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Estimation of allele and haplotype frequencies for 23 YSTR markers of Iraqi populations in Baghdad 巴格达地区伊拉克人群23个YSTR标记等位基因和单倍型频率的估计
Pub Date : 2022-07-06 DOI: 10.35118/apjmbb.2022.030.3.02
M. Al-Zubaidi, R. Ameen, Reem Husam Al-Tabra, Ban Ameen
Specialized class of short tandem repeats located on human Y (male) chromosomes called Y-chromosome short tandem repeats (Y-STRs) are transferred from one generation to the next with unchanged (barring a mutation). Also, these loci have high discriminatory capacities among individuals of the same population or ethnicity due to the non-recombining nature of it. Peripheral blood sample from 160 unrelated Iraqi males in Baghdad are collected and DNA was extracted from it. Amplification of 23 Y-STR markers (DYS576, DYS3891, DYS448, DYS389II ,DYS19, DYS481, DYS549, DYS533, DYS438, DYS437, DYS570, DYS635, DYS390, DYS439, DYS392, DYS643, DYS393, DYS458a/b, DYS456 and YGATAH4) was performed using PowerPlex Y 23 System (Promega Corporation), PCR amplicons were analyzed on 4-capillary ABI Prism® 3100 Genetic Analyzer. Collected data were analyzed and haplotypes were obtained using Gene Mapper ID-X software version 1.4 (Applied Biosystems). Results indicated that the most polymorphic loci were DYS385a/b with 43 alleles and The GD value was 0.929, while 4 alleles at the DYS576 and DYS391, with the genetic diversity of 0.459 and 0.480 respectively. At the loci DYS570 and DYS458 the allele frequency were 10 and 12 alleles with a genetic diversity 0.780 and 0.844 respectively. Gene diversity values for the South of Iraq males ranged from 0.447 to 0.844. The highest GD was detected at DYS458loci with a value of 0.856 and the lowest GD at DYS448 locus with a value of 0.447, 143 Haplotype was identified, 130 (81, 25%) as a unique Haplotype and 13 (18, 75%) as replicated haplotype among individuals. The highest haplotype were found in sample H19, H43, H72 and H122 at frequency 0.01875, While 130 haplotype with 0.00625 frequency and haplotype diversity was 0.99835 with a discrimination capacity 0.91. The study revealed that the loci under study and the used kit are suitable for use in identification, discrimination and forensic applications in the Iraqi population.
位于人类Y(男性)染色体上的一类特殊的短串联重复序列,称为Y染色体短串联重复序列(Y- strs),从一代转移到下一代而不变(除非突变)。此外,由于这些基因座的非重组性质,它们在同一种群或种族的个体之间具有很高的歧视性。在巴格达收集了160名无血缘关系的伊拉克男性的外周血样本,并从中提取了DNA。采用PowerPlex Y 23系统(Promega Corporation)对23个Y- str标记(DYS576、DYS3891、DYS448、DYS389II、DYS19、DYS481、DYS549、DYS533、DYS438、DYS437、DYS570、DYS635、DYS390、DYS439、DYS392、DYS643、DYS393、DYS458a/b、DYS456和YGATAH4)进行扩增,PCR扩增结果在4-毛细管ABI Prism®3100遗传分析仪上进行分析。使用Gene Mapper ID-X软件1.4版(Applied Biosystems)对收集的数据进行分析并获得单倍型。结果表明,多态性位点最多的是DYS385a/b,共有43个等位基因,GD值为0.929;DYS576和DYS391位点共有4个等位基因,遗传多样性分别为0.459和0.480。DYS570和DYS458位点等位基因频率分别为10个和12个,遗传多样性分别为0.780和0.844。伊拉克南部男性的基因多样性值为0.447 ~ 0.844。dys458位点GD值最高,为0.856,DYS448位点GD值最低,为0.447,共鉴定出143个单倍型,其中130个(81.25%)为独特单倍型,13个(18.75%)为复制单倍型。H19、H43、H72和H122的单倍型频率最高,为0.01875,而130单倍型频率为0.00625,单倍型多样性为0.99835,辨别能力为0.91。研究表明,所研究的基因座和使用的试剂盒适合用于伊拉克人口的鉴定、歧视和法医应用。
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引用次数: 1
Progression in plant phosphate uptake studies 植物磷酸吸收研究进展
Pub Date : 2022-06-30 DOI: 10.35118/apjmbb.2022.030.2.07
Umaiyal Munusamy, Zailani Khuzaimah, S. Kong, S. Abdullah
Phosphate is an important macronutrient essential for various enzymatic reactions, biological processes and biosynthesis of different compounds in plants. There are multiple factors affecting phosphate uptake such as crop physiology, soil structure and texture, plantation management and environmental conditions. There is no specific solution that can be employed for better phosphate uptake by plants but clearly, sustainable agriculture management facilitated by precision crop assessment could be an effective solution. The ability for a better phosphate uptake by plants and that information will ensure the success of small and big scale farmers role in securing the demand for food by the growing population. Therefore, various approach has been taken to identify the phosphate uptake hence with the help of digitalization, we believe there will be innovated phosphate uptake studies compared to how these were previously carried out. In the next decade, more phosphate uptake information data with seamless accessibility will be available to various users. However, data alone will not be able to produce anything, analysis and advisory services are required in helping farmers to use and apply those obtained information for subsequent application in the field. Software applications with advance machine learning will customized the interactions between devices and data for the user. As they interact, they provide an untapped opportunity for better farm decision-making in real time. In this review, we will discuss how digitalization has improved to change the overall plant phosphate uptake studies and by what means the generated information can be efficiently utilized by the farmers and the various stakeholders.
