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Enhanced breast cancer cell targeting: RGD integrin ligand potentiates RWQWRWQWR’s cytotoxicity and inhibits migration 增强乳腺癌细胞靶向性:RGD 整合素配体可增强 RWQWRWQWR 的细胞毒性并抑制迁移
Pub Date : 2024-07-19 DOI: 10.37349/eds.2024.00052
A. Barragán-Cárdenas, Daniel Castellar-Almonacid, Yerly Vargas-Casanova, C. Parra-Giraldo, Adriana Umaña-Pérez, J. López-Meza, Z. Rivera-Monroy, J. García-Castañeda
Aim: Evaluate the selective cytotoxic effect of the palindromic sequence RWQWRWQWR and its analogues obtained by replacement of L-amino acids by D-amino acids or the functionalization by adding the RGD (integrin ligand motif) to the peptide. Methods: Peptides were obtained by SPPS, characterized by RP-HPLC and ESI-QTOF and its biological activity was evaluated using MTT assays. Evaluation of mechanism associated to the cytotoxic effect were carried out by flow cytometry, RT-qPCR, wound healing, transwell and zymography. Results: The peptides with replacements of D-amino acid showed a lesser cytotoxic effect against breast cancer cell lines, regardless it was one or several residues modified which suggested a possible specific interaction between the peptide and the cancer cell membrane besides its initial electrostatically contact. On the other hand, addition of the RGD sequence to the palindromic peptide in the N-terminal end resulted in a greater cytotoxic effect against cell lines derived from the three mainly diagnosed breast cancer molecular subtypes. An approximation on mechanisms associated to this effect was evaluated on MCF-7 cells, it shows that the peptide induced apoptosis by activating intrinsic and extrinsic pathway, which correlates with the possibility of a specific interaction, and induces mitochondrial depolarization with release of oxygen reactive species. Also, this peptide induces a reduction in migration and invasion associated with a diminish in metalloprotease 9 activity and a lesser release of IL-6, IL-10 and arginase cytokines. Conclusions: Our results suggest that this promising peptide can be considered for preclinical evaluation in the development of drugs to treat breast cancer and thus mitigate the impact of this disease.
目的:评估回文序列 RWQWRWQWR 及其类似物的选择性细胞毒性作用,这些类似物是通过将 L-氨基酸替换为 D-氨基酸或在肽中添加 RGD(整合素配体基团)进行功能化而得到的。方法:通过 SPPS 获得多肽,用 RP-HPLC 和 ESI-QTOF 对其进行表征,并用 MTT 试验评估其生物活性。通过流式细胞术、RT-qPCR、伤口愈合、transwell 和酶图法评估与细胞毒性作用相关的机制。结果显示替换了 D-氨基酸的肽对乳腺癌细胞株的细胞毒性作用较弱,不管是修饰了一个残基还是多个残基,这表明除了最初的静电接触外,肽与癌细胞膜之间还可能存在特定的相互作用。另一方面,在 N 端添加 RGD 序列的回旋肽对来自三种主要诊断乳腺癌分子亚型的细胞株具有更大的细胞毒性作用。对 MCF-7 细胞进行的近似评估显示,该肽通过激活内在和外在途径诱导细胞凋亡,这与特异性相互作用的可能性有关,并诱导线粒体去极化,释放氧活性物质。此外,该肽还能降低金属蛋白酶 9 的活性,减少 IL-6、IL-10 和精氨酸酶等细胞因子的释放,从而减少肿瘤的迁移和侵袭。结论我们的研究结果表明,在开发治疗乳腺癌的药物时,可以考虑对这种有前景的多肽进行临床前评估,从而减轻这种疾病的影响。
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引用次数: 0
Plants and fungi metabolites as novel autophagy inducers and senescence inhibitors 作为新型自噬诱导剂和衰老抑制剂的植物和真菌代谢物
Pub Date : 2024-07-01 DOI: 10.37349/eds.2024.00051
Rivka Ofir
Premature aging can be partially explained by inefficient autophagy (the process of cellular self-digestion that recycles intracellular components) and premature senescence (cease of cellular division without cell death activation). Autophagy and senescence are among the basic biochemical pathways in plants and fungi suggesting that some of their metabolites have the potential to act as autophagy inducers (AI) and senescence inhibitors (SI) and to inhibit inflammation and human aging. Several compounds have already been identified: trehalose and resveratrol are natural compounds that act as AI; flavonoids found in fruit and vegetables (curcumin, quercetin, and fisetin) are among the first SI discovered so far. New AI/SI can be identified using various approaches like hypothesis-driven approach for screening receptor agonists using an in-silico library of thousands of natural compounds; cheminformatics studies of phytochemicals using docking and molecular dynamics simulation, structure similarities/mimicry in vitro, “blind” high throughput screening (HTS) of libraries of natural metabolites against relevant models, and more. This article aims to promote the use of plant and fungi novel resources to identify bioactive molecules relevant for healthy aging based on the knowledge that plants and fungi use autophagy and senescence mechanisms for their own survival and homeostasis. As autophagy and senescence are interconnected, how drugs targeting autophagy, senescence, or both could contribute to healthy aging in humans will be speculated.
