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Peptides in COVID-19 Clinical Trials—A Snapshot COVID-19临床试验中的肽
Pub Date : 2021-10-14 DOI: 10.3390/biologics1030018
K. Hilpert
Since the beginning of the COVID-19 pandemic, there has been a strong drive and desire to find effective treatments for and protection against the disease. On the webpage ClinicalTrials.gov, a total of 6505 clinical trials currently (September 2021) investigating various aspects of COVID-19 are registered. Of these, 124 studies involving peptides were identified. These 124 were further evaluated, and 88 trials that used peptides only for routine diagnostics were excluded. The remaining 36 trials were classified into 5 different classes according to their function: immunomodulatory (5 trials), regain homeostasis (10 trials), diagnostics/biomarkers (8 trials), vaccination (9 trials), and antiviral activity (4 trials, all overlap with immunomodulatory activities). In the current review, these 36 trials are briefly described and tabularly summarised. According to the estimated finish date, 14 trials have not yet finished. All of the finished trials are yet to report their results. Seven trials were based in the USA, and Egypt, France, the UK, Turkey, and the Russian Federation conducted three trials each. This review aims to present a snapshot of the current situation of peptides in COVID-19 clinical trials and provides a template to follow up on trials of interest; it does not claim to be a complete overview.
自新冠肺炎大流行开始以来,人们一直强烈希望找到有效的治疗方法和保护措施。在ClinicalTrials.gov网页上,目前(2021年9月)共注册了6505项临床试验,调查新冠肺炎的各个方面。在这些研究中,鉴定了124项涉及肽的研究。对这124项进行了进一步评估,排除了88项仅使用肽进行常规诊断的试验。其余36项试验根据其功能分为5类:免疫调节(5项试验)、恢复稳态(10项试验),诊断/生物标志物(8项试验)和疫苗接种(9项试验)以及抗病毒活性(4项试验,均与免疫调节活性重叠)。在目前的综述中,对这36项试验进行了简要描述和表格总结。根据预计完成日期,14项试验尚未完成。所有已完成的试验尚未报告结果。七项试验在美国进行,埃及、法国、英国、土耳其和俄罗斯联邦各进行了三项试验。这篇综述旨在简要介绍新冠肺炎临床试验中肽的现状,并为后续感兴趣的试验提供模板;它并不声称是一个完整的概述。
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引用次数: 1
Is the Gut Microbiome a Target for Adjuvant Treatment of COVID-19? 肠道微生物群是COVID-19辅助治疗的目标吗?
Pub Date : 2021-09-30 DOI: 10.3390/biologics1030017
K. Hilpert
High expression of the transmembrane protein angiotensin I converting enzyme 2 (ACE2), more than 100-times higher as in the lung, and transmembrane serine protease 2 (TMPRSS2) in the gastrointestinal tract leads to infection with SARS-CoV-2. According to meta-analysis data, 9.8–20% of COVID-19 patients experience gastrointestinal symptoms, where diarrhoea is the most frequent, and about 50% shed viruses with high titre through their faeces, where a first faecal transmission was reported. Furthermore, gut inflammation, intestinal damage, and weakening of the gut mucosal integrity that leads to increased permeability has been shown in different studies for COVID-19 patients. This can lead to increased inflammation and bacteraemia. Low mucosal integrity combined with low intestinal damage is a good predictor for disease progression and submission to the intensive care unit (ICU). Several pilot studies have shown that the gut microbiome of COVID-19 patients is changed, microbial richness and diversity were lower, and opportunistic pathogens that can cause bacteraemia were enriched compared to a healthy control group. In a large proportion of these patients, dysbiosis was not resolved at discharge from the hospital and one study showed dysbiosis is still present after 3 months post COVID-19. Consequently, there might be a link between dysbiosis of the gut microbiome in COVID-19 patients and chronic COVID-19 syndrome (CCS). Various clinical trials are investigating the benefit of probiotics for acute COVID-19 patients, the majority of which have not reported results yet. However, two clinical trials have shown that a certain combination of probiotics is beneficial and safe for acute COVID-19 patients. Mortality was 11% for the probiotic treatment group, and 22% for the control group. Furthermore, for the probiotic group, symptoms cleared faster, and an 8-fold decreased risk of developing a respiratory failure was calculated. In conclusion, evidence is arising that inflammation, increased permeability, and microbiome dysbiosis in the gut occur in COVID-19 patients and thus provide new targets for adjuvant treatments of acute and chronic COVID-19. More research in this area is needed.
