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Fusarium lini Potential for the Biotransformation of Norandrostenedione and Evaluation of Urease and Chymotrypsin Properties of the Transformed Products 镰刀菌对去甲雄烯二酮的生物转化潜力及转化产物脲酶和糜蛋白酶性质的评价
Pub Date : 2021-04-21 DOI: 10.4236/ABC.2021.112006
S. P. Fodouop, Alex Doris Kengni Mboussaah, Didiane Yemele Mefokou, A. Fowa, Mahwish Siddiqui, G. T. Kamsu, D. Gatsing, M. Choudhary
Several androgenic steroids have been biotransformed by fungi into metabolites with numerous biological properties. Incubation of norandrostenedione (1) with Fusarium lini NRRL 2204 was carried out for the first time, yielding two new metabolites, 3,7β-dihydroxy-19-norandrost-1,3,5-trien-17-one (3) and 6α,10β,17β-trihydroxy-19-nor-4-androsten-3-one (4), along with three known compounds, 3-hydroxy-19-norandrost-1,3,5-trien-17-one (2), 10β, 17β-dihydroxy-19-nor-4-androsten-3-one (5) and 10β-hydroxy-19-nor-4- androsten-3,17-dione (6). Their structures were elucidated by extensive spectroscopic analyses, including 1D-, 2D-NMR, and HR-MS experiments. Substrate 1 and its derivatives 2-6 were evaluated in vitro for their urease and chymotrypsin inhibitory properties. Compounds 2 and 3 were found to have strong urease activity with IC50 = 23.7 ± 0.17 and 10.2 ± 0.28 μm, respectively, as compared to the standard drug thiourea (IC50 = 21.6 ± 0.12 μm). Compounds 4, 5 and 6 showed good chymotrypsin activity with IC50 values of 6.4 ± 0.19, 15.6 ± 0.46 and 18.4 ± 0.65 μm, respectively, as compared to standard chymostatin with IC50 = 5.7 ± 0.14 μm. These transformed metabolites may form the basis for the future development of new drugs against ulcer, inflammation, bacterial and viral diseases.
真菌已将几种雄性类固醇生物转化为具有多种生物学特性的代谢产物。首次将去甲雄烯二酮(1)与Fusarium lini NRRL 2204孵育,产生了两种新的代谢产物,3,7β-二羟基-19-壬烯-1,3,5-三烯17-酮(3)和6α,10β,17β-三羟基-19-或-4-雄烯-3-酮(4),17β-二羟基-19-或-4-雄烯-3-酮(5)和10β-羟基-19-无-4-雄烯-3,17-二酮(6)。通过广泛的光谱分析,包括1D-、2D-NMR和HR-MS实验,阐明了它们的结构。底物1及其衍生物2-6在体外评估其脲酶和糜蛋白酶抑制特性。与标准药物硫脲(IC50=21.6±0.12μm)相比,化合物2和3具有较强的脲酶活性,IC50分别为23.7±0.17和10.2±0.28μm。化合物4、5和6显示出良好的糜蛋白酶活性,IC50值分别为6.4±0.19、15.6±0.46和18.4±0.65μm,而标准糜蛋白酶的IC50值为5.7±0.14μm。这些转化的代谢产物可能为未来开发抗溃疡、炎症、细菌和病毒疾病的新药奠定基础。
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引用次数: 1
New Hemisynthetic Oleanane Saponin with Antimicrobial Activities 具有抗菌活性的新型半合成齐墩烷皂苷
Pub Date : 2021-01-13 DOI: 10.4236/ABC.2021.111001
Cyrille Ngoufack Tagousop, J. Tamokou, Léonel Donald Tsamo Feugap, D. Harakat, L. Voutquenne-Nazabadioko, D. Ngnokam
A new hemisynthetic oleanane saponin: 4',2",3",4",6"-penta-O-acetyl-6'-O- methyl-3-O-β-D-glucopyranosyl-(1→2)-β-D-glucuronopyranosyl oleanolic acid (2) was obtained after acetylation and methylation reaction on 3-O-β-D- glucopyranosyl-(1→2)-β-D-glucuronopyranosyl oleanolic acid (1). Its structure was established by extensive analysis of 1D-(1H, 13C), 2D-(COSY, HSQC and HMBC) NMR data in conjunction with mass spectrometry (HR- TOFESIMS). The evaluation of antimicrobial activities using microdilution method showed that, reaction product (2) presented the lowest values of MIC against E. coli (MIC = 16 μg/mL), S. aureus (MIC = 8 μg/mL), C. tropicalis (MIC = 16 μg/mL) C. albicans (MIC = 8 μg/mL) compare to the substrate (1) against the same microbial strains: E. coli (MIC = 32 μg/mL), S. aureus (MIC = 16 μg/mL), C. tropicalis (MIC = 32 μg/mL), C. albicans (MIC = 16 μg/mL). These results indicate that, acetylation and methylation reactions of compound 1 increase its antimicrobial activities against the tested microorganisms.
