt) TPH2 molecules with those of BH<sub>4</sub>. Mt TPH2 and wt TPH2 molecules were extracted from the midbrain of BALB/c and C57BL/6 mice, respectively. Thermal stability was examined using a thermal denaturation curve and assessed by T<sub>50</sub>, the temperature at which half of the enzyme molecules are denatured. L-tryptophan at a concentration of 0.2 mM did not stabilize TPH2. BH<sub>4</sub> increased T<sub>50</sub> of the mt enzyme at concentration of 0.2 mM, but not 0.1 mM. It was shown for the first time that divalent and trivalent iron ions at concentrations of 0.01, 0.05, and 0.2 mM increased T<sub>50</sub> of the mt and wt enzyme significantly higher than BH<sub>4</sub>. The results prompt using iron ions for elucidation of the molecular mechanisms of thermal stability of TPH2 in order to create pharmacological chaperones for correcting mutation-induced disturbances in TPH2 activity and the associated psychopathologies.</p>","PeriodicalId":9331,"journal":{"name":"Bulletin of Experimental Biology and Medicine","volume":" ","pages":"447-452"},"PeriodicalIF":0.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A A Gladkov, M S Zemlyanskov, Y I Pigareva, V N Kolpakov, V B Kazantsev, I V Mukhina, A S Pimashkin
{"title":"Microfluidic Chip for Studying the Mechanisms of Allogeneic Progenitor Neuronal Cells Integration into a Mature Neural Network In Vitro.","authors":"A A Gladkov, M S Zemlyanskov, Y I Pigareva, V N Kolpakov, V B Kazantsev, I V Mukhina, A S Pimashkin","doi":"10.1007/s10517-025-06342-w","DOIUrl":"10.1007/s10517-025-06342-w","url":null,"abstract":"<p><p>The formation of functional connections between cells derived from neuronal progenitor cells (NPCs) and the developed neuronal network is a crucial task in neurobiology and cellular technologies for medical applications. We developed a technique to co-culture NPCs and mature neuronal cells in a three-chamber microfluidic chip in vitro and studied the features of functional connections among cells derived from NPCs during their integration into a network of differentiated neurons. Starting from day 20 of primary culture development, a network forms from integrated NPCs, which ensures the distribution of bioelectrical activity among neurons in a manner similar to that of differentiated cells.</p>","PeriodicalId":9331,"journal":{"name":"Bulletin of Experimental Biology and Medicine","volume":" ","pages":"387-392"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R I Zaripova, G G Yafarova, V V Andrianov, M I Sungatullina, N I Ziyatdinova, Kh L Gainutdinov, T L Zefirov
{"title":"Effect of Motor Activity Restriction on Copper Content in Rats.","authors":"R I Zaripova, G G Yafarova, V V Andrianov, M I Sungatullina, N I Ziyatdinova, Kh L Gainutdinov, T L Zefirov","doi":"10.1007/s10517-025-06326-w","DOIUrl":"10.1007/s10517-025-06326-w","url":null,"abstract":"<p><p>In rats subjected to increasing restriction of motor activity starting from day 21 days of life, copper content was evaluated by electron paramagnetic resonance (EPR) spectroscopy by analyzing the levels of copper-containing paramagnetic complexes in the heart and liver tissues. Copper content was assessed by the intensity of the characteristic EPR signal from the Cu<sup>2+</sup>-diethyldithiocarbamate complex (Cu<sup>2+</sup>-(DETC)<sub>2</sub>). It was found that after restriction of motor activity for 30 days, copper content in the heart and liver tissues increased by 2.2 and 2.9 times, respectively.</p>","PeriodicalId":9331,"journal":{"name":"Bulletin of Experimental Biology and Medicine","volume":" ","pages":"307-310"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T V Sukhacheva, R A Serov, A I Kim, V P Podzolkov, L A Bockeria
