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Emerging Marine Immunomodulatory Small-molecules (2010- Present) 新兴的海洋免疫调节小分子(2010年至今)
Pub Date : 2019-11-30 DOI: 10.2174/2212796813666190716102614
Ran Li, Yucheng Gu, Wen Zhang
Immunomodulation-based therapy has achieved a breakthrough inthe last decade, which stimulates the passion of searching for potential immunomodulatorysubstances in recent years.Marine natural products are a unique source of immunomodulatory substances.This paper summarized the emerging marine natural small-molecules and related synthesizedderivatives with immunomodulatory activities to provide readers an overview of these bioactivemolecules and their potential in immunomodulation therapy.An increasing number of immunomodulatory marine small-molecules with diverseintriguing structure-skeletons were discovered. They may serve as a basis for furtherstudies of marine natural products for their chemistry, related mechanism of action and structure-activity relationships.
近十年来,基于免疫调节的治疗取得了突破性进展,这激发了近年来寻找潜在免疫调节物质的热情。海洋天然产品是免疫调节物质的独特来源。本文综述了新兴的具有免疫调节活性的海洋天然小分子及其合成衍生物,概述了这些生物活性分子及其在免疫调节治疗中的潜力。近年来,越来越多具有不同结构骨架的免疫调节海洋小分子被发现。它们可以为进一步研究海洋天然产物的化学性质、作用机理和构效关系奠定基础。
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引用次数: 1
Prospective of Natural Gum Nanoparticulate Against Cardiovascular Disorders 天然纳米胶抗心血管疾病的前景
Pub Date : 2019-11-30 DOI: 10.2174/2212796813666190328194825
A. Deep, N. Rani, Ashok Kumar, Rimmy Nandal, P. C. Sharma, A. Sharma
Objective: Various natural gums can be synergistically used innanoparticulate drug delivery systems to treat cardiovascular diseases. Nanotechnology hasbeen integrated into healthcare in terms of theranostics. In this review, we consider variousnatural gums that can be used for the preparation of nanoparticles and their role to treat cardiovasculardisease.Nanoparticles can carry drugs at nanoscales and deliver them to the targeted siteswith the desired pattern of drug release. They have specialized uptake mechanisms (e.g. - absorptiveendocytosis) which improve the bioavailability of drugs.By considering cardiovascular diseases at the molecular level, it is possible to modifythe materials with nanotechnology and apply nano-formulations efficiently as comparedwith conventional preparations, due to the fact that the extracellular matrix (ECM) comprisescomponents at the nanoscale range. The interactions of ECM components with cellular componentsoccur at the nanoscale, therefore the nanomaterials have the potential to maintain thenanoscale properties of cells. The synthetic materials used to develop the nanoparticulatedrug delivery system may cause toxicity.This problem can be overcome by using natural polymers. Natural gums can beused in nanoparticulate drug delivery systems as reducing and stabilizing agents and in somecases; they may directly or indirectly influence the rate of drug release and absorption fromthe preparation.
