Doklady Biochemistry and Biophysics最新文献

{"title":"The Role of Changes in the Redox Status in the Pathogenesis of Chronic Lymphocytic Leukemia","authors":"M. V. Osikov,&nbsp;E. A. Korobkin,&nbsp;A. A. Fedosov,&nbsp;A. V. Sineglazova","doi":"10.1134/S1607672924701217","DOIUrl":"10.1134/S1607672924701217","url":null,"abstract":"<p>Chronic lymphocytic leukemia is a hemoblastosis of CD5⁺ B lymphocytes with lymphocytosis, damage to the lymphatic organs, occurring in the older age group, the etiology and pathogenesis of which are not fully understood. Oxidative stress is an important factor in the regulation of stem cells and the activation of intracellular survival signaling pathways in chronic lymphocytic leukemia cells. The aim of the study was to analyze the current data on the role of redox status changes in the pathogenesis of chronic lymphocytic leukemia. A review of published relevant studies 2018–2023, scientific articles in scientific electronic bibliographic databases PubMed and Social Sciences Citation Index, devoted to the pathogenesis of chronic lymphocytic leukemia and the role of free-radical oxidation processes in it was carried out. In chronic lymphocytic leukemia, oxidative stress with a systemic excess of reactive oxygen species, an imbalance in the effectiveness of antioxidant defense is caused mainly by activation of oxidative phosphorylation in mitochondria, low levels of NADPH-oxidase type 2, increased expression of heme oxygenase-1, glutathione peroxidase and glutathione recycling enzymes, superoxide dismutase-2, thioredoxins and decreased expression of catalase. One of the mechanisms of resistance to drug therapy and oxidative stress of chronic lymphocytic leukemia cells is the intracellular signaling pathway dependent on erythroid nuclear factor-2, due to the activation of expression in cells of superoxide dismutase-2, catalase, glutathione peroxidase, peroxiredoxin-3 and -5, heme oxygenase-1, thioredoxin-1 and -2, reduced glutathione, natural killer cell activity, which is associated with lifespan, chemotaxis, proliferation, and survival. FOXO family proteins are believed to suppress carcinogenesis. FOXO3a increases the expression of superoxide dismutase-2, catalase, glutathione peroxidase, peroxiredoxin-3 and -5, and the activity of natural killer cells, which promotes the survival of tumor cells. The development of new targeted pharmacological agents that are capable of accumulating reactive oxygen species and reducing antioxidant protection due to the degradation of erythroid nuclear factor-2 and activation of NADPH-quinone oxidoreductase-1 is underway, which modernizes the therapy of chronic lymphocytic leukemia.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"519 1","pages":"564 - 570"},"PeriodicalIF":0.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Study of the Comparability of the Pharmacodynamic, Toxicological, and Pharmacokinetic Properties of the Reference Drug Pulmozyme® and the Biosimilar Drug Tigerase®","authors":"M. S. Aksenova,&nbsp;E. N. Bocharova,&nbsp;S. G. Abbasova,&nbsp;A. S. Ponomarev,&nbsp;V. V. Loginova,&nbsp;M. V. Bolotnikova,&nbsp;N. V. Belskaya,&nbsp;A. A. Kazarov,&nbsp;A. E. Lisova,&nbsp;N. K. Kudina,&nbsp;M. S. Pantyushenko,&nbsp;M. V. Zhilyaeva,&nbsp;D. S. Kopein,&nbsp;Yu. M. Karelov,&nbsp;G. G. Erastov,&nbsp;M. V. Lykov,&nbsp;R. A. Khamitov","doi":"10.1134/S1607672924701151","DOIUrl":"10.1134/S1607672924701151","url":null,"abstract":"<p>The article presents the results of studies of the drug Tigerase® (inhalation solution manufactured by JSC GENERIUM, Russia), conducted to obtain evidence of its similarity (comparability) to the reference drug Pulmozyme® (inhalation solution, manufactured by Hoffmann-La Roche Ltd., Switzerland). Both drugs contain human recombinant deoxyribonuclease I (dornase alfa) as an active substance and are intended for the treatment of cystic fibrosis with pulmonary manifestations (mucoviscidosis). The enzymatic activity of dornase alfa, contained in the studied drugs, was investigated in vitro and ex vivo on samples of purulent sputum of patients. The pharmacokinetic parameters of the drugs in the blood serum, bronchi, and lungs, as well as the main physiological parameters (body weight and temperature, the state of the cardiovascular, respiratory, excretory systems, hematological and biochemical blood parameters, pathomorphological changes in internal organs (including the state of the cornea), and mortality rates) were investigated in comparative studies of subchronic toxicity in juvenile and mature rats with 28-day inhalation at doses of 0.2 mg/kg for mature animals and 0.26 mg/kg for juvenile animals (the dose was 6 times higher than the dose recommended for clinical use). The results of the studies allow us to conclude that the drugs are comparable in enzymatic, mucolytic (secretolytic) DNase activity, safety profile and main pharmacokinetic parameters.