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Optimization of a New Antihyperglycemic Formulation Using a Mixture of Linum usitatissimum L., Coriandrum sativum L., and Olea europaea var. sylvestris Flavonoids: A Mixture Design Approach 以亚麻、五味子、木犀总黄酮为主要成分的降血糖新配方的优化设计
Pub Date : 2021-07-21 DOI: 10.3390/BIOLOGICS1020009
Hamza Mechchate, Wessal Ouedrhiri, I. Es-safi, Amal Amaghnouje, F. Jawhari, D. Bousta
Flavonoids are a class of natural chemicals with variable phenolic structures that have long been recognized for their health advantages, they have recently attracted researchers’ attention for treating diabetes and hyperglycemia. The goal of this research is to develop a novel antihyperglycemic formulation using a combination of three plant flavonoids: Linum usitatissimum L. seeds (FLU), Coriandrum sativum L. seeds (FCS), and Olea europaea var. sylvestris leaves (FOE) based on a mixture design experiment approach which generates the most effective ratio of each component in a mixture instead of the trial-and-error method. Prior to the test, sub-acute toxicity research was conducted to establish a safe and effective dosage. The Oral Glucose Tolerance Test (OGTT) was used to assess the antihyperglycemic impact of these extracts and their combinations in Swiss albino mice. The dose that showed efficacy and safety was 25 mg/kg, which was utilized in all formulations. According to the results, the binary and ternary combinations showed the most significant synergetic effects. The optimum combination with the most potent effect was 37% FLU, 20% FCS, and 43% FOE. This study’s mixture design and prediction model for glycemic variation (GV) may be utilized at an industrial level to develop a novel antidiabetic and antihyperglycemic formulation that is safe and effective.
黄酮类化合物是一类具有可变酚类结构的天然化学物质,长期以来被认为具有健康优势,近年来在治疗糖尿病和高血糖方面引起了研究人员的关注。本研究的目的是利用三种植物黄酮类化合物:Linum usitatissimum L.种子(FLU), Coriandrum sativum L.种子(FCS)和Olea europaea var. sylvestris叶片(FOE)的组合开发一种新的降糖配方,该配方基于混合设计实验方法,该方法可以产生混合物中每种成分的最有效比例,而不是采用试错法。试验前进行亚急性毒性研究,确定安全有效的剂量。采用口服葡萄糖耐量试验(OGTT)评估这些提取物及其组合对瑞士白化小鼠的降糖作用。有效、安全的剂量为25mg /kg,所有制剂均采用25mg /kg。结果表明,二元和三元组合的协同效应最为显著。最有效的最佳组合是37% FLU, 20% FCS和43% FOE。本研究的血糖变化(GV)混合设计和预测模型可用于工业水平,以开发安全有效的新型降糖和降糖配方。
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引用次数: 20
Induction of the CD24 Surface Antigen in Primary Undifferentiated Human Adipose Progenitor Cells by the Hedgehog Signaling Pathway Hedgehog信号通路诱导CD24表面抗原在原代未分化人脂肪祖细胞中的作用
Pub Date : 2021-07-21 DOI: 10.3390/BIOLOGICS1020008
F. Muoio, S. Panella, Yves Harder, T. Tallone
In the murine model system of adipogenesis, the CD24 cell surface protein represents a valuable marker to label undifferentiated adipose progenitor cells. Indeed, when injected into the residual fat pads of lipodystrophic mice, these CD24 positive cells reconstitute a normal white adipose tissue (WAT) depot. Unluckily, similar studies in humans are rare and incomplete. This is because it is impossible to obtain large numbers of primary CD24 positive human adipose stem cells (hASCs). This study shows that primary hASCs start to express the glycosylphosphatidylinositol (GPI)-anchored CD24 protein when cultured with a chemically defined medium supplemented with molecules that activate the Hedgehog (Hh) signaling pathway. Therefore, this in vitro system may help understand the biology and role in adipogenesis of the CD24-positive hASCs. The induced cells’ phenotype was studied by flow cytometry, Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) techniques, and their secretion profile. The results show that CD24 positive cells are early undifferentiated progenitors expressing molecules related to the angiogenic pathway.
