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Metabolic Tagging Technology of Exosomes- An Updated Review.
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-21 DOI: 10.2174/0113816128338023241210140702
Aniruddha Sen, Palani Selvam Mohanraj, Srinivas Nagaram, Anita Samanta, Sumel Ashique, Anas Islam, Shriyansh Srivastava, Harpreet Singh, Arun Kumar Mishra, Shivani Chopra, Hitesh Chopra

Exosomes are small extracellular vesicles secreted by various cell types, playing a crucial role in intercellular communication by carrying proteins, lipids, and nucleic acids, thus holding significant potential in diagnostics and therapeutics. Accurate labeling of exosomes is vital for studying their biogenesis, trafficking, and functional properties, enabling precise tracking and manipulation. This review examines current labeling techniques, including metabolic glycan labeling, chemical tagging, membrane fluorescent dyes, bio-conjugation, non-covalent labeling, and cell-engineering approaches. Each method is analyzed for its efficiency, specificity, and practicality, with attention to potential artifacts and challenges. Advancements in these techniques are essential for improving our understanding of exosome biology and developing exosome-based diagnostic and therapeutic strategies, providing researchers with valuable insights into state-of-the-art techniques and their applications in exosome research.

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引用次数: 0
Network Pharmacology, Molecular Docking, Molecular Dynamics to Explore the Mechanism of Danggui Shaoyao Powder for Hepatic Encephalopathy. 网络药理学、分子对接、分子动力学探讨当归少药散治疗肝性脑病的作用机制。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-20 DOI: 10.2174/0113816128363445241218062155
Miao Zhang, Rongxin Liu, Yusen Zhao, Zixin Chen, Honglin Zhai, Hongzong Si

Background: Patients with hepatic encephalopathy (HE) have many triggers and a high mortality rate. The protective effect of existing therapeutic drugs on the liver is weak. We found that Danggui Shaoyao Powder can improve the symptoms of HE and may have a better liver protection effect. And the mechanism of it is unclear.

Objective: The research explores the mechanism of Danggui Shaoyao Powder for the treatment of HE through network pharmacology, molecular docking and molecular dynamics.

Methods: Targets of Danggui Shaoyao Powder were screened from Traditional Chinese Medicine System Pharmacology Platform (TCMSP), SwissTargetPrediction, and Uniport. GeneCards was used to gain targets of HE. Further, core targets and ingredients were screened by protein-protein interaction network (PPI) and herbs-compounds-targets network. Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were completed to screen relative sites and signaling pathways. Molecular docking and dynamics were used to show the stability of ligand-receptor complexes.

Results: IL6, SRC and kaempferol, beta-sitosterol were screened as the top two core targets and ingredients. Dendrites, dendritic trees, and membrane sides were defined as the main sites of action. Core signaling pathways were screened such as: PI3K-Akt and MAPK. Molecular docking shows well-defined binding sites and the stability of the binding is demonstrated by molecular dynamics.

Conclusion: Through this study, Danggui Shaoyao Powder may act on IL6, SRC, and other targets through ingredients such as kaempferol and beat-sitosterol and regulate signaling pathways such as PI3K-Akt, MAPK and NF-κB to the treatment of HE.

背景:肝性脑病(HE)的发病诱因多,死亡率高。现有治疗药物对肝脏的保护作用较弱。我们发现当归少药散可以改善HE的症状,并可能具有较好的护肝作用。其机制尚不清楚。目的:通过网络药理学、分子对接、分子动力学等方法探讨当归少药散治疗HE的作用机制。方法:从中药系统药理学平台(TCMSP)、SwissTargetPrediction和Uniport中筛选当归少药散的靶点。GeneCards用于获得HE目标。通过蛋白质-蛋白质相互作用网络(PPI)和草药-化合物-靶点网络筛选核心靶点和成分。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,筛选相关位点和信号通路。用分子对接和动力学方法来表征配体-受体配合物的稳定性。结果:筛选出il - 6、SRC和山奈酚、β -谷甾醇为前两大核心靶点和成分。树突、树突树和膜侧被定义为主要的作用位点。筛选核心信号通路,如:PI3K-Akt和MAPK。分子对接具有明确的结合位点,并通过分子动力学证明了其结合的稳定性。结论:通过本研究,当归少药散可能通过山奈酚、谷甾醇等成分作用于il - 6、SRC等靶点,调节PI3K-Akt、MAPK、NF-κB等信号通路,治疗HE。
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引用次数: 0
Evaluation of the Therapeutic Potential of the Methanolic Extract and Fractions of Datura stramonium in Paracetamol-intoxicated Rabbits. 曼陀罗甲醇提取物及其组分对扑热息痛中毒家兔治疗作用的评价。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-17 DOI: 10.2174/0113816128365599241226113546
Mohammad Attaullah, Hussain Ul Haq, Abdullah Khan, Bashir Ahmad, Alaa Alhegaili, Muhammad Hamayun, Sajid Ali

