Doklady Biochemistry and Biophysics最新文献

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Detection of Tissue Macrophages in Different Organs Using Antibodies to the Microglial Marker Iba-1 用小胶质细胞标记物 Iba-1 的抗体检测不同器官中的组织巨噬细胞
IF 0.8 4区 生物学
Doklady Biochemistry and Biophysics Pub Date : 2024-09-16 DOI: 10.1134/S160767292470114X
V. V. Guselnikova, V. A. Razenkova, O. V. Kirik, I. A. Nikitina, V. S. Pavlova, S. I. Zharkina, D. E. Korzhevskii
{"title":"Detection of Tissue Macrophages in Different Organs Using Antibodies to the Microglial Marker Iba-1","authors":"V. V. Guselnikova,&nbsp;V. A. Razenkova,&nbsp;O. V. Kirik,&nbsp;I. A. Nikitina,&nbsp;V. S. Pavlova,&nbsp;S. I. Zharkina,&nbsp;D. E. Korzhevskii","doi":"10.1134/S160767292470114X","DOIUrl":"10.1134/S160767292470114X","url":null,"abstract":"<p>Resident macrophages of different organs have structural and functional features, which can complicate their identification and analysis. A promising candidate for the role of a universal immunohistochemical marker of resident macrophages is the calcium-binding protein Iba-1, a well-known marker of brain microglia. The purpose of this work was to study the possibility of using one variant of antibodies to the Iba-1 protein for the immunohistochemical detection of resident macrophages in the liver, myocardium, lung, and choroid plexus of the rat brain. The study was performed on male Wistar rats (<i>n</i> = 15). It was shown that the use of rabbit monoclonal antibodies against Iba-1 allows highly effective detection of Kupffer cells in the liver, resident macrophages in the myocardium, alveolar and interstitial macrophages in the lung, and Kolmer cells in the choroid plexus of the rat brain. In all cases, the reaction is characterized by a high specificity and the absence of background staining. In contrast to the classical marker of macrophages, the CD68 molecule, the Iba-1 protein is evenly distributed in the cytoplasm of cell bodies and processes. This makes it possible to more fully identify cells using immunostaining for Iba-1, carry out their three-dimensional reconstructions, and study their structural and functional organization. Immunohistochemical reaction against Iba-1 can be successfully used as a universal alternative to other common methods for identifying resident macrophages.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"519 1","pages":"506 - 511"},"PeriodicalIF":0.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256096","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
Effects of Intrahypothalamic Administration of microRNA Inhibitors and Mimetics on Blood Plasma Biomarkers in the Rat Aging 下丘脑内施用 microRNA 抑制剂和模拟物对大鼠血浆生物标志物的影响
IF 0.8 4区 生物学
Doklady Biochemistry and Biophysics Pub Date : 2024-09-16 DOI: 10.1134/S1607672924701138
P. M. Masliukov, V. V. Porseva, P. A. Anfimova, L. G. Pankrasheva, A. A. Baranov, N. Yu. Levshin, K. Yu. Moiseev
{"title":"Effects of Intrahypothalamic Administration of microRNA Inhibitors and Mimetics on Blood Plasma Biomarkers in the Rat Aging","authors":"P. M. Masliukov,&nbsp;V. V. Porseva,&nbsp;P. A. Anfimova,&nbsp;L. G. Pankrasheva,&nbsp;A. A. Baranov,&nbsp;N. Yu. Levshin,&nbsp;K. Yu. Moiseev","doi":"10.1134/S1607672924701138","DOIUrl":"10.1134/S1607672924701138","url":null,"abstract":"<p>The effect of let-7a-5p, miR-9a-3p, miR-132-3p, miR-218a-5p microRNA inhibitors and mimetics, when administered into the dorsomedial nucleus of the hypothalamus (DMN), on the markers of age-related changes in blood plasma in 3-month-old and 24-month-old male rats was studied. In the 24-month-old control rats, the content of C-reactive protein (CRP) increased, and the level of myoglobin decreased compared to the 3-month-old animals. After te administration of miRNA inhibitors, the level of CRP significantly increased, and the content of myoglobin decreased, and after the administration of miRNA mimetics, opposite changes were observed. We found no significant differences in the content of somatotropic hormone and testosterone between the control and experimental groups, as well as between the 3-month-old and 24-month-old animals.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"519 1","pages":"521 - 524"},"PeriodicalIF":0.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256100","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