跨膜蛋白血管紧张素I转换酶2(ACE2)和跨膜丝氨酸蛋白酶2(TMPRSS2)在胃肠道中的高表达导致严重急性呼吸系统综合征冠状病毒2型的感染,前者是肺部的100多倍。根据荟萃分析数据,9.8-20%的新冠肺炎患者出现胃肠道症状,其中腹泻最为常见,约50%的患者通过粪便传播高滴度病毒,报告了首次粪便传播。此外,新冠肺炎患者的不同研究表明,肠道炎症、肠道损伤和肠道粘膜完整性减弱会导致通透性增加。这会导致炎症和菌血症的增加。低粘膜完整性和低肠道损伤是疾病进展和进入重症监护室(ICU)的良好预测指标。几项试点研究表明,与健康对照组相比,新冠肺炎患者的肠道微生物组发生了变化,微生物丰富度和多样性较低,可导致菌血症的机会性病原体富集。在这些患者中,很大一部分患者出院时生态失调没有得到解决,一项研究表明,新冠肺炎后3个月,生态失调仍然存在。因此,新冠肺炎患者肠道微生物组的生态失调与慢性新冠肺炎综合征(CCS)之间可能存在联系。各种临床试验正在调查益生菌对急性新冠肺炎患者的益处,其中大多数尚未报告结果。然而,两项临床试验表明,某种益生菌组合对急性新冠肺炎患者有益且安全。益生菌治疗组的死亡率为11%,对照组为22%。此外,益生菌组的症状清除得更快,患呼吸衰竭的风险降低了8倍。总之,有证据表明,新冠肺炎患者出现肠道炎症、通透性增加和微生物组微生态失调,从而为急性和慢性新冠肺炎的辅助治疗提供了新的靶点。这方面还需要更多的研究。
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引用次数: 1
Clinical Efficacy and Safety of Antiviral Drugs in the Extended Use against COVID-19: What We Know So Far 抗病毒药物在COVID-19长期使用中的临床疗效和安全性:迄今为止我们所知道的
Pub Date : 2021-09-15 DOI: 10.3390/biologics1020016
Md. Jamal Hossain, Tabassum Jannat, Shejuti Rahman Brishty, Urmi Roy, Saikat Mitra, Md. Oliullah Rafi, Md. Rabiul Islam, M. Nesa, Md Ariful Islam, T. Emran
Human beings around the globe have been suffering from a devastating novel pandemic and public health emergency, coronavirus disease 2019 (COVID-19), for more than one and a half years due to the deadly and highly pathogenic severe acute respiratory coronavirus 2 (SARS-CoV-2) infection worldwide. Notably, no effective treatment strategy has been approved for the complete recovery of COVID-19 patients, though several vaccines have been rolled out around the world upon emergency use authorization. After the emergence of the COVID-19 outbreak globally, plenty of clinical investigations commenced to screen the safety and efficacy of several previously approved drugs to be repurposed against the SARS-CoV-2 pathogen. This concise review aims at exploring the current status of the clinical efficacy and safety profile of several antiviral medications for the treatment of patients with COVID-19 and other respiratory complications caused by SARS-CoV-2 infection. The paper covers all kinds of human studies (January 2020 to June 2021) except case reports/series to highlight the clear conclusion based on the current clinical evidence. Among the promising repositioned antivirals, remdesivir has been recommended in critical conditions to mitigate the fatality rate and improve clinical conditions. In addition, boosting the immune system is believed to be beneficial in treating COVID-19 patients, so interferon type I might exert immunomodulation through its antiviral effects by stimulating interferon-stimulated gene (ISG). However, more extensive clinical studies covering all ethnic groups globally are warranted based on current data to better understand the clinical efficacy of the currently proposed repurposed drugs against COVID-19.
