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From Data to Knowledge: A Mini-Review on Molecular Network Modeling and Analysis for Therapeutic Target Discovery 从数据到知识:分子网络模型和治疗靶点发现分析综述
Pub Date : 2023-07-05 DOI: 10.33696/pharmacol.4.043
Mustafa Ozen, E. Emamian, A. Abdi
Successful drug development is a risky and lengthy process that can take over ten years and consume billions of dollars. Target discovery is a critical stage of drug development for the identification of key molecules and pathways that can be targeted by novel therapeutics to find more effective treatments. Due to the rapid development in artificial intelligence and machine learning techniques over the past decade, computational approaches have now emerged as powerful tools to unravel complex interactions within biological systems to identify novel therapeutic targets. In particular, modeling and analysis of intracellular molecular networks play a pivotal role in target discovery by enabling researchers to efficiently and simultaneously navigate massive amounts of biological data to identify potential therapeutic targets. Such technologies can significantly accelerate the prolonged process of development of innovative therapies for complex diseases. Besides highlighting the findings of the recently introduced extreme signaling failures in intracellular molecular networks, here we briefly review various methods for modeling and analysis of intracellular molecular networks and discuss how they can be utilized to predict potential drug targets within such complex signaling systems. Overall, this review emphasizes the significance of modeling and analysis of molecular networks for fast-tracking and rapid discovery of novel therapeutic targets; to pave the way for the development of more effective treatments.
成功的药物开发是一个危险而漫长的过程,可能需要10年以上的时间,耗资数十亿美元。靶标发现是药物开发的关键阶段,用于识别关键分子和途径,这些分子和途径可以被新疗法靶向,从而找到更有效的治疗方法。由于人工智能和机器学习技术在过去十年中的快速发展,计算方法现在已经成为揭示生物系统内复杂相互作用以确定新的治疗靶点的强大工具。特别是,细胞内分子网络的建模和分析在靶点发现中起着关键作用,使研究人员能够有效地同时导航大量的生物数据以识别潜在的治疗靶点。这些技术可以显著加快复杂疾病创新疗法的长期开发进程。除了强调最近在细胞内分子网络中引入的极端信号失败的发现外,在这里我们简要回顾了细胞内分子网络建模和分析的各种方法,并讨论了如何利用它们来预测这种复杂信号系统中的潜在药物靶点。总之,这篇综述强调了分子网络的建模和分析对于快速跟踪和快速发现新的治疗靶点的重要性;为开发更有效的治疗方法铺平道路。
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引用次数: 0
Proto-oncogenes Crosstalk, Feedback and Expression, and Anticancer Drugs Resistance 原癌基因串扰、反馈与表达与抗癌药物耐药
Pub Date : 2023-04-18 DOI: 10.33696/pharmacol.4.040
M. Elalfy, M. G. Elhadidy, E. M. El Nashar
Proto-oncogenes like C-MYC, EGFR and others have physiological function in regeneration, wound and any stressfully injury to maintain tissue echotexture and healing. Notably, these growth factors work together and had life span to retain to basal level after tissue remodeling and retain its function like what happen in partial hepatectomy. While in cancer, as we work out in 2 transgenic model of liver cancer, we notice that oncogenes do not like each other and just one of them was highly expressive, it keeps other ones at basal level or degraded. Moreover, if one oncogene was inhibited or silenced, other oncogenes become active or expressed and result in anticancer drug resistance. So bispecific antibody could successfully reduce anti-cancer drug resistance.
原癌基因如C-MYC、EGFR等在再生、伤口和任何应激性损伤中具有维持组织回声和愈合的生理功能。值得注意的是,这些生长因子共同作用,在组织重塑后,其寿命保持在基础水平,并保持其功能,就像部分肝切除术一样。而在癌症中,正如我们在肝癌的2个转基因模型中所做的那样,我们注意到致癌基因彼此不喜欢,只有其中一个是高度表达的,它使其他基因保持在基础水平或降解。此外,如果一个癌基因被抑制或沉默,其他癌基因就会变得活跃或表达,从而导致抗癌耐药。因此,双特异性抗体可以成功地降低抗癌药物的耐药性。
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引用次数: 0
Keeping Ready against Omicron and Future Variants: Can Ivermectin Prophylactic Effects Improve the Vaccination Effects against COVID-19? 为欧米克隆和未来变异做好准备:伊维菌素的预防作用能提高COVID-19疫苗接种效果吗?