磷酸盐是植物体内各种酶促反应、生物过程和各种化合物的生物合成所必需的重要营养素。影响磷素吸收的因素包括作物生理、土壤结构和质地、人工林管理和环境条件等。目前还没有具体的解决方案可以用于植物更好地吸收磷酸盐,但显然,通过精确作物评估促进可持续农业管理可能是一个有效的解决方案。植物更好地吸收磷酸盐的能力和这些信息将确保小型和大型农民在确保不断增长的人口对粮食的需求方面发挥成功的作用。因此,已经采取了各种方法来确定磷酸盐摄取,因此在数字化的帮助下,我们相信与以前进行的研究相比,将会有创新的磷酸盐摄取研究。在未来十年,将有更多无缝访问的磷酸盐吸收信息数据提供给各种用户。但是,仅凭数据不能产生任何结果,需要提供分析和咨询服务,以帮助农民使用和应用所获得的信息,以便随后在田间应用。具有先进机器学习的软件应用程序将为用户定制设备和数据之间的交互。当它们相互作用时,它们为更好的实时农业决策提供了一个尚未开发的机会。在这篇综述中,我们将讨论数字化如何改进以改变整个植物磷酸盐吸收研究,以及通过什么方式生成的信息可以被农民和各种利益相关者有效利用。
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引用次数: 0
Effect of medium supplementation on very high gravity bioethanol fermentation using sago hampas hydrolysate as a feedstock 培养基添加对以西米水解液为原料的极重生物乙醇发酵的影响
Pub Date : 2022-06-30 DOI: 10.35118/apjmbb.2022.030.2.08
Nur Adila Muradi, Dayang Salwani Awang Adeni, N. Suhaili
Bioethanol fermentation under very high gravity (VHG) conditions by using sago hampas hydrolysate (SHH) supplemented with yeast extract as a fermentation medium has resulted in an incomplete metabolism of glucose, leading to relatively low bioethanol production in comparison to the theoretical titre. Therefore, additional supplementation of the fermentation medium is necessary to increase the yeast tolerance towards inhibitors and high concentration of glucose and bioethanol. This work investigates the effect of supplementing SHH media with various nutrients on bioethanol fermentation under VHG conditions. The nutrients included magnesium sulphate (0.12 g/L), urea (3 g/L), glutamic acid (5 g/L), and peptone (5 g/L). Our results showed that culture supplemented with peptone has significantly improved the yeast growth by 0.9-fold and glucose consumption efficiency by 10% compared to the control cultures. Besides that, the media formulation has also increased bioethanol production by 13%, with a maximum concentration of 126.20 ± 3.0 g/L. In general, the results suggest an improved formulation of fermentation medium consisting of SHH for bioethanol production under VHG conditions. These results will provide useful insights into the development of bioethanol production from sago-based feedstock in the future.