Introduction: Datura stramonium (DS) possesses strong medicinal and therapeutic potential but has been rarely evaluated in this context.

Methods: The present study was intended to evaluate the antioxidant, hepatoprotective, and nephroprotective potential of the crude methanolic leaf extract and ethyl acetate, chloroform, n-hexane, and aqueous fractions of DS in paracetamol-intoxicated rabbits. Paracetamol (2 g/Kg BW) was applied to induce liver and kidney injury in rabbits while the methanolic extract and fractions of DS were applied in the dose range of 150 mg/Kg to 300 mg/Kg body weight for 21 days. Histopathology of the liver, and kidney and analysis of ALT (Alanine Transaminase), ALP (Alkaline Phosphatase), total bilirubin, serum urea, serum creatinine, and serum uric acid were carried out. In-vitro antioxidant potential of the extract and fractions of DS was carried out through DPPH (1,1-diphenyl 2-picrylhydrazyl) free radical scavenging assays.

Results: The hepatoprotective and nephroprotective potential of the extract and fractions of DS at the dose level of 300 mg/Kg BW was highly significant (P ˂ 0.01). ALT was found elevated in the paracetamol-treated group (117.3 ± 1.61 U/L) compared to the group treated with methanolic extract of DS, (57.3 ± 0.87 U/L) and normal control group (60.6 ± 1.58 U/L) at 300 mg/kg BW. Elevated levels of ALP (120 ± 1.58 U/L) and Bilirubin (1.6 ± 0.32 mg/dl) were found in the paracetamol-treated group compared with the group treated with methanolic extract of DS (67.5 ± 1.35 U/L; 0.2 ± 1.0 mg/dl) and normal control group (70.1 ± 1.53 U/L; 0.4 ± 0.16 mg/dl) respectively at 300 mg/kg BW. The methanolic extract of DS produced a marked scavenging activity of the DPPH free radicals (88.2 ± 0.006 %) followed by the fractions of DS compared to ascorbic acid (95.5 + 0.003 %) at a concentration of 1000 μg/ml. The effects were comparable to those produced by ascorbic acid. Liver and kidney histology of the rabbits treated with extract, fractions, and ascorbic acid of DS caused reductions in the pathological features compared to the paracetamol-treated animals. The histological observations and chemical pathological alterations demonstrated the significant hepatoprotective and nephroprotective benefits of the DS extract and its fractions.

Conclusion: It has been concluded that the methanolic extract and fractions of DS possess antioxidant, hepatoprotective, and nephroprotective properties in paracetamol-intoxicated rabbits.