由于全球范围内致命且高致病性的严重急性呼吸道冠状病毒2型(SARS-CoV-2)感染,全球各地的人类在一年半的时间里一直遭受着毁灭性的新冠疫情和公共卫生紧急事件2019冠状病毒病(新冠肺炎)的折磨。值得注意的是,尽管已根据紧急使用授权在世界各地推出了几种疫苗,但尚未批准新冠肺炎患者完全康复的有效治疗策略。新冠肺炎疫情在全球爆发后,大量临床调查开始筛选几种先前批准的用于对抗SARS-CoV-2病原体的药物的安全性和有效性。这篇简明综述旨在探讨几种抗病毒药物治疗新冠肺炎和其他由SARS-CoV-2感染引起的呼吸道并发症患者的临床疗效和安全性现状。该论文涵盖了除病例报告/系列外的所有类型的人体研究(2020年1月至2021年6月),以强调基于当前临床证据的明确结论。在有前景的重新定位的抗病毒药物中,瑞德西韦被推荐在危急情况下使用,以降低死亡率并改善临床状况。此外,增强免疫系统被认为对治疗新冠肺炎患者有益,因此I型干扰素可能通过刺激干扰素刺激基因(ISG)的抗病毒作用发挥免疫调节作用。然而,根据目前的数据,有必要对全球所有种族群体进行更广泛的临床研究,以更好地了解目前拟议的重新用途药物对新冠肺炎的临床疗效。
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引用次数: 13
Implications of Endothelial Cell-Mediated Dysfunctions in Vasomotor Tone Regulation 血管舒缩性张力调节中内皮细胞介导的功能障碍的意义
Pub Date : 2021-09-08 DOI: 10.3390/biologics1020015
Carolina Mangana, Margarida Lorigo, E. Cairrão
Cardiovascular diseases (CVD) constitute the major cause of death worldwide and show a higher prevalence in the adult population. The human umbilical cord consistsof two arteries and one vein, both composed of three tunics. The tunica intima, lined with endothelial cells, regulates vascular tone through the production/release of vasoregulatory substances. These substances can be vasoactive factors released by endothelial cells (ECs) that cause vasodilation (NO, PGI2, EDHF, and Bradykinin) or vasoconstriction (ET1, TXA2, and Ang II) depending on the cell type (ECs or SMC) that reacts to the stimulus. Vascular studies using ECs are important for the analysis of cardiovascular diseases since endothelial dysfunction is an important CVD risk factor. In this paper, we will address the morphological characteristics of the human umbilical cord and its component vessels. the constitution of the vascular endothelium, and the evolution of human umbilical cord-derived endothelial cells when isolated. Moreover, the role played by the endothelium in the vasomotor tone regulation, and how it may be associated with the existence of CVD, were discussed.
心血管疾病(CVD)是全球死亡的主要原因,在成年人群中的患病率更高。人的脐带由两条动脉和一条静脉组成,都由三层膜组成。内膜衬有内皮细胞,通过血管调节物质的产生/释放来调节血管张力。这些物质可以是由内皮细胞(EC)释放的血管活性因子,其根据对刺激反应的细胞类型(EC或SMC)引起血管舒张(NO、PGI2、EDHF和缓激肽)或血管收缩(ET1、TXA2和Ang II)。使用内皮细胞的血管研究对心血管疾病的分析很重要,因为内皮功能障碍是心血管疾病的重要危险因素。在这篇论文中,我们将讨论人类脐带及其组成血管的形态特征。血管内皮的组成,以及分离时人脐带来源的内皮细胞的进化。此外,还讨论了内皮在血管舒缩张力调节中的作用,以及它如何与CVD的存在有关。
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引用次数: 11
Suitable Interpretation of Skin Prick Test and Biomedical Guidance Leads to a Better Clinical State in Atopic Individuals with High Indoor Permanence: Possible Therapeutic Implications 皮肤点刺试验和生物医学指导的适当解释导致高室内持久性的特应性个体更好的临床状态:可能的治疗意义
Pub Date : 2021-09-03 DOI: 10.3390/biologics1020014
B. Y. Nakamatsu, A. Fernandes, Débora da Silva, L. S. Santos, Thamires Rodrigues de Sousa, J. R. Victor
Indoor conditions contribute to allergen sensitization and multiple allergens reactivity, mainly for inhaled allergens. This study analyzes if Skin Prick Test (SPT) combined with efficient individual biomedical guidance about allergy development’s social, biological, and environmental aspects can yield a better clinical state with therapeutic implications for atopic individuals with high indoor permanence. We recruited atopic and non-atopic volunteers (clinically and in vitro diagnosed) with indoor permanence above 15 h per day and without previous SPT evaluation. The SPT and serum anti-allergen IgE analyses were performed individually in person, demonstrated, and discussed by the practitioners. Six months after, SPT and specific IgE titers determination were repeated, and a questionnaire to evaluate the effectiveness of the practitioner’s orientation was performed. After six months, 14% of atopic volunteers reported changes in their social habits, 30% said that they avoid the development of allergies clinical symptoms, and 68% reported a substantial improvement in their health after being informed mentored about their allergen reactivity. The control non-atopic group, as expected, reported no changes in social habits, the maintenance of total avoidance of allergic symptoms, and almost no improvement of their health. Reduced SPT and serum allergen-specific IgE titers were detected in the atopic individuals corroborating with questionnaire results. Our results indicated that SPT, followed by an individual and efficient discussion about the main biomedical aspects of allergy development, could exert a pronounced therapeutic role in allergy development by high indoor permanence individuals.
