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Nobel prize winner Erwin Schrodinger: the physicist, philosopher, and godfather of molecular biology and genetics 诺贝尔奖得主埃尔温·薛定谔:物理学家、哲学家、分子生物学和遗传学教父
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-08-13 DOI: 10.15407/ubj92.03.093
T. Danylova
The brilliant book “What is life? The Physical aspect of the living Cell” authored by the prominent Nobel Prize-winning austrian physicist erwin Schrödinger became a successful attempt to bridge the gap between physics and biology. The philosophical thought of one of the founders of quantum mechanics inspired him to look closer at the enigma of life through the lens of quantum physics. a prominent physicist was focused on the thermodynamics of the living organisms and the nature of heredity. Schrödinger introduced the concept and notion of “negative entropy”, suggested the idea of a genetic code and argued that the genetic material had to have a non-repetitive molecular structure. He considered a molecule as a solid – aperiodic crystal that forms the hereditary substance. Despite the fact that his book provoked different interpretations and his ideas were modified by later scientific development, it was Schrödinger who paved the way for the future research of genes: his book inspired the next generation of scientists to look for a secret life code, which was eventually found. His outstanding writing is still one of the most profound introductions into the subject and raises new questions. Schrödinger’s genius reshapes our view on the nature and essence of life creating a launching pad for the new transdisciplinary paradigm, which can contribute to the development of a unified theory of everything in the spirit of Schrödinger’s philosophy.
《生命是什么?》杰出的诺贝尔奖得主奥地利物理学家erwin Schrödinger所著的《活细胞的物理方面》一书成功地弥合了物理学与生物学之间的鸿沟。量子力学创始人之一的哲学思想启发他通过量子物理学的镜头更近距离地观察生命之谜。一位杰出的物理学家专注于生物体的热力学和遗传的本质。Schrödinger介绍了“负熵”的概念和概念,提出了遗传密码的想法,并认为遗传物质必须具有非重复的分子结构。他认为分子是形成遗传物质的固体非周期晶体。尽管他的书引发了不同的解释,他的想法也被后来的科学发展所修改,但为未来基因研究铺平了道路的是Schrödinger:他的书激励了下一代科学家寻找秘密的生命密码,最终被发现了。他的杰出作品仍然是对这一主题最深刻的介绍之一,并提出了新的问题。Schrödinger的天才重塑了我们对生命本质和本质的看法,为新的跨学科范式创造了一个发射台,这可以促进Schrödinger哲学精神中万物统一理论的发展。
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引用次数: 6
The human genome sequencing race ended 20 years ago 人类基因组测序竞赛在20年前就结束了
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-08-13 DOI: 10.15407/ubj92.03.091
M. Grigorieva, S. Komisarenko
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引用次数: 1
Men of the molecules 分子中的人
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-08-13 DOI: 10.15407/ubj92.03.086
V. Chernyshenko
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引用次数: 0
D-dimer as a potential predictor of thromboembolic and cardiovascular complications in patients with chronic kidney disease d -二聚体作为慢性肾病患者血栓栓塞和心血管并发症的潜在预测因子
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-08-13 DOI: 10.15407/ubj92.03.071
I. Mykhaloiko, Dudar Io, I. Mykhaloiko, O. J. Mykhaloiko
The aim of the study was to evaluate the relationship between D-dimer levels and different biomarkers of renal diseases to identify the relationship between hypercoagulation and chronic kidney disease (CkD). To achieve this aim, we conducted a one-step prospective observational study involving 140 patients with CkD who were hospitali zed in Ivano-Frankivsk regional Clinical hospital in Ukraine during 2018-2019. of these patients, 100 patients (71.4%; 95% CI 53.4-76.7) had glomerulonephritis (GN) and 40 patients (28,6%; 95% CI 21.3-36.8) had diabetic nephropathy (DN). all patients underwent standard examination, which included general clinical, biochemical and instrumental research methods. D-dimer was quantitatively determined in blood serum by enzyme-linked immunosorbent assay (ElISa). The 140 patients were divided into two groups according to the level of D-dimers: normal level (<0.5 mg/l) and elevated level (≥0.5 mg/l). Elevated D-dimer levels were associated with an increased age of patients, decreased glomerular filtration rate, decreased blood albumin level, increased daily protein excretion and a tendency to develop thromboembolic complications during 1 year of monitoring. D-dimer is a biological marker that can detect hypercoagulation at an early preclinical stage in patients with CkD and identify patients with an increased cardiovascular risk, thereby promoting the earliest use of antiplatelet agents and anticoagulants and, consequently, it can reduce mortality .
