Biochemistry (Moscow)最新文献

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Effects of the RNA-Binding Protein Sam68 on Poly(ADP-Ribose)polymerase 1 Activity rna结合蛋白Sam68对聚(adp -核糖)聚合酶1活性的影响
IF 2.3 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-01-17 DOI: 10.1134/S0006297924120046
Konstantin N. Naumenko, Egor A. Berezhnev, Tatyana A. Kurgina, Maria V. Sukhanova, Olga I. Lavrik
{"title":"Effects of the RNA-Binding Protein Sam68 on Poly(ADP-Ribose)polymerase 1 Activity","authors":"Konstantin N. Naumenko,&nbsp;Egor A. Berezhnev,&nbsp;Tatyana A. Kurgina,&nbsp;Maria V. Sukhanova,&nbsp;Olga I. Lavrik","doi":"10.1134/S0006297924120046","DOIUrl":"10.1134/S0006297924120046","url":null,"abstract":"<p>Taking into account involvement of the RNA-binding proteins in regulation of activity of poly(ADP-ribose) polymerase 1 (PARP1), a key factor of DNA repair, the effect of the intrinsically disordered protein Sam68 (Src-associated substrate during mitosis of 68 kDa) on catalytic activity of this enzyme was studied. Plasmid containing coding sequence of the Sam68 protein was obtained. Using the obtained construct, conditions for the Sam68 expression in <i>Escherichia coli</i> cells were optimized and procedure for protein purification was developed. It was found that Sam68 is able to regulate catalytic activity of PARP1, stimulating auto-poly(ADP-ribosyl)ation of PARP1, interacting with the damaged DNA and purified poly(ADP-ribose) (PAR). Based on the experimental data, a hypothesis on the mechanism of PARP1 activity stimulation by the Sam68 protein was proposed, which involves formation of a complex of Sam68 with poly(ADP-ribosyl)ated PARP1. Sam68 interacts with PAR, shielding its negative charge, which increases the time of PARP1 in the complex with damaged DNA and the overall yield of PAR synthesized by this enzyme.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 12-13","pages":"2143 - 2154"},"PeriodicalIF":2.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995388","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}
引用次数: 0
Post-Selection Design of Aptamers: Comparative Study of Affinity of the DNA Aptamers to Recombinant Extracellular Domain of Human Epidermal Growth Factor Receptors 核酸适配体的后选择设计:DNA适配体对人表皮生长因子受体细胞外重组结构域亲和力的比较研究
IF 2.3 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-01-17 DOI: 10.1134/S0006297924120071
Valeria L. Moiseenko, Olga M. Antipova, Aleksandra A. Rybina, Liliya I. Mukhametova, Sergei A. Eremin, Galina V. Pavlova, Alexey M. Kopylov
{"title":"Post-Selection Design of Aptamers: Comparative Study of Affinity of the DNA Aptamers to Recombinant Extracellular Domain of Human Epidermal Growth Factor Receptors","authors":"Valeria L. Moiseenko,&nbsp;Olga M. Antipova,&nbsp;Aleksandra A. Rybina,&nbsp;Liliya I. Mukhametova,&nbsp;Sergei A. Eremin,&nbsp;Galina V. Pavlova,&nbsp;Alexey M. Kopylov","doi":"10.1134/S0006297924120071","DOIUrl":"10.1134/S0006297924120071","url":null,"abstract":"<p>The current work presents comparative assessment of affinity of the designed DNA aptamers for extracellular domain of the human epidermal growth factor receptor (EGFR*). The affinity data of the 20 previously published aptamers are summarized. Diversity of the aptamer selection methods and techniques requires unification of the comparison algorithms, which is also necessary for designing aptamers used in the post-selection fitting to the target EGFR* protein. In this study affinities of the DNA aptamers from two families, U31 and U2, previously obtained by Wu et al. from the same selection [Wu et al. (2014) <i>PLoS One</i>, <b>9</b>, e90752] and their derivatives – GR20, U2s, and Gol1 obtained by us through rational design, were compared. Affinity of the aptamers to EGFR* was measured by two different methods: a solution-phase technique – fluorescence polarization of FAM-labeled aptamers, and by a kinetic method using biolayer interferometry technique with aptamers immobilized on the surface. Unlike the values of equilibrium dissociation constants obtained through titration and expressed in units of protein concentration, analysis of the titration curve profiles themselves and kinetics of interaction proved to be more informative. This allowed us to identify how even subtle changes in the aptamers and their structures affect affinity. Hypotheses regarding the “structure–function” relationships and recognition mechanisms were formulated. The data obtained for the set of aptamer constructs are critical for moving forward to examination of aptamer interactions with EGFR on the cell surface.