在小鼠脂肪生成模型系统中,CD24细胞表面蛋白是标记未分化脂肪祖细胞的有价值的标志物。事实上,当注射到脂肪营养不良小鼠的残余脂肪垫中时,这些CD24阳性细胞重建了正常的白色脂肪组织(WAT)库。不幸的是,在人类身上进行的类似研究很少而且不完整。这是因为不可能获得大量的原代CD24阳性的人脂肪干细胞(hASCs)。这项研究表明,当与补充有激活Hedgehog(Hh)信号通路分子的化学定义培养基培养时,原代hASCs开始表达糖基磷脂酰肌醇(GPI)锚定的CD24蛋白。因此,该体外系统可能有助于理解CD24阳性hASCs的生物学和在脂肪生成中的作用。通过流式细胞术、实时定量聚合酶链反应(RT-qPCR)技术研究诱导细胞的表型及其分泌谱。结果表明,CD24阳性细胞是表达与血管生成途径相关分子的早期未分化祖细胞。
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引用次数: 0
Computational Chemistry to Repurposing Drugs for the Control of COVID-19 计算化学重新利用药物控制新冠肺炎
Pub Date : 2021-07-15 DOI: 10.3390/biologics1020007
Majid Hassanzadeganroudsari, Amirmasoud Ahmadi, Niloufar Rashidi, Md Kamal Hossain, Amanda Habib, V. Apostolopoulos
Thus far, in 2021, 219 countries with over 175 million people have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a positive sense, single-stranded RNA virus, and is the causal agent for coronavirus disease (COVID-19). Due to the urgency of the situation, virtual screening as a computational modeling method offers a fast and effective modality of identifying drugs that may be effective against SARS-CoV-2. There has been an overwhelming abundance of molecular docking against SARS-CoV-2 in the last year. Due to the massive volume of computational studies, this systematic review has been created to evaluate and summarize the findings of existing studies. Herein, we report on computational articles of drugs which target, (1) viral protease, (2) Spike protein-ACE 2 interaction, (3) RNA-dependent RNA polymerase, and (4) other proteins and nonstructural proteins of SARS-CoV-2. Based on the studies presented, there are 55 identified natural or drug compounds with potential anti-viral activity. The next step is to show anti-viral activity in vitro and translation to determine effectiveness into human clinical trials.
到目前为止,2021年有219个国家和超过1.75亿人感染了严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)。SARS-CoV-2是一种积极意义上的单链RNA病毒,是冠状病毒病(COVID-19)的致病因子。鉴于形势的紧迫性,虚拟筛选作为一种计算建模方法,为识别可能对SARS-CoV-2有效的药物提供了一种快速有效的方式。去年,针对SARS-CoV-2的分子对接出现了压倒性的丰富。由于大量的计算研究,本系统综述的创建是为了评估和总结现有研究的发现。在此,我们报告了针对(1)病毒蛋白酶,(2)刺突蛋白- ace 2相互作用,(3)RNA依赖的RNA聚合酶,以及(4)SARS-CoV-2的其他蛋白质和非结构蛋白的药物的计算文章。根据所提出的研究,有55种已确定的天然或药物化合物具有潜在的抗病毒活性。下一步是在体外展示抗病毒活性,并将其转化为人体临床试验,以确定有效性。
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引用次数: 6
Involvement of Probiotics and Postbiotics in the Immune System Modulation 益生菌和后益生菌在免疫系统调节中的作用
Pub Date : 2021-07-06 DOI: 10.3390/BIOLOGICS1020006
Neslihan Yeşilyurt, Birsen Yılmaz, D. Ağagündüz, R. Capasso
Intestinal microbiota interacts with other systems, especially the immune system, which is responsible for protecting the body by recognizing “stranger” (pathogen associated molecular patterns-PAMPs) and “danger” (damage-associated molecular patterns-DAMPs) molecular motifs. In this manner, it plays an important role in the pathogenesis of various diseases and health. Despite the use of probiotics that modulate the intestinal microbiota in providing health benefits and in the treatment of diseases, there are some possible concerns about the possibility of developing adverse effects, especially in people with suppressed immune systems. Since probiotics provide health benefits with bioactive compounds, studies are carried out on the use of products containing non-living probiotic microorganisms (paraprobiotics) and/or their metabolites (postbiotics) instead of probiotic products. It is even reported that these microbial compounds have more immunomodulatory activities than living microorganisms via some possible mechanism and eliminates some disadvantages of probiotics. Considering the increasing use of functional foods in health and disease, further studies are needed with respect to the benefits and advantages of parabiotic and/or postbiotic use in the food and pharmaceutical industry as well as immune system modulation. Although probiotics have been extensive studied for a long time, it seems that postbiotics are promising tools for future research and applications according to the recent literature. This review aimed to evaluate the interaction of probiotics and postbiotics with the immune systems and also their advantages and disadvantages in the area of food-pharmaceutical industry and immune system modulation.