目的:多种天然牙龈可协同应用于纳米颗粒给药系统治疗心血管疾病。纳米技术已被纳入医疗保健的治疗方面。在这篇综述中,我们考虑了各种可用于制备纳米颗粒的天然牙龈及其在治疗心血管疾病中的作用。纳米颗粒可以在纳米尺度上携带药物,并以所需的药物释放模式将药物输送到目标部位。它们具有特殊的摄取机制(如吸收性内吞作用),可提高药物的生物利用度。通过在分子水平上考虑心血管疾病,与传统制剂相比,有可能用纳米技术修饰材料并有效地应用纳米配方,因为细胞外基质(ECM)包含纳米级范围的成分。ECM组分与细胞组分的相互作用发生在纳米尺度上,因此纳米材料具有保持细胞纳米尺度特性的潜力。用于开发纳米颗粒药物递送系统的合成材料可能会引起毒性。这个问题可以通过使用天然聚合物来克服。天然胶可用于纳米颗粒给药系统中作为还原剂和稳定剂,在某些情况下;它们可能直接或间接地影响药物从制剂中释放和吸收的速度。
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引用次数: 6
Specific Enzymatic Activity of Ceruloplasmin as a Potential Indicator of Copper Status 铜蓝蛋白特异性酶活性作为铜状态的潜在指标
Pub Date : 2019-11-30 DOI: 10.2174/2212796813666190903115853
K. Upadhyay, Ankit Viramgami
The serum copper (Cu) and ceruloplasmin (Cp) concentrations are common blood markers of copper metabolism. In altered physiological conditions, Cp can act as an acute phase reactant and its concentration may increase.To evaluate specific enzymatic activity of Cp as a potential indicator of Cu status and its correlation with serum Cu level.Serum Cu levels were estimated as per NIOSH method. Specific enzymatic activity of Cp was determined from enzymatic activity and immune concentration of Cp as per standard methods. The statistical analysis was carried out using the package of social science (SPSS) software.The difference in mean specific enzymatic activity of Cp was statistically significant between clinical and control groups. In control population, the correlation between serum Cu level and specific enzymatic activity of Cp was moderate and statistically significant (r=0.566, p=0.014, N=18) as compared to the clinical group (r=0.338, p=0.016, N=50).The study revealed that clinical group was significantly different in specific enzymatic activity of Cp as compared to control group. Besides this, the specific enzymatic activity of Cp was moderately but significantly correlated with serum Cu level in control group but did not reveal conclusive evidence in clinical population.
血清铜(Cu)和铜蓝蛋白(Cp)浓度是铜代谢的常见血液标志物。在生理条件改变时,Cp可作为急性相反应物,其浓度可升高。评价血清铜水平与血清铜水平的相关性。根据NIOSH方法估计血清铜水平。按标准方法从酶活性和免疫浓度两方面测定Cp的特异性酶活性。采用SPSS软件包进行统计分析。临床组与对照组Cp平均比酶活性差异有统计学意义。对照组血清Cu水平与血清Cp特异性酶活性的相关性为中等,与临床组(r=0.338, p=0.016, N=50)相比有统计学意义(r=0.566, p=0.014, N=18)。研究发现,临床组与对照组相比,Cp的特异酶活性有显著差异。此外,Cp比酶活性在对照组中与血清Cu水平有中度但显著的相关性,而在临床人群中没有确凿的证据。
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引用次数: 0
Investigating Structural Requirements of Some Pyrimidine-linked Benzimidazole Derivatives as Anticancer Agents Against MCF-7 Cancerous Cell Line Through the use of 2D and 3D QSARs 通过使用2D和3D QSARs研究一些嘧啶连接的苯并咪唑衍生物作为抗癌剂对MCF-7癌细胞系的结构要求
Pub Date : 2019-11-30 DOI: 10.2174/2212796813666190207144407
K. Mayura, S. L. Khan, Hature Jyoti
Cancer is an extremely fast, unrestrained and pathological propagationof cells. Yet there is no cancer treatment that is 100% efficient against scattered cancer.Heterocycles have been considered as a boon to treat several cancers of which pyrimidine isa core nucleus and holds an important place in cancer chemotherapy which is reflected in theuse of drugs such as 5-fluorouracil, erlotinib, gefitinib and caneratinib. Also, many good antitumoractive agents possess benzimidazoleas its core nucleus.To design novel pyrimidine-linked benzimidazoles and to explore their structuralrequirements related to anticancer potential.2D and 3D Quantitative structure–activity relationship (QSAR) studies were carriedout on a series of already synthesized 27 pyrimidine-benzimidazole derivatives.Statistically significant and optimum 2D-QSAR model was developed by usingstep-wise variable multiple linear regression method, yielding correlation coefficient r2 =0.89, cross-validated squared correlation coefficient q2 = 0.79 and external predictive abilityof pred_r2 = 0.73 Best 3D-QSAR model was developed by employing molecular field analysisusing step-wise variable k-nearest neighbor method which showed good correlative andpredictive abilities in terms of q2 =0.77 and pred_r2= 0.93.These 2D and 3D models were found to give dependable indications whichhelped to optimize the pyrimidine-benzimidazole derivatives of the data set. The data yieldedby 2D- QSAR and 3D-QSAR models will aid in giving better perceptions about structuralrequirements for developing newer anticancer agents.