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 12-13","pages":"2183 - 2193"},"PeriodicalIF":2.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995389","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}
引用次数: 0
Pathogenesis-Associated Bacterial Amyloids: The Network of Interactions 致病相关的细菌淀粉样蛋白:相互作用的网络
IF 2.3 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-01-17 DOI: 10.1134/S0006297924120022
Haidar Fayoud, Mikhail V. Belousov, Kirill S. Antonets, Anton A. Nizhnikov
{"title":"Pathogenesis-Associated Bacterial Amyloids: The Network of Interactions","authors":"Haidar Fayoud,&nbsp;Mikhail V. Belousov,&nbsp;Kirill S. Antonets,&nbsp;Anton A. Nizhnikov","doi":"10.1134/S0006297924120022","DOIUrl":"10.1134/S0006297924120022","url":null,"abstract":"<p>Amyloids are protein fibrils with a characteristic cross-β structure that is responsible for the unusual resistance of amyloids to various physical and chemical factors, as well as numerous pathogenic and functional consequences of amyloidogenesis. The greatest diversity of functional amyloids was identified in bacteria. The majority of bacterial amyloids are involved in virulence and pathogenesis either via facilitating formation of biofilms and adaptation of bacteria to colonization of a host organism or through direct regulation of toxicity. Recent studies have shown that, beside their commonly known activity, amyloids may be involved in the spatial regulation of proteome by modulating aggregation of other amyloidogenic proteins with multiple functional or pathological effects. Although the studies on the role of microbiome-produced amyloids in the development of amyloidoses in humans and animals have only been started, it is clear that humans as holobionts contain amyloids encoded not only by the host genome, but also by microorganisms that constitute the microbiome. Amyloids acquired from external sources (e.g., food) can interact with holobiont amyloids and modulate the effects of bacterial and host amyloids, thus adding another level of complexity to the holobiont-associated amyloid network. In this review, we described bacterial amyloids directly or indirectly involved in disease pathogenesis in humans and discussed the significance of bacterial amyloids in the three-component network of holobiont-associated amyloids.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 12-13","pages":"2107 - 2132"},"PeriodicalIF":2.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995019","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}
引用次数: 0
Novel Rhamnose-Containing Glycopolymers from the Cell Wall of Rathayibacter festucae VKM Ac-1390T 恶臭拉撒伊菌VKM Ac-1390T细胞壁含鼠李糖的新型糖共聚物
IF 2.3 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-01-17 DOI: 10.1134/S0006297924120095
Alexander S. Shashkov, Natalia V. Potekhina, Elena M. Tulskaya, Andrey S. Dmitrenok, Sof’ya N. Senchenkova, Lubov V. Dorofeeva, Lyudmila I. Evtushenko
{"title":"Novel Rhamnose-Containing Glycopolymers from the Cell Wall of Rathayibacter festucae VKM Ac-1390T","authors":"Alexander S. Shashkov,&nbsp;Natalia V. Potekhina,&nbsp;Elena M. Tulskaya,&nbsp;Andrey S. Dmitrenok,&nbsp;Sof’ya N. Senchenkova,&nbsp;Lubov V. Dorofeeva,&nbsp;Lyudmila I. Evtushenko","doi":"10.1134/S0006297924120095","DOIUrl":"10.1134/S0006297924120095","url":null,"abstract":"<p><i>Rathayibacter festucae</i> VKM Ac-1390<sup>T</sup> (family Microbacteriaceae, class Actinomycetes) contains three rhamnose-containing glycopolymers in the cell wall, the structures of which were established by chemical and NMR spectroscopy methods. The first polymer, a rhamnomannan, consists of repeating tetrasaccharide units with xylopyranose side