Pharmacological Modulation of Cognitive Test Solution in Mice of Two Genotypes 药物调节两种基因型小鼠的认知测试方案
IF 0.8 4区 生物学
Doklady Biochemistry and Biophysics Pub Date : 2024-08-28 DOI: 10.1134/S1607672924701096
O. V. Perepelkina, I. I. Poletaeva
{"title":"Pharmacological Modulation of Cognitive Test Solution in Mice of Two Genotypes","authors":"O. V. Perepelkina,&nbsp;I. I. Poletaeva","doi":"10.1134/S1607672924701096","DOIUrl":"10.1134/S1607672924701096","url":null,"abstract":"<p>Mice of two strains selected for successful solution of “object permanence” test and for lack of such solution demonstrated the differential reaction to injections of two drugs. The effects of injections of atomoxetine. which blocks the noradrenaline reuptake, and of ‘non-benzodiazepine” anxiolytic afobazol was different. The success of solutions increased in mice selected for this test “non-solution”: and decreased or was inefficient in mice, selected for successful solution of object permanence cognitive test.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"518 1","pages":"417 - 419"},"PeriodicalIF":0.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078703","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
Preliminary Study on Polymerization between Hemoglobin and Enzymes during the Preparation of PolyHb-SOD-CAT-CA 制备 PolyHb-SOD-CAT-CA 过程中血红蛋白与酶之间聚合作用的初步研究
IF 0.8 4区 生物学
Doklady Biochemistry and Biophysics Pub Date : 2024-08-28 DOI: 10.1134/S1607672924600477
Lili Zhang, Renci Tian, Jiawei Xiao, Yaoxi Wang, Kun Feng, Gang Chen
{"title":"Preliminary Study on Polymerization between Hemoglobin and Enzymes during the Preparation of PolyHb-SOD-CAT-CA","authors":"Lili Zhang,&nbsp;Renci Tian,&nbsp;Jiawei Xiao,&nbsp;Yaoxi Wang,&nbsp;Kun Feng,&nbsp;Gang Chen","doi":"10.1134/S1607672924600477","DOIUrl":"10.1134/S1607672924600477","url":null,"abstract":"<p>The objective of this study was to explore the influence of different factors on the aggregation effect on hemoglobin (Hb) and enzymes during the preparation of Polyhemoglobin-Superoxide dismutase-Catalase-Carbonic anhydrase (PolyHb-SOD-CAT-CA). Several factors including temperatures, pH values, Glutaraldehyde (GDA) amounts and enzymes amounts were investigated systematically to study their effects on the enzymes recoveries and polymerization rates including the Superoxide dismutase (SOD), Catalase (CAT) and Carbonic anhydrase (CA), as well as their effects on the molecular weight distribution of PolyHb-SOD-CAT-CA. Then the oxygen affinity and methemoglobin (MetHb) contents of obtained PolyHb-SOD-CAT-CA were measured to evaluate the effects of enzyme crosslinking on the properties of Polyhemoglobin (PolyHb) moieties in the molecular structure of obtained PolyHb-SOD-CAT-CA conjugate. The results showed that the enzyme recoveries and polymerization rates could be decreased with the temperatures increasing and could be generally kept stable in the physiological pH conditions, but presented only slight changes among the investigated enzyme amounts ranges. Although the GDA concentration increasing could promote the enzyme polymerization rates, the enzyme recoveries decreased in whole. The polymerization rate and molecular size of PolyHb-SOD-CAT-CA conjugate increased with the elevation of temperature and the concentration of GDA. Lastly, the P50 values, Hill coefficients, and MetHb contents of PolyHb-SOD-CAT-CA conjugate with different enzyme crosslinking degrees exhibited no obvious differences with each other. In conclusion, the polymerization reactions between enzymes and Hb molecules could be remarkably affected by temperatures, pH values, and GDA amounts, and the enzyme crosslinking presented no obvious effects on the Hb properties, especially about the oxygen affinity and oxidation degrees.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"518 1","pages":"463 - 474"},"PeriodicalIF":0.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078704","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