该研究的目的是评估d -二聚体水平与肾脏疾病的不同生物标志物之间的关系,以确定高凝与慢性肾脏疾病(CkD)之间的关系。为了实现这一目标,我们开展了一项为期一步的前瞻性观察性研究,纳入了2018-2019年在乌克兰伊万诺-弗兰科夫斯克地区临床医院住院的140例CkD患者。其中100例(71.4%);95% CI 53.4-76.7)有肾小球肾炎(GN), 40例(28.6%;95% CI 21.3 ~ 36.8)为糖尿病肾病(DN)。所有患者均接受标准检查,包括一般临床、生化和仪器研究方法。采用酶联免疫吸附法(ElISa)定量测定血清中d -二聚体的含量。140例患者根据d -二聚体水平分为正常组(<0.5 mg/l)和升高组(≥0.5 mg/l)。d -二聚体水平升高与患者年龄增加、肾小球滤过率降低、血白蛋白水平降低、每日蛋白质排泄增加以及在1年监测期间发生血栓栓塞并发症的倾向有关。d -二聚体是一种生物标志物,可以在CkD患者的早期临床前阶段检测到高凝,并识别心血管风险增加的患者,从而促进抗血小板药物和抗凝剂的早期使用,从而降低死亡率。
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引用次数: 1
The fibrin B?125-135 site is involved in the lateral association of protofibrils 纤维蛋白B?125-135位点参与原纤维的横向结合
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-08-13 DOI: 10.15407/ubj92.03.033
E. Lugovskoi, N. Pydiura, Y. Makogonenko, L. Urvant, P. Gritsenko, Kolesnikova In, N. Lugovska, S. Komisarenko
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引用次数: 3
Identification of the binding site for plasminogen kringle 5 in the ?-chain of fibrin(ogen) D-fragment 纤维蛋白(原)d片段?-链中纤溶酶原kringle 5结合位点的鉴定
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-08-13 DOI: 10.15407/ubj92.03.046
L. G. Kapustianenko, T. Grinenko, A. Rebriev, O. Yusova, A. Tykhomyrov
The interaction of the fifth kringle of Glu-plasminogen with fibrin triggers activation and initiation of fibrinolysis, yet the site on fibrin that binds kringle 5 remains unknown. The aim of our work was to determine an amino acid sequence in the D-fragment of fibrin(ogen) molecule, which is complementary to the lysine-binding site (LBS) in kringle 5. We studied the interaction between kringle 5 of plasminogen with polypeptide chains of the D-fragments of fibrin and cyanogen bromide fragments FCB-2 and t-NDSK and showed that kringle 5 bound specifically to αand γ-chains of the D-fragment and the α-chain of FCB-2. Tryptic peptides of D-fragment α-chain were obtained, separated by their ability to bind with the immobilized kringle 5, and then all studied peptides were characterized by MALDI-TOF analysis. The critical amino acid residues of the α-chain of D-fragment, which provide its interaction with kringle 5, turned out to be α171Arg and/or α176Lys. The binding site of Glu-plasminogen complementary to the LBS of kringle 5 is located within Аα168Ala−183Lys, a sequence in a weakly structured loop between two supercoils in the α-chain of the Dfragment of the fibrin(ogen) molecule.