residues, →2)-α-[β-D-Xyl<i>p</i>-(1→3)]-D-Rha<i>p</i>-(1→3)-α-D-Man<i>p</i>-(1→2)-α-D-Rha<i>p</i>-(1→3)-α-D-Man<i>p</i>-(1→. The second polymer found in minor amounts, is a rhamnan, →2)-α-D-Rha<i>p</i>-(1→3)-α-D-Rha<i>p</i>-(1→. The third polymer is a teichuronic acid acetalated with pyruvic acid, →2)-α-[4,6-<i>S</i>-Pyr]-D-Man<i>p</i>-(1→4)-α-L-Rha<i>p</i>-(1→4)-β-D-Glc<i>p-</i>(1→4)-α-D-Glc<i>p-</i>(1→4)-β-D-Glc<i>p</i>A<i>-</i>(1→. The structures of rhamnomannan and teichuronic acid are new for <i>Ratayibacter </i>and prokaryotes in a whole. The results of this study expand our understanding of the structural diversity of microbial glycopolymers and are consistent with previous reports on the species specificity of glycopolymer structures and composition in the genus <i>Rathayibacter.</i></p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 12-13","pages":"2204 - 2213"},"PeriodicalIF":2.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995385","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}
引用次数: 0
Characterization of Carbohydrate Specificity of Monoclonal Antibodies to Fungal Antigenic Markers Using Biotinylated Oligosaccharides as Coating Antigens 以生物素化寡糖为包被抗原的真菌抗原标记单克隆抗体碳水化合物特异性鉴定
IF 2.3 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-01-17 DOI: 10.1134/S0006297924120083
Marina L. Gening, Alina V. Polyanskaya, Anton N. Kuznetsov, Alexandra D. Titova, Viktor I. Yudin, Dmitry V. Yashunskiy, Yury E. Tsvetkov, Olga N. Yudina, Vadim B. Krylov, Nikolay E. Nifantiev
{"title":"Characterization of Carbohydrate Specificity of Monoclonal Antibodies to Fungal Antigenic Markers Using Biotinylated Oligosaccharides as Coating Antigens","authors":"Marina L. Gening,&nbsp;Alina V. Polyanskaya,&nbsp;Anton N. Kuznetsov,&nbsp;Alexandra D. Titova,&nbsp;Viktor I. Yudin,&nbsp;Dmitry V. Yashunskiy,&nbsp;Yury E. Tsvetkov,&nbsp;Olga N. Yudina,&nbsp;Vadim B. Krylov,&nbsp;Nikolay E. Nifantiev","doi":"10.1134/S0006297924120083","DOIUrl":"10.1134/S0006297924120083","url":null,"abstract":"<p>Mannan and β-(1→3)-glucan are two polysaccharide markers that are characteristic for a number of fungal pathogens, including <i>Candida albicans</i>, which is the most common cause of invasive mycoses in humans. In this study, we examined epitope specificity of two monoclonal antibodies, CM532 and FG70, which recognize certain oligosaccharide fragments of these fungal polysaccharides. Using a panel of biotinylated oligosaccharides as coating antigens, we found that the CM532 antibody obtained by immunization with the pentamannoside β-Man-(1→2)-β-Man-(1→2)-α-Man-(1→2)-α-Man-(1→2)-α-Man KLH conjugate, selectively recognizes the trisaccharide β-Man-(1→2)-α-Man-(1→2)-α-Man epitope. Another antibody, FG70, obtained by immunization with heptaglucan β-Glc-(1→3)-[β-Glc-(1→3)]<sub>5</sub>-β-Glc conjugate with KLH, interacts with the linear β-(1→3)-linked pentaglucoside fragment, and presence of 3,6-branches within this epitope does not significantly affect the interaction efficiency. The data obtained indicate that the monoclonal antibodies under consideration could be used to create effective diagnostics for detection of fungal infections, which are not available at present.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 12-13","pages":"2194 - 2203"},"PeriodicalIF":2.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995384","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}
引用次数: 0
Activation of P38 MAPK Signaling Cascade is Linked with Clinical Outcomes and Therapeutic Responses in Human Cancers P38 MAPK信号级联的激活与人类癌症的临床结果和治疗反应有关
IF 2.3 4区 生物学
Biochemistry (Moscow) Pub Date : 2025-01-17 DOI: 10.1134/S0006297924120058
Aleksandra Emelyanova, Marianna Zolotovskaia, Elena Poddubskaya, Aleksander Modestov, Anton Buzdin, Denis Kuzmin