曼陀罗(DS)具有很强的药用和治疗潜力,但很少在这方面进行评估。方法:本研究旨在评价粗甲醇叶提取物和乙酸乙酯、氯仿、正己烷和DS水溶液组分对扑热息痛中毒家兔的抗氧化、肝保护和肾保护作用。采用扑热息痛(2 g/Kg BW)诱导家兔肝、肾损伤,DS的甲醇提取物和组分以150 mg/Kg ~ 300 mg/Kg体重的剂量范围给药21 d。进行肝、肾组织病理学检查,分析ALT(丙氨酸转氨酶)、ALP(碱性磷酸酶)、总胆红素、血清尿素、血清肌酐、血清尿酸。通过DPPH(1,1-二苯基- 2-苦基肼基)自由基清除实验,研究了DS提取物及其组分的体外抗氧化能力。结果:黄芪提取物和部位在300 mg/Kg BW剂量水平下具有极显著的肝保护和肾保护作用(P值小于0.01)。在300 mg/kg BW时,对乙酰氨基酚处理组ALT升高(117.3±1.61 U/L),而丹参甲醇提取物处理组ALT升高(57.3±0.87 U/L),正常对照组ALT升高(60.6±1.58 U/L)。对乙酰氨基酚治疗组ALP(120±1.58 U/L)和胆红素(1.6±0.32 mg/dl)高于丹参醇提物治疗组(67.5±1.35 U/L);0.2±1.0 mg/dl),正常对照组(70.1±1.53 U/L);在300 mg/kg BW时分别为0.4±0.16 mg/dl)。黄芪甲醇提取物对DPPH自由基的清除率(88.2±0.006%)高于抗坏血酸(95.5 + 0.003%),浓度为1000 μg/ml。其效果与抗坏血酸产生的效果相当。与扑热息痛处理的动物相比,用DS提取物、组分和抗坏血酸处理的家兔的肝脏和肾脏组织学改变导致病理特征减少。组织学观察和化学病理改变表明,DS提取物及其组分具有显著的肝和肾保护作用。结论:对扑热息痛中毒家兔具有抗氧化、保肝、保肾作用。
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引用次数: 0
ALS: A Silent Slayer of Motor Neurons. Traditional Chinese Herbal Medicine as an Effective Therapy. 肌萎缩侧索硬化症:运动神经元的无声杀手。中药作为一种有效的治疗方法。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-17 DOI: 10.2174/0113816128329141241205063352
Anjali Rai, Shivang Shukla, Ramesh Kumar Gupta, Anuradha Mishra

Amyotrophic Lateral Sclerosis (ALS), is a progressive neurodegenerative disease characterized by motor symptoms, and cognitive impairment. The complexity in treating ALS arises from genetic and environmental factors, contributing to the gradual decline of lower and upper motor neurons. The anticipated pharmaceutical market valuation for ALS is projected to reach $1,038.94 million by 2032. This projection underscores the escalating impact of ALS on global healthcare systems. ALS prevalence is expected to surge to 376,674 cases by 2040. In 2022, India ranked among the top 3 Asian-Pacific nations, while North America dominated the global ALS market. Ongoing investigations explore the potential of neuroprotective drugs like riluzole and edaravone in ALS treatment. Recently approved drugs, Relyvrio (sodium phenylbutyrate and taurursodiol) and Tofersen (Qalsody) have completed the trials, and others are currently undergoing extensive clinical trials. Continuous research and exploration of therapeutic avenues, including gene therapy and neuroprotective treatments, are imperative to address the challenges posed by ALS and other neurodegenerative diseases. Traditional Chinese Medicine (TCM) approaches and clinical trials are being explored for treating ALS symptoms, targeting neuroinflammation, oxidative damage, and muscle weakness, showcasing the potential benefits of integrating traditional and modern approaches in ALS management.

肌萎缩性侧索硬化症(ALS)是一种进行性神经退行性疾病,以运动症状和认知障碍为特征。治疗ALS的复杂性来自遗传和环境因素,导致上下运动神经元逐渐下降。预计到2032年,ALS的制药市场估值将达到10.394亿美元。这一预测凸显了ALS对全球卫生保健系统的影响日益加剧。到2040年,ALS患病率预计将飙升至376674例。2022年,印度在亚太地区排名前三,而北美在全球ALS市场占据主导地位。正在进行的研究探索神经保护药物如利鲁唑和依达拉奉在ALS治疗中的潜力。最近批准的药物Relyvrio(苯基丁酸钠和牛磺酸钠)和Tofersen (Qalsody)已经完成了试验,其他药物目前正在进行广泛的临床试验。持续研究和探索治疗途径,包括基因治疗和神经保护治疗,是解决ALS和其他神经退行性疾病带来的挑战的必要条件。中医方法和临床试验正在探索治疗ALS症状,针对神经炎症、氧化损伤和肌肉无力,展示了将传统和现代方法结合起来治疗ALS的潜在益处。
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引用次数: 0
Auranofin-loaded PLGA Nanoparticles for Neuroprotection against Aluminium-induced Alzheimer's Disease. 负载auranofin的PLGA纳米颗粒对铝诱导的阿尔茨海默病的神经保护作用。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-17 DOI: 10.2174/0113816128336703241202182209
Shiv Kumar Kushwaha, Mahendra Singh Ashawat, Rimpi Arora, Ashish Baldi

Aim: The aim of the current study was to explore nano-formulation for effective neuroprotection by auranofin.