Renal Protective Effect of Umbelliferone on Acute Kidney Injury in Rats via Alteration of HO-1/Nrf2 and NF-κB Signaling Pathway 伞形酮通过改变 HO-1/Nrf2 和 NF-κB 信号通路对大鼠急性肾损伤的肾保护作用
IF 0.8 4区 生物学
Doklady Biochemistry and Biophysics Pub Date : 2024-08-28 DOI: 10.1134/S160767292460043X
RuiJuan Yan, Hui Yang, XiaoQi Jiang, XiaoDong Lai
{"title":"Renal Protective Effect of Umbelliferone on Acute Kidney Injury in Rats via Alteration of HO-1/Nrf2 and NF-κB Signaling Pathway","authors":"RuiJuan Yan,&nbsp;Hui Yang,&nbsp;XiaoQi Jiang,&nbsp;XiaoDong Lai","doi":"10.1134/S160767292460043X","DOIUrl":"10.1134/S160767292460043X","url":null,"abstract":"<p>Acute kidney injury (AKI), formerly known as acute renal failure, refers to a sudden and often reversible decline in kidney function. Inflammatory reaction and oxidative stress play a crucial role in the expansion of renal disease. In this experimental study, we scrutinized the renal protective effect of umbelliferone against gentamicin induced renal injury in the rats and explore the mechanism. Wistar rats were used in this study and Gentamicin was used for the induction the AKI in the rats and rats were received the oral administration of umbelliferone. The body weight, organ weight, renal, oxidative stress, cytokines, inflammatory parameters were estimated. The mRNA expression caspase-3, Bax, Bcl-2, TNF-α, IL-1β, IL-6, IL-10, HO-1, and Nrf2 were estimated. Umbelliferone remarkably improved the body weight and altered the absolute and relative weight of hepatic and renal tissue. Umbelliferone significantly suppressed the level of BUN, Scr, magnesium, calcium, phosphorus, sodium, and potassium along with altered the level of oxidative stress parameters like CAT, SOD, GSH, LPO, and GPx. Umbelliferone altered the level of cytokines viz., TNF-α, Il-1β, IL-6, IL-10; inflammatory parameters like PGE2, COX-2, TGF-β, NF-κB, respectively. Umbelliferone significantly altered the mRNA expression of caspase-3, Bax, Bcl-2, TNF-α, IL-1β, IL-6, IL-10, HO-1, and Nrf2. The result showed the renal protective effect of umbelliferone against gentamycin induced renal disease via alteration of HO-1/Nrf2 and NF-κB Signaling Pathway.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"518 1","pages":"442 - 451"},"PeriodicalIF":0.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078762","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
Long-term GABA Supplementation Regulates Diabetic Gastroenteropathy through GABA Receptor/trypsin-1/PARs/Akt/COX-2 Axis 长期补充 GABA 可通过 GABA 受体/胰蛋白酶-1/PARs/Akt/COX-2 轴调节糖尿病胃肠病。
IF 0.8 4区 生物学
Doklady Biochemistry and Biophysics Pub Date : 2024-08-28 DOI: 10.1134/S1607672924600386
Farzaneh Yazdanimoghaddam, Hossein Rezazadeh, Nepton Soltani, Nasrin Mehranfard, Azadesadat Hosseini Dastgerdi, Mahtab Ghanbari Rad, Maedeh Ghasemi
{"title":"Long-term GABA Supplementation Regulates Diabetic Gastroenteropathy through GABA Receptor/trypsin-1/PARs/Akt/COX-2 Axis","authors":"Farzaneh Yazdanimoghaddam,&nbsp;Hossein Rezazadeh,&nbsp;Nepton Soltani,&nbsp;Nasrin Mehranfard,&nbsp;Azadesadat Hosseini Dastgerdi,&nbsp;Mahtab Ghanbari Rad,&nbsp;Maedeh Ghasemi","doi":"10.1134/S1607672924600386","DOIUrl":"10.1134/S1607672924600386","url":null,"abstract":"<p><b>Aim.</b> Molecular alterations of diabetic gastroenteropathy are poorly identified. This study investigates the effects of prolonged GABA supplementation on key protein expression levels of trypsin-1, PAR-1, PAR-2, PAR-3, PI3K, Akt, COX-2, GABAA, and GABAB receptors in the gastric tissue of type 2 diabetic rats (T2DM).</p><p>To induce T2DM, a 3-month high-fat diet and 35 mg/kg of streptozotocin was used. Twenty-four male Wistar rats were divided into 4 groups: (1) control, (2) T2DM, (3) insulin-treated (2.5 U/kg), and (4) GABA-treated (1.5 g/kg GABA). Blood glucose was measured weekly. The protein expressions were assessed using western blotting. Histopathological changes were examined by H&amp;E and Masson’s staining.