{"title":"Activation of P38 MAPK Signaling Cascade is Linked with Clinical Outcomes and Therapeutic Responses in Human Cancers","authors":"Aleksandra Emelyanova,&nbsp;Marianna Zolotovskaia,&nbsp;Elena Poddubskaya,&nbsp;Aleksander Modestov,&nbsp;Anton Buzdin,&nbsp;Denis Kuzmin","doi":"10.1134/S0006297924120058","DOIUrl":"10.1134/S0006297924120058","url":null,"abstract":"<p>Activation of the p38 mitogen-activated protein kinase (MAPK) pathways is vital in regulating cell growth, differentiation, apoptosis, and stress response, significantly affecting tumorigenesis and cancer progression. We developed a bioinformatic technique to construct an interactome network-based molecular pathways for genes of interest and quantify their activation levels using high-throughput gene expression data. This study is focused on the p38α, p38β, p38γ, and p38δ kinases, examining their activation levels (PALs) based on transcriptomic data and their associations with survival and drug responsiveness across various cancer types. We analyzed 11,287 human tumor profiles from 31 cancer types and 53 datasets to assess patient survival and clinical response to 29 therapies. Activation of p38 pathways showed varying prognostic significance depending on the cancer type. In astrocytoma, glioblastoma, thymoma, renal, bladder, esophageal, colorectal, stomach cancers, and lung squamous cell carcinoma, p38 pathway activation correlated with poor survival. Conversely, it indicated better survival in the gender-associated tumors (HER2+, luminal A and B subtypes of breast cancer, prostate carcinoma), sarcomas, lung adenocarcinoma, and others. These trends are aligned with the response-to-therapy analysis. For instance, higher activation of the p38β and p38γ pathways was linked to positive responses to taxane and anthracycline therapies in breast cancer, while lower activation of the p38α and p38β pathways correlated with better responses to 5-fluorouracil-based treatments in colorectal cancer. However, associations with individual MAPK14, MAPK11, MAPK12, and MAPK13 gene expression levels were less robust. Hence, the p38 pathway activation levels could serve as potential biomarkers for predicting clinical outcomes and personalizing treatment strategies, including use of the selective p38 MAPK inhibitors.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 12-13","pages":"2155 - 2173"},"PeriodicalIF":2.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995387","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}
引用次数: 0
Alcohol-Induced Activation of Chemokine System and Neuroinflammation Development. 酒精诱导的趋化因子系统激活和神经炎症的发展。
IF 2.3 4区 生物学
Biochemistry (Moscow) Pub Date : 2024-11-01 DOI: 10.1134/S0006297924110038
Ekaterina V Mikhalitskaya, Natalya M Vyalova, Nikolay A Bokhan, Svetlana A Ivanova
{"title":"Alcohol-Induced Activation of Chemokine System and Neuroinflammation Development.","authors":"Ekaterina V Mikhalitskaya, Natalya M Vyalova, Nikolay A Bokhan, Svetlana A Ivanova","doi":"10.1134/S0006297924110038","DOIUrl":"10.1134/S0006297924110038","url":null,"abstract":"<p><p>Chemokines are immunoregulatory proteins with pleiotropic functions involved in neuromodulation, neurogenesis, and neurotransmission. The way chemokines affect the CNS plays an important role in modulating various conditions that could have negative impact on CNS functions, including development of alcohol use disorders. In this review, we analyzed the literature data available on the problem of chemokine participation in pathogenesis, clinical presentation, and remission of alcohol use disorders both in animal models and in the study of patients with alcoholism. The presented information confirms the hypothesis that the alcohol-induced chemokine production could modulate chronic neuroinflammation. Thus, the data summarized and shown in this review are focused on the relevant direction of research in the field of psychiatry, which is in demand by both scientists and clinical specialists.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 11","pages":"1889-1903"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793931","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}
引用次数: 0
Extracellular Vesicles as Potential Biomarkers in Addictive Disorders. 细胞外囊泡作为成瘾障碍的潜在生物标志物。
IF 2.3 4区 生物学
Biochemistry (Moscow) Pub Date : 2024-11-01 DOI: 10.1134/S0006297924110117
Vsevolod V Severtsev, Margarita A Pavkina, Nikolay N Ivanets, Maria A Vinnikova, Alexander A Yakovlev