在非常高重力(VHG)条件下,使用西米水解物(SHH)补充酵母提取物作为发酵培养基,导致葡萄糖代谢不完全,导致生物乙醇产量相对较低,与理论滴度相比。因此,额外补充发酵培养基是必要的,以增加酵母对抑制剂和高浓度葡萄糖和生物乙醇的耐受性。本研究探讨了在VHG条件下,在SHH培养基中添加不同营养物质对生物乙醇发酵的影响。营养物质包括硫酸镁(0.12 g/L)、尿素(3 g/L)、谷氨酸(5 g/L)和蛋白胨(5 g/L)。结果表明,与对照组相比,添加蛋白胨的培养物显著提高了酵母生长0.9倍,葡萄糖消耗效率提高了10%。此外,培养基配方也使生物乙醇产量提高了13%,最大浓度为126.20±3.0 g/L。总的来说,结果表明,在VHG条件下,由SHH组成的发酵培养基的改进配方用于生物乙醇生产。这些结果将为未来以sago为原料生产生物乙醇的发展提供有用的见解。
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引用次数: 0
Recombinant cell penetrating peptides and intrabodies targeting membrane-bound mutated KRAS antigens 靶向膜结合突变KRAS抗原的重组细胞穿透肽和体内
Pub Date : 2022-06-27 DOI: 10.35118/apjmbb.2022.030.2.06
J. Ng, Zhi Xuan Low, L. Alessandro, Jung Yin Fong, Au Yong, Minn-E Ng, Michelle Yee Mun Teo, Hokchai Yam, L. L. In
One of the drivers for early carcinogenesis involves specific somatic point substitution mutations in the KRAS gene which damages its ability to conduct signal transduction. Although antibodies can be used for the targeting of KRAS antigen, their localization along the cell’s inner membrane serves as a barrier against the accessibility of the antibodies. This study describes the evaluation of two internalization strategies, namely the endocytosis-based cell penetrating peptide (CPP) approach and the adenoviral-based intrabody (IB) approach, for the delivery of an anti-mutant KRAS single-chain variable fragment (scFv) into the cell. Splicing by overhang extension polymerase chain reaction (SOE-PCR) was used for the fusion of scFv with an enhanced green fluorescence protein (eGFP) and Antennapedia-PTD (Antp), a cell penetrating signal peptide. The fused construct (Antp-scFv-eGFP) at a concentration of 0.085 mg/ml was expressed in E. coli (BL21), while recombinant adenoviral particles containing the scFv-eGFP gene were harvested from HEK 293 cells. Both SW480 and HeLa cells were treated with Antp-scFv-eGFP and recombinant adenoviral particles, and their eGFP localization and intensity were compared to determine their scFv binding efficiencies. The IB approach was shown to exhibit a 3-fold higher fluorescence signal intensity compared to the CPP approach. This proof-of-concept study demonstrated that both antigens for either screening, diagnostic approaches can be potentially adopted when targeting various intracellular or therapeutic purposes.
早期癌变的驱动因素之一涉及KRAS基因中特定的体细胞点替代突变,这种突变损害了KRAS基因进行信号转导的能力。虽然抗体可以用于KRAS抗原的靶向,但它们沿细胞内膜的定位对抗体的可及性起着屏障作用。本研究描述了两种内化策略的评估,即基于内吞作用的细胞穿透肽(CPP)方法和基于腺病毒的体内(IB)方法,用于将抗突变KRAS单链可变片段(scFv)递送到细胞中。采用悬垂延伸聚合酶链式反应(sod - pcr)进行剪接,将scFv与增强型绿色荧光蛋白(eGFP)和细胞穿透信号肽Antennapedia-PTD (Antp)进行融合。融合构建物(Antp-scFv-eGFP)以0.085 mg/ml的浓度在大肠杆菌(BL21)中表达,同时在HEK 293细胞中收获含有scFv-eGFP基因的重组腺病毒颗粒。用Antp-scFv-eGFP和重组腺病毒颗粒处理SW480和HeLa细胞,比较它们的eGFP定位和强度,以确定它们的scFv结合效率。与CPP方法相比,IB方法显示出3倍高的荧光信号强度。这一概念验证研究表明,这两种抗原的筛选,诊断方法可以潜在地采用针对各种细胞内或治疗目的。
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引用次数: 0
The physical characteristics and yield of grey oyster mushroom (Pleurotus sajor-caju) cultivated on sawdust and sago hampas as substrate 以木屑和西米为基质栽培灰平菇(Pleurotus saor -caju)的物理特性和产量
Pub Date : 2022-06-22 DOI: 10.35118/apjmbb.2022.030.2.05
Michelle Ngassy Mering, M. H. Bolhassan, D. S. Awg-Adeni
