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High Altitude Cerebral Edema: Improving Treatment Options. 高海拔地区脑水肿:改进治疗方案。
Pub Date : 2022-03-01 Epub Date: 2022-03-17 DOI: 10.3390/biologics2010007
Rebecca Zelmanovich, Kevin Pierre, Patrick Felisma, Dwayne Cole, Matthew Goldman, Brandon Lucke-Wold

High altitude illness in its most severe form can lead to high altitude cerebral edema (HACE). Current strategies have focused on prevention with graduated ascents, pharmacologic prophylaxis, and descent at first signs of symptoms. Little is understood regarding treatment with steroids and oxygenation being commonly utilized. Pre-clinical studies with turmeric derivatives have offered promise due to its anti-inflammatory and antioxidant properties, but they warrant validation clinically. Ongoing work is focused on better understanding the disease pathophysiology with an emphasis on the glymphatic system and venous outflow obstruction. This review highlights what is known regarding diagnosis, treatment, and prevention, while also introducing novel pathophysiology mechanisms warranting further investigation.

高原病最严重时可导致高原脑水肿(HACE)。目前的策略主要是通过逐步登高、药物预防和在症状初现时下山来进行预防。人们对通常使用的类固醇和吸氧治疗了解甚少。姜黄衍生物具有抗炎和抗氧化特性,其临床前研究为治疗提供了希望,但仍需临床验证。目前的工作重点是更好地了解疾病的病理生理学,重点是甘液系统和静脉流出阻塞。本综述重点介绍了诊断、治疗和预防方面的已知知识,同时还介绍了值得进一步研究的新型病理生理学机制。
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引用次数: 0
The Promising Role of Mushrooms as a Therapeutic Adjuvant of Conventional Cancer Therapies 蘑菇作为常规癌症治疗辅助剂的前景
Pub Date : 2022-01-29 DOI: 10.3390/biologics2010005
A. Plácido, F. Roque, M. Morgado
Complementary and alternative medicine (CAM) has been fronted as an alternative due to its potential for holistic treatment. Many CAMs are plant-derived, including algae and mushrooms that have been used widely in many parts of the world, where they are regarded as biological response modifiers. The purpose of this article was to review the role of mushrooms as an adjuvant in conventional therapies, to reveal the therapeutic substances of mushrooms as an adjuvant in conventional therapies, to bring together the available scientific data on the medical effects of mushrooms in oncology, and verify its efficacy and safety. A literature search was conducted in September 2021 on the MEDLINE-PubMed and Cochrane databases to identify relevant randomized controlled trials or clinical trials studies addressing the use of whole mushroom formulations as complementary therapy during conventional cancer treatment.: The findings from the present study suggest that mushrooms may act as a potentiator of host defense mechanisms and decrease adverse events for patients with cancer undergoing conventional therapies. New protocols to conduct clinical trials are needed to elucidate the possible active mechanisms and clinical benefits of these fungi in various types of cancer.
补充和替代医学(CAM)由于其整体治疗的潜力而成为一种替代疗法。许多CAMs是植物衍生的,包括藻类和蘑菇,它们在世界许多地方被广泛使用,在那里它们被视为生物反应调节剂。本文的目的是综述蘑菇在常规治疗中的辅助作用,揭示蘑菇在常规治疗中的辅助治疗物质,汇集蘑菇在肿瘤学中的医学作用的现有科学资料,并验证其有效性和安全性。文献检索于2021年9月在MEDLINE-PubMed和Cochrane数据库中进行,以确定相关的随机对照试验或临床试验研究,以解决在常规癌症治疗中使用全蘑菇配方作为补充疗法的问题。本研究的结果表明,蘑菇可能作为宿主防御机制的增强剂,并减少癌症患者接受常规治疗的不良事件。需要新的临床试验方案来阐明这些真菌在各种类型癌症中的可能的活性机制和临床益处。
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引用次数: 4
Acknowledgment to Reviewers of Biologics in 2021 向2021年生物制剂审稿人致谢
Pub Date : 2022-01-26 DOI: 10.3390/biologics2010004
Rigorous peer-reviews are the basis of high-quality academic publishing [...]