Pub Date : 2023-02-23 DOI: 10.33696/pharmacol.4.039
Hamidreza Zalpoor, M. Nabi-Afjadi, F. Aziziyan, Chanour Tavakol
The standard treatment options for Coronavirus disease 2019 (COVID-19) remain challenging despite community vaccinations and reduced mortality. As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus continues to evolve and new strains emerge, diversity in the use of existing antiviral drugs has become a crucial therapeutic tool in combating the COVID-19 epidemic. Many types of infectious diseases, including DNA and RNA viruses, have traditionally been treated with ivermectin, a broad-spectrum anti-parasitic, and anti-viral drug. In spite of this, the effectiveness of ivermectin as a treatment for SARS-CoV-2 is still controversial, based on currently available data. The aim of this study was to provide comprehensive information on ivermectin, including its safety and efficacy. We hypothesized that ivermectin prophylactic effects may enhance vaccine effectiveness against SARS-CoV-2 infection in this study. Also, the combination of ivermectin with other drugs to reduce its adverse effects could be beneficial and we suggest that it can be evaluated in future studies.
尽管社区接种疫苗并降低了死亡率,但2019年冠状病毒病(COVID-19)的标准治疗方案仍然具有挑战性。随着严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)病毒的不断进化和新毒株的出现,多样化使用现有抗病毒药物已成为抗击COVID-19流行病的关键治疗工具。许多类型的传染病,包括DNA和RNA病毒,传统上用伊维菌素治疗,这是一种广谱抗寄生虫和抗病毒药物。尽管如此,根据目前可用的数据,伊维菌素作为SARS-CoV-2治疗的有效性仍然存在争议。本研究的目的是提供有关伊维菌素的全面信息,包括其安全性和有效性。在本研究中,我们假设伊维菌素的预防作用可能会增强疫苗对SARS-CoV-2感染的有效性。此外,伊维菌素与其他药物联合使用以减少其不良反应可能是有益的,我们建议可以在未来的研究中进行评估。
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引用次数: 0
The Role of the General Practitioner in Vaccination against COVID-19 全科医生在COVID-19疫苗接种中的作用
Pub Date : 2023-02-22 DOI: 10.33696/pharmacol.4.037
J. Turabián
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引用次数: 0
POSTCOVID-19WAR Era, Interaction between Cancer-Hematologic Disorders- Diabetes Significantly Increased by COVID-19 Variants, Aggressively COVID-19后时代,COVID-19变异显著增加了癌症-血液病-糖尿病之间的相互作用
Pub Date : 2023-02-22 DOI: 10.33696/pharmacol.4.038
B. Badlou
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引用次数: 0
Application of Halides Complexes of Ruthenium (II) in Metallopharmaceuticals and in Material Science: Part-I 钌卤化物配合物在金属制药和材料科学中的应用(一)
Pub Date : 2023-02-18 DOI: 10.33696/pharmacol.4.042
V. K. Sahu, A. Soni, Kavindra Kumar Mishra, Rajesh K Singh
Ruthenium readily forms coordinate-complexes and these complexes have their applications in diverse fields. A survey of literature shows that designing of new ligands that can be complexed with Ruthenium (Ru) in various oxidation states can lead to development of new materials with diverse applications. In 21st century the gravity of approach of material science together with computer science has shifted from, how to make a molecule to what molecule to make, in other words molecular design. And now these are also quantized. As we know that physics, chemistry, and biology were explored at atomic levels and finally mathematical data were fed to grow required software for aimed simulations. The aim of present study is to study halides and mixed halides of Ru(II), which more precisely can help in the development of new Ru(II) complexes of desired application and or can help in fine tuning the property of pre-existing Ru(II) complexes. Thus, this study of atomistic details of halides of Ru(II) compounds along with construction of molecular orbital diagram at a glance will provide an insight of physicochemical, biochemical, electrochemical, thermochemical, magnetic, spectrochemical, catalytic, photoactive, and materialistic details. And this will help to solve the difficulties of synthesis of various complexes yet not synthesized. We know that all chemical reaction of complex compounds will be affected firstly by availability of vacant orbital(s) on metal ion (Ru2+) and secondly by the easiness of donation of electron pair(s) by ligands as we have also studied cloud-expanding effect, nephelauxetic effect, and electrochemical series of these Ruthenium(II) halides. The substitution reaction of complex compounds will also be mechanized and new substitution products (compounds) can also be prepared as topological analysis have also been made, those yet cannot synthesize by ordinary methods in required time and required cost too. Hence the halides of Ru(II) studied firstly. With the help of results of these studies, we will able to study complexation of these halides with selective ligands to form selective complex compounds of Ru(II) yet not prepared or have difficulties in preparation.