</p><p>Diabetic rats show reduced NOS1 and elevated COX-2 and trypsin-1 protein expression levels in gastric tissue. Insulin and GABA therapy restored the NOS1 and COX-2 levels to control values. Insulin treatment increased PI3K, Akt, and p-Akt and, decreased trypsin-1, PAR-1, PAR-2, and PAR-3 levels in the diabetic rats. Levels of GABAA and GABAB receptors normalized following insulin and GABA therapy. H&amp;E staining indicated an increase in mucin secretion following GABA treatment.</p><p>These results suggest that GABA by acting on GABA receptors may regulate the trypsin-1/PARs/Akt/COX-2 pathway and thereby improve complications of diabetic gastroenteropathy.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"518 1","pages":"452 - 462"},"PeriodicalIF":0.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078702","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
Astilbin Induces Apoptosis in Oral Squamous Cell Carcinoma through p53 Reactivation and Mdm-2 Inhibition 阿斯替滨通过 p53 重激活和 Mdm-2 抑制诱导口腔鳞状细胞癌细胞凋亡
IF 0.8 4区 生物学
Doklady Biochemistry and Biophysics Pub Date : 2024-08-28 DOI: 10.1134/S1607672924600374
Aimin Wu, Chungang Zhao
{"title":"Astilbin Induces Apoptosis in Oral Squamous Cell Carcinoma through p53 Reactivation and Mdm-2 Inhibition","authors":"Aimin Wu,&nbsp;Chungang Zhao","doi":"10.1134/S1607672924600374","DOIUrl":"10.1134/S1607672924600374","url":null,"abstract":"<p>Oral squamous cell carcinoma (OSCC) is a frequently occurring malignancy in the head and neck region. The most commonly mutated gene in OSCC is the tumor suppressor gene p53 (TP53), linked to lower survival and treatment resistance in OSCC patients. Astilbin is a flavonoid amongst several herbal treatments with a variety of pharmacological actions mainly including antioxidant, anti-inflammatory, and anti-cancer characteristics. This study evaluated the effects of astilbin on proliferation of OSCC cell lines SCC90 and SCC4 (bearing a p53 mutation) in relevance to p53 and Mdm-2 pathways. Astilbin inhibited the proliferation of SCC4 and SCC90 cells in a dose- and time-dependent manner. The IC50 values for both the cell lines were about 75 μM for astilbin. A p53 activator (RITA) was used to determine the effects of astilbin on p53 activity, and the results demonstrated synergistic reduction in cell growth. However, when combined with pifithrin-α (a p53 inhibitor), astilbin demonstrated a strong inhibition of its response. Astilbin reduced the mitochondrial membrane potential in SCC4 cells, which is a sign of apoptotic activity. Astilbin decreased the amounts of Mdm-2 (negative regulator of p53) and increased the expression of the p53 gene and protein. In a p53-dependent manner, astilbin suppressed the ability of SCC4 cells to form colonies and heal wounds. This was followed by the induction of mitochondrial intrinsic apoptosis via the activation of caspases 9 and 3, cleavage of PARP, and the suppression of pro-apoptotic Bid. Astilbin-induced p53-mediated apoptosis in OSCC cells as herbal medicinal ingredients.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"518 1","pages":"429 - 441"},"PeriodicalIF":0.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078698","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
Efficacy and Safety of Levilimab in Combination with Methotrexate in Patients with Active Rheumatoid Arthritis: 56-Week Results of Phase III Randomized Double-Blind Placebo-Controlled Trial SOLAR 利维利单抗与甲氨蝶呤联用对活动性类风湿性关节炎患者的疗效和安全性:SOLAR.III 期随机双盲安慰剂对照试验 56 周的结果
IF 0.8 4区 生物学
Doklady Biochemistry and Biophysics Pub Date : 2024-08-28 DOI: 10.1134/S1607672924701072
V. I. Mazurov,  E. L. Nasonov, A. M. Lila, M. A. Korolev, A. M. Prystrom, E. V. Kundzer, N. F. Soroka, A. A. Kastanayan, T. V. Povarova, T. V. Plaksina, O. V. Antipova, D. G. Krechikova, S. A. Smakotina, O. A. Tciupa, E. V. Puntus, T. A. Raskina, L. N. Shilova, T. V. Kropotina, O. B. Nesmeyanova, T. A. Popova, I. B. Vinogradova, E. A. Dokukina, A. V. Plotnikova, P. S. Pukhtinskaia, A. V. Zinkina-Orikhan, Yu. N. Linkova, A. V. Eremeeva, A. A. Lutckii