Background: Currently, the treatment options for various CNS disorders, particularly neurodegenerative disorders, are greatly constrained. A significant obstacle in this pursuit is the blood-brain barrier, a shielding covering that hinders the route of numerous biochemical treatments into the brain. To overcome this problem, nanoformulation- based approaches are gaining interest, increasing the compound's BBB penetrability.

Objective: The objective of this study was to evaluate whether nanoparticles fabricated from poly(lactic-co-glycolic acid) encapsulated with auranofin could oppose aluminium chloride-induced Alzheimer's disease.

Method: Auranofin-encapsulated PLGA nanoparticles were prepared, and their particle size, Entrapment Efficiency (EE), distribution of particles, morphological surface charge, and structural characteristics were characterized. During the in vivo study, rats were orally administered AlCl3 at 100 mg/kg for 21 days. Meanwhile, auranofin and auranofin nanoparticles were orally administered at doses of 5 and 10 mg/kg and 2.5 and 5 mg/kg, respectively, within 2 weeks. After the course therapy, the rats were decapitated, and the hippocampus was collected for the estimated biochemical and neuroinflammatory markers.

Results: The auranofin nanoparticles were characterized, revealing % entrapment efficiency (98%) and % loading dose (76%). The nanoparticles exhibited a morphological surface charge of 27.5 ± 5.10 mV, a polydispersity index of 0.438 ± 0.12, and a mean particle size of 101.5 ± 10.3 nm. In the in vivo study, administering a gold compound (auranofin) and formulation (auranofin nanoparticles) resulted in a significant improvement in cognitive deficits, changes in biochemical parameters, and markers of neuroinflammation triggered with aluminium chloride.

Conclusion: The results have suggested that auranofin nanoparticles demonstrate abilities to protect neurons compared to auranofin alone. The noticed therapeutic benefits of the auranofin-encapsulated PLGA nanoparticles can be attributed to modulation in particle size with antioxidative and anti-inflammatory impacts of auranofin. Consequently, the outcome of the research has revealed that gold compound nanoparticles hold the potential to be a promising option for altering the therapeutic course of Alzheimer's disease.