钌很容易形成配位配合物,这些配合物在许多领域都有应用。一项文献调查表明,设计可以与不同氧化态的钌(Ru)络合的新配体可以导致具有多种应用的新材料的开发。进入21世纪,材料科学和计算机科学研究的重心已经从“如何制造分子”转向了“制造什么分子”,也就是分子设计。现在这些也是量子化的。正如我们所知,物理学、化学和生物学都是在原子水平上进行探索的,最后,数学数据被输入到目标模拟所需的软件中。本研究的目的是研究Ru(II)的卤化物和混合卤化物,这可以更精确地帮助开发新的应用所需的Ru(II)配合物,或者可以帮助微调已有的Ru(II)配合物的性质。因此,对Ru(II)化合物卤化物原子细节的研究以及分子轨道图的构建一目了然,将提供对物理化学、生化、电化学、热化学、磁性、光谱化学、催化、光活性和物质细节的洞察。这将有助于解决各种尚未合成的配合物的合成困难。我们还研究了钌卤化物的云膨胀效应、浊化效应和电化学系列,发现影响络合物化学反应的首要因素是金属离子(Ru2+)空轨道的可用性,其次是配体给电子对的难易性。复杂化合物的取代反应也将机械化,通过拓扑分析也可以制备出新的取代产物(化合物),而那些用普通方法在规定的时间和成本下还无法合成的取代产物(化合物)。因此首先对Ru(II)卤化物进行了研究。在这些研究结果的帮助下,我们将能够研究这些卤化物与选择性配体的络合,形成尚未制备或难以制备的Ru(II)的选择性络合化合物。
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引用次数: 0
Reflections on COVID-19 Pharmacological Treatment and Beyond: Beware of “Salads” with Many Ingredients but Low Scientific Content 对COVID-19药物治疗及后续治疗的思考:小心成分多但科学含量低的“沙拉”
Pub Date : 2023-02-18 DOI: 10.33696/pharmacol.4.041
J. Turabián
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引用次数: 0
Off Label Use as an Indicator of Therapeutic Need in Pediatrics 标签外使用作为儿科治疗需求的指标
Pub Date : 2022-12-12 DOI: 10.33696/pharmacol.4.036
S. Cammarata
There are therapeutic areas where the unauthorized use of a medicine is very wide, for example the pediatric field. The spread of off-label use in the pediatric field derives mainly from the difficulty in starting trials in this context, situation which it has long been reflected in a social and ethical paradigm. The pediatric population should be protected from research, but the difficulty in starting trials involving this population makes it “orphan” of authorized therapies. Ethical and, sometimes, methodological and economic issues make the pediatric trials “unattractive”. Furthermore, children are not a homogeneous population; in fact, within this category it is possible to distinguish different groups based on age groups characterized by biological diversity and for which starting a trial would be an expensive and complex process [2].