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"519 1","pages":"525 - 533"},"PeriodicalIF":0.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IGFBP6 Modulates Proteostasis by Activating ATF4 Targets and Reducing ER Retrotranslocon Expression","authors":"O. E. Kolodeeva,&nbsp;O. E. Kolodeeva,&nbsp;I. D. Antipenko,&nbsp;A. A. Fatkulin,&nbsp;M. R. Yakhina,&nbsp;J. A. Makarova","doi":"10.1134/S1607672924600714","DOIUrl":"10.1134/S1607672924600714","url":null,"abstract":"<p>Reduced expression of the IGFBP6 protein leads to an increase in the metastatic potential of breast cancer (BC) cells. The level of protein synthesis in tumor cells is increased, leading to a compensatory adjustment of proteostasis. One of the tools used to study proteostasis is protein toxins of the RIP-II family, which irreversibly inactivate ribosomes (particularly, viscumin). We investigated the effect of <i>IGFBP6</i> gene knockdown on the proteostasis in the BC cell line MDA-MB-231. Ribosomes from MDA-MB-231^IGFBP6 cells, knockdown for the <i>IGFBP6</i> gene, are less efficiently modified by the toxin. This is probably due to the reduced transport of the viscumin catalytic subunit from the ER to the cytoplasm. MDA-MB-231^IGFBP6 cells showed reduced expression of the retrotranslocon HRD1/Derlin subunit, which is a component of the ER-associated protein degradation system (ERAD). For ATF4 transcription factor, which is a part of the ER unfolded protein response (UPR) pathway, an increased expression of its targets was found.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"519 1","pages":"486 - 492"},"PeriodicalIF":0.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1134/S1607672924600714.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Overexpression of Specific Subunits SAYP, BAP170 of the Chromatin Remodeling Complex in Drosophila Melanogaster","authors":"V. K. Chmykhalo,&nbsp;Y. V. Shidlovskii,&nbsp;L. A. Lebedeva,&nbsp; P. Schedl,&nbsp;E. Giordano","doi":"10.1134/S160767292460088X","DOIUrl":"10.1134/S160767292460088X","url":null,"abstract":"<p>The phenotypic manifestations of increased expression of the <i>Bap170</i> and <i>e(y)3 (SAYP)</i> genes in <i>D. melanogaster</i> were analyzed. Using the wing disc model, we show that moderate co-expression of <i>Bap170</i> and <i>e(y)3</i> genes in wing discs leads to abnormalities in wing veining. which was probably caused by suppression of EGFR/Ras/MAPK signaling pathways. Strong induction of co-expression of the above genes in wing discs leads to complete suppression of wing development in adults. Ubiquitous co-expression of <i>Bap170</i> and <i>e(y)3</i> is lethal at the 1st instar larval stage and leads to the formation of melanotic tumors. The above phenotypes are observed exclusively when <i>Bap170</i> and <i>e(y)3</i> are co-expressed. This evidence suggests a robust synergistic effect of the combined action of these genes, which is manifested in the hyperactivity of cell proliferation and differentiation.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"519 1","pages":"588 - 592"},"PeriodicalIF":0.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and Antitumour Activity of Hybrid Compounds Based on 4-Aminophenylarsonic Acid and Spatially Hindered Phenols","authors":"S. V. Bukharov,&nbsp;R. R. Rakhmatullin,&nbsp;D. M. Zamaletdinova,&nbsp;A. V. Bogdanov,&nbsp;A. D. Voloshina","doi":"10.1134/S1607672924701163","DOIUrl":"10.1134/S1607672924701163","url":null,"abstract":"<p>One of the main modern approaches to the creation of effective drugs is the design of new biologically active substances containing two or more pharmacophore groups in their structure. In recent years, there have been many publications on the synthesis and study of biological activity, including antitumour activity, of new organo-arsenic compounds. It is known that spatially hindered phenols can also have antitumor activity, so the synthesis and study of hybrid compounds based on organo-arsenic compounds and spatially hindered phenols is a relevant area of research. In this work, the modification of 4-aminophenylarsonic acid with 3,5-di-tert-butyl-4-hydroxybenzylacetate was carried out. In contrast to a similar transformation of 2-aminophenylarsonic acid, in this case it was possible to obtain both mono- and di-benzyl derivatives of the acid. Using the Zandmeyer method, the oxime isatin containing an arsonic acid fragment in the fifth position of the heterocycle was synthesised. Azo derivatives containing fragments of <i>para</i>-aminophenylarsonic acid and sterically hindered phenols were obtained. 