癌症是一种极快的、无限制的、病态的细胞繁殖。然而,没有一种癌症治疗方法对分散的癌症100%有效。杂环化合物被认为是治疗以嘧啶为核心的几种癌症的一种福利,在癌症化疗中占有重要地位,这体现在5-氟尿嘧啶、厄洛替尼、吉非替尼和caneratinib等药物的使用上。此外,许多良好的抗肿瘤药物都含有苯并咪唑作为其核心核。设计新型嘧啶连接的苯并咪唑并探索其抗癌潜力的结构要求。对一系列已合成的27个嘧啶-苯并咪唑衍生物进行了二维和三维定量构效关系(QSAR)研究。采用步进变量多元线性回归方法建立最佳2D-QSAR模型,相关系数r2= 0.89,交叉验证平方相关系数q2 = 0.79, pred_r2的外部预测能力= 0.73。采用步进变量k近邻法进行分子场分析,q2 =0.77, pred_r2= 0.93,具有良好的相关和预测能力。发现这些2D和3D模型给出了可靠的指示,这有助于优化数据集的嘧啶-苯并咪唑衍生物。2D- QSAR和3D-QSAR模型产生的数据将有助于更好地了解开发新型抗癌药物的结构要求。
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引用次数: 1
Green Synthesis of Silver Nanostructures Using Aqueous Extract of Dracocephalum kotschyi and Evaluation of Antioxidant Properties of Herbal Extracts and Antibacterial Feature of Green- Synthesized Nanostructures 用龙头草水提物绿色合成银纳米结构及其抗氧化性能和绿色合成纳米结构的抗菌性能评价
Pub Date : 2019-11-30 DOI: 10.2174/2212796813666190307162405
Z. Izanloo
Silver nanoparticles have a profound role in the field of high sensitivitybiomolecular detection, catalysis, biosensors and medicine. In the present study,aqueous extract of Dracocephalum kotschyi has been used for the synthesis of silvernanoparticles.In this study, we evaluated the antioxidant features and the possibility of biosynthesisof AgNPs using an aqueous extract of Dracocephalum kotschyi and also evaluated theantibacterial activities of the synthesized nanoparticles.An eco-friendly and cost-effective protocol for the synthesis of Ag nanoparticles byutilizing a renewable natural resource, aqueous solution of Dracocephalum kotschyi, wasproposed. Synthesized nanoparticles were characterized by UV–Vis spectroscopy, SEM,EDS, and XRD pattern.At first, the extract of Dracocephalum kotschyi was assessed to determine and confirmthe presence of an antioxidant feature. Resuscitation of one mM silver nitrate solutionwas carried out by the herbal extract. The solution containing AgNPs obtained from greensynthesis had a maximum optical density at 225 nm. In addition, the presence of AgNPs wasapproved by energy-dispersive X-ray spectroscopy (EDS). Images of the scanning electronmicroscope demonstrated that the synthesized AgNPs had the shape of rods and the size distributionof 48-51 nm. One of the benefits of this method is a uniform size distribution.Moreover, the effects of reaction time and concentration of the herbal extract were assessedby ultraviolet-visible (UV-Vis) spectroscopy. In the end, we assessed the antibacterial impactof the synthesized AgNPs against some pathogenic bacterial strains. According to the results,the produced nanostructures had a proper impact on two bacteria of Escherichia coli andStaphylococcus aureus.According to the results of the present study, Dracocephalum kotschyi can be asuitable compound for the synthesis of nanostructures due to its indigenous cultivation andgreat medicinal properties.