In Malaysia, sawdust is widely used as a substrate for the cultivation of grey oyster mushrooms (Pleurotus sajor-caju). Due to the scarcity and increasing cost of sawdust, this research investigated the feasibility of employing sago hampas as an alternative substrate for the cultivation of P. sajor-caju. In Sarawak, sago hampas were discarded into the river together with wastewater or incinerated, causing water and air pollution. In this study, P. sajor-caju was grown in five different formulations which are 100% sawdust (100SD) as control, 100% sago hampas (100SH), 75% sawdust + 25% sago hampas (75SD:25SH), 50% sawdust + 50% sago hampas (50SD:50SH), and 25% sawdust + 75% sago hampas (25SD:75SH). The substrate was mixed with rice bran and calcium carbonate at a dry matter basis in the ratio of 100:10:1. For the biological efficiency, 50SD:50SH recorded the highest yield (115.07%) compared to singular substrate 100SD (19.52%) and 100SH (37.04%). The higher lignin content and moisture-holding capacity in 100SD might not give better physical characteristics of P. sajor-caju. At the end of the study, supplementation sawdust with sago hampas especially formulation 50SD:50SH is recommended as the best formulation to reduce sawdust and utilise sago hampas as an alternative substrate for P. sajor-caju.
在马来西亚,锯末被广泛用作培养灰平菇(Pleurotus saor -caju)的基质。由于木屑的稀缺和成本的增加,本研究探讨了利用西米作为替代基材栽培西米木的可行性。在沙捞越,西米袋与废水一起被丢弃到河里或焚烧,造成水和空气污染。以100%木屑(100SD)为对照,100%西米豆(100SH), 75%木屑+ 25%西米豆(75SD:25SH), 50%木屑+ 50%西米豆(50SD:50SH), 25%木屑+ 75%西米豆(25SD:75SH) 5种不同的配方生长。将底物与米糠和碳酸钙按干物质比100:10:1混合。在生物效率方面,50SD:50SH的产率为115.07%,高于单一底物100SD(19.52%)和100SH(37.04%)。100SD内较高的木质素含量和保水能力可能并不能提供较好的物理特性。在研究结束时,建议在西米中添加锯末,特别是配方50SD:50SH是减少锯末的最佳配方,并利用西米作为P. saor -caju的替代底物。
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引用次数: 0
Molecular study of Cryptosporidium spp. among diarrheal patients at Wasit province, Iraq 伊拉克瓦西特省腹泻患者隐孢子虫的分子研究
Pub Date : 2022-06-22 DOI: 10.35118/apjmbb.2022.030.2.03
May Naji Alkhanaq, Ghadeer Thamer Al-Hadidi
Cryptosporidium is a coccidian protozoan parasite infecting alimentary system and epithelial respiratory tract of humans and a wide range of vertebrates such as mammals, birds, reptiles, and fish. This study was carried out in Al-Kut city, Iraq, in two major hospitals: Al-Kut Hospital for Gynecology, Obstetric and Pediatric and Al-Karama Teaching Hospital, which included collection of stool samples from diarrheal patients. 96 stool samples taken from patients with different ages and both genders were examined by multiplex PCR technique. The results showed that the percentage of Cryptosporidium spp. infection was 39.6% and 4.2% for C. parvum and C. hominis, respectively. There are no statistically significant associates between gender and Cryptosporidium infection. The higher infection for C. parvum (41.2%) appeared in females, while the higher infection for C. hominis was found in male (4.8%). The study showed that the percentage of C. parvum infection in the rural areas is more than the urban, where the percentage in rural areas (52.9%) showed a significant difference at p = 0.004, while the infection rate for C. hominis was 6.7% in urban area. Regarding the water source, higher cryptosporidiosis rate was found in participants who used bottled water than in those who used tap water, and there is statistical significant between C. parvum infection and water source (p = 0.03), while the high infection in individuals who used bottled water were 58%. The present study aimed to determine the common Cryptosporidium species in diarrhea samples.