以3- o -β- d -glucopyranosyl-(1→2)-β- d -glucuronopyranosyl -(1→2)-β- d -glucuronopyranosyl齐墩果酸(1)为原料,经乙酰化和甲基化反应,得到了一种新的半合成齐墩烷皂苷:4',2 ',3 ',4',6'- 5 - o -乙酰基-6'- o -甲基-3- o -β- d -glucuronopyranosyl齐墩果酸(2)。通过对1D-(1H, 13C), 2D-(COSY, HSQC和HMBC) NMR数据和质谱(HR- TOFESIMS)的广泛分析,确定了其结构。用微量稀释法评价其抑菌活性表明,与底物(1)相比,反应产物(2)对大肠杆菌(MIC = 16 μg/mL)、金黄色葡萄球菌(MIC = 8 μg/mL)、热带葡萄球菌(MIC = 16 μg/mL)、白色葡萄球菌(MIC = 8 μg/mL)的抑菌活性最低,对大肠杆菌(MIC = 32 μg/mL)、金黄色葡萄球菌(MIC = 16 μg/mL)、热带葡萄球菌(MIC = 32 μg/mL)、白色葡萄球菌(MIC = 16 μg/mL)的抑菌活性最低。这些结果表明,化合物1的乙酰化和甲基化反应增强了其对被试微生物的抑菌活性。
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引用次数: 1
Assessment of Rapid Diagnostic Tests Algorithms in Transfusion Medicine Setting 输血医学环境中快速诊断测试算法的评估
Pub Date : 2021-01-13 DOI: 10.4236/ABC.2021.111005
M. Coulibaly, B. Maiga, D. Samaké, M. Diawara, M. Traoré, Valentin Sagara, B. Traoré, O. Guindo, A. Dolo
Background: The rapid diagnostic tests play a pivotal role in the screening of viral markers in blood qualification for transfusion in limited resource setting. Therefore, it is important to assess their analytical performances to ensure their proper functioning. Material and Methods: We performed a cross- sectional study by successive recruitment to assess the diagnostic value of rapid diagnostic tests algorithms using ELISA as a reference test. A total of 661 blood from donors were enrolled for this study. Rapid Diagnostic Tests (RDTs) and ELISA tests were performed for each sample by a couple of double-blinded biotechnologists. Data were collected on case report form and captured in Microsoft Excel then the file was imported and analyzed using R software version 4.0.3. Results: The diagnostic accuracy for the algorithms are summarized in Table 1. For HIV-algorithm, the internal validity parameters were as follow: sensitivity (sens) 99.0% (95% CI = 97.8, 99.5); specificity (spec) 98.3% (95% CI = 90.9, 99.7); positive likelihood ratio (PLR) 57.4 (95% CI = 8.2, 401.0); negative likelihood ratio (NLR) 0.01 (95% CI = 0.0005, 0.02); diagnostic odd ratio (DOR) 4710. HBV-Ag/Ab RDTs achieve the following diagnostic accuracy: sens 99.7% (95% CI = 98.3, 99.9); spec 98.8% (95% CI = 96.9, 95.5); PLR 81.8 (95% CI = 30.9, 217.0); NLR 0.003 (95% CI = 0.0004, 0.02); DOR 14,110. The analytical performances of HCV-Ab RDTs were as follow: sens 98.7% (95% CI = 97.5, 99.4); spec 93.1% (95% CI = 78.0, 98.1); PLR 14.3 (95% CI = 3.8, 54.5); NLR 1.5 (95% CI = 0.8, 2.8); DOR 962.6. The