严谨的同行评审是高质量学术出版的基础〔…〕
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引用次数: 0
In Silico Analysis of Honeybee Venom Protein Interaction with Wild Type and Mutant (A82V + P375S) Ebola Virus Spike Protein 蜂毒蛋白与野生型和突变型(A82V + P375S)埃博拉病毒刺突蛋白相互作用的计算机分析
Pub Date : 2022-01-07 DOI: 10.3390/biologics2010003
M. Muzammal, Muzammil Ahmad Khan, M. A. Mohaini, A. Alsalman, M. A. A. Hawaj, A. Farid
Venom from different organisms was used in ancient times to treat a wide range of diseases, and to combat a variety of enveloped and non-enveloped viruses. The aim of this in silico research was to investigate the impact of honeybee venom proteins and peptides against Ebola virus. In the current in silico study, different online and offline tools were used. RaptorX (protein 3D modeling) and PatchDock (protein–protein docking) were used as online tools, while Chimera and LigPlot + v2.1 were used for visualizing protein–protein interactions. We screened nine venom proteins and peptides against the normal Ebola virus spike protein and found that melittin, MCD and phospholipase A2 showed a strong interaction. We then screened these peptides and proteins against mutated strains of Ebola virus and found that the enzyme phospholipase A2 showed a strong interaction. According to the findings, phospholipase A2 found in honeybee venom may be an effective source of antiviral therapy against the deadly Ebola virus. Although the antiviral potency of phospholipase A2 has been recorded previously, this is the first in silico analysis of honeybee phospholipase A2 against the Ebola viral spike protein and its more lethal mutant strain.
来自不同生物体的毒液在古代被用于治疗各种疾病,并对抗各种包膜和非包膜病毒。这项计算机研究的目的是研究蜂毒蛋白和肽对埃博拉病毒的影响。在当前的计算机研究中,使用了不同的在线和离线工具。RaptorX(蛋白质3D建模)和PatchDock(蛋白质-蛋白质对接)被用作在线工具,而Chimera和LigPlot+v2.1被用于可视化蛋白质-蛋白质相互作用。我们筛选了9种针对正常埃博拉病毒刺突蛋白的毒液蛋白和肽,发现蜂毒肽、MCD和磷脂酶A2表现出强烈的相互作用。然后,我们针对埃博拉病毒的突变株筛选了这些肽和蛋白质,发现磷脂酶A2表现出强烈的相互作用。根据研究结果,在蜂毒中发现的磷脂酶A2可能是对抗致命埃博拉病毒的抗病毒治疗的有效来源。尽管先前已经记录了磷脂酶A2的抗病毒效力,但这是首次对蜜蜂磷脂酶A2对抗埃博拉病毒刺突蛋白及其更致命的突变株进行计算机分析。
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引用次数: 6
Peptide Multimerization as Leads for Therapeutic Development 多肽多重化作为治疗发展的先导
Pub Date : 2021-12-30 DOI: 10.3390/biologics2010002
D. Sheard, Wenyi Li, N. O’Brien-Simpson, F. Separovic, J. Wade
Multimerization of peptide structures has been a logical evolution in their development as potential therapeutic molecules. The multivalent properties of these assemblies have attracted much attention from researchers in the past and the development of more complex branching dendrimeric structures, with a wide array of biocompatible building blocks is revealing previously unseen properties and activities. These branching multimer and dendrimer structures can induce greater effect on cellular targets than monomeric forms and act as potent antimicrobials, potential vaccine alternatives and promising candidates in biomedical imaging and drug delivery applications. This review aims to outline the chemical synthetic innovations for the development of these highly complex structures and highlight the extensive capabilities of these molecules to rival those of natural biomolecules.
肽结构的多重化是其作为潜在治疗分子发展的逻辑进化。这些组装体的多价性质在过去引起了研究人员的极大关注,具有广泛生物相容性构建块的更复杂分支树枝状聚合物结构的开发揭示了以前从未见过的性质和活性。与单体形式相比,这些分支多聚体和树枝状大分子结构可以对细胞靶点产生更大的影响,并在生物医学成像和药物递送应用中作为有效的抗菌剂、潜在的疫苗替代品和有前景的候选者。这篇综述旨在概述开发这些高度复杂结构的化学合成创新,并强调这些分子与天然生物分子竞争的广泛能力。
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引用次数: 3
Identification and Effects of Skim Milk-Derived Bioactive Antihypertensive Peptides 脱脂牛奶来源的抗高血压生物活性肽的鉴定及其作用
Pub Date : 2021-12-28 DOI: 10.3390/biologics2010001
Fatah B Ahtesh, L. Stojanovska, V. Mishra, O. Donkor, J. Feehan, M. Bosevski, M. Mathai, V. Apostolopoulos
Bioactive peptides are generated during milk fermentation or enzymatic hydrolysis. Lactobacillus (L) helveticus is commonly used to produce some types of fermented milk products. Fermented milk derived bioactive peptides are known to be beneficial in human health. Anti-hypertensive peptides play a dual role in the regulation of hypertension through the production of the vasoconstrictor angiotensin II and its inactivation of the vasodilator bradykinin. MALDI MS/MS, nano-LC/MS/MS and RP-HPLC were used to isolate peptides showing angiotensin converting enzyme inhibition (ACE-I) from 12% fermented skim milk using a combination of L. helveticus and Flavourzyme®. The fermentation procedure facilitated the identification of 133 anti-hypertensive peptides and 75% short chain amino acids, and the three with the highest ACE-I activity reduced blood pressure in a rat model of hypertension. The freeze- dried extract was supplemented in rodent chow. In this study 14-week-old male spontaneously hypertensive rats were fed for 10 weeks with the identified peptides added to chow and compared to controls supplemented with skim milk powder. Blood pressure (BP) decreased significantly (p < 0.05) from 6 to 10 weeks of FS groups (120/65 mmHg) compared with the NFS control groups, where the BP increased significantly (220/150 mmHg) (p < 0.05). The F6 fraction provided bioactive peptides with stronger antihypertensive properties than other fractions. Skim milk fermented by L. helveticus and Flavourzyme® generates several bioactive peptides which have a blood pressure lowering effect in hypertensive disease.