葡萄糖-纤溶酶原第5个kringle与纤维蛋白的相互作用触发了纤维蛋白溶解的激活和开始,但纤维蛋白上与kringle 5结合的位点尚不清楚。我们的工作目的是确定纤维蛋白(原)分子d片段的氨基酸序列,该序列与kringle 5中赖氨酸结合位点(LBS)互补。我们研究了纤溶酶原kringle 5与纤维蛋白d片段多肽链和溴化氰片段FCB-2和t-NDSK的相互作用,发现kringle 5特异性结合d片段α和γ链和FCB-2 α-链。获得d片段α-链的色氨酸肽,通过其与固定kringle 5的结合能力进行分离,然后用MALDI-TOF分析对所研究的肽进行表征。d片段α-链上与kringle 5相互作用的关键氨基酸残基为α171Arg和/或α176Lys。与kringle 5的LBS互补的glu -纤溶酶原的结合位点位于Аα168Ala−183Lys内,这是纤维蛋白(原)分子d片段α-链两个超线圈之间的弱结构环中的一个序列。
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引用次数: 0
Novel monoclonal antibody to fibrin(ogen) ?C-region for detection of the earliest forms of soluble fibrin 新型抗纤维蛋白单克隆抗体?检测最早形式可溶性纤维蛋白的C区
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-08-13 DOI: 10.15407/ubj92.03.058
N. Lugovska, Kolesnikova Im, Y. Stohnii, V. Chernyshenko, A. Rebriev, O. Kostiuchenko, G. K. Gogolinska, N. A. Dziubliuk, L. Varbanets, T. Platonova, S. Komisarenko
Obtaining new monoclonal antibodies (mAbs) towards fibrin(ogen) and its fragments is an important task for studying mechanisms of blood clot formation, searching for novel antithrombotic agents and developing immunodiagnostics. The aim of the present work was to create and characterize a new mAb towards the fibrin(ogen) αС-region. We surmise that having a specific mAb towards this flexible part of the molecule will allow us to study the role of the αС-region in fibrin polymerization and also to develop an approach for detecting the earliest forms of soluble fibrin by sandwich ELISA. Using hybridoma technology we оbtained mAb 1-5A to the αC-region of fibrinogen.. It was characterized using several variations of ELISA and Western blot. Application of specific proteases together with MALDI-TOF analysis allowed us to localize its epitope that is located in fragment 537-595 of the Aα-chain of fibrin(ogen). МAb 1-5A can be used as a detecting tag-antibody in sandwich ELISA for the quantification of the earliest forms of soluble fibrin which are uncleaved by plasmin and preserved C-terminal portions of αC-regions. These earliest forms of soluble fibrin are direct evidence of blood coagulation system activation, thrombin generation and the danger of intravascular thrombus formation. Their determination will provide additional, more accurate information about the state of the blood coagulation system and the risk of blood clotting, which is very important for the timely and correct selection of adequate antithrombotic therapy. MAb 1-5A effectively binds the αC-containing molecules of fibrinogen and fibrin in blood plasma. It also can be used for studying protein-protein and protein-cellular interactions of the αC-regions of fibrin(ogen).