隐孢子虫是一种球虫原生动物寄生虫,可感染人类的消化系统和上皮呼吸道,也可感染多种脊椎动物,如哺乳动物、鸟类、爬行动物和鱼类。这项研究是在伊拉克Al-Kut市两家主要医院进行的:Al-Kut妇科、产科和儿科医院和Al-Karama教学医院,其中包括收集腹泻患者的粪便样本。采用多重PCR技术对96例不同年龄、不同性别患者的粪便样本进行检测。结果表明,小隐孢子虫和人隐孢子虫的感染率分别为39.6%和4.2%。性别与隐孢子虫感染之间无统计学意义的关联。雌虫幼虫感染率较高(41.2%),男虫感染率较高(4.8%)。研究表明,农村地区小恙虫感染率高于城市地区,农村感染率为52.9%,差异有统计学意义(p = 0.004),而城市地区人型恙虫感染率为6.7%。在水源方面,使用瓶装水的参与者隐孢子虫感染率高于使用自来水的参与者,并且细小孢子虫感染与水源之间存在统计学差异(p = 0.03),而使用瓶装水的个体高感染率为58%。本研究旨在确定腹泻样品中常见的隐孢子虫种类。
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引用次数: 1
Molecular docking and simulation studies to prove the antimicrobial property of cowpea extract 通过分子对接和模拟实验验证豇豆提取物的抗菌性能
Pub Date : 2022-06-22 DOI: 10.35118/apjmbb.2022.030.2.04
D. Kingsley, J. Abraham
This study is undertaken to prove the antimicrobial potential of the methanolic extracts of the seeds of cowpea (Vigna unguiculata) for the antimicrobial assay and biochemical characterization. The knowledge about the type of compound and its nature were obtained using characterizations including UV-Visible analysis and GC-MS. The extracts of cowpea displayed a zone of inhibition which is 13-17 mm, against Staphylococcus aureus being the most sensitive. Thin-layer chromatography, GC-MS and UV-Vis results showed the presence of methyl esters in higher amounts in the extracts with small amounts of sterols, suggesting that methyl esters can be the cause of the biological activity seen in the present work. SwissADME tool helped in screening the absorption, distribution, metabolism and excretion parameters of the identified phytoligands. Molecular docking results were following the in vitro studies performed. Protein-ligand docking using AutoDock 4.0 software was used for the validation of the wet-lab results. Binding energies were calculated for each ligand and its interaction with amino acids in the active site of the target protein. Among all the ligands tested 9-Octadecenoic Acid has emerged most promising against DNA topoisomerase of Staphylococcus aureus. The molecular dynamic simulation was also done to access the stability of the docked complex concerning temperature, hydrogen bonds, and hydrophobic interactions. Cowpea could be used as an effective antimicrobial agent in human welfare.
本研究旨在证明豇豆(Vigna unguiculata)种子甲醇提取物的抗菌潜力,并进行抗菌试验和生化表征。通过紫外-可见分析和气相色谱-质谱等表征手段,对化合物的类型和性质进行了了解。豇豆提取物对金黄色葡萄球菌的抑制范围为13 ~ 17 mm,其中对金黄色葡萄球菌的抑制最敏感。薄层色谱、GC-MS和UV-Vis结果表明,甾醇含量较少的提取物中存在较多的甲酯,表明甲酯可能是本研究中所见生物活性的原因。SwissADME工具有助于筛选鉴定的植物配体的吸收、分布、代谢和排泄参数。分子对接结果遵循体外研究进行。使用AutoDock 4.0软件进行蛋白质配体对接,验证湿实验室结果。计算了每个配体的结合能及其与靶蛋白活性位点氨基酸的相互作用。在所有测试的配体中,9-十八烯酸被认为最有希望对抗金黄色葡萄球菌的DNA拓扑异构酶。通过分子动力学模拟研究了对接物在温度、氢键和疏水相互作用等方面的稳定性。豇豆可作为一种有效的抗菌剂,造福人类。
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引用次数: 0
Effect of distinct nitrate concentrations on pigment content of mixed culture of Chlorella vulgaris and Dunaliella sp. 不同硝酸盐浓度对普通小球藻与杜氏藻混合培养色素含量的影响。
Pub Date : 2022-06-08 DOI: 10.35118/apjmbb.2022.030.2.02
Rahayu Dian Eka Putri, Y. S. Pradana, M. Koerniawan, L. T. Suwanti, U. J. Siregar, A. Budiman, E. Suyono
Chlorella vulgaris and Dunaliella sp. are prominent microalgae that are generally used for natural pigment stocks. These species have been established as producer of valuable bio compounds such as chlorophyll, carotenoids, and astaxanthin. For this research, C. vulgaris and Dunaliella sp. were cultivated in mixed culture under nitrogen stress treatments. Total four treatments at distinct nitrate concentrations of 0.012, 0.025, 0.5 NaNO3 g/L, respectively including nitrogen starvation was incorporated in this study. Nitrogen limitation and nitrogen starvation are widely used techniques to manipulate metabolic pathways into secondary pigments biosynthesis in microalgae cells. In addition, spectrophotometric measurement was conducted to investigate every single pigment content in all four treatments of distinct nitrogen concentrations for 14 days. The highest chlorophyll-a (23.65 mg/L), chlorophyll-b (10.02 mg/L), and total carotenoids (7.61 mg/L) were obtained from mixed culture with a concentration of 0.025 g/L NaNO3 in the last period cultivation. Conversely, the highest content of astaxanthin (0.6 mg/L) in mixed culture of C. vulgaris and Dunaliella sp. in the last period cultivation was achieved from starvation of nitrogen as well. The microalgae demonstrated robust growth in the presence of diverse bacterial community in the culture. It is well known that microalgae are associated with the microbiota on its phycosphere biofilm. Yet, it is unclear which specific bacteria taxa have a role in supporting or inhibiting microalgae growth.