生物活性肽是在牛奶发酵或酶解过程中产生的。helveticus乳杆菌(L)通常用于生产某些类型的发酵乳制品。众所周知,发酵乳衍生的生物活性肽对人体健康有益。降压肽通过产生血管收缩剂血管紧张素II和使血管舒张剂缓激素失活,在高血压调节中发挥双重作用。采用MALDI质谱/质谱、纳米lc /MS/MS和反相高效液相色谱(RP-HPLC)技术,利用L. helveticus和Flavourzyme®组合,从12%发酵脱脂乳中分离出血管紧张素转换酶抑制肽(ACE-I)。发酵过程可以鉴定出133种降压肽和75%的短链氨基酸,其中ACE-I活性最高的3种可以降低高血压大鼠的血压。冻干提取物被添加到啮齿动物饲料中。在这项研究中,14周龄的雄性自发性高血压大鼠在饲料中添加鉴定的肽,并饲喂10周,与添加脱脂奶粉的对照组进行比较。与NFS对照组相比,FS组6 ~ 10周血压(120/65 mmHg)显著降低(p < 0.05), NFS对照组血压(220/150 mmHg)显著升高(p < 0.05)。F6部位具有较强的抗高血压活性肽。由L. helveticus和Flavourzyme®发酵的脱脂乳产生几种生物活性肽,对高血压疾病有降血压作用。
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引用次数: 1
In Silico Evaluation of Different Flavonoids from Medicinal Plants for Their Potency against SARS-CoV-2 药用植物中不同黄酮类化合物对严重急性呼吸系统综合征冠状病毒2型的有效性的硅胶评价
Pub Date : 2021-11-25 DOI: 10.3390/biologics1030024
H. A. El-Mageed, Doaa A. Abdelrheem, Md. Oliullah Rafi, Md. Takim Sarker, Khattab Al-Khafaji, Md. Jamal Hossain, R. Capasso, T. Emran
The ongoing pandemic situation of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global threat to both the world economy and public health. Therefore, there is an urgent need to discover effective vaccines or drugs to fight against this virus. The flavonoids and their medicinal plant sources have already exhibited various biological effects, including antiviral, anti-inflammatory, antioxidant, etc. This study was designed to evaluate different flavonoids from medicinal plants as potential inhibitors against the spike protein (Sp) and main protease (Mpro) of SARS-CoV-2 using various computational approaches such as molecular docking, molecular dynamics. The binding affinity and inhibitory effects of all studied flavonoids were discussed and compared with some antiviral drugs that are currently being used in COVID-19 treatment namely favipiravir, lopinavir, and hydroxychloroquine, respectively. Among all studies flavonoids and proposed antiviral drugs, luteolin and mundulinol exhibited the highest binding affinity toward Mpro and Sp. Drug-likeness and ADMET studies revealed that the chosen flavonoids are safe and non-toxic. One hundred ns-MD simulations were implemented for luteolin-Mpro, mundulinol-Mpro, luteolin-Sp, and mundulinol-Sp complexes and the results revealed strong stability of these flavonoid-protein complexes. Furthermore, MM/PBSA confirms the stability of luteolin and mundulinol interactions within the active sites of this protein. In conclusion, our findings reveal that the promising activity of luteolin and mundulinol as inhibitors against COVID-19 via inhibiting the spike protein and major protease of SARS CoV-2, and we urge further research to achieve the clinical significance of our proposed molecular-based efficacy.