室内环境会导致过敏原致敏和多种过敏原反应,主要是吸入性过敏原。本研究分析了皮肤点刺试验(SPT)结合对变态反应发展的社会、生物和环境方面的有效的个体生物医学指导是否能对具有高室内持久性的特应性个体产生更好的临床状态和治疗意义。我们招募了特应性和非特应性志愿者(临床和体外诊断),他们每天在室内停留15小时以上,没有以前的SPT评估。SPT和血清抗过敏原IgE分析是单独进行的,由医生演示和讨论。6个月后,再次进行SPT和特异性IgE滴度测定,并进行问卷调查以评估医生指导的有效性。六个月后,14%的过敏性反应志愿者报告说他们的社交习惯发生了变化,30%的人说他们避免了过敏临床症状的发展,68%的人报告说,在被告知他们的过敏原反应后,他们的健康状况有了实质性的改善。如预期的那样,非特应性反应的对照组在社交习惯上没有改变,保持完全避免过敏症状,而且他们的健康状况几乎没有改善。在特应性个体中检测到SPT和血清过敏原特异性IgE滴度降低,与问卷调查结果相吻合。我们的研究结果表明,SPT,然后是对过敏发展的主要生物医学方面的个体和有效的讨论,可以在高室内持久性个体的过敏发展中发挥显著的治疗作用。
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引用次数: 0
Immunomodulatory Properties of Polyphenol-Rich Sugarcane Extract on Human Monocytes 富含多酚的甘蔗提取物对人单核细胞的免疫调节特性
Pub Date : 2021-08-25 DOI: 10.3390/biologics1020013
J. Feehan, M. Prakash, L. Stojanovska, M. Flavel, B. Kitchen, V. Apostolopoulos
As inflammatory lifestyle factors become more prevalent and as the population ages, the management of inflammation will become increasingly relevant. Plant polyphenols are powerful antioxidants that are known to have beneficial effects in a number of diseases with an inflammatory or oxidative component, such as malignancy, cardiovascular disease and arthritis. Polyphenol-rich sugarcane extract (PRSE) is a novel preparation with high concentrations of polyphenolic antioxidants, with some evidence to show benefits in health, but there is limited research investigating its effects on immunomodulation. This study determined the effects of PRSE on human monocyte cells in vitro. We show that PRSE has an immunomodulatory effect in U937 human monocyte cells, altering the expression of cellular surface markers, with an increased expression of CD16 and CD11b, as well as small changes in CD40, CD80, CD80, CD206 and MHCI. It also modulates the profile of secreted cytokines, increasing IL-1β, TNFα, IL-6, IL-8, IL-4 and IL-10. These changes are consistent with the advanced differentiation of the monocyte, as well as the switch from the M1 to M2 phenotype in macrophages. We also demonstrate that this effect is likely to be independent of the NF-κB signalling pathway, suggesting that other mechanisms drive this effect. PRSE exerts an immunomodulatory effect on U937 monocytes in vitro, potentially facilitating the conversion from inflammation to healing. Future studies should identify specific mechanisms underlying the changes and evaluate their effectiveness in animal models of disease.