小球藻(Chlorella vulgaris)和杜氏藻(Dunaliella sp.)是重要的微藻,通常用于天然色素原料。这些物种已被确定为有价值的生物化合物的生产者,如叶绿素,类胡萝卜素和虾青素。在氮胁迫条件下,采用双歧杆菌(C. vulgaris)和杜氏藻(Dunaliella sp.)混合培养。本研究共采用0.012、0.025、0.5 NaNO3 g/L不同硝酸盐浓度的4个处理,包括氮饥饿处理。氮限制和氮饥饿是调控微藻细胞次生色素合成代谢途径的常用技术。此外,用分光光度法测定了不同氮浓度处理14 d各单色素含量。在末期培养中,NaNO3浓度为0.025 g/L时,叶绿素-a (23.65 mg/L)、叶绿素-b (10.02 mg/L)和总类胡萝卜素(7.61 mg/L)含量最高。相反,在末期培养中,青虾素与杜氏藻混合培养的最高含量(0.6 mg/L)也是通过氮饥饿实现的。微藻在多种细菌群落的存在下表现出强劲的生长。众所周知,微藻与其藻球生物膜上的微生物群有关。然而,目前尚不清楚哪些特定的细菌类群在支持或抑制微藻生长中起作用。
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引用次数: 1
Identification of natural product inhibitors of de novo lipogenesis enzymes as an anti-cancer strategy: An in silico approach 作为抗癌策略的新生脂肪生成酶天然产物抑制剂的鉴定:一种计算机方法
Pub Date : 2022-05-23 DOI: 10.35118/apjmbb.2022.030.2.01
Mirushan Arunasalam, Vivian Chong, Sharanya Ranee Mareshvaran, Venessa Ngui Fern Yee, A. Gaurav, S. Salvamani, C. S. Lim, B. Gunasekaran
Dysregulation of the metabolic pathways is fundamental to cancer formation. The differential expression and activation of de novo fatty acid synthase (FASN) and lipogenesis enzymes ATP citrate lyase (ACLY) have been observed in various cancer types making them a promising metabolic target in cancer therapy. Natural products (NP) are a major contributor to the development of novel non-toxic anti-tumour drugs with greater efficiency. An attempt has been made in this study to identify potent orally active ACLY and FASN inhibitors from Universal Natural Product Database (UNPD) through virtual screening (VS). The VS resulted in the discovery of two hit compounds UNPD 80894 and UNPD 100156 as inhibitors of ACLY and FASN respectively. Molecular docking revealed that UNPD 80894 and UNPD 100156 bind at the substrate binding site of ACLY and the entry channel of FASN with a docking score of -8.0 kcal/mol and -5.0 kcal/mol, respectively. Identified hit compounds also obeyed the Rule of Three (RO3) thus making them possible candidates for future fragment-based drug design studies. In silico absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis of the hits predicted desirable pharmacokinetic profiles with no aberrant toxicity. The anti-cancer potentialities of the hits were also analysed using the prediction of activity spectra for substances (PASS) prediction tool which predicted the potential of UNPD 80894 as an inhibitor of ubiquinol-cytochrome-c reductase and UNPD 100156 as a lipoprotein lipase inhibitor and probable application in preneoplastic conditions treatment. These two natural compounds are proposed as potential candidates for the development of a novel ACLY and FASN inhibitors in this study.