过早衰老的部分原因可能是低效的自噬(细胞自我消化过程,回收细胞内成分)和过早衰老(细胞停止分裂而不激活细胞死亡)。自噬和衰老是植物和真菌的基本生化途径之一,这表明它们的一些代谢物有可能作为自噬诱导剂(AI)和衰老抑制剂(SI),抑制炎症和人体衰老。目前已经发现了几种化合物:曲哈糖和白藜芦醇是作为自噬诱导剂的天然化合物;水果和蔬菜中的类黄酮(姜黄素、槲皮素和鱼黄素)是迄今发现的首批自噬抑制剂。新的 AI/SI 可以通过各种方法鉴定出来,如利用由数千种天然化合物组成的室内化合物库筛选受体激动剂的假设驱动法;利用对接和分子动力学模拟对植物化学物质进行化学信息学研究;体外结构相似性/模仿;根据相关模型对天然代谢物库进行 "盲法 "高通量筛选 (HTS),等等。基于植物和真菌利用自体吞噬和衰老机制维持自身生存和平衡的知识,本文旨在促进利用植物和真菌新资源来鉴定与健康衰老相关的生物活性分子。由于自噬和衰老是相互关联的,因此将推测针对自噬、衰老或两者的药物如何促进人类的健康衰老。
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引用次数: 0
Interaction of norsecurinine-type monomeric and dimeric alkaloids with α-tubulin: a molecular docking study 去甲苏氨酸类单体生物碱和二聚生物碱与α-微管蛋白的相互作用:分子对接研究
Pub Date : 2024-05-21 DOI: 10.37349/eds.2024.00047
Gérard Vergoten, Christian Bailly
Aim: New microtubule-targeting agents are needed to improve cancer treatment. The recent characterization of the anticancer alkaloid securinine as a tubulin-binding agent prompted us to explore the interaction of related monomeric and dimeric analogues with tubulin. The interaction between the α/β-tubulin dimer and alkaloids fluevirines A–F and flueggenines A–I, isolated from the bush Flueggea virosa (Roxb. ex Willd.) Royle, was investigated using molecular docking. Methods: Two molecular models were initially compared for the binding of securinine to α/β-tubulin. The pironetin-binding site model (5FNV) was selected for the subsequent docking analysis with all compounds. Empirical energies of interaction (ΔE) were measured and compared. Results: Fluevirine A has been identified as a potent tubulin binder. This dimeric alkaloid formed more stable complexes with tubulin than the monomeric counterparts, such as fluevirines B–D. The bis-indole derivative fluevirine E also provided more stable complexes than (nor)securinine. The study was extended to the dimeric alkaloids flueggenines A–I and three compounds were identified as potential tubulin binders: the polycyclic product flueggenine B, the norsecurinine-indole hybrid flueggenine E, and the norsecurinine dimer flueggenine I. This later compound proved to be well adapted to fit into the pironetin site of tubulin, extending its two norsecurinine units between the colchicine-binding area and the pironetin site, in close proximity to the pironetin-reactive cysteine-316 residue. Structure-binding relationships were delineated. Conclusions: The study identifies the dimeric alkaloids fluevirine A and flueggenine I as potential α-tubulin binding agents. For the first time, dimeric alkaloids including two C-C connected norsecurinine units are characterized as tubulin ligands. The study contributes to a better understanding of the mechanism of action of Flueggea alkaloids and should help the design of anticancer analogues targeting the pironetin site of α-tubulin.