肠道微生物群与其他系统相互作用,特别是免疫系统,免疫系统通过识别“陌生人”(病原体相关分子模式- pamps)和“危险”(损伤相关分子模式- damps)分子基序来保护身体。因此,它在各种疾病的发病机制和健康中起着重要作用。尽管使用益生菌可以调节肠道微生物群,提供健康益处和治疗疾病,但仍存在一些可能出现不良反应的可能性,特别是在免疫系统受到抑制的人群中。由于益生菌具有生物活性化合物,对健康有益,因此研究使用含有非活的益生菌微生物(副益生菌)和/或其代谢产物(后益生菌)的产品来代替益生菌产品。甚至有报道称,这些微生物化合物通过某种可能的机制比活微生物具有更强的免疫调节活性,并消除了益生菌的一些缺点。考虑到功能性食品在健康和疾病方面的使用越来越多,需要进一步研究在食品和制药工业以及免疫系统调节方面的异体和/或后生物使用的益处和优势。虽然益生菌已经被广泛研究了很长时间,但从最近的文献来看,后益生菌似乎是未来研究和应用的有前途的工具。本文综述了益生菌和后益生菌与免疫系统的相互作用,以及它们在食品制药工业和免疫系统调节领域的优缺点。
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引用次数: 54
How to Train Your Phage: The Recent Efforts in Phage Training 如何训练你的噬菌体:噬菌体训练的最新进展
Pub Date : 2021-07-05 DOI: 10.3390/BIOLOGICS1020005
Abdallah S. Abdelsattar, Alyaa Dawooud, Nouran Rezk, Salsabil Makky, Anan Safwat, P. Richards, A. El-Shibiny
Control of pathogenic bacteria by deliberate application of predatory phages has potential as a powerful therapy against antibiotic-resistant bacteria. The key advantages of phage biocontrol over antibacterial chemotherapy are: (1) an ability to self-propagate inside host bacteria, (2) targeted predation of specific species or strains of bacteria, (3) adaptive molecular machinery to overcome resistance in target bacteria. However, realizing the potential of phage biocontrol is dependent on harnessing or adapting these responses, as many phage species switch between lytic infection cycles (resulting in lysis) and lysogenic infection cycles (resulting in genomic integration) that increase the likelihood of survival of the phage in response to external stress or host depletion. Similarly, host range will need to be optimized to make phage therapy medically viable whilst avoiding the potential for deleteriously disturbing the commensal microbiota. Phage training is a new approach to produce efficient phages by capitalizing on the evolved response of wild-type phages to bacterial resistance. Here we will review recent studies reporting successful trials of training different strains of phages to switch into lytic replication mode, overcome bacterial resistance, and increase their host range. This review will also highlight the current knowledge of phage training and future implications in phage applications and phage therapy and summarize the recent pipeline of the magistral preparation to produce a customized phage for clinical trials and medical applications.
通过故意使用捕食性噬菌体来控制致病菌,有可能成为对抗抗生素耐药性细菌的强大疗法。噬菌体生物控制相对于抗菌化疗的关键优势是:(1)在宿主细菌内自我繁殖的能力,(2)对特定物种或菌株的靶向捕食,(3)克服目标细菌耐药性的适应性分子机制。然而,实现噬菌体生物控制的潜力取决于利用或适应这些反应,因为许多噬菌体物种在裂解感染周期(导致裂解)和裂解源感染周期(产生基因组整合)之间切换,这增加了噬菌体响应外部应力或宿主耗竭而存活的可能性。同样,宿主范围也需要优化,以使噬菌体疗法在医学上可行,同时避免对共生微生物群造成有害干扰的可能性。噬菌体训练是一种利用野生型噬菌体对细菌耐药性的进化反应来产生高效噬菌体的新方法。在这里,我们将回顾最近的研究,这些研究报告了训练不同菌株的噬菌体进入裂解复制模式、克服细菌耐药性并增加其宿主范围的成功试验。这篇综述还将强调噬菌体训练的当前知识以及在噬菌体应用和噬菌体治疗中的未来意义,并总结最近生产用于临床试验和医学应用的定制噬菌体的权威制备方法。
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引用次数: 18
Can the European Hedgehog (Erinaceus europaeus) Be a Sentinel for One Health Concerns? 欧洲刺猬(Erinaceus europaeus)能否成为一种健康问题的哨兵?