目的:本研究的目的是探索金糠蛋白对神经保护的纳米配方。背景:目前,各种中枢神经系统疾病,特别是神经退行性疾病的治疗选择受到很大限制。这方面的一个重大障碍是血脑屏障,这是一种屏蔽物,阻碍了许多生化治疗进入大脑的途径。为了克服这个问题,基于纳米配方的方法引起了人们的兴趣,增加了化合物的血脑屏障穿透性。目的:本研究的目的是评价由聚乳酸-羟基乙酸包被金糠蛋白制备的纳米颗粒是否能对抗氯化铝诱导的阿尔茨海默病。方法:制备auranofin包封的PLGA纳米颗粒,对其粒径、包封效率(EE)、颗粒分布、形貌、表面电荷和结构特征进行表征。在体内研究中,大鼠以100 mg/kg的剂量口服AlCl3 21天。同时,在2周内分别口服剂量为5、10 mg/kg和2.5、5 mg/kg的金糠蛋白和纳米金糠蛋白。疗程结束后,将大鼠斩首,收集海马用于估计生化和神经炎症标志物。结果:对纳米金糠烯进行了表征,获得了98%的包封率和76%的载药量。纳米粒子的形态表面电荷为27.5±5.10 mV,多分散性指数为0.438±0.12,平均粒径为101.5±10.3 nm。在体内研究中,给予金化合物(金糠蛋白)和配方(金糠蛋白纳米颗粒)可显著改善认知缺陷、改变生化参数和由氯化铝引发的神经炎症标志物。结论:与单独的金糠蛋白相比,金糠蛋白纳米颗粒显示出保护神经元的能力。金萘芬封装的PLGA纳米颗粒的显著治疗效果可归因于金萘芬的抗氧化和抗炎作用的颗粒大小调节。因此,研究结果表明,金化合物纳米颗粒有可能成为改变阿尔茨海默病治疗过程的一个有希望的选择。
{"title":"Auranofin-loaded PLGA Nanoparticles for Neuroprotection against Aluminium-induced Alzheimer's Disease.","authors":"Shiv Kumar Kushwaha, Mahendra Singh Ashawat, Rimpi Arora, Ashish Baldi","doi":"10.2174/0113816128336703241202182209","DOIUrl":"https://doi.org/10.2174/0113816128336703241202182209","url":null,"abstract":"<p><strong>Aim: </strong>The aim of the current study was to explore nano-formulation for effective neuroprotection by auranofin.</p><p><strong>Background: </strong>Currently, the treatment options for various CNS disorders, particularly neurodegenerative disorders, are greatly constrained. A significant obstacle in this pursuit is the blood-brain barrier, a shielding covering that hinders the route of numerous biochemical treatments into the brain. To overcome this problem, nanoformulation- based approaches are gaining interest, increasing the compound's BBB penetrability.</p><p><strong>Objective: </strong>The objective of this study was to evaluate whether nanoparticles fabricated from poly(lactic-co-glycolic acid) encapsulated with auranofin could oppose aluminium chloride-induced Alzheimer's disease.</p><p><strong>Method: </strong>Auranofin-encapsulated PLGA nanoparticles were prepared, and their particle size, Entrapment Efficiency (EE), distribution of particles, morphological surface charge, and structural characteristics were characterized. During the in vivo study, rats were orally administered AlCl3 at 100 mg/kg for 21 days. Meanwhile, auranofin and auranofin nanoparticles were orally administered at doses of 5 and 10 mg/kg and 2.5 and 5 mg/kg, respectively, within 2 weeks. After the course therapy, the rats were decapitated, and the hippocampus was collected for the estimated biochemical and neuroinflammatory markers.</p><p><strong>Results: </strong>The auranofin nanoparticles were characterized, revealing % entrapment efficiency (98%) and % loading dose (76%). The nanoparticles exhibited a morphological surface charge of 27.5 ± 5.10 mV, a polydispersity index of 0.438 ± 0.12, and a mean particle size of 101.5 ± 10.3 nm. In the in vivo study, administering a gold compound (auranofin) and formulation (auranofin nanoparticles) resulted in a significant improvement in cognitive deficits, changes in biochemical parameters, and markers of neuroinflammation triggered with aluminium chloride.</p><p><strong>Conclusion: </strong>The results have suggested that auranofin nanoparticles demonstrate abilities to protect neurons compared to auranofin alone. The noticed therapeutic benefits of the auranofin-encapsulated PLGA nanoparticles can be attributed to modulation in particle size with antioxidative and anti-inflammatory impacts of auranofin. Consequently, the outcome of the research has revealed that gold compound nanoparticles hold the potential to be a promising option for altering the therapeutic course of Alzheimer's disease.</p>","PeriodicalId":10845,"journal":{"name":"Current pharmaceutical design","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synthetic Cannabinoids are Genotoxic in Cultured Human Lymphocytes. 合成大麻素对培养的人淋巴细胞具有遗传毒性。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-17 DOI: 10.2174/0113816128340465241227095853
Alla Abdulwahab Almestafa, Omar Falah Khabour, Laith Naser Al-Eitan, Karem Hasan Alzoubi

Background: Synthetic cannabinoids are one of the most identified abused drugs nowadays. Their popularity is due to their psychoactive effects, which resemble delta 9 tetrahydrocannabinol. This study investigates the genotoxic potential of three synthetic cannabinoids of indazole-passed drugs, AB-Fubinaca, AMBFubinaca, and EMB-Fubinaca (at a final concentration of 200 nM).

Methods: Genotoxicity was examined using Sister Chromatid Exchanges (SCEs) and Chromosomal Aberrations (CAs) assays in cultured human lymphocytes. Blood for lymphocyte cultures was obtained from healthy adult young males.

Results: A significant increase in the frequency of SCEs was detected for all examined drugs (range: 5.4-6.1, p < 0.05) compared to the control group (4.70 ± 0.31). The order of synthetic cannabinoids in terms of their ability to induce SCEs was EMB-Fubinaca (6.04 ± 0.63) > AMB-Fubinaca (5.65 ± 0.6) > AB-Fubinaca (5.33 ± 0.58). None of the examined drugs induced significant changes to the frequency of CAs (p > 0.05). Additionally, there were no effects of the synthetic cannabinoids at the studied concentration on proliferation and mitotic indices.

Conclusion: Synthetic cannabinoids have been found to increase the frequency of SCEs in cultured human lymphocytes. The results should be confirmed in in vivo studies using lymphocytes derived from synthetic cannabinoid users.