{"title":"Extracellular Vesicles as Potential Biomarkers in Addictive Disorders.","authors":"Vsevolod V Severtsev, Margarita A Pavkina, Nikolay N Ivanets, Maria A Vinnikova, Alexander A Yakovlev","doi":"10.1134/S0006297924110117","DOIUrl":"10.1134/S0006297924110117","url":null,"abstract":"<p><p>Small extracellular vesicles (sEVs) and their role in mental and addictive disorders are extremely promising research areas. Because of their small size, sEVs can pass through the blood-brain barrier. The membrane of sEVs contain proteins that protect them against destruction by the organism's immune system. Due to these properties, sEVs circulating in the blood can be used as potential biomarkers of processes occurring in the brain. Exposure to psychoactive substances <i>in</i> <i>vitro</i> and <i>in vivo</i> affects sEV biogenesis and significantly alters the amount of sEVs and chemical composition of their cargo. Based on the published reports, sEVs carry numerous potential biomarkers of addictive pathologies, although the diagnostic significance of these markers still has to be evaluated. A large body of evidence indicates that psychoactive substances influence Rab family GTPases, Toll-like receptors, complement system components, and cytokines. In some studies, the effect of psychoactive substances on sEVs was found to be sex-dependent. It has become commonly accepted that sEVs are involved in the regulation of neuroinflammation and interaction between glial cells and neurons, as well as between peripheral cells and cells of the central nervous system. Here, we formulated a hypothesis on the existence of two mechanisms/stages involved in the effect of psychoactive substances on sEVs: the \"fast\" mechanism that provides neuroplasticity, and the \"slow\" one, resulting from the impaired biogenesis of sEVs and formation of aberrant vesicles.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 11","pages":"1970-1984"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794278","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}
引用次数: 0
Role of MMP-2 and MMP-9 in the Relationship between Inflammation, Fibrosis, and Apoptosis during Progression of Non-Alcoholic Fatty Liver Disease and Diagnostic Significance of Plasma Levels of Their Active Forms. MMP-2和MMP-9在非酒精性脂肪性肝病进展过程中炎症、纤维化和凋亡关系中的作用及其血浆活性形式水平的诊断意义
IF 2.3 4区 生物学
Biochemistry (Moscow) Pub Date : 2024-11-01 DOI: 10.1134/S0006297924110130
Irina V Kurbatova, Lyudmila V Topchieva, Olga P Dudanova, Anastasia A Shipovskaya
{"title":"Role of MMP-2 and MMP-9 in the Relationship between Inflammation, Fibrosis, and Apoptosis during Progression of Non-Alcoholic Fatty Liver Disease and Diagnostic Significance of Plasma Levels of Their Active Forms.","authors":"Irina V Kurbatova, Lyudmila V Topchieva, Olga P Dudanova, Anastasia A Shipovskaya","doi":"10.1134/S0006297924110130","DOIUrl":"https://doi.org/10.1134/S0006297924110130","url":null,"abstract":"<p><p>MMP-2 and MMP-9 play an important role in pathogenesis of chronic liver diseases, participating in the processes of inflammation and fibrosis. Their role in progression of non-alcoholic fatty liver disease (NAFLD) is poorly understood. Analysis of MMP-2, -9 levels in the blood plasma of patients with different forms of NAFLD [liver steatosis (LS) and non-alcoholic steatohepatitis (NASH) of weak (-WA), moderate (MA), high (-HA) activity without pronounced fibrosis] was performed. Correlations between the levels of MMP-2, -9 and mRNA of the genes <i>MMP2</i>, <i>MMP9</i>, <i>ADAM17</i>, <i>NLRP3</i>, caspase 3 activity in peripheral blood leukocytes (PBL), TNFα, IL-6, sIL-6R, cytokeratin-18 fragments in plasma were assessed. In steatosis, the levels of <i>MMP2</i> gene mRNA in PBL and MMP-2 in plasma are lower than in the control, and expression of the <i>NLRP3</i> gene in PBL is increased relative to other groups. In the NASH-WA, the level of MMP-9 is higher than in the control, in LS, and in NASH-MA, which could be associated with activation of inflammation during transformation of LS into NASH. The plasma level of MMP-9 over 389.50 pg/ml has been shown to be diagnostically significant for identification of NASH-WA among the patients with steatosis (<i>AUC ROC</i> = 0.818, 95% CI = 0.689-0.948, <i>p</i> &lt; 0.001). In