由严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)引起的新冠肺炎持续大流行对世界经济和公共卫生构成了全球威胁。因此,迫切需要发现有效的疫苗或药物来对抗这种病毒。黄酮类化合物及其药用植物来源已经表现出多种生物学作用,包括抗病毒、抗炎、抗氧化等。本研究旨在使用各种计算方法,如分子对接,评估药用植物中的不同黄酮类化合物作为对抗严重急性呼吸系统综合征冠状病毒2型刺突蛋白(Sp)和主要蛋白酶(Mpro)的潜在抑制剂,分子动力学。讨论了所有研究的黄酮类化合物的结合亲和力和抑制作用,并分别与目前用于治疗新冠肺炎的一些抗病毒药物,即法匹拉韦、洛匹那韦和羟氯喹进行了比较。在所有黄酮类化合物和拟用抗病毒药物的研究中,木犀草素和蒙都醇对Mpro和Sp表现出最高的结合亲和力。药物相似性和ADMET研究表明,所选黄酮类化合物是安全无毒的。一百 对木犀草素Mpro、木犀草醇Mpro、木犀草素Sp和木犀草醇Sp复合物进行ns MD模拟,结果显示这些类黄酮蛋白复合物具有很强的稳定性。此外,MM/PBSA证实了木犀草素和木犀草醇相互作用在该蛋白活性位点内的稳定性。总之,我们的研究结果揭示了木犀草素和蒙杜林醇通过抑制SARS-CoV-2的刺突蛋白和主要蛋白酶作为新冠肺炎抑制剂的有前景的活性,我们敦促进一步研究以实现我们提出的基于分子的功效的临床意义。
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引用次数: 14
Calcium Signaling Involves Na+/H+ Exchanger and IP3 Receptor Activation in T. cruzi Epimastigotes 克鲁兹乳杆菌钙信号传导与Na+/H+交换和IP3受体激活
Pub Date : 2021-11-08 DOI: 10.3390/biologics1030022
Melina Usorach, A. Gimenez, Micaela Peppino Margutti, G. Racagni, E. Machado
The calcium ion (Ca2+) plays a fundamental role in the metabolism and cell physiology of eukaryotic cells. In general, increases in cytosolic Ca2+ may come from both of the extracellular environment through specific channels and/or calcium release from intracellular stores. The mechanism by which the ion calcium (Ca2+) is released from intracellular stores in higher eukaryotes is well known; however, in lower eukaryotes is still a subject of study. In the present work, it was elucidated that Trypanosoma cruzi epimastigotes can release Ca2+ from intracellular stores in response to high osmolarity, in a process involving a protein kinase-regulated Na+/H+ exchanger present in the acidocalsisomes of the parasite. In addition, we demonstrated that epimastigote membranes are able to release Ca2+ in response to exogenous activators of both inositol 1,4,5-triphosphate (IP3) and Ryanodine receptors. Furthermore, we also summarize the involvement of calcium-related signaling pathways in biochemical and morphological changes triggered by hyperosmotic stress in T. cruzi epimastigotes.
钙离子(Ca2+)在真核细胞的代谢和细胞生理中起着重要作用。一般来说,细胞质Ca2+的增加可能来自细胞外环境通过特定通道和/或钙从细胞内储存释放。在高等真核生物中,钙离子(Ca2+)从细胞内储存中释放的机制是众所周知的;然而,在低等真核生物中仍是一个研究课题。在目前的工作中,研究人员阐明了克氏锥虫表皮毛囊体可以在高渗透压下从细胞内释放Ca2+,这一过程涉及到一种蛋白激酶调节的Na+/H+交换,这种交换存在于寄生虫的酸溶体中。此外,我们证明了外源性肌醇1,4,5-三磷酸(IP3)和Ryanodine受体的激活剂能够释放Ca2+。此外,我们还总结了钙相关信号通路在高渗胁迫引发的克氏绦虫生化和形态变化中的作用。
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引用次数: 0
A Comprehensive Overview of the Newly Emerged COVID-19 Pandemic: Features, Origin, Genomics, Epidemiology, Treatment, and Prevention 新出现的新冠肺炎大流行的全面概述:特征、起源、基因组学、流行病学、治疗和预防
Pub Date : 2021-10-25 DOI: 10.3390/biologics1030021
Md. Takim Sarker, A. Hasan, Md. Oliullah Rafi, Md. Jamal Hossain, H. A. El-Mageed, Reem M. Elsapagh, R. Capasso, T. Emran
The coronavirus disease 2019 (COVID-19), a life-threatening pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has resulted in massive destruction and is still continuously adding to its death toll. The advent of this global outbreak has not yet been confirmed; however, investigation for suitable prophylaxis against this lethal virus is being carried out by experts all around the globe. The SARS-CoV-2 belongs to the Coronaviridae superfamily, like the other previously occurring human coronavirus variants. To better understand a new virus variant, such as the SARS-CoV-2 delta variant, it is vital to investigate previous virus strains, including their genomic composition and functionality. Our study aimed at addressing the basic overview of the virus’ profile that may provide the scientific community with evidence-based insights into COVID-19. Therefore, this study accomplished a comprehensive literature review that includes the virus’ origin, classification, structure, life cycle, genome, mutation, epidemiology, and subsequent essential factors associated with host–virus interaction. Moreover, we summarized the considerable diagnostic measures, treatment options, including multiple therapeutic approaches, and prevention, as well as future directions that may reduce the impact and misery caused by this devastating pandemic. The observations and data provided here have been screened and accumulated through extensive literature study, hence this study will help the scientific community properly understand this new virus and provide further leads for therapeutic interventions.