在一些治疗领域,未经授权使用药物的情况非常普遍,例如儿科领域。说明书外用药在儿科领域的蔓延主要源于在这种情况下开始试验的困难,这种情况长期以来一直反映在社会和伦理范式中。儿科人群应该受到保护,不受研究的影响,但开始涉及这一人群的试验的困难使其成为授权治疗的“孤儿”。伦理问题,有时还有方法学和经济问题,使得儿科试验“没有吸引力”。此外,儿童并不是一个单一的群体;事实上,在这一类别中,可以根据以生物多样性为特征的年龄组区分不同的群体,而开始试验将是一个昂贵而复杂的过程[2]。
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引用次数: 0
Relative COVID-19 Vaccine Booster Effectiveness and Clinical- Epidemiological Characteristics Before and After 29 Days of Shot COVID-19疫苗增强剂的相对有效性和注射前后29天的临床流行病学特征
Pub Date : 2022-11-09 DOI: 10.33696/pharmacol.4.031
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引用次数: 0
Use of second Anti-Tumour Necrosis Factor Agent in Inflammatory Bowel Disease When First Agent Failed: A South African Retrospective Study 当第一种抗肿瘤坏死因子药物无效时,在炎性肠病中使用第二种抗肿瘤坏死因子药物:一项南非回顾性研究
Pub Date : 2022-11-09 DOI: 10.33696/pharmacol.4.033
E. Fredericks, A. Titis, Suereta Fortuin, Shiraaz Gabriel, M. Setshedi
Background: Inflammatory bowel disease is a chronic relapsing and remitting inflammation of the bowel. Tumour necrosis factor α antagonists are safe and effective in the treatment of inflammatory bowel disease. Indications and outcomes with consecutive anti-tumour necrosis factor agents, although often used, are not clear. Since data for this treatment choice is scarce, we set out to evaluate the use of consecutive anti-tumour necrosis factor agents in patients with inflammatory bowel disease. Method: A national registry established by The South African Gastroenterology Society was used for retrospective data extraction in patients with consecutive anti-tumour necrosis factor agent use. Demographic, clinical details, treatment outcomes and adverse events were documented. Results: Eight-six (7.5%) of 1150 patients received consecutive tumour necrosis factor-antagonists. There were 41 (48%) patients with Crohn’s disease and 45 (52%) with ulcerative colitis. Gender distribution was equal with 45 (52%) male and 41 (48%) female patients. Patients failed the first anti-tumour necrosis factor agent over 30 months, but remission rates improved with second agent. Immunomodulator therapy had no effect of anti-tumour necrosis agent discontinuation rates. Adalimumab treatment had higher rate of dose escalation/switching as well as adverse events compared to infliximab. Most patients remained in clinical remission except a few with CD who required surgery. Conclusion: Using a second anti-tumour necrosis factor agent when the first agent failed is often necessary in inflammatory bowel disease. Although cost-effective, this strategy lacks clarity. Patient selection is crucial and therapeutic drug monitoring should be central in that decision. Adalimumab is associated with higher rates of dose escalation and a worse side-effect profile. Patients with UC switched earlier compared to CD. First Agent Failed: South African Retrospective Study. persistence was longer at 39 months for CD compared to only 13 months for UC. They further noted that males with CD had longer treatment persistence than females but showed no gender difference in UC regarding persistence of treatment. study showed no gender predominance with respect to length of treatment or withdrawal of treatment for either UC or CD.
背景:炎症性肠病是一种慢性复发和缓解的肠道炎症。肿瘤坏死因子α拮抗剂治疗炎症性肠病安全有效。连续使用抗肿瘤坏死因子药物的适应症和结果,虽然经常使用,但尚不清楚。由于这种治疗选择的数据很少,我们开始评估炎症性肠病患者连续使用抗肿瘤坏死因子药物的情况。方法:使用南非胃肠病学学会建立的国家登记处,对连续使用抗肿瘤坏死因子药物的患者进行回顾性数据提取。记录了人口统计学、临床细节、治疗结果和不良事件。结果:1150例患者中有86例(7.5%)连续接受肿瘤坏死因子拮抗剂治疗。克罗恩病41例(48%),溃疡性结肠炎45例(52%)。性别分布相同,男性45例(52%),女性41例(48%)。患者使用第一种抗肿瘤坏死因子药物30个月后失败,但使用第二种药物缓解率提高。免疫调节剂治疗对抗肿瘤坏死药物停药率无影响。与英夫利昔单抗相比,阿达木单抗治疗具有更高的剂量升级/转换率以及不良事件。除了少数需要手术治疗的乳糜泻患者外,大多数患者仍处于临床缓解期。结论:当第一种抗肿瘤坏死因子药物无效时,使用第二种抗肿瘤坏死因子药物治疗炎症性肠病是必要的。这一战略虽然具有成本效益,但缺乏明确性。患者选择是至关重要的,治疗药物监测应在这一决定的中心。阿达木单抗与较高的剂量递增率和更严重的副作用相关。与CD相比,UC患者更早切换。南非回顾性研究:第一种药物失败。与UC的13个月相比,CD的持续时间更长,为39个月。他们进一步指出,患有乳糜泻的男性比女性治疗持续时间更长,但UC的治疗持续时间没有性别差异。研究显示,无论是UC还是CD,在治疗时间或停药方面没有性别优势。
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Archives of Pharmacology and Therapeutics
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