parameters evaluating the external validity of RDTs screening for the three viral markers when the theorical prevalence was 5% are summarized in Figure 3. At the prevalence , 99.99% and 99.94%. At the same prevalence, we found the following Positive Predictive Values (PPV) 70.82%, 77.59% and 37.35% for HIV-Ag/Ab RDTs, HBV-Ag RDTs and HCV-Ab RDTs algorithms, respectively. The overall areas under the received operating characteristic (ROC) curves were 98.6%, 99.2% and 99.2%; 95.9% for HIV-Ag/Ab RDTs, HBV-Ag RDTs and HCV-Ab RDTs algorithms, respectively. Conclusion: RDTs algorithms can play a pivotal role in the screening of HIV-Ab/Ag, HBs-Ag in the setting of resources limited-countries where financial and technical expertise shortages are a standard fare. However, their use for diagnostic purposes must be done with great caution and the result must necessarily be confirmed with an ELISA or molecular technique particularly for HCV-RDTs algorithm which achieved an NLR value > 0.1.
背景:在资源有限的情况下,快速诊断测试在筛选血液中的病毒标志物以获得输血资格方面发挥着关键作用。因此,重要的是要评估其分析性能,以确保其正常运行。材料和方法:我们通过连续招募进行了一项横断面研究,以评估使用ELISA作为参考测试的快速诊断测试算法的诊断价值。本研究共招募了661名献血者的血液。由两位双盲生物技术专家对每个样本进行快速诊断测试(RDT)和ELISA测试。在病例报告表上收集数据并在Microsoft Excel中捕获,然后导入文件并使用4.0.3版R软件进行分析。结果:表1总结了算法的诊断准确性。HIV算法的内部有效性参数如下:敏感性(sens)为99.0%(95%CI=97.899.5);特异性(spec)98.3%(95%CI=90.999.7);阳性似然比(PLR)57.4(95%可信区间为8.2401.0);负似然比(NLR)0.01(95%CI=0.0005,0.02);诊断奇数比(DOR)4710。HBV-Ag/Ab-RDTs的诊断准确率为99.7%(95%CI=98.399.9);规格98.8%(95%置信区间=96.9,95.5);PLR 81.8(95%CI=30.9217.0);NLR 0.003(95%CI=0.0004,0.02);DOR 14110。HCV-Ab-RDTs的分析性能如下:敏感度98.7%(95%CI=97.5,99.4);规格93.1%(95%CI=78.0,98.1);PLR 14.3(95%CI=3.8,54.5);NLR 1.5(95%CI=0.8,2.8);或962.6。当理论流行率为5%时,评估三种病毒标志物RDT筛选的外部有效性的参数总结在图3中。在相同的流行率下,我们发现HIV Ag/Ab RDTs、HBV Ag-RDTs和HCV Ab-RDTs算法的阳性预测值(PPV)分别为70.82%、77.59%和37.35%。接收操作特性(ROC)曲线下的总面积分别为98.6%、99.2%和99.2%;HIV Ag/Ab RDTs、HBV Ag RDTs和HCV Ab-RDTs算法分别为95.9%。结论:在资源有限的国家,在资金和技术专业知识短缺的情况下,RDTs算法可以在HIV抗体/抗原、HBs抗原的筛查中发挥关键作用。然而,必须非常谨慎地将其用于诊断目的,并且必须使用ELISA或分子技术来确认结果,特别是对于NLR值>0.1的HCV RDTs算法。
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引用次数: 1
Separation, Identification, Isolation and Characterization of Degradation Product of Osimertinib Tablets by UPLC-QTOF-MS/MS and NMR: Evaluation of In-Silico Safety Assessment for Osimertinib (OSM) and Degradation Product (DP) UPLC-QTOF-MS/MS和NMR分离、鉴定、分离和表征奥西替尼片降解产物:奥西替尼片(OSM)和降解产物(DP)的硅安全性评价
Pub Date : 2021-01-13 DOI: 10.4236/ABC.2021.111003
Arun D. Bhutnar, Seema R. Saple, V. Vaidya