银纳米粒子在高灵敏度生物分子检测、催化、生物传感器和医学等领域有着深远的作用。本研究以龙头草水提物为原料,制备银纳米颗粒。在这项研究中,我们评估了用龙头草水提取物生物合成AgNPs的抗氧化特性和可能性,并评估了合成的AgNPs纳米颗粒的抗菌活性。提出了一种利用可再生自然资源龙头草水溶液合成银纳米粒子的环保、经济方案。采用紫外可见光谱、扫描电镜、能谱仪和XRD对合成的纳米颗粒进行了表征。首先,对龙头草提取物进行评估,以确定并确认其抗氧化特性的存在。用该草药提取物对1 mM硝酸银溶液进行复苏。通过绿色合成获得的含AgNPs溶液的最大光密度为225 nm。此外,能量色散x射线光谱(EDS)证实了AgNPs的存在。扫描电镜图像显示,合成的AgNPs具有棒状,尺寸分布在48 ~ 51 nm之间。这种方法的好处之一是尺寸分布均匀。采用紫外-可见光谱法考察了反应时间和提取物浓度的影响。最后,我们评估了合成的AgNPs对一些病原菌的抑菌效果。结果表明,所制备的纳米结构对大肠杆菌和金黄色葡萄球菌两种细菌有一定的影响。根据本研究结果,龙头草因其本土栽培和良好的药用特性,可作为纳米结构合成的合适化合物。
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引用次数: 0
Meet Our Editor-in-Chief 认识我们的总编辑
Pub Date : 2019-11-14 DOI: 10.2174/221279681303191114141723
R. Riguera
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引用次数: 0
CRISPR-Cas Technology: A Role in Transcriptional Recording and Chromatin Remodeling Events CRISPR-Cas技术:转录记录和染色质重塑事件中的作用
Pub Date : 2019-08-23 DOI: 10.2174/2212796813666190823091033
N. Sharma
This is an Editorial type of article.
这是一篇社论式的文章。
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引用次数: 0
Evaluation of Toll-like Receptor 2 Gene Expression in Rheumatoid Arthritis and Correlation with the Disease Activity 类风湿关节炎toll样受体2基因表达的评价及其与疾病活动度的相关性
Pub Date : 2019-07-31 DOI: 10.2174/2212796813666181219124924
M. Nasser, N. Hazem, A. Atwa, A. Baiomy
Rheumatoid Arthritis (RA) is an autoimmune, chronic, and systematicdisease. It affects joints and bones. The exact etiology of RA is still unclear. Varied geneticand environmental factors have been associated with the increased risk for RA. Overactivationof Toll-Like Receptors (TLRs) could initiate the development of autoimmune diseasesincluding RA.The aim of the study was to evaluate TLR2 gene expression in rheumatoid arthritispatients and investigate its correlation with the disease activity.This study included 60 patients and 20 healthy individuals. The patientswere diagnosed with RA according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria (ACR/EULAR). All included subjectsdid not have any joint disorders and /or autoimmune diseases. RA disease activity was determinedby the disease activity score of 28 joints. Whole blood was collected from all participants.Total RNA extraction was done. TLR2 mRNA expression was assessed by reversetranscription-PCR (RT-PCR).TLR2 mRNA expression was found to be significantly higher in RA patients comparedto healthy controls. Also, a strong positive correlation was found between TLR2 expressionlevel and the disease activity score. A non significant positive correlation was foundbetween TLR2 expression and serum Rheumatoid Factor (RF) level.TLR2 pathway may have an important role in RA pathogenesis and could be anew biomarker for diagnosis and monitoring disease activity.