目的:改善癌症治疗需要新的微管靶向药物。最近,抗癌生物碱 securinine 作为一种微管蛋白结合剂的表征促使我们探索相关单体和二聚体类似物与微管蛋白的相互作用。我们采用分子对接法研究了α/β-微管蛋白二聚体与从灌木 Flueggea virosa (Roxb. ex Willd.) Royle 中分离出来的生物碱 fluevirines A-F 和 flueggenines A-I 之间的相互作用。研究方法首先比较了两种securinine与α/β-tubulin结合的分子模型。在随后与所有化合物的对接分析中,选择了 pironetin 结合位点模型(5FNV)。测量并比较了相互作用的经验能量(ΔE)。结果Fluevirine A 被鉴定为一种强效的小管蛋白粘合剂。这种二聚生物碱与小管蛋白形成的复合物比单体化合物(如氟韦林 B-D)更稳定。双吲哚衍生物氟病毒因子 E 也能提供比 (nor)securinine 更稳定的复合物。研究扩展到了二聚生物碱氟矢车菊碱 A-I,并确定了三种化合物为潜在的小管蛋白结合剂:多环产物氟矢车菊碱 B、去甲琥珀酰-吲哚杂化物氟矢车菊碱 E 和去甲琥珀酰二聚物氟矢车菊碱 I。后一种化合物被证明能很好地适应微管蛋白的 pironetin 位点,在秋水仙碱结合区和 pironetin 位点之间延伸出两个去甲苏氨酸单元,非常靠近 pironetin 反应半胱氨酸-316 残基。对结构-结合关系进行了描述。结论:这项研究确定了二聚生物碱氟卫宁 A 和氟卫宁 I 是潜在的 α-管蛋白结合剂。这是首次将包括两个 C-C 连接的去甲嘌呤单位的二聚生物碱鉴定为微管蛋白配体。这项研究有助于人们更好地了解 Flueggea 生物碱的作用机制,并有助于设计以 α-微管蛋白的 pironetin 位点为靶点的抗癌类似物。
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引用次数: 1
Pain management for the neurosurgical patient in spinal procedures: overview of historic and new modalities 脊柱手术中神经外科患者的疼痛管理:历史和新模式概述
Pub Date : 2024-05-21 DOI: 10.37349/eds.2024.00046
Ashley M. Carter, Samantha Yost, Jessica Tobin, Simran Phuyal, Brandon Lucke-Wold
The potent pain-relieving properties of opioids come at a steep price. Their addictive nature and side effects raise critical concerns in managing pain after surgical spine procedures. Postoperatively, spinal surgeries often accompany acute intense pain, which presents a significant challenge in optimal recovery. This paper reviews the historical approach to pain management in spine surgeries and expands on the use of alternatives and novel agents with reduced addictive potential. Additionally showcasing individualized multimodal strategies for postoperative pain management beyond pharmacological approaches such as cognitive behavioral therapy (CBT), physical therapy, and transcutaneous electrical nerve stimulation (TENS). Given the global opioid addiction crisis, there is a growing need for a fundamental shift towards safer and effective alternatives. Transitioning beyond opioid-centric practices in spinal surgery can optimize pain relief while improving patient outcomes and minimizing risk.