获得针对纤维蛋白(原)及其片段的单克隆抗体(mab)是研究血凝块形成机制、寻找新的抗血栓药物和发展免疫诊断的重要任务。目前工作的目的是创建和表征一种新的单克隆抗体针对纤维蛋白(原)αС-region。我们推测,拥有针对分子这一柔性部分的特异性单抗,将使我们能够研究αС-region在纤维蛋白聚合中的作用,并开发一种通过夹心ELISA检测可溶性纤维蛋白最早形式的方法。利用杂交瘤技术,我们在纤维蛋白原α c区获得了mAb 1-5A。采用多种ELISA和Western blot方法对其进行了表征。应用特异性蛋白酶结合MALDI-TOF分析,我们确定了其表位位于纤维蛋白(原)a α-链的537-595片段。МAb 1-5A可作为夹心ELISA的检测标记抗体,用于定量最早形式的未被纤溶酶切割的可溶性纤维蛋白和α c区保存的c端部分。这些最早形式的可溶性纤维蛋白是凝血系统激活、凝血酶生成和血管内血栓形成危险的直接证据。它们的测定将提供关于凝血系统状态和凝血风险的额外、更准确的信息,这对于及时、正确地选择适当的抗血栓治疗非常重要。MAb 1-5A能有效结合血浆中含α c的纤维蛋白原和纤维蛋白分子。它也可用于研究纤维蛋白(原)α c区蛋白-蛋白和蛋白-细胞相互作用。
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引用次数: 1
Structure and function of fibrinogen BβN-domains. 纤维蛋白原B的结构和功能?N-结构域
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-05-01 DOI: 10.15407/ubj92.03.022
Leonid Medved, Sergiy Yakovlev

Two BβN-domains of fibrinogen are formed by the N-terminal portions of its two Bβ chains including amino acid residues Bβ1-65. Although their folding status is not well understood and the recombinant disulfide-linked (Bβ1-66)2 fragment corresponding to a pair of these domains was found to be unfolded, some data suggest that these domains may be folded in the parent molecule. In contrast, their major functional properties are well established. Removal of fibrinopeptides B (amino acid residues Bβ1-14) from these domains upon fibrinogen to fibrin conversion results in the exposure of multiple binding sites in fibrin βN-domains (residues β15-65). These sites provide interactions of the βN-domains with different proteins and cells and their participation in various physiological and pathological processes including fibrin assembly, fibrin-dependent angiogenesis, and fibrin-dependent leukocyte transmigration and thereby inflammation. The major goal of the present review is to summarize current view on the structure and function of these domains in fibrinogen and fibrin and their role in the above-mentioned processes.

纤维蛋白原是一种多功能血浆蛋白,通过其多个结构域与不同配体和细胞受体的相互作用,参与各种生理和病理过程。在纤维蛋白原结构域中,两个BβN-结构域由其两个B?链的N-末端部分形成,包括氨基酸残基B?1-64。尽管它们的折叠状态尚不清楚,并且发现与一对这些结构域相对应的重组二硫键合(Bβ1-66)2片段是未折叠的,但一些数据表明,这些结构域可能在母体分子中折叠。相比之下,它们的主要功能特性已经得到了很好的证实。纤维蛋白原转化为纤维蛋白时,从这些结构域中去除纤维蛋白肽B(氨基酸残基Bβ1-14)会导致纤维蛋白βN-结构域(残基β15-64)中的多个结合位点暴露。这些位点提供βN-结构域与不同蛋白质和细胞的相互作用,并参与各种过程,包括纤维蛋白组装、纤维蛋白依赖性血管生成和纤维蛋白依赖的白细胞迁移,从而引发炎症。这篇综述的目的是总结目前对纤维蛋白原和纤维蛋白中这些结构域的结构和功能及其在上述过程中的作用的看法。
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引用次数: 4
Exogenous hydrogen sulfide for the treatment of mesenteric damage associated with fructose-induced malfunctions via inhibition of oxidative stress 外源性硫化氢通过抑制氧化应激治疗与果糖诱导的功能障碍相关的肠系膜损伤
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-04-25 DOI: 10.15407/ubj92.02.086
O. Revenko
Remodeling of adipocytes in mesentery (aM) associated with nutritional overload from high fructose diet (hFD) is a source of several comorbidities. however, its pathogenesis is still unclear and there are no specific effective drugs for AM remodeling. Recently hydrogen sulfide (H2S) demonstrated potent cytoprotective actions. The purpose of this study was to investigate the effects and underlying mechanisms of AM remodeling in rats fed hFD and with h2S pre-treatment. adult male rats on standard diet (SD, control group) or hFD that underwent acute water-immersion restraint stress (WIS) were evaluated for subcellular aM adaptive responses by electron microscopy. The effects on AM of exogenous sodium hydrosulfide (NaHS, 5.6 mg/ kg/day for 9 days) and the Н2S-releasing aspirin (aSa) derivative (h2S-ASA [ATB-340], 17.5 mg/kg/day) vs conventional ASA (10 mg/kg/day) vs vehicle were investigated. Serum glucose level, thiobarbituric acid reactive substances (TBARS), and activities of cystathionine γ-lyase (CSE) and cystathionine β-synthase (CBS) were examined biochemically using spectrophotometry. In the HFD groups, treatment with NaHS protected aM, as mesenteric microvascular endothelial and sub-endothelial structures were observed vs the vehicletreated group that had signs of endothelial dysfunction, aM damage and dysfunctional mitochondria. The effect of H2S-aSa was characterized by protection of aM against hFD and WIS-induced injury, with lower TBARS blood level and increased CSE and CBS activities. Carbohydrate overload for 4 weeks is sufficient to cause AM oxidative damage, mitochondrial dysfunction and endothelial changes. H2S plays an important role in mesenteric adipocyte cellular survival against HFD-induced oxidative stress by decreasing overproduction of TBaRS and mitochondrial dysfunction. The use of h2S could lead to a novel approach for anti-obesity treatment.