类风湿性关节炎(RA)是一种自身免疫性慢性全身性疾病。它会影响关节和骨骼。类风湿性关节炎的确切病因尚不清楚。各种遗传和环境因素与类风湿性关节炎的风险增加有关。toll样受体(TLRs)的过度激活可引发包括RA在内的自身免疫性疾病的发展。本研究的目的是评估TLR2基因在类风湿关节炎患者中的表达,并探讨其与疾病活动度的相关性。这项研究包括60名患者和20名健康人。根据2010年美国风湿病学会/欧洲抗风湿病联盟标准(ACR/EULAR),患者被诊断为RA。所有纳入的受试者均无任何关节疾病和/或自身免疫性疾病。通过28个关节的疾病活动度评分确定RA疾病活动度。采集所有参与者的全血。提取总RNA。采用逆转录- pcr (RT-PCR)检测TLR2 mRNA的表达。与健康对照组相比,RA患者的TLR2 mRNA表达明显升高。TLR2表达水平与疾病活动度评分呈正相关。TLR2表达与血清类风湿因子(RF)水平无显著正相关。TLR2通路可能在RA发病机制中发挥重要作用,可能成为诊断和监测疾病活动性的新的生物标志物。
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引用次数: 1
Endogenous Repair System of Oxidative Damage of DNA DNA氧化损伤的内源性修复系统
Pub Date : 2019-07-31 DOI: 10.2174/2212796813666190221152908
Anmol Sharma, Pawan Gupta, Pranav Kumar Prabhakar
DNA is one of the most important biomolecules of living cells which carries genetic information from generation to generation. Many endogenous and exogenous agents may disrupt the structure of DNA. Change in the cellular genome can lead to errors in replication, transcription and in protein synthesis. DNA damage occurs naturally or result from a metabolic and hydrolytic process which release some very active chemical entities like free radicals, Reactive Oxygen Species (ROS), Reactive Nitrogen Intermediate (RNI), Reactive Carbonyl Species (RCS), lipid peroxidation products and alkylating agents. Superoxide radical, hydroxyl radical and hydrogen peroxide cause a significant threat to cellular integrity by damaging the DNA, lipids, proteins and other biomolecules. Oxidative stress may be explained as a disturbance in the number of free radicals and our system’s ability to neutralize these free radicals. Imbalances in the normal redox potential can also lead to toxic effects via the generation of peroxides. Oxidation of DNA bases leads to the base damage, nick in the strand and break in the strand either single or double strand. Oxidative stress can also cause modifications in normal mechanisms of cell signaling. DNA mutation can result in a number of genetic abnormalities such as cancer, heart failure, Alzheimer’s disease, and depression. Human body has special protection in the form of antioxidant molecules and enzymes against these free radicals. Generation of ROS and its neutralization must be regulated to protect cells and signalling biomolecules from the deleterious effect of oxidative stress with the involvement of antioxidant systems, enzymes, and specific proteins. DNA repair system is a complex system which helps in the identification, removal of the wrong nucleotide and repairs them and as a result, the cell will produce correct and functional protein and active enzyme.