The present work encompasses identification and characterization of major degradation product (DP) of OSM observed in base hydrolytic stress study. The separation of DP was carried out on a non-polar stationary phase by using high-performance liquid chromatography system (HPLC). Using waters X-bridge (250 mm × 4.6 mm, 5 μm) C18 column with gradient elution program. For the characterization study, stress samples were subjected to HPLC and UPLC-QTOF-MS/MS and based on mass fragmentation pattern, plausible structure was deduced. Further, the DP was isolated using semi-prepara- tive liquid chromatography and concentrated the fractions using lyophilization. The isolated DP was subjected to extensive 1D (1H, 13C, and DEPT-135) and 2D (COSY, HSQC and HMBC) nuclear magnetic resonance (NMR) studies to authenticate the structure. The impurity was unambiguously named as N-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-metho-xy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidin-2-yl)amino)phenyl)-3-methoxypropanamide. Add- itionally, the In-Silico structure activity relation (QSAR) assessed through statistical based software’s DEREK NexusTM, and MultiCASE, Case UltraTM widely accepted and respected software’s for DP and OSM.
目前的工作包括在碱水解应力研究中观察到的OSM主要降解产物(DP)的鉴定和表征。采用高效液相色谱法(HPLC)在非极性固定相上分离DP。采用waters X-bridge (250 mm × 4.6 mm, 5 μm) C18色谱柱,采用梯度洗脱程序。为了进行表征研究,对应力样品进行了HPLC和UPLC-QTOF-MS/MS,并根据质量破碎模式推断出合理的结构。此外,采用半制备液相色谱法分离DP,并用冻干法浓缩。对分离的DP进行了广泛的1D (1H, 13C和DEPT-135)和2D (COSY, HSQC和HMBC)核磁共振(NMR)研究以鉴定其结构。该杂质被明确命名为N-(2-(2-(二甲氨基)乙基)(甲基)氨基)-4-甲氧基-5-((4-(1-甲基- 1h -吲哚-3-基)嘧啶-2-基)氨基)苯基)-3-甲氧基丙酰胺。此外,通过基于统计的软件DEREK NexusTM和MultiCASE、Case UltraTM评估了硅内结构活度关系(QSAR),这些软件在DP和OSM中被广泛接受和推崇。
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引用次数: 2
Central Role of Innate B-Cell Immunity in Cancer Prevention 先天性B细胞免疫在癌症预防中的核心作用
Pub Date : 2021-01-13 DOI: 10.4236/ABC.2021.111002
N. Tupitsyn
There are some forgotten items. There is a specific way to eradicate cancer cells at the very early stage of their appearance. Natural humoral immunity with CD5+ B-cell produced pentameric IgM to cancer associated glycans normally to eliminate arising cancer cells. This branch of innate immunity is decreasing with age and that is a basis for selective immunodeficieny which may be corrected. This area of research was well studied and proved by the team of Prof. Vollmers (Germany), but then forgotten for about 15 years.