{"title":"Patterns of Increased Cardiomyocyte Ploidy in Myocardial Hypertrophy of Various Origins.","authors":"T V Sukhacheva, R A Serov, A I Kim, V P Podzolkov, L A Bockeria","doi":"10.1007/s10517-025-06325-x","DOIUrl":"10.1007/s10517-025-06325-x","url":null,"abstract":"<p><p>An increase in the ploidy of cardiomyocytes (CMCs) determines the potential for their hypertrophic growth. We analyzed the changes in CMC ploidy and size of the interventricular septum in patients with hypertrophic cardiomyopathy (HCM) and tetralogy of Fallot (TF). The ploidy of CMCs in children and adult patients with HCM and children with TF was 1.5-2-fold higher than in individuals without cardiovascular pathology, and it did not change with age. The size of the CMCs was also larger by 1.3-2 times in patients with HCM and TF, compared to the control groups. However, the increase in CMCs size was more significant in HCM than in TF. The proportion of multinucleated CMCs was significantly lower in patients with HCM compared to controls and was by almost 2 times higher in patients with TF. Thus, myocardial hypertrophy in HCM is mainly due to the polyploidy of mononucleated CMCs, whereas in TF, the proportion of multinucleated CMCs increases.</p>","PeriodicalId":9331,"journal":{"name":"Bulletin of Experimental Biology and Medicine","volume":" ","pages":"301-306"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I V Yakovleva, N F Gavrilova, E A Kurbatova, D S Vorobyev, E S Petukhova, I B Semenova, A E Zaitsev, Yu V Volokh, A Yu Leonova, A V Poddubikov
{"title":"Immunochemical Characteristics and Functional Activity of Monoclonal Antibodies Obtained to the Recombinant Form of Pneumolysin.","authors":"I V Yakovleva, N F Gavrilova, E A Kurbatova, D S Vorobyev, E S Petukhova, I B Semenova, A E Zaitsev, Yu V Volokh, A Yu Leonova, A V Poddubikov","doi":"10.1007/s10517-025-06334-w","DOIUrl":"10.1007/s10517-025-06334-w","url":null,"abstract":"<p><p>Monoclonal antibodies (mAbs) of the IgG1 isotype obtained to the full-length recombinant pneumolysin (rPly) did not recognize or poorly recognized conformational epitopes of native pneumolysin in ELISA. At the same time, polyclonal antibodies (pAbs(rPly)) detected native pneumolysin in sandwich ELISA when they were used as capture and detecting antibodies simultaneously. All mAbs(rPly) inhibited erythrocyte hemolysis induced by native pneumolysin. The combined use of mAbs(rPly) did not reveal an increase in optical density in ELISA and an increase in inhibition hemolytic activity, which suggests that mAbs(rPly) are directed to the same or spatially closely located epitopes. pAbs(rPly) more effectively inhibited erythrocyte hemolysis than mAbs(rPly).</p>","PeriodicalId":9331,"journal":{"name":"Bulletin of Experimental Biology and Medicine","volume":" ","pages":"346-350"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Total and Reduced Aminothiols in Blood Plasma as Biochemical Markers of the Effectiveness of Hemodialysis Therapy in Patients with End-Stage Renal Disease.","authors":"S G Dzugkoev, F S Dzugkoeva, V A Gadieva","doi":"10.1007/s10517-025-06328-8","DOIUrl":"10.1007/s10517-025-06328-8","url":null,"abstract":"<p><p>The redox status of aminothiols in the blood plasma of 15 patients with end-stage renal disease before and against the background of hemodialysis therapy was compared with that of relatively healthy volunteers. An increase in the plasma content of total cysteine and homocysteine in patients before dialysis was revealed. An increase in the level of oxidized forms of these compounds was also noted. The hemodialysis procedure was accompanied by a significant shift of the redox status towards an increase in the reduced forms typical of healthy people. Oxidized forms of aminothiols can be used as biomarkers of uremic conditions in patients with end-stage renal disease. At the same time, the predominance of reduced forms of compounds may be an indicator of the effectiveness of renal replacement therapy, including hemodialysis.</p>","PeriodicalId":9331,"journal":{"name":"Bulletin of Experimental Biology and Medicine","volume":" ","pages":"315-318"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A A Boshchenko, B K Kurbatov, M Kilin, L N Maslov, N V Naryzhnaya, V V Saushkin, K V Zavadovsky, I V Stepanov, S V Gusakova, Yu G Birulina, T N Zaitseva, L V Smagliy