阿片类药物具有强效止痛作用,但代价也很高昂。阿片类药物的成瘾性和副作用引起了人们对脊柱手术后疼痛管理的严重关切。脊柱手术后通常会伴随急性剧烈疼痛,这给最佳康复带来了巨大挑战。本文回顾了脊柱手术疼痛管理的历史方法,并阐述了可减少成瘾性的替代品和新型药物的使用。此外,本文还展示了除认知行为疗法(CBT)、物理疗法和经皮神经电刺激(TENS)等药物治疗方法之外的个性化多模式术后疼痛管理策略。鉴于全球阿片类药物成瘾危机,人们越来越需要从根本上转向更安全有效的替代品。在脊柱手术中超越以阿片类药物为中心的做法,可以优化疼痛缓解,同时改善患者预后并最大限度地降低风险。
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引用次数: 0
Stryphnodendron adstringens have a modulatory effect on inflammatory cytokines markers of in vitro activated macrophages Stryphnodendron adstringens 对体外活化巨噬细胞的炎症细胞因子标记有调节作用
Pub Date : 2024-05-11 DOI: 10.37349/eds.2024.00045
I. D. da Cruz, C. F. Teixeira, N. L. Pellenz, M. Mastella, V. Azzolin, Euler Esteves Ribeiro, F. Barbisan
Aim: The purpose of this study is to conduct a comprehensive investigation into the modulatory effects of Stryphnodendron adstringens (Mart.; S. adstringens), a Brazilian wound-healing plant, on the expression of inflammatory cytokines. This will be achieved using an in vitro protocol with the commercial macrophage cell line RAW 264.7. Methods: The macrophage inflammatory response was induced by the natural antigen phytohemagglutinin (PHA), with and without supplementation of different concentrations of S. adstringens extract. The effects on cell proliferation rate and the concentration and production of transcripts of pro-inflammatory cytokines interleukin 1β (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), as well as the anti-inflammatory cytokine IL-10, were assessed using spectrophotometric, immunoassay, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) techniques. Results: S. adstringens extract at all concentrations tested here reduced the cellular proliferation rate of activated macrophages. Extracts at concentrations of 0.49 mg/mL and 0.99 mg/mL decreased the protein and gene expression of pro-inflammatory cytokines, exhibiting the opposite effect concerning IL-10. Conclusions: The findings suggest that the wound-healing action of S. adstringens may encompass differential modulation of inflammation associated with tissue injury.
目的:本研究旨在全面调查巴西伤口愈合植物 Stryphnodendron adstringens(Mart.这项研究将采用商业巨噬细胞系 RAW 264.7 的体外实验方案来实现。研究方法用天然抗原植物血凝素(PHA)诱导巨噬细胞炎症反应,同时添加或不添加不同浓度的 S. adstringens 提取物。使用分光光度法、免疫测定法和定量反转录聚合酶链反应(qRT-PCR)技术评估了对细胞增殖率、促炎细胞因子白细胞介素 1β (IL-1β)、IL-6、肿瘤坏死因子-α (TNF-α)、干扰素-γ (IFN-γ)以及抗炎细胞因子 IL-10 的浓度和转录物产生的影响。结果显示所有测试浓度的 S. adstringens 提取物都能降低活化巨噬细胞的细胞增殖率。浓度为 0.49 毫克/毫升和 0.99 毫克/毫升的提取物可降低促炎细胞因子的蛋白和基因表达,而对 IL-10 则表现出相反的效果。结论研究结果表明,S. adstringens 的伤口愈合作用可能包括对组织损伤相关炎症的不同调节。
{"title":"Stryphnodendron adstringens have a modulatory effect on inflammatory cytokines markers of in vitro activated macrophages","authors":"I. D. da Cruz, C. F. Teixeira, N. L. Pellenz, M. Mastella, V. Azzolin, Euler Esteves Ribeiro, F. Barbisan","doi":"10.37349/eds.2024.00045","DOIUrl":"https://doi.org/10.37349/eds.2024.00045","url":null,"abstract":"Aim: The purpose of this study is to conduct a comprehensive investigation into the modulatory effects of Stryphnodendron adstringens (Mart.; S. adstringens), a Brazilian wound-healing plant, on the expression of inflammatory cytokines. This will be achieved using an in vitro protocol with the commercial macrophage cell line RAW 264.7. Methods: The macrophage inflammatory response was induced by the natural antigen phytohemagglutinin (PHA), with and without supplementation of different concentrations of S. adstringens extract. The effects on cell proliferation rate and the concentration