NAFLD, the level of MMP-9 could be associated not only with inflammation, but also with apoptosis. ADAM17 probably plays a certain role in this regard. In the advanced NASH, hepatocyte apoptosis is increased, the level of caspase 3 activity in PBL is increased, the level of MMP-9 in the blood is reduced to the level of the control and LS. In the NASH-HA, the level of mRNA of the <i>ADAM17</i> gene in PBL is increased compared to the control, NASH-WA, and NASH-MA. Thus, MMP-2 and MMP-9 are involved in pathogenesis of NAFLD already at the early stages and their level in blood could be associated with the presence and severity of inflammation in the liver parenchyma.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 11","pages":"1998-2022"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794286","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}
引用次数: 0
Study of Neuroinflammation in the Rat Hippocampus during Ethanol Exposure and Pharmacological Correction with Azithromycin: New Data and Future Perspectives. 乙醇暴露和阿奇霉素药物纠正大鼠海马神经炎症的研究:新数据和未来展望。
IF 2.3 4区 生物学
Biochemistry (Moscow) Pub Date : 2024-11-01 DOI: 10.1134/S0006297924110051
Marat I Airapetov, Sergei O Eresko, Sofiia A Shamaeva, Evgenii R Bychkov, Andrei A Lebedev, Petr D Shabanov
{"title":"Study of Neuroinflammation in the Rat Hippocampus during Ethanol Exposure and Pharmacological Correction with Azithromycin: New Data and Future Perspectives.","authors":"Marat I Airapetov, Sergei O Eresko, Sofiia A Shamaeva, Evgenii R Bychkov, Andrei A Lebedev, Petr D Shabanov","doi":"10.1134/S0006297924110051","DOIUrl":"https://doi.org/10.1134/S0006297924110051","url":null,"abstract":"<p><p>With prolonged ethanol ingestion, disturbances in the emotional spectrum develop, and memory problems are noted. These symptoms could be mediated by the development of neurochemical changes in the hippocampus of the brain. Although there is evidence that hippocampus is vulnerable to chronic alcohol intoxication and that neuroinflammation and neurodegeneration develop in this brain region, the key molecular mechanisms have not been identified. The aim of the study was to investigate changes in the immune system in the periphery as well as in the hippocampus of rat brain during ethanol exposure and during pharmacological correction with azithromycin (AZM). Long-term ethanol exposure was modeled by injecting rats with a 20% ethanol solution (4 g/kg) for 4 weeks. General biochemical and clinical blood analysis was performed in animals. Expression levels of the cytokine genes (<i>Il1β</i>, <i>Ccl2</i>, <i>Il6</i>, <i>Il11</i>, <i>Il13</i>, <i>Tnfα</i>, <i>Tgfβ</i>), Toll-like receptor system genes (<i>Tlr3</i>, <i>Tl4</i>, <i>Tlr7</i>, <i>Nfkb1</i>, <i>Hmgb1</i>), and TLR system-related microRNA molecules (miR-182, miR-155-5p, miR-96-5p, miR-let-7b) were evaluated in the hippocampus. IL-1β protein content was also assessed in the hippocampus. Prolonged exposure to alcohol caused increase in the mRNA and protein levels of IL-1β, and decrease in the mRNA levels of <i>Tnfα</i>, <i>Il11</i>, <i>Tlr3</i>, and <i>Tlr7</i>. The contents of miRlet7b, miR96, and miR155 were downregulated in the hippocampus after long-term alcohol exposure. Elevated levels of THE <i>Il1β</i> mRNA and protein and <i>Hmgb1</i> mRNA were maintained under conditions of ethanol abstinence. The <i>Tlr3</i> mRNA levels were decreased after abstinence. Administration of AZM reduced the IL1β, TLR3, and HMGB1 mRNA levels under conditions of ethanol abstinence; and at higher doses of the drug decrease in the IL-1β protein levels in the hippocampus of rat brain was observed. Thus, the study provided new insights into the mechanisms of neuroinflammation in the hippocampus during prolonged exposure to ethanol and upon abstinence. The obtained results allowed us to suggest a number of tasks for further studies in this direction.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"89 11","pages":"1911-1921"},"PeriodicalIF":2.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794287","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}
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