DNA是活细胞中最重要的生物分子之一,它携带着遗传信息代代相传。许多内源性和外源性药物都可能破坏DNA的结构。细胞基因组的改变会导致复制、转录和蛋白质合成的错误。DNA损伤是自然发生的,或者是代谢和水解过程的结果,这些过程释放出一些非常活跃的化学实体,如自由基、活性氧(ROS)、活性氮中间体(RNI)、活性羰基(RCS)、脂质过氧化产物和烷基化剂。超氧自由基、羟基自由基和过氧化氢通过破坏DNA、脂质、蛋白质和其他生物分子对细胞完整性造成重大威胁。氧化应激可以解释为自由基数量的紊乱和我们系统中和这些自由基的能力的紊乱。正常氧化还原电位的不平衡也可通过生成过氧化物导致毒性作用。DNA碱基的氧化导致碱基损伤,链上的缺口和单链或双链断裂。氧化应激也能引起细胞信号传导正常机制的改变。DNA突变会导致许多基因异常,如癌症、心力衰竭、阿尔茨海默病和抑郁症。人体以抗氧化分子和酶的形式对这些自由基具有特殊的保护作用。在抗氧化系统、酶和特定蛋白质的参与下,必须调节ROS的产生及其中和,以保护细胞和信号生物分子免受氧化应激的有害影响。DNA修复系统是一个复杂的系统,它有助于识别,去除错误的核苷酸并修复它们,从而使细胞产生正确的功能蛋白质和活性酶。
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引用次数: 22
Telomere DNA Binding, Cleavage and Anticancer Activity of [Cu(phendione)(Hpyramol)Cl] [Cu(phendione)(Hpyramol)Cl]端粒DNA结合、切割及抗癌活性研究
Pub Date : 2019-07-31 DOI: 10.2174/2212796813666190214112129
P. Maheswari, Renuga Duraisamy, M. Kanagavel, K. Natarajaseenivasan, K. M. M. S. Begum, R. Kandasamy
The ligand Hpyramol is a redox active, which on coordination with Cu(II) cleaves DNA without any added reductant. Another ligand phendione is known for its wide application towards anticancer activities. We combined the ligands with CuCl2 to have an intercalation moiety and a redox active ligand in participation towards telomere DNA cleavage and anticancer activity.In this study, our aim is to interact it with Human telomere DNA and to see their effects on cancer cells.The complex [Cu(L)(L’)Cl] has interacted with the human telomere DNA sequence (TTAGGG), HTelo20. The HTelo20 was stabilized under both parallel and antiparallel G-quadruplex conformations and the complex [Cu(L)(L’)Cl] has interacted followed by circular dichroism spectroscopy and gel electrophoresis.The parallel G-quadruplex and randomly coiled conformations of HTelo20 were easily cleaved than the anti-parallel G-quadruplex conformation. The nature of DNA cleavage was found to be oxidative rather hydrolytic. The formation of phenoxyl radical species under electrochemical and controlled potential electrolysis conditions by the complex [Cu(L)(L’)Cl] proves the possibility of oxidative nature of DNA cleavage. The comet assay also proves the DNA cleavage induced by the complex [Cu(L)(L’)Cl] inside the nucleus of HeLa cancer cells.The complex [Cu(L)(L’)Cl] was tested for anticancer activity, induced by ROS and DNA cleavage. The IC50 values resulted in nanomolar concentrations with selected cancer cell lines. Relatively the Cu complex shows less toxicity with the normal cell line L132.
配体Hpyramol具有氧化还原活性,与Cu(II)配合可在不添加还原剂的情况下切割DNA。另一种配体苯二酮因其抗癌活性的广泛应用而闻名。我们将这些配体与CuCl2结合,使其具有嵌入段和氧化还原活性配体,参与端粒DNA的切割和抗癌活性。在这项研究中,我们的目标是使其与人类端粒DNA相互作用,并观察它们对癌细胞的影响。络合物[Cu(L)(L ')Cl]与人类端粒DNA序列(TTAGGG) HTelo20相互作用。HTelo20在平行和反平行g -四重构象下均稳定,配合物[Cu(L)(L ')Cl]相互作用,经圆二色光谱和凝胶电泳分析。HTelo20的平行g -四重构象和随机卷曲构象比反平行g -四重构象更容易断裂。DNA分裂的性质被发现是氧化而不是水解。在电化学和控制电位电解条件下,络合物[Cu(L)(L ')Cl]生成苯氧基,证明了DNA裂解的氧化性质。彗星实验还证实了HeLa癌细胞细胞核内的络合物[Cu(L)(L ')Cl]诱导的DNA切割。复合物[Cu(L)(L’)Cl]在ROS和DNA切割诱导下具有抗癌活性。IC50值在选定的癌细胞系中产生纳摩尔浓度。相对而言,铜配合物对正常细胞株L132的毒性较小。
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引用次数: 0
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Current Chemical Biology
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