and production of transcripts of pro-inflammatory cytokines interleukin 1β (IL-1β), IL-6, tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), as well as the anti-inflammatory cytokine IL-10, were assessed using spectrophotometric, immunoassay, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) techniques. Results: S. adstringens extract at all concentrations tested here reduced the cellular proliferation rate of activated macrophages. Extracts at concentrations of 0.49 mg/mL and 0.99 mg/mL decreased the protein and gene expression of pro-inflammatory cytokines, exhibiting the opposite effect concerning IL-10. Conclusions: The findings suggest that the wound-healing action of S. adstringens may encompass differential modulation of inflammation associated with tissue injury.","PeriodicalId":72998,"journal":{"name":"Exploration of drug science","volume":"117 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140987797","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
Daropeptide natural products 达罗肽天然产品
Pub Date : 2024-04-19 DOI: 10.37349/eds.2024.00042
Suze Ma, Sijia Guo, Wei Ding, Qi Zhang
Cyclophane-containing peptides comprise an important group of macrocyclic peptides with unique structural properties and pharmaceutical relevance. Darobactin A is a ribosomally synthesized and post-translationally modified peptide (RiPP) antibiotic, which features an unusual biscyclophane moiety formed via the class-defining ether crosslink in addition to a carbon-carbon (C-C) crosslink. Because darobactin-like peptides (daropeptides) are widespread in nature, further exploration of these emerging RiPP natural products featuring ether crosslinked cyclophane could facilitate the discovery and development of new bioactive peptides. This perspective provides updated insights into the biosynthesis and classification of daropeptides, highlighting the potential to manipulate daropeptide maturases to access novel bioactive peptide cyclophanes.
含环烷肽是一类重要的大环肽,具有独特的结构特性和药用价值。Darobactin A 是一种经核糖体合成和翻译后修饰的多肽(RiPP)抗生素,其特点是除了碳-碳(C-C)交联外,还通过定义类别的醚交联形成不寻常的双环烷分子。由于达罗巴肽类多肽(daropeptides)在自然界中广泛存在,进一步探索这些以醚交联环烷为特征的新兴 RiPP 天然产物,有助于发现和开发新的生物活性多肽。这一观点提供了关于达拉肽的生物合成和分类的最新见解,强调了操纵达拉肽成熟酶以获得新型生物活性肽环烷的潜力。
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引用次数: 0
Stapled peptides: targeting protein-protein interactions in drug development 带钉肽:在药物开发中瞄准蛋白质与蛋白质之间的相互作用
Pub Date : 2024-04-18 DOI: 10.37349/eds.2024.00041
Qian Zhang, Ziyang Wang, Xiaohan Mei, Quan Chen, Chunqiu Zhang
Protein-protein interactions (PPIs) impersonate a significant role in many biological processes and are potential therapeutic targets in numerous human diseases. Stapled peptides, as the most promising therapeutic candidate for interfering with PPIs, have a higher degree of α-helicity, improved binding affinity, more resistance to proteolytic digestion, longer serum half-life, and enhanced cell permeability, which exhibits higher pharmacological activity compared with small molecule drugs and biologics. This review outlined the continuous progress of stapled peptides mainly concerning the design principle, structural stability, bioactivity, cell permeability, and potential applications in therapeutics, which is aimed at providing a broad reference for the design and exploration of stapled peptides with enhanced biological and pharmacokinetic properties as the next-generation therapeutic peptide drugs targeting various diseases.