{"title":"Efficacy and Safety of Levilimab in Combination with Methotrexate in Patients with Active Rheumatoid Arthritis: 56-Week Results of Phase III Randomized Double-Blind Placebo-Controlled Trial SOLAR","authors":"V. I. Mazurov,&nbsp; E. L. Nasonov,&nbsp;A. M. Lila,&nbsp;M. A. Korolev,&nbsp;A. M. Prystrom,&nbsp;E. V. Kundzer,&nbsp;N. F. Soroka,&nbsp;A. A. Kastanayan,&nbsp;T. V. Povarova,&nbsp;T. V. Plaksina,&nbsp;O. V. Antipova,&nbsp;D. G. Krechikova,&nbsp;S. A. Smakotina,&nbsp;O. A. Tciupa,&nbsp;E. V. Puntus,&nbsp;T. A. Raskina,&nbsp;L. N. Shilova,&nbsp;T. V. Kropotina,&nbsp;O. B. Nesmeyanova,&nbsp;T. A. Popova,&nbsp;I. B. Vinogradova,&nbsp;E. A. Dokukina,&nbsp;A. V. Plotnikova,&nbsp;P. S. Pukhtinskaia,&nbsp;A. V. Zinkina-Orikhan,&nbsp;Yu. N. Linkova,&nbsp;A. V. Eremeeva,&nbsp;A. A. Lutckii","doi":"10.1134/S1607672924701072","DOIUrl":"10.1134/S1607672924701072","url":null,"abstract":"&lt;p&gt;&lt;b&gt;.&lt;/b&gt; Previously, 24-week results of phase III double-blind, placebo-controlled randomized clinical study (SOLAR) of levilimab in subjects with active rheumatoid arthritis (RA) proved a superiority of levilimab over placebo. Here, we present 1-year efficacy and safety data of the SOLAR study.&lt;/p&gt;&lt;p&gt;&lt;b&gt;.&lt;/b&gt; To evaluate the efficacy and safety of levilimab in combination with methotrexate (MTX) in subjects with MTX resistant active RA.&lt;/p&gt;&lt;p&gt;The study was conducted at 21 clinical sites in Russia and Belarus. All randomized subjects have completed the study between November 2019 and October 2021. Adult subjects (154) aged ≥18 years with confirmed diagnosis of RA&lt;sup&gt;1&lt;/sup&gt; were randomly assigned (2 : 1) to receive either levilimab (162 mg, SC, QW) + MTX (&lt;i&gt;n&lt;/i&gt; = 102) or placebo + MTX (&lt;i&gt;n&lt;/i&gt; = 52). After W24 of the study all subjects continued to  receive open label levilimab. Subjects who have achieved DAS28-CRP ≤ 2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab at W28 (LVL QW/Q2W and PBO/LVL Q2W arms). Those with DAS28-CRP &gt; 2.6 at W28 continued with QW regimen (LVL QW and PBO/LVL QW arm). The PBO/LVL Q2W arm contained only one subject, thus not included in the analysis.&lt;/p&gt;&lt;p&gt;The efficacy analysis was performed in a population of all randomized subjects. Those with missing data due to study discontinuation or rescue therapy prescription were considered non-responders. Otherwise, the analysis was performed on complete cases. Safety was assessed through monitoring of adverse events (AEs) in a population of those, who received at least on dose of LVL (&lt;i&gt;n&lt;/i&gt; = 152).&lt;/p&gt;&lt;p&gt;Better response to treatment was observed in LVL QW/Q2W as it composed of those who reach DAS28-CRP ≤ 2.6 at W24. At this time point 15/27 (55.6%) of them achieved ACR70; 23/27 (85.2%) achieved DAS28-CRP remission (&lt;2.6) and 7/27 (25.9%) achieved ACR/EULAR2011 remission of RA. After switching to LVL Q2W, rates of ACR70 and DAS28-CRP&lt;2.6 did not significantly changed until W52: 17/27 (63.0%) and 21/27 (77.8%), respectively, yet the proportion of subject with ACR/EULAR 2011 remission further increased and reached 12/27 (44.4%). LVL QW arm was diminished by subjects who achieved high response to treatment at W24 and composed LVL QW/Q2W arm. Thus, ACR70, and remissions rate in this arm was close to zero at W24. However, continuation of LVL QW in those who not achieved DAS28-CRP ≤ 2.6 at W24 induced ACR70 response in 37/75 (36.0%), DAS28-CRP remission in 35/75 (46.7%) and ACR/EULAR 2011 remission in 8/75 (10.7%) at W52. The most common adverse events (reported in ≥5% of subjects) were blood cholesterol increase (30.3%), ALT increase (23.0%), lymphocyte count decrease (17.1%), ANC decrease (16.4%), blood triglycerides increase (13.8%), bilirubin increase (11.2%), AST increase (9.9%), WBC decrease (9.9%), IGRA with &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt; antigen positive (7.2%), and injection site reactions (5.9%). No deaths occurred.&lt;/p&gt;&lt;p&gt;Open label p","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"518 1","pages":"403 - 416"},"PeriodicalIF":0.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078700","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