随着炎症生活方式因素的日益普遍和人口的老龄化,炎症的管理将变得越来越重要。植物多酚是一种强大的抗氧化剂,已知对许多具有炎症或氧化成分的疾病具有有益作用,如恶性肿瘤、心血管疾病和关节炎。富含多酚的甘蔗提取物(PRSE)是一种具有高浓度多酚抗氧化剂的新制剂,有一些证据表明其对健康有益,但研究其对免疫调节作用的研究有限。本研究测定了PRSE对体外培养的人单核细胞的影响。我们发现,PRSE在U937人单核细胞中具有免疫调节作用,改变了细胞表面标志物的表达,CD16和CD11b的表达增加,CD40、CD80、CD206和MHCI也发生了微小变化。它还调节分泌的细胞因子,增加IL-1β、TNFα、IL-6、IL-8、IL-4和IL-10。这些变化与单核细胞的高级分化以及巨噬细胞从M1表型向M2表型的转变一致。我们还证明,这种作用可能独立于NF-κB信号通路,这表明其他机制驱动了这种作用。PRSE在体外对U937单核细胞发挥免疫调节作用,可能促进炎症向愈合的转化。未来的研究应该确定这些变化的具体机制,并评估它们在疾病动物模型中的有效性。
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引用次数: 2
Biological Treatments in Inflammatory Bowel Disease: A Complex Mix of Mechanisms and Actions 炎症性肠病的生物治疗:复杂的机制和作用
Pub Date : 2021-08-10 DOI: 10.3390/biologics1020012
L. O. Moreno, S. Fernández-Tomé, R. Abalo
Inflammatory bowel disease (IBD) is a chronic disease that requires lifelong medication and whose incidence is increasing over the world. There is currently no cure for IBD, and the current therapeutic objective is to control the inflammatory process. Approximately one third of treated patients do not respond to treatment and refractoriness to treatment is common. Therefore, pharmacological treatments, such as monoclonal antibodies, are urgently needed, and new treatment guidelines are regularly published. Due to the extremely important current role of biologics in the therapy of IBD, herein we have briefly reviewed the main biological treatments currently available. In addition, we have focused on the mechanisms of action of the most relevant groups of biological agents in IBD therapy, which are not completely clear but are undoubtfully important for understanding both their therapeutic efficacy and the adverse side effects they may have. Further studies are necessary to better understand the action mechanism of these drugs, which will in turn help us to understand how to improve their efficacy and safety. These studies will hopefully pave the path for a personalized medicine.
炎症性肠病(IBD)是一种需要终生服药的慢性疾病,其发病率在世界范围内呈上升趋势。目前还没有治愈IBD的方法,目前的治疗目标是控制炎症过程。大约三分之一的治疗患者对治疗没有反应,治疗难治性是常见的。因此,迫切需要单克隆抗体等药物治疗,并定期发布新的治疗指南。鉴于生物制剂目前在IBD治疗中的重要作用,我们在此简要回顾目前可用的主要生物治疗方法。此外,我们重点研究了最相关的生物制剂在IBD治疗中的作用机制,这些机制尚不完全清楚,但对于了解它们的治疗效果和可能产生的不良副作用无疑是重要的。为了更好地了解这些药物的作用机制,有必要进行进一步的研究,从而帮助我们了解如何提高其疗效和安全性。这些研究有望为个性化医疗铺平道路。
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引用次数: 3
A COVID-19 Overview and Potential Applications of Cell Therapy COVID-19细胞治疗综述及潜在应用
Pub Date : 2021-08-02 DOI: 10.3390/biologics1020011
D. Câmara, A. Porcacchia, N. Lizier, P. L. de-Sá-Júnior
The COVID-19 pandemic has already reaped thousands of lives, although many scientific studies already showed the possibility of this scenario. Currently, further attention is provided to patients depicting comorbidities such as respiratory or immunocompromised diseases, hypertension, and diabetes, as these individuals show a worse prognosis. Cell therapies using stem cells and/or defense cells, combined or not with traditional treatment, could be an outstanding strategy for COVID-19 management since these treatments can act by modulating the immune system, reducing proliferation, and favoring the complete elimination of the virus. In this review, we highlight the main molecular characteristics of this novel coronavirus, as well as the main pathognomonic signs of COVID-19. Furthermore, possible cell therapies are pointed out to show alternative treatments against COVID-19 and its sequels.