蛋白质-蛋白质相互作用(PPIs)在许多生物过程中扮演着重要角色,是许多人类疾病的潜在治疗靶点。钉钉肽作为最有希望干扰PPIs的候选治疗药物,具有更高的α-螺旋度、更强的结合亲和力、更强的抗蛋白酶消化能力、更长的血清半衰期和更强的细胞渗透性,与小分子药物和生物制剂相比具有更高的药理活性。本综述主要从设计原理、结构稳定性、生物活性、细胞渗透性以及在治疗中的潜在应用等方面概述了钉状肽的研究进展,旨在为设计和探索具有更强生物学和药代动力学特性的钉状肽作为针对各种疾病的下一代治疗肽药物提供广泛的参考。
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引用次数: 0
Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives 旨在延缓或逆转正常衰老过程的药物和生物制剂临床研究--新成果和未来展望
Pub Date : 2024-04-10 DOI: 10.37349/eds.2024.00040
Ricardo P. Garay
Five families of investigational products are in clinical investigation to slow or reverse normal aging processes [longevity candidates, mesenchymal stem cells, senolytics drugs, sirtuin activators, and nicotinamide adenine dinucleotide (NAD)+ precursors]. The longevity candidates, vitamin D and metformin, appear to significantly reduce all-cause mortality and prolong life expectancy. This should be confirmed by interventional studies. The mesenchymal stem cell family is the most advanced in clinical trial development [phase 2b randomized controlled trial (RCT)]. An allogeneic bone marrow stem cell preparation (Lomecel-B) reduced locomotor frailty in older people. The improvement in locomotion was modest. In the future, attempts could be made to improve potency through a precondition or genetic modification of naive bone marrow stem cells. Autologous adipose stem cell-assisted fat grafting increased graft survival, facial volume, and skin quality. The association of the senolytic drugs dasatinib and quercetin was well tolerated, with low brain penetration of dasatinib and undetectable levels of quercetin. The sirtuin-1 activator resveratrol (combined with physical exercise) improved physical function in older adults with physical limitations. The NAD+ precursor nicotinamide riboside improved physical exercise performance. In conclusion, Lomecel-B is the most advanced agent in clinical trial development for normal aging processes (phase 2b for locomotion frailty), followed by resveratrol and nicotinamide riboside.
目前有五种在研产品[长寿候选药物、间充质干细胞、衰老药物、sirtuin 激活剂和烟酰胺腺嘌呤二核苷酸(NAD)+ 前体]正在接受临床研究,以延缓或逆转正常衰老过程。长寿候选药物维生素 D 和二甲双胍似乎能显著降低全因死亡率并延长预期寿命。这一点应通过干预研究加以证实。间充质干细胞家族是临床试验发展最前沿的[2b期随机对照试验(RCT)]。异体骨髓干细胞制剂(Lomecel-B)减轻了老年人的运动虚弱。对运动能力的改善不大。未来,可尝试通过对天真骨髓干细胞进行先决条件或基因修饰来提高其效力。自体脂肪干细胞辅助脂肪移植提高了移植存活率、面部容积和皮肤质量。衰老药物达沙替尼和槲皮素的联合用药耐受性良好,达沙替尼的脑穿透率低,而槲皮素的含量则检测不到。sirtuin-1激活剂白藜芦醇(与体育锻炼相结合)可改善身体机能受限的老年人的身体机能。NAD+前体物烟酰胺核苷可改善体育锻炼表现。总之,Lomecel-B 是针对正常衰老过程(运动虚弱的 2b 阶段)进行临床试验开发的最先进药物,其次是白藜芦醇和烟酰胺核苷。
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引用次数: 0
Glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide agonists for the treatment of obesity and diabetes mellitus 治疗肥胖症和糖尿病的胰高血糖素样肽-1 和葡萄糖依赖性促胰岛素多肽激动剂
Pub Date : 2024-04-03 DOI: 10.37349/eds.2024.00039
Alexander C Martins, B. G. de la Torre, Fernando Albericio
Pharmaceutical interventions play a vital role in managing various conditions, including weight-related issues such as obesity. In this context, lifestyle changes are often challenging to maintain, especially for individuals struggling with this condition. Obesity is strongly linked to serious health conditions like cardiovascular disease and insulin resistance, leading to a cascade of health risks. Importantly, the development of effective and safe weight loss medications has been challenging. Diabetes mellitus (DM), the incidence of which is also rising, is closely related to obesity. The annual rate of DM cases has increased significantly, mirroring trends in obesity. Pharmaceutical companies have made significant progress in developing drugs that address both diabetes and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a promising class of medications with dual benefits in managing diabetes and aiding weight loss such as semaglutide, liraglutide, dulaglutide, exenatide, among others. However, despite their effectiveness, they can be expensive. The availability of various GLP-1RAs offers flexibility in diabetes management, but the surge in their prescription has led to a global shortage. Health authorities are working to address this issue, while pharmaceutical companies are exploring new paths to improve the quality of these drugs. In this context, tirzepatide stands out as a medication targeting key hormones involved in obesity and DM. Another potential breakthrough, retatrutide, is also being developed for these two conditions, but it requires further research. In this paper, the authors address all the GLP-1RA options developed to date, covering their mechanisms of action, efficacy, and chemical structures, among other aspects.