代谢途径的失调是癌症形成的基础。新生脂肪酸合成酶(FASN)和脂肪生成酶ATP柠檬酸裂解酶(ACLY)的差异表达和激活已在不同类型的癌症中被观察到,使它们成为癌症治疗中有希望的代谢靶点。天然产物(NP)是开发新型高效无毒抗肿瘤药物的主要贡献者。本研究试图通过虚拟筛选(VS)从通用天然产品数据库(UNPD)中鉴定出有效的口服活性ACLY和FASN抑制剂。VS结果发现了两个hit化合物UNPD 80894和UNPD 100156分别作为ACLY和FASN的抑制剂。分子对接发现,UNPD 80894和UNPD 100156分别结合在ACLY的底物结合位点和FASN的进入通道,对接评分分别为-8.0 kcal/mol和-5.0 kcal/mol。确定的命中化合物也遵循三规则(RO3),从而使它们成为未来基于片段的药物设计研究的可能候选物。在硅的吸收、分布、代谢、排泄和毒性(ADMET)分析中,hit预测了理想的药代动力学特征,没有异常毒性。利用物质活性谱预测(PASS)预测工具预测了UNPD 80894作为泛醇-细胞色素-c还原酶抑制剂的潜力和UNPD 100156作为脂蛋白脂肪酶抑制剂的潜力以及在肿瘤前疾病治疗中的应用前景。在本研究中,这两种天然化合物被认为是开发新型ACLY和FASN抑制剂的潜在候选者。
{"title":"Identification of natural product inhibitors of de novo lipogenesis enzymes as an anti-cancer strategy: An in silico approach","authors":"Mirushan Arunasalam, Vivian Chong, Sharanya Ranee Mareshvaran, Venessa Ngui Fern Yee, A. Gaurav, S. Salvamani, C. S. Lim, B. Gunasekaran","doi":"10.35118/apjmbb.2022.030.2.01","DOIUrl":"https://doi.org/10.35118/apjmbb.2022.030.2.01","url":null,"abstract":"Dysregulation of the metabolic pathways is fundamental to cancer formation. The differential expression and activation of de novo fatty acid synthase (FASN) and lipogenesis enzymes ATP citrate lyase (ACLY) have been observed in various cancer types making them a promising metabolic target in cancer therapy. Natural products (NP) are a major contributor to the development of novel non-toxic anti-tumour drugs with greater efficiency. An attempt has been made in this study to identify potent orally active ACLY and FASN inhibitors from Universal Natural Product Database (UNPD) through virtual screening (VS). The VS resulted in the discovery of two hit compounds UNPD 80894 and UNPD 100156 as inhibitors of ACLY and FASN respectively. Molecular docking revealed that UNPD 80894 and UNPD 100156 bind at the substrate binding site of ACLY and the entry channel of FASN with a docking score of -8.0 kcal/mol and -5.0 kcal/mol, respectively. Identified hit compounds also obeyed the Rule of Three (RO3) thus making them possible candidates for future fragment-based drug design studies. In silico absorption, distribution, metabolism, excretion and toxicity (ADMET) analysis of the hits predicted desirable pharmacokinetic profiles with no aberrant toxicity. The anti-cancer potentialities of the hits were also analysed using the prediction of activity spectra for substances (PASS) prediction tool which predicted the potential of UNPD 80894 as an inhibitor of ubiquinol-cytochrome-c reductase and UNPD 100156 as a lipoprotein lipase inhibitor and probable application in preneoplastic conditions treatment. These two natural compounds are proposed as potential candidates for the development of a novel ACLY and FASN inhibitors in this study.","PeriodicalId":8566,"journal":{"name":"Asia-pacific Journal of Molecular Biology and Biotechnology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86660082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Malaysian herbs as potential natural resources of anticancer drugs: From folklore to discovery 马来西亚草药作为抗癌药物的潜在天然资源:从民间传说到发现
Pub Date : 2022-04-13 DOI: 10.35118/apjmbb.2022.030.1.06
F. Ismail, Yusmazura Zakaria, Nik Fakhuruddin Nik Hassan, M. L. MD ISA
Cancer is a complex disease and ranks as a leading cause of death globally. Despite many advances made in cancer therapeutics, adverse side effects and treatment resistance remain a great problem. In that sense, there are increasing demands to discover new anticancer agents from naturally-derived compounds. Medicinal plants represent a valuable source of new drugs with promising efficacy and safety. They produce various secondary metabolites, which exhibit unique structures and a pharmacological spectrum of activity, including antitumour activity. Clinacanthus nutans, Strobilanthes crispus, Ficus deltoidea, Curcuma longa, Centella asiatica and Piper betle are among the plants species commonly used to cure cancer in traditional medicine formulae in Malaysia. The present review aims to highlight the anticancer properties of the listed Malaysian herbs with a focus on their bioactive compounds and the mode of action. Overall, many studies have disclosed the presence of active metabolites in these plants, including phenols, alkaloids, flavonoids, terpenoids, saponin, curcumin and Asiatic acid. They possess significant cytotoxic or antiproliferative effects primarily via the induction of apoptosis, elevation of antioxidant activity and inhibition of cancer activating enzymes. Hence, further investigation into their clinical therapeutic potential may be noteworthy. Additionally, this review article also provides the reader with information concerning the conventional anticancer drugs and their limitations, recent developments and milestones achieved in plant- derived cancer therapeutics as well as different approaches to enhance the production of these anticancer molecules.