Pub Date : 2021-06-17 DOI: 10.3390/BIOLOGICS1010004
C. Jota Baptista, F. Seixas, J. M. Gonzalo-Orden, P. Oliveira
Erinaceus europaeus is a cosmopolitan mammalian species broadly distributed in Europe, from natural to suburban areas. Due to its ecological role and susceptibility to distinct zoonotic agents, E. europaeus could be a suitable sentinel candidate for many global problems that negatively affect human and animal health. Hedgehogs can work as bioindicators to environmental contamination and can be hosts for multiple tickborne zoonotic agents. Thus, people who directly or indirectly make physical contact with this species are exposed to a variety of threats. Moreover, it has also been studied as an indicator for antibiotic resistance, which was already confirmed for tetracyclines. Additionally, it was also reported as a reservoir for methicillin-resistant Staphylococcus aureus (MRSA). More recently, hedgehogs have been recently recognised as potential reservoirs of MERS-CoV-like strains. Among other animals, this species can possibly represent an intermediate reservoir for SARS-CoV-2. The aim of this review is to briefly expose the scientific attainments about hedgehog health, namely agents, diseases, and threats that significantly affect general health concerns and that contribute to achieve One Health principles.
欧洲鹰尾兽是一种世界性的哺乳动物,广泛分布于欧洲,从自然到郊区。由于其生态作用和对不同人畜共患病原体的易感性,欧洲棘球绦虫可能是许多对人类和动物健康产生负面影响的全球性问题的合适哨兵候选人。刺猬可以作为环境污染的生物指示物,并且可以是多种蜱传人畜共患病病原体的宿主。因此,直接或间接与这个物种进行身体接触的人都面临着各种各样的威胁。此外,它也被研究作为抗生素耐药性的指标,这已经被证实为四环素类药物。此外,据报道,它也是耐甲氧西林金黄色葡萄球菌(MRSA)的储存库。最近,刺猬被认为是中东呼吸综合征样冠状病毒株的潜在宿主。在其他动物中,该物种可能代表SARS-CoV-2的中间储存库。本综述的目的是简要介绍有关刺猬健康的科学成就,即显著影响一般健康问题并有助于实现“同一个健康”原则的因子、疾病和威胁。
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引用次数: 7
The Peptide TAT-I24 with Antiviral Activity against DNA Viruses Binds Double-Stranded DNA with High Affinity 具有抗DNA病毒活性的肽TAT-I24与高亲和力双链DNA结合
Pub Date : 2021-06-10 DOI: 10.3390/BIOLOGICS1010003
H. Harant, S. Höfinger, F. Kricek, C. Ruf, Z. Ruzsics, H. Hengel, I. Lindley
The peptide TAT-I24, composed of the 9-mer peptide I24 and the TAT (48-60) peptide, exerts broad-spectrum antiviral activity against several DNA viruses. The current model of the mode of action suggests a reduction of viral entry and also a possible interaction with the viral DNA upon virus entry. To further support this model, the present study investigates the DNA binding properties of TAT-I24. DNA binding was analysed by gel retardation of a peptide-complexed DNA, fluorescence reduction of DNA labelled with intercalating dyes and determination of binding kinetics by surface plasmon resonance. Molecular dynamics simulations of DNA-peptide complexes predict high-affinity binding and destabilization of the DNA by TAT-I24. The effect on viral DNA levels of infected cells were studied by real-time PCR and staining of viral DNA by bromodeoxyuridine. TAT-I24 binds double-stranded DNA with high affinity, leading to inhibition of polymerase binding and thereby blocking of de novo nucleic acid synthesis. Analysis of early steps of virus entry using a bromodeoxyuridine-labelled virus as well as quantification of viral genomes in the cells indicate direct binding of the peptide to the viral DNA. Saturation of the peptide with exogenous DNA can fully neutralize the inhibitory effect. The antiviral activity of TAT-I24 is linked to its ability to bind DNA with high affinity. This mechanism could be the basis for the development of novel antiviral agents.