有些东西被遗忘了。有一种特殊的方法可以在癌症细胞出现的早期阶段根除它们。CD5+B细胞的自然体液免疫通常产生对癌症相关聚糖的五聚体IgM,以消除正在发生的癌症细胞。先天免疫的这一分支随着年龄的增长而减少,这是选择性免疫缺陷的基础,可以纠正。Vollmers教授(德国)的团队对这一研究领域进行了充分的研究和证明,但随后被遗忘了大约15年。
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引用次数: 0
Synthesis, Characterization, Antimicrobial and DNA Binding Studies of a Tetradentate N2O2 Amino Acid Schiff Base and Its Coordination Compounds 四齿N2O2氨基酸席夫碱及其配位化合物的合成、表征、抗菌及DNA结合研究
Pub Date : 2021-01-13 DOI: 10.4236/ABC.2021.111004
T. Aiyelabola, D. Otto, J. Jordaan, E. Akinkunmi, I. Olawuni
Aminoethanoic acid undergoes condensation with 1,4-benzenedicarboxaldehyde to form an O, N, N, O donor Schiff base, N,N'-di(carboxymethylene) terephthalaldehyde, Ligand L. Coordination compounds of this Schiff base using Ni (II), Cu (II), VO (IV) and Co (II) were then obtained in-situ. The Schiff base and the complexes were evaluated for their antimicrobial and DNA binding abilities. Molecular docking studies of the ligand and synthesized compounds were also carried out. Evidence for the formation of the Schiff base coordination compounds and the coordinating atoms was obtained from 1H NMR, infrared and ultraviolet spectral data, EDX, EDTA complexometric titration and magnetic susceptibility measurement. The results obtained are consistent with octahedral geometry for Ni (II) complex, the metal ion coordinating to one molecule of Ligand L and with additional coordination with two oxygen atoms of two molecules of the solvent. A square-planar geometry was suggested for both Co (II), and Cu (II) complexes and a five-coordinate, square pyramidal geometry for the VO (IV) complex. The results further indicated that the carboxylic acid of Ligand L was not deprotonated both in the free base and also the complexes. In addition, the results showed that Compound 2 elicited the best antimicrobial activity potential. Generally, the compounds exhibited considerable good affinity to CT-DNA.
氨基乙醇酸与1,4-苯二甲醛缩合形成O,N,N,O供体席夫碱,N,N'-二(羧亚甲基)对苯二甲醛,配体L。然后原位获得该席夫碱与Ni(II)、Cu(II),VO(IV)和Co(II)的配位化合物。对席夫碱和配合物的抗菌能力和DNA结合能力进行了评价。还对配体和合成的化合物进行了分子对接研究。从1H NMR、红外和紫外光谱数据、EDX、EDTA络合滴定和磁化率测量中获得了席夫碱配位化合物和配位原子形成的证据。所获得的结果与Ni(II)络合物的八面体几何结构一致,金属离子与配体L的一个分子配位,并与溶剂的两个分子的两个氧原子额外配位。对于Co(II)和Cu(II)配合物,提出了正方形平面几何结构,对于VO(IV)配合物提出了五坐标正方形棱锥几何结构。结果进一步表明,配体L的羧酸在游离碱和配合物中都没有去质子化。此外,结果表明,化合物2具有最佳的抗菌活性潜力。通常,这些化合物对CT-DNA表现出相当好的亲和力。
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引用次数: 4
Correlation of Quantitative Changes in Bone Marrow Lymphocyte Subpopulations with Some Rhabdomyosarcoma Prognosis Factors in Children 儿童骨髓淋巴细胞亚群定量变化与横纹肌肉瘤预后因素的相关性研究
Pub Date : 2021-01-01 DOI: 10.4236/abc.2021.115016
O. P. Kolbatskaya, T. V. Gorbunova, S. Chulkova, A. Khachatryan, N. Tupitsyn, V. Polyakov
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引用次数: 0
Fruit-Based Non-Dairy Beverage: A New Approach for Probiotics 基于水果的非乳制品饮料:益生菌的新途径
Pub Date : 2021-01-01 DOI: 10.4236/abc.2021.116021
I. Gomes, A. Venâncio, J. P. Lima, O. Freitas-Silva
The growing interest of consumers in using foods that improve health has motivated researchers and the food industry to develop new functional products such as foods with probiotics. Probiotic cultures, for example, from lactic acid bacteria and bifidobacteria have been highlighted for their ability to promote balance in the intestinal microbiota as well as other benefits such as anticarcinogenic and antimutagenic effects, reduced plasma cholesterol levels, decreased symptoms of lactose intolerance, and stimulation of the immune response. Traditionally, probiotics are incorporated into dairy products. How-ever, because of the growing number of individuals affected by lactose intolerance and/or vegans, other food matrices have been studied as potential carriers for these microorganisms. Considering all the facts mentioned above, cereals, legumes, fruits, and vegetables could be potential substrates, where probiotic bacteria can be used for the development of non-dairy beverages. This review aimed to highlight the research carried out on 1) probiotic mi-cro-organisms, including the more recent reclassification according to their phylogenetic position, 2) probiotic beverages from non-dairy sources which emerged as an alternative for lactose-intolerant consumers and, 3) the aspects of improving the gut microbiota.