癌症是一种复杂的疾病,是全球死亡的主要原因。尽管癌症治疗取得了许多进展,但副作用和治疗耐药性仍然是一个大问题。从这个意义上说,从天然化合物中发现新的抗癌药物的需求越来越大。药用植物是开发新药的重要来源,具有良好的疗效和安全性。它们产生各种次生代谢物,这些代谢物具有独特的结构和药理活性,包括抗肿瘤活性。在马来西亚的传统医药配方中,常用于治疗癌症的植物有:肉苁蓉、洋桔梗、三角榕、姜黄、积雪草和花椒。本综述旨在突出列出的马来西亚草药的抗癌特性,重点是它们的生物活性化合物和作用方式。总体而言,许多研究揭示了这些植物中存在活性代谢物,包括酚类、生物碱、黄酮类、萜类、皂素、姜黄素和亚细亚酸。它们具有显著的细胞毒性或抗增殖作用,主要通过诱导细胞凋亡,提高抗氧化活性和抑制癌症激活酶。因此,对其临床治疗潜力的进一步研究值得关注。此外,本文还介绍了传统抗癌药物及其局限性,植物源性癌症治疗的最新进展和里程碑,以及提高这些抗癌分子产生的不同途径。
{"title":"Malaysian herbs as potential natural resources of anticancer drugs: From folklore to discovery","authors":"F. Ismail, Yusmazura Zakaria, Nik Fakhuruddin Nik Hassan, M. L. MD ISA","doi":"10.35118/apjmbb.2022.030.1.06","DOIUrl":"https://doi.org/10.35118/apjmbb.2022.030.1.06","url":null,"abstract":"Cancer is a complex disease and ranks as a leading cause of death globally. Despite many advances made in cancer therapeutics, adverse side effects and treatment resistance remain a great problem. In that sense, there are increasing demands to discover new anticancer agents from naturally-derived compounds. Medicinal plants represent a valuable source of new drugs with promising efficacy and safety. They produce various secondary metabolites, which exhibit unique structures and a pharmacological spectrum of activity, including antitumour activity. Clinacanthus nutans, Strobilanthes crispus, Ficus deltoidea, Curcuma longa, Centella asiatica and Piper betle are among the plants species commonly used to cure cancer in traditional medicine formulae in Malaysia. The present review aims to highlight the anticancer properties of the listed Malaysian herbs with a focus on their bioactive compounds and the mode of action. Overall, many studies have disclosed the presence of active metabolites in these plants, including phenols, alkaloids, flavonoids, terpenoids, saponin, curcumin and Asiatic acid. They possess significant cytotoxic or antiproliferative effects primarily via the induction of apoptosis, elevation of antioxidant activity and inhibition of cancer activating enzymes. Hence, further investigation into their clinical therapeutic potential may be noteworthy. Additionally, this review article also provides the reader with information concerning the conventional anticancer drugs and their limitations, recent developments and milestones achieved in plant- derived cancer therapeutics as well as different approaches to enhance the production of these anticancer molecules.","PeriodicalId":8566,"journal":{"name":"Asia-pacific Journal of Molecular Biology and Biotechnology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83816465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
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Asia-pacific Journal of Molecular Biology and Biotechnology
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