背景:合成大麻素是当今最常见的滥用药物之一。它们受欢迎的原因是它们的精神活性作用,类似于德尔塔9四氢大麻酚。本研究考察了吲哚唑通过的药物AB-Fubinaca、AMBFubinaca和EMB-Fubinaca三种合成大麻素(终浓度为200 nM)的遗传毒性潜力。方法:采用姐妹染色单体交换法(sce)和染色体畸变法(CAs)检测培养的人淋巴细胞的遗传毒性。用于淋巴细胞培养的血液取自健康的年轻成年男性。结果:与对照组(4.70±0.31)相比,各药物组SCEs检出率均显著升高(范围:5.4 ~ 6.1,p < 0.05)。合成大麻素诱导sce的能力依次为EMB-Fubinaca(6.04±0.63)、AMB-Fubinaca(5.65±0.6)、abb1 - fubinaca(5.33±0.58)。两种药物均未引起ca发生频率的显著变化(p < 0.05)。此外,在研究浓度下,合成大麻素对细胞增殖和有丝分裂指标没有影响。结论:合成大麻素可增加培养的人淋巴细胞中SCEs的发生频率。该结果应在使用合成大麻素使用者的淋巴细胞的体内研究中得到证实。
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引用次数: 0
Activation of the cGAS-sting Pathway Mediated by Nanocomplexes for Tumor Therapy. 纳米复合物介导的cgas刺痛通路的激活用于肿瘤治疗。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-16 DOI: 10.2174/0113816128339788241221160639
Yuxuan Qian, Shujuan Cao, Li He, Yanfei Cai, Zhaoqi Yang

cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway is an natural immune response signaling pathway in the human body that is essential for sensing abnormal DNA aggregation in the cell. When the cGAS protein senses abnormal or damaged DNA, it forms a second messenger called cyclic dinucleotide (cGAMP). The cycled dinucleotide will activate the downstream STING protein, thereby inducing the expression of inflammatory cytokines such as type I interferon, which binds to receptors on its own cell membrane and ultimately initiates multiple immune response pathways. This signaling pathway plays an important immune role in antimicrobial and antitumor functions, etc. so the development of drugs targeting this signaling pathway has important clinical application value. In recent years nanocomplexes based cGAS-STING signaling pathway activation and inhibition treatments have been gradually developed. In this review, on the basis of elaborating the main activation mechanism of the cGAS-STING pathway, we further introduced the nanocomplexes that effectively activate the cGAS-STING pathway, focusing on the composition, types and applications of the nanocomplexes. In addition, we discussed the key challenges and future research directions of the way that stimulating the cGAS-STING signaling pathway in the form of nanocomplexes to activate immuno-tumor therapy. Our work aims to provide a better understanding of the progress of nanotherapeutics in the cGAS-STING pathway, providing a promising anti-tumor therapeutic strategy.

cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes)通路是人体内的一种天然免疫应答信号通路,是感知细胞内DNA异常聚集所必需的。当cGAS蛋白感知到异常或受损的DNA时,它会形成第二个信使环二核苷酸(cGAMP)。循环后的二核苷酸会激活下游的STING蛋白,从而诱导I型干扰素等炎性细胞因子的表达,与自身细胞膜上的受体结合,最终启动多种免疫应答途径。该信号通路在抗菌、抗肿瘤等方面具有重要的免疫作用,因此针对该信号通路开发药物具有重要的临床应用价值。近年来,基于纳米复合物的cGAS-STING信号通路激活和抑制治疗逐渐得到发展。本文在阐述cGAS-STING途径主要激活机制的基础上,进一步介绍了有效激活cGAS-STING途径的纳米配合物,重点介绍了纳米配合物的组成、类型和应用。此外,我们讨论了以纳米复合物的形式刺激cGAS-STING信号通路激活免疫肿瘤治疗的关键挑战和未来的研究方向。我们的工作旨在更好地了解cGAS-STING通路的纳米治疗进展,提供有前景的抗肿瘤治疗策略。
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引用次数: 0
Unraveling the Therapeutic Potential of Sophora flavescens Aiton in Myocardial Infarction: An Integrative Approach Combining Bioinformatics, Network Pharmacology, and Experimental Validation. 揭示苦参对心肌梗死的治疗潜力:结合生物信息学、网络药理学和实验验证的综合方法。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-16 DOI: 10.2174/0113816128342405241204055321
Zhongbai Zhang, Yang Tong, Hongwei Xie, Mengting Jiang, Yanchun