4-((3,5-Di-tert-butyl-2-hydroxyphenyl)diazenyl)phenylarsonic acid was isolated in pure form. At the same time, it was found that the reaction of the diazonium azo salt of 4-aminophenylarsonic acid with 2-hydroxymethyl-4-tert-butylphenol proceeds in two directions. In addition to the classical diazotisation reaction at the 6-position of 2-hydroxymethyl-4-tert-butylphenol, a diazotisation accompanied by a dehydroxymethylation process occurs. The obtained compounds showed cytotoxic activity against human tumor cell lines M-HeLa (cervical epithelioid carcinoma) and HuTu 80 (duodenal adenocarcinoma cells). The most promising is the sodium salt of 4-((3,5-di-tert-butyl-2-hydroxyphenyl)diazenyl)phenylarsonic acid, which is superior to Tamoxifen and 5-fluorouracil in terms of selectivity index towards M-HeLa and HuTu 80 cells.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"519 1","pages":"534 - 539"},"PeriodicalIF":0.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142556862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventive Effect of 3,3'-dimethoxy-4,4'-dihydroxy-stilbene Triazole on Pulmonary Fibrosis through Inhibition of Inflammation and Down-regulation of TGF-b Signaling Pathway","authors":"Yanping Yang,&nbsp;Lianjun Lin,&nbsp;Shanshan Zhang","doi":"10.1134/S1607672924600350","DOIUrl":"10.1134/S1607672924600350","url":null,"abstract":"<p>In the present study effect of 3,3'-dimethoxy-4,4'-dihydroxy-stilbene triazole (STT) on plmonary fibrosis development was investigated in vitro in primary lung fibroblasts as well as in vivo in mice model. The results demonstrated that STT treatment effectively inhibited the TGF-β1 induced increase in expression of α-SMA and collagen I proteins in PLFs. STT treatment effectively reversed the TGF-β1 induced increase in expression of LOXL2 protein and phosphorylation of Smad2/3 proteins. Treatment of PLFs with STT reversed the TGF-β1-induced increase in expression of NOX4 and suppression of p-AMPK protein. In mice model of pulmonary fibrosis STT treatment significantly inhibited the BLM-mediated decrease in body weight and survival rate. The BLM induced increase in pulmonary index in mice was also effectively inhibited on treatment with STT. Treatment of the mice with STT inhibited the BLM-induced increase in α-SMA and Col I protein expression in pulmonary tissues. The BLM-induced increase in TGF-β1 protein expression in pulmonary tissues of the mice was inhibited on treatment with STT. Treatment with STT effectively promoted the AMPK activation in lung tissues of the BLM administered mice. In summary, the present study demonstrates that STT treatment prevents TGF-β1 induced up-regulation of α-SMA, collagen I, LOXL2 protein expression and targets phosphorylation of Smad2/3 proteins in PLFs. Moreover, it inhibits TGF-β1-induced increase in expression of NOX4 and reverses TGF-β1-mediated suppression in expression of p-AMPK protein. Therefore, STT inhibits fibrosis development in vitro as well as in vivo and therefore can be investigated further as a therapeutic agent for the treatment of lung fibrosis.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"519 1","pages":"571 - 579"},"PeriodicalIF":0.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-Related Changes in Heart Rate Variability from the Neonatal Period to Adulthood","authors":"A. A. Grinevich,&nbsp;N. K. Chemeris","doi":"10.1134/S1607672924600829","DOIUrl":"10.1134/S1607672924600829","url":null,"abstract":"<p>The aim of the study was to reveal the patterns of the age-related dynamics of the frequency-dependent regulation of heart rate variability (HRV) based on the analysis of Holter ECG recordings from healthy subjects of four age groups: neonates, one-year-old infants, adolescents, and adults. A wide spectral composition of HRV is shown, consisting of nine Hilbert–Huang modes in the frequency range from 0.0001 to 2 Hz. A decrease in the central frequencies of all modes is shown in the postnatal period with a plateau in adolescence. A rapid progression of systemic humoral regulation of HRV, characterized by a consolidated increase in the amplitudes of the corresponding modes with a plateau in adolescence, is demonstrated. The dome-shaped character of age-related changes in amplitude of modes associated with autonomic control with a maximum in adolescence is shown. The results obtained quantitatively demonstrate age-related consolidated changes in HRV parameters from neonates to adulthood.