由9聚肽I24和TAT(48-60)肽组成的肽TAT-I24对多种DNA病毒具有广谱抗病毒活性。目前的作用模式模型表明,病毒进入减少,也可能与病毒DNA在病毒进入时相互作用。为了进一步支持这一模型,本研究研究了TAT-I24的DNA结合特性。通过凝胶阻滞肽络合DNA,用插层染料标记DNA的荧光还原和表面等离子体共振测定结合动力学来分析DNA的结合。DNA-肽复合物的分子动力学模拟预测了TAT-I24对DNA的高亲和力结合和不稳定。采用实时荧光定量PCR法和溴脱氧尿嘧啶染色法研究其对感染细胞病毒DNA水平的影响。TAT-I24以高亲和力结合双链DNA,抑制聚合酶结合,从而阻断从头核酸合成。使用溴脱氧尿嘧啶标记的病毒对病毒进入的早期步骤进行分析,以及对细胞中的病毒基因组进行定量分析,表明该肽与病毒DNA直接结合。外源DNA对肽的饱和可以完全中和抑制作用。TAT-I24的抗病毒活性与其高亲和力结合DNA的能力有关。这一机制可能是开发新型抗病毒药物的基础。
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引用次数: 2
Overview of COVID-19 Disease: Virology, Epidemiology, Prevention Diagnosis, Treatment, and Vaccines COVID-19疾病概述:病毒学、流行病学、预防、诊断、治疗和疫苗
Pub Date : 2021-05-12 DOI: 10.3390/BIOLOGICS1010002
Iman Salahshoori, Noushin Mobaraki-asl, A. Seyfaee, Nasrin Mirzaei Nasirabad, Z. Dehghan, Mehrdad Faraji, Mina Ganjkhani, A. Babapoor, Seyede Zahra Shadmehr, A. Hamrang
Coronaviruses belong to the “Coronaviridae family”, which causes various diseases, from the common cold to SARS and MERS. The coronavirus is naturally prevalent in mammals and birds. So far, six human-transmitted coronaviruses have been discovered. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019 in Wuhan, China. Common symptoms include fever, dry cough, and fatigue, but in acute cases, the disease can lead to severe shortness of breath, hypoxia, and death. According to the World Health Organization (WHO), the three main transmission routes, such as droplet and contact routes, airborne transmission and fecal and oral for COVID-19, have been identified. So far, no definitive curative treatment has been discovered for COVID-19, and the available treatments are only to reduce the complications of the disease. According to the World Health Organization, preventive measures at the public health level such as quarantine of the infected person, identification and monitoring of contacts, disinfection of the environment, and personal protective equipment can significantly prevent the outbreak COVID-19. Currently, based on the urgent needs of the community to control this pandemic, the BNT162b2 (Pfizer), mRNA-1273 (Moderna), CoronaVac (Sinovac), Sputnik V (Gamaleya Research Institute, Acellena Contract Drug Research, and Development), BBIBP-CorV (Sinofarm), and AZD1222 (The University of Oxford; AstraZeneca) vaccines have received emergency vaccination licenses from health organizations in vaccine-producing countries. Vasso Apostolopoulos, Majid Hassanzadeganroudsari
冠状病毒属于“冠状病毒科”,它会引起各种疾病,从普通感冒到SARS和MERS。冠状病毒在哺乳动物和鸟类中自然流行。到目前为止,已经发现了六种人类传播的冠状病毒。2019年12月,中国武汉首次报告了严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)。常见症状包括发烧、干咳和疲劳,但在急性病例中,该病可导致严重的呼吸短促、缺氧和死亡。根据世界卫生组织(世卫组织)的说法,已经确定了新冠病毒的三种主要传播途径,即飞沫和接触途径、空气传播以及粪便和口腔传播。到目前为止,还没有发现针对COVID-19的明确治疗方法,现有的治疗方法只是为了减少疾病的并发症。世界卫生组织认为,公共卫生层面的预防措施,如隔离感染者、识别和监测接触者、环境消毒、个人防护装备等,可以有效预防COVID-19的爆发。目前,基于社会控制此次大流行的迫切需要,BNT162b2(辉瑞)、mRNA-1273 (Moderna)、CoronaVac(中国科创)、Sputnik V (Gamaleya研究所、Acellena合同药物研究与开发)、BBIBP-CorV(中国农化)和AZD1222(牛津大学;阿斯利康(AstraZeneca)的疫苗已获得疫苗生产国卫生组织颁发的紧急疫苗接种许可证。Vasso Apostolopoulos, Majid Hassanzadeganroudsari
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引用次数: 18
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Biologics (Basel, Switzerland)
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