Error-Prone DNA Synthesis on Click-Ligated Templates 点击连接模板上的无差错 DNA 合成。
IF 0.8 4区 生物学
Doklady Biochemistry and Biophysics Pub Date : 2024-08-28 DOI: 10.1134/S1607672924600416
A. V. Endutkin, A. O. Yakovlev, T. D. Zharkov, V. M. Golyshev, A. V. Yudkina,  D. O. Zharkov
{"title":"Error-Prone DNA Synthesis on Click-Ligated Templates","authors":"A. V. Endutkin,&nbsp;A. O. Yakovlev,&nbsp;T. D. Zharkov,&nbsp;V. M. Golyshev,&nbsp;A. V. Yudkina,&nbsp; D. O. Zharkov","doi":"10.1134/S1607672924600416","DOIUrl":"10.1134/S1607672924600416","url":null,"abstract":"<p>Click ligation is a technology of joining DNA fragments based on azide–alkyne cycloaddition. In the most common variant, click ligation introduces a 4-methyl-1,2,3-triazole (trz) group instead of the phosphodiester bond between two adjacent nucleosides. While this linkage is believed to be biocompatible, little is known about the possibility of its recognition by DNA repair systems or its potential for DNA polymerase stalling and miscoding. Here we report that trz linkage is resistant to several human and bacterial endonucleases involved in DNA repair. At the same time, it strongly blocks some DNA polymerases (Pfu, DNA polymerase β) while allowing bypass by others (phage RB69 polymerase, Klenow fragment). All polymerases, except for DNA polymerase β, showed high frequency of misinsertion at the trz site, incorporating dAMP instead of the next complementary nucleotide. Thus, click ligation can be expected to produce a large amount of errors if used in custom gene synthesis.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"518 1","pages":"376 - 381"},"PeriodicalIF":0.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078701","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
Xmas-2 Protein, the Core Protein of the TREX-2 mRNA Export Complex, Does not Determine the Specificity of ras2 mRNA Binding by the Complex TREX-2 mRNA导出复合体的核心蛋白 Xmas-2 蛋白并不决定该复合体与 ras2 mRNA 结合的特异性。
IF 0.8 4区 生物学
Doklady Biochemistry and Biophysics Pub Date : 2024-08-28 DOI: 10.1134/S1607672924600519
M. M. Kurshakova, Y. A. Vdovina,  S. G. Georgieva, D. V. Kopytova
{"title":"Xmas-2 Protein, the Core Protein of the TREX-2 mRNA Export Complex, Does not Determine the Specificity of ras2 mRNA Binding by the Complex","authors":"M. M. Kurshakova,&nbsp;Y. A. Vdovina,&nbsp; S. G. Georgieva,&nbsp;D. V. Kopytova","doi":"10.1134/S1607672924600519","DOIUrl":"10.1134/S1607672924600519","url":null,"abstract":"<p>The TREX-2 complex of eukaryotes is responsible for the export of a wide range of mRNAs from the nucleus to the cytoplasm. Previously, we showed that a subunit of the <i>D. melanogaster</i> TREX-2 complex, the PCID2 protein, has a domain that specifically interacts with RNA. However, it remains unknown whether other components of the complex are involved in interaction with and recognition of the target mRNA. In the present study, we determined the role of Xmas-2, the core structural subunit of the complex, in the specific recognition of <i>ras2</i> mRNA fragments. In this work, we showed that Xmas-2 interacts with <i>ras2</i> mRNA independently of other subunits of the complex. We showed that RNA-binding domains are located in both the N-terminal domain and the C-terminal domain of Xmas-2. However, the interaction of the protein with <i>ras2</i> mRNA fragments is independent of RNA sequence and structure and is nonspecific. Thus, the Xmas-2 subunit is not involved in the recognition of specific RNA sequences by the complex.</p>","PeriodicalId":529,"journal":{"name":"Doklady Biochemistry and Biophysics","volume":"518 1","pages":"398 - 402"},"PeriodicalIF":0.8,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078763","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
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