2019冠状病毒病(COVID-19)是由严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2)引起的一种危及生命的大流行,造成了大规模破坏,死亡人数仍在不断增加。这次全球疫情的到来尚未得到证实;然而,全球各地的专家正在开展针对这种致命病毒的适当预防措施的调查。SARS-CoV-2与以前发生的其他人类冠状病毒变种一样,属于冠状病毒超家族。为了更好地了解新的病毒变体,例如SARS-CoV-2 delta变体,研究以前的病毒株,包括它们的基因组组成和功能至关重要。我们的研究旨在解决病毒概况的基本概述,这可能为科学界提供基于证据的COVID-19见解。因此,本研究对该病毒的起源、分类、结构、生命周期、基因组、突变、流行病学以及与宿主-病毒相互作用相关的后续重要因素进行了全面的文献综述。此外,我们总结了大量的诊断措施、治疗方案,包括多种治疗方法和预防,以及可能减少这一毁灭性流行病造成的影响和痛苦的未来方向。这里提供的观察和数据是通过广泛的文献研究筛选和积累的,因此这项研究将有助于科学界正确认识这种新病毒,并为治疗干预提供进一步的线索。
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引用次数: 7
Nucleic Acid Vaccines for COVID-19: A Paradigm Shift in the Vaccine Development Arena 新冠肺炎核酸疫苗:疫苗研发领域的范式转变
Pub Date : 2021-10-23 DOI: 10.3390/biologics1030020
Vivek P. Chavda, Md Kamal Hossain, Jayesh V. Beladiya, V. Apostolopoulos
Coronavirus disease, COVID-19, has touched every country globally except five countries (North Korea, Turkmenistan, Tonga, Tuvalu and Nauru). Vaccination is the most effective method to protect against infectious diseases. The objective is to ensure that everyone has access to a COVID-19 vaccine. The conventional vaccine development platforms are complex and time-consuming to obtain desired approved vaccine candidates through rigorous regulatory pathways. These safeguards guarantee that the optimized vaccine product is safe and efficacious for various demographic populations prior to it being approved for general use. Nucleic acid vaccines employ genetic material from a pathogen, such as a virus or bacteria, to induce an immune response against it. Based on the vaccination, the genetic material might be DNA or RNA; as such, it offers instructions for producing a specific pathogen protein that the immune system will perceive as foreign and mount an immune response. Nucleic acid vaccines for multiple antigens might be made in the same facility, lowering costs even more. Most traditional vaccine regimens do not allow for this. Herein, we demonstrate the recent understanding and advances in nucleic acid vaccines (DNA and mRNA based) against COVID-19, specifically those in human clinical trials.
除了朝鲜、土库曼斯坦、汤加、图瓦卢、瑙鲁等5个国家外,新冠肺炎疫情已经蔓延到世界各国。接种疫苗是预防传染病最有效的方法。目标是确保每个人都能获得COVID-19疫苗。传统的疫苗开发平台复杂且耗时,通过严格的监管途径获得所需的批准候选疫苗。这些保障措施确保优化后的疫苗产品在被批准普遍使用之前对各种人口群体是安全有效的。核酸疫苗利用来自病原体(如病毒或细菌)的遗传物质来诱导对其的免疫反应。根据疫苗接种情况,遗传物质可能是DNA或RNA;因此,它为产生一种特定的病原体蛋白质提供了指令,免疫系统将其视为外来物并发起免疫反应。针对多种抗原的核酸疫苗可以在同一工厂生产,从而进一步降低成本。大多数传统的疫苗方案不允许这种情况发生。在此,我们展示了针对COVID-19的核酸疫苗(基于DNA和mRNA)的最新认识和进展,特别是在人体临床试验中的核酸疫苗。
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引用次数: 43
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