药物干预在控制各种疾病(包括肥胖等与体重有关的问题)方面发挥着重要作用。在这种情况下,生活方式的改变往往很难坚持下去,尤其是对于饱受肥胖困扰的人来说。肥胖与心血管疾病和胰岛素抵抗等严重健康问题密切相关,会导致一系列健康风险。重要的是,开发有效、安全的减肥药物一直是一项挑战。糖尿病(DM)的发病率也在上升,这与肥胖密切相关。糖尿病病例的年增长率与肥胖症的趋势如出一辙。制药公司在开发治疗糖尿病和肥胖症的药物方面取得了重大进展。胰高血糖素样肽-1受体激动剂(GLP-1RAs)已成为一类前景看好的药物,具有控制糖尿病和帮助减肥的双重功效,如塞马鲁肽、利拉鲁肽、度拉鲁肽和艾塞那肽等。然而,这些药物虽然有效,但价格昂贵。各种 GLP-1RA 的出现为糖尿病治疗提供了灵活性,但其处方量的激增已导致全球短缺。卫生部门正在努力解决这一问题,而制药公司也在探索提高这些药物质量的新途径。在这种情况下,针对肥胖和糖尿病关键激素的药物--替扎帕肽(tirzepatide)脱颖而出。另一种潜在的突破性药物--雷他鲁肽,也正在针对这两种病症进行研发,但还需要进一步的研究。在本文中,作者讨论了迄今为止开发的所有 GLP-1RA 选择,涵盖了它们的作用机制、疗效和化学结构等方面。
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引用次数: 0
Mini-review on the antimicrobial potential of actinobacteria associated with seagrasses 与海草有关的放线菌抗菌潜力小综述
Pub Date : 2024-02-29 DOI: 10.37349/eds.2024.00038
Galana Siro, Atanas Pipite
The search for novel therapeutic agents to combat the crisis of antimicrobial resistance has spanned from terrestrial to unique, marine environments. Currently, most of the drugs available for usage are derived from microbial metabolites, especially those belonging to the bacterial group, actinobacteria. Actinobacteria are hotspot organisms that exist in all habitats with a myriad of unique biosynthetic metabolites. Seagrasses appear to be a key ecosystem within the coastal environment worth bioprospecting for novel natural products. Unfortunately, literature about the bioactive potential of their associated prokaryotes, including actinobacteria remains limited. In this context, this review focused on actinobacteria with antibiotic-producing capabilities derived from different parts of seagrass plants (i.e. roots, rhizomes, and leaves). To date, there were no purified molecules derived from seagrass-associated actinobacteria that were subjected to structure elucidation. From the underpinning of numerous biological profiles such as antibacterial, antifungal, and algicidal activities of seagrass-derived actinobacteria reported in this review during the period from 2012–2020, it provides a continual growth of knowledge accruing overtime, providing a foundation for future research.
从陆地环境到独特的海洋环境,人们一直在寻找新型治疗药物来应对抗菌药耐药性危机。目前,大多数可用药物都来自微生物代谢产物,尤其是属于放线菌细菌群的代谢产物。放线菌是存在于所有栖息地的热点生物,具有无数独特的生物合成代谢物。海草似乎是沿海环境中一个重要的生态系统,值得对其进行生物勘探,以获得新型天然产品。遗憾的是,有关与海草相关的原核生物(包括放线菌)的生物活性潜力的文献仍然有限。在这种情况下,本综述侧重于从海草植物的不同部位(即根、根茎和叶)提取的具有抗生素生产能力的放线菌。迄今为止,还没有从海草相关放线菌中提取的纯化分子进行结构阐释。本综述报告了 2012-2020 年间海草衍生放线菌的抗菌、抗真菌和杀藻活性等众多生物学特征,这些特征为知识的不断积累提供了基础,为未来的研究奠定了基础。
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引用次数: 0
期刊
Exploration of drug science
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