新冠肺炎大流行已经夺走了数千人的生命,尽管许多科学研究已经表明了这种情况的可能性。目前,人们进一步关注患有呼吸道或免疫功能低下疾病、高血压和糖尿病等合并症的患者,因为这些患者的预后较差。使用干细胞和/或防御细胞的细胞疗法,无论是否与传统治疗相结合,都可能是新冠肺炎治疗的杰出策略,因为这些治疗可以通过调节免疫系统、减少增殖和有利于完全消除病毒来发挥作用。在这篇综述中,我们强调了这种新型冠状病毒的主要分子特征,以及新冠肺炎的主要病理特征。此外,还指出了可能的细胞疗法,以显示针对新冠肺炎及其后续疾病的替代疗法。
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引用次数: 2
Isolation and Characterization of Bacteriophage ZCSE6 against Salmonella spp.: Phage Application in Milk 沙门氏菌噬菌体ZCSE6的分离与鉴定:在牛奶中的应用
Pub Date : 2021-08-02 DOI: 10.3390/biologics1020010
Abdallah S. Abdelsattar, Anan Safwat, Rana Nofal, Amera Elsayed, Salsabil Makky, A. El-Shibiny
Food safety is very important in the food industry as most pathogenic bacteria can cause food-borne diseases and negatively affect public health. In the milk industry, contamination with Salmonella has always been a challenge, but the risks have dramatically increased as almost all bacteria now show resistance to a wide range of commercial antibiotics. This study aimed to isolate a bacteriophage to be used as a bactericidal agent against Salmonella in milk and dairy products. Here, phage ZCSE6 has been isolated from raw milk sample sand molecularly and chemically characterized. At different multiplicities of infection (MOIs) of 0.1, 0.01, and 0.001, the phage–Salmonella interaction was studied for 6 h at 37 °C and 24 h at 8 °C. In addition, ZCSE6 was tested against Salmonella contamination in milk to examine its lytic activity for 3 h at 37 °C. The results showed that ZCSE6 has a small genome size (<48.5 kbp) and belongs to the Siphovirus family. Phage ZCSE6 revealed a high thermal and pH stability at various conditions that mimic milk manufacturing and supply chain conditions. It also demonstrated a significant reduction in Salmonella concentration in media at various MOIs, with higher bacterial eradication at higher MOI. Moreover, it significantly reduced Salmonella growth (MOI 1) in milk, manifesting a 1000-fold decrease in bacteria concentration following 3 h incubation at 37 °C. The results highlighted the strong ability of ZCSE6 to kill Salmonella and control its growth in milk. Thus, ZCSE6 is recommended as a biocontrol agent in milk to limit bacterial growth and increase the milk shelf-life.
食品安全在食品工业中非常重要,因为大多数致病菌可引起食源性疾病并对公众健康产生负面影响。在牛奶行业,沙门氏菌污染一直是一个挑战,但风险急剧增加,因为几乎所有的细菌现在都表现出对各种商业抗生素的耐药性。本研究旨在分离一种噬菌体,作为牛奶和乳制品中沙门氏菌的杀菌剂。本文从原料牛奶样品中分离出噬菌体ZCSE6,并对其进行了分子和化学表征。在感染多重度(MOIs)分别为0.1、0.01和0.001时,噬菌体与沙门氏菌在37℃和8℃条件下分别作用6 h和24 h。此外,ZCSE6对牛奶中的沙门氏菌污染进行了检测,检测了其在37°C下3小时的裂解活性。结果表明,ZCSE6具有较小的基因组大小(<48.5 kbp),属于Siphovirus科。噬菌体ZCSE6在模拟牛奶生产和供应链条件的各种条件下显示出很高的热稳定性和pH稳定性。它还表明,培养基中沙门氏菌浓度在不同MOI下显著降低,高MOI下细菌根除率更高。此外,它显著降低了牛奶中沙门氏菌的生长(MOI 1),在37°C孵育3小时后,细菌浓度降低了1000倍。结果表明,ZCSE6对牛奶中的沙门氏菌具有较强的杀灭和控制能力。因此,ZCSE6被推荐作为牛奶中的生物防治剂,以限制细菌的生长,延长牛奶的保质期。
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引用次数: 14
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
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Biologics (Basel, Switzerland)
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