消费者对食用增进健康的食品越来越感兴趣,这促使研究人员和食品工业开发新的功能性产品,如含有益生菌的食品。例如,来自乳酸菌和双歧杆菌的益生菌培养物因其促进肠道微生物群平衡的能力以及其他益处而被强调,如抗癌和抗诱变作用、降低血浆胆固醇水平、减轻乳糖不耐受症状和刺激免疫反应。传统上,益生菌被添加到乳制品中。然而,由于越来越多的人受到乳糖不耐症和/或素食者的影响,其他食物基质被研究为这些微生物的潜在载体。考虑到上述所有事实,谷物、豆类、水果和蔬菜可能是潜在的底物,其中益生菌可以用于开发非乳制品饮料。本综述旨在重点介绍以下方面的研究:1)益生菌微生物,包括最近根据其系统发育位置进行的重新分类;2)非乳制品来源的益生菌饮料成为乳糖不耐症消费者的替代品;3)改善肠道微生物群方面的研究。
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引用次数: 7
Adsorption of Toluene on Film Membranes of Chitosan/Nа-CMC 壳聚糖/ n4 - cmc膜对甲苯的吸附研究
Pub Date : 2021-01-01 DOI: 10.4236/abc.2021.116020
Abdullaev Nodirkhon Juraxonovich, Kodirkhonov Murodkhon Rashidhonovich
The sorption properties of films on bases of chitosan and sodium carboxyl methylcellulose (Na-CMC) with toluene have been checked. The sorption rate, sorption thermodynamics and isothermal properties of toluene molecules in chitosan/Na-CMC films are analyzed by adsorption-calorimetric method. Thus, it was found that toluene is adsorbed on the chitosan/Na-CMC film by the same patterns of sorption of aromatic compounds, due to the process of penetration of toluene molecules into the network of chitosan macromolecules and this is preceded by the absorption process by the surface of the chitosan/Na-CMC film.
考察了壳聚糖和羧甲基纤维素钠(Na-CMC)对甲苯的吸附性能。采用吸附量热法分析了甲苯分子在壳聚糖/Na-CMC膜中的吸附速率、吸附热力学和等温性质。因此,我们发现,甲苯在壳聚糖/Na-CMC膜上的吸附模式与芳香族化合物的吸附模式相同,这是由于甲苯分子渗透到壳聚糖大分子网络中的过程,并且这一过程先于壳聚糖/Na-CMC膜表面的吸附过程。
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引用次数: 0
Phytochemical Study and Comparative Antioxidant Activity of Extracts from Aerial Parts of Chenopodium ambrosioides Linn. (Chenopodiaceae) 凤梨藜地上部分提取物的植物化学研究及抗氧化活性比较。(藜科)
Pub Date : 2021-01-01 DOI: 10.4236/abc.2021.115015
Gneiny Whad Tchani, Kossi Sitsopé Agbeme, Kokou Agbékonyi Agbodan, G. Baba, K. Kpegba
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引用次数: 3
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