与高果糖饮食(hFD)营养超负荷相关的肠系膜脂肪细胞重塑是几种合并症的来源。然而,其发病机制尚不清楚,也没有治疗AM重塑的特效药。最近,硫化氢(H2S)显示出强大的细胞保护作用。本研究的目的是研究喂食hFD和h2S预处理的大鼠AM重塑的影响和潜在机制。通过电子显微镜评估接受标准饮食(SD,对照组)或hFD的成年雄性大鼠的亚细胞aM适应性反应。研究了外源性亚硫酸氢钠(NaHS,5.6 mg/kg/天,持续9天)和释放Н2S的阿司匹林(aSa)衍生物(h2S aSa[ATB-340],17.5 mg/kg/天)与常规aSa(10 mg/kg/天和赋形剂)对AM的影响。采用分光光度法对血糖水平、硫代巴比妥酸反应物质(TBARS)、胱硫醚γ-裂解酶(CSE)和胱硫醚β-合酶(CBS)活性进行了生化检测。在HFD组中,NaHS治疗可保护aM,因为与有内皮功能障碍、aM损伤和线粒体功能障碍迹象的载体治疗组相比,观察到肠系膜微血管内皮和亚内皮结构。H2S-aSa的作用的特征是aM对hFD和WIS诱导的损伤的保护,具有较低的TBARS血液水平和增加的CSE和CBS活性。碳水化合物超负荷4周足以引起AM氧化损伤、线粒体功能障碍和内皮细胞变化。H2S通过减少TBaRS的过度产生和线粒体功能障碍,在肠系膜脂肪细胞抵抗HFD诱导的氧化应激的存活中发挥重要作用。硫化氢的使用可能会带来一种新的抗肥胖治疗方法。
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引用次数: 2
Development of effective anti-inflammatory drug candidates among novel thiazolopyridines 新型噻唑吡啶类有效抗炎候选药物的研制
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2020-04-17 DOI: 10.15407/ubj92.02.132
T. Chaban, V. Matiychuk, V. Ogurtsov, I. Chaban, I. Nektegayev
In an effort to develop novel anti-inflammatory agents, a series of thiazolo[4,5-b]pyridines were synthesized and modified at the N3 position. The structures of the obtained compounds were confirmed by 1h NMr spectroscopy and elemental analysis. The synthesized substances were preselected via molecular docking to be tested for their anti-inflammatory activity in vitro. Evaluation of compounds using the carrageenaninduced rat paw edema method showed strong anti-inflammatory action of some compounds (1, 2, 8) which exceeded that of ibuprofen.
为了开发新的抗炎剂,合成了一系列噻唑并[4,5-b]吡啶,并在N3位进行了修饰。通过1h-NMr光谱和元素分析证实了所得化合物的结构。通过分子对接预先选择合成的物质,以在体外测试其抗炎活性。使用卡拉胶诱导的大鼠爪水肿法对化合物进行评估显示,一些化合物(1,2,8)具有强的抗炎作用,其超过布洛芬。
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引用次数: 7
期刊
Ukrainian Biochemical Journal
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