{"title":"Role of β-Adrenergic Receptors in Stress-Induced Cardiac Injury.","authors":"A A Boshchenko, B K Kurbatov, M Kilin, L N Maslov, N V Naryzhnaya, V V Saushkin, K V Zavadovsky, I V Stepanov, S V Gusakova, Yu G Birulina, T N Zaitseva, L V Smagliy","doi":"10.1007/s10517-025-06327-9","DOIUrl":"10.1007/s10517-025-06327-9","url":null,"abstract":"<p><p>Stress-induced cardiac injury (SICI) was modeled on female Wistar rats using a 24-h immobilization. SICI was quantified by <sup>99m</sup>Tc-pyrophosphate accumulation in the myocardium. Blockade of β<sub>1</sub>- and β<sub>2</sub>-adrenergic receptors (AR) led to a decrease in SICI. β<sub>1</sub>-AR antagonists nebivolol and atenolol almost completely prevented SICI. The selective β<sub>2</sub>-AR antagonist ICI 118,551 increased SICI, while the selective β<sub>3</sub>-AR antagonist L-748337 did not affect heart damage. The selective β<sub>2</sub>-AR agonist formoterol increased cardiac tolerance to stress. These findings suggest that β<sub>1</sub>-AR play a key role in the pathogenesis of SICI. Stimulation of β<sub>2</sub>-AR enhances cardiac tolerance to stress. β<sub>3</sub>-AR are not involved in the pathogenesis of SICI.</p>","PeriodicalId":9331,"journal":{"name":"Bulletin of Experimental Biology and Medicine","volume":" ","pages":"311-314"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N I Ziyatdinova, A M Kuptsova, L I Faskhutdinov, R R Shakirov, T L Zefirov
{"title":"The Effect of α<sub>2</sub>-Adrenergic Receptor Stimulation on the Isolated Hearts from Rats with Acute Myocardial Infarction against the Background of I<sub>f</sub> Blockade.","authors":"N I Ziyatdinova, A M Kuptsova, L I Faskhutdinov, R R Shakirov, T L Zefirov","doi":"10.1007/s10517-025-06324-y","DOIUrl":"10.1007/s10517-025-06324-y","url":null,"abstract":"<p><p>We studied the effect of α<sub>2</sub>-adrenoreceptor stimulation after preliminary I<sub>f</sub> blockade on the function of the Langendorff-isolated rat heart in the acute stage of experimental myocardial infarction. Stimulation of α<sub>2</sub>-adrenoreceptors with clonidine (10<sup>-6</sup> M) against the background of I<sub>f</sub> blockade with ZD7288 (10<sup>-9</sup> M) reduced the contractility of the left ventricular myocardium, HR, coronary blood flow, and the duration of the left ventricular myocardium contraction in sham-operated rats and animals with acute myocardial infarction. The duration of relaxation and contraction cycle during α<sub>2</sub>-adrenoreceptor stimulation after preliminary I<sub>f</sub> blockade (10<sup>-9</sup> M) was increased in sham-operated rats and in animals with acute myocardial infarction. Stimulation of adrenoreceptors against the background of application of ZD7288 in a concentration of 10<sup>-5</sup> M decreased the left ventricular pressure, HR, coronary blood flow, and the duration of left ventricular myocardial contraction in both groups. The duration of the relaxation and contraction cycle during α<sub>2</sub>-adrenoreceptor stimulation against the background of I<sub>f</sub> blockade (10<sup>-5</sup> M) increased in sham-operated rats and animals with acute myocardial infarction.</p>","PeriodicalId":9331,"journal":{"name":"Bulletin of Experimental Biology and Medicine","volume":" ","pages":"295-300"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A S Tomyshev, A N Dudina, E V Ilina, P G Iuzbashian, E I Voronova, M M Magomedagaev, G P Kostyuk, A V Andriushchenko, D V Romanov, A B Smulevich, I S Lebedeva
{"title":"MRI Study of the Brain Structural Characteristic in Persecutory Delusions.","authors":"A S Tomyshev, A N Dudina, E V Ilina, P G Iuzbashian, E I Voronova, M M Magomedagaev, G P Kostyuk, A V Andriushchenko, D V Romanov, A B Smulevich, I S Lebedeva","doi":"10.1007/s10517-025-06340-y","DOIUrl":"10.1007/s10517-025-06340-y","url":null,"abstract":"<p><p>The structural MRI of the cortex, subcortical structures, hippocampal subfields, and brainstem regions in patients with persecutory delusions in schizophrenia (ICD-10 code: F20) and delusional disorder (ICD-10 code: F22.0) were analyzed. Patients demonstrated multiple regions of decreased cortical gray matter thickness, reduced volumes of the left thalamus and some hippocampal sub-fields compared to mentally healthy subjects. No alterations in brainstem structures were found. The results were analyzed within the framework of the transnosological model of delusions.</p>","PeriodicalId":9331,"journal":{"name":"Bulletin of Experimental Biology and Medicine","volume":" ","pages":"376-380"},"PeriodicalIF":0.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143405883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}