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"519 1","pages":"477 - 481"},"PeriodicalIF":0.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Escherichia coli and Micrococcus luteus Activate the CG45045 Gene in Drosophila S2 Cell Line","authors":"Yu. A. Polunina,&nbsp;A. E. Pravednikova,&nbsp;M. Ghassah,&nbsp; P. G. Georgiev,&nbsp;Yu. V. Shidlovskii,&nbsp;Z. M. Kachaev","doi":"10.1134/S160767292460074X","DOIUrl":"10.1134/S160767292460074X","url":null,"abstract":"<p>The humoral immune system of <i>Drosophila melanogaster</i>, which is the best studied of all eukaryotes, is activated by the canonical IMD and Toll signalling pathways. Recently, long non-coding RNAs (lncRNAs) and genes encoding short polypeptides have been identified as potential regulators of the innate immune response. S2 cells are a macrophage-like cell line. They are used as a model system to study the molecular mechanisms of immune response gene activation. We used this cell line to study the effect of <i>Escherichia coli</i> and <i>Micrococcus luteus</i> bacteria on the transcription of the <i>lncRNA-CR30055</i> and the <i>CG45045</i> and <i>CG44404</i> genes, encoding short polypeptides. We found that pathogens activate only <i>CG45045</i>, while the transcription levels of <i>CR30055</i> and <i>CG44404</i> remain unchanged. No activation of <i>Cecropin C</i> and some Bomanin family genes was observed, suggesting differing patterns of immune response gene activation in S2 cells and adult flies. The highest activation of <i>CG45045</i> was observed between 6 and 12 hours of cell incubation with pathogens. The activation patterns of <i>CG45045</i> after exposure to <i>E. coli</i> and <i>M. luteus</i> were similar, suggesting common mechanisms of transcriptional activation of this gene. Thus, <i>CG45045</i> may be a novel gene involved in the humoral immune response of <i>Drosophila</i>.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"519 1","pages":"482 - 485"},"PeriodicalIF":0.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in FoxO3a, NF-κB, and MuRF1 Expression in the Soleus Muscle of Male Rats Following High-Intensity Interval Training and Detraining","authors":"Shahin Sheibani,&nbsp;Farhad Daryanoosh,&nbsp;Amir Hossein Zarifkar","doi":"10.1134/S1607672924600817","DOIUrl":"10.1134/S1607672924600817","url":null,"abstract":"<p>Activation of the transcription factors FoxO3a and NF-κB is necessary for muscle atrophy, which occurs during cancer cachexia and detraining. It is not known how high-intensity interval training (HIIT) and detraining affect activation of these pathways. Two-month-old male Sprague-Dawley rats were assigned to sedentary control (SC) (<i>n</i> = 6) and HIIT (HIIT) (<i>n</i> = 18) groups. The HIIT group was divided into three subgroups: HIIT (<i>n</i> = 6), HIIT + 7-day detraining (<i>n</i> = 6), and HIIT + 14-day detraining (<i>n</i> = 6). The expression of FoxO3a, NF-κB, MuRF1, and PGC-1α in the soleus muscle was examined by RT-PCR using CYBR Green. The 2-Ct, Livak method was used to calculate the changes in data expression. The soleus muscle mass increased after HIIT (35.10%) and decreased after 7- and 14-day of detraining (15 and 21%, respectively). The mRNA expression levels of NF-κB, MuRF1, and PGC1α in the soleus muscle were upregulated, and FoxO3a levels were significantly lower in the HIIT group compare to the SC group (<i>p</i> = 0.001). Taken together, the activity of the FoxO3a/MuRF1 pathway, but not NF-κB /MuRF1, can promote atrophy due to detraining, and MuRF1 is not always a good marker of atrophy.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"519 1","pages":"580 - 587"},"PeriodicalIF":0.8,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to: Reconstruction of Derogenes varicus Miracidium (Digenea: Derogenidae): First Ultrastructural Description of Spines on the Surface of Hemiurata Larvae","authors":"P. A. Smirnov,&nbsp;D. Yu. Krupenko","doi":"10.1134/S1607672924550015","DOIUrl":"10.1134/S1607672924550015","url":null,"abstract":"","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"518 1","pages":"475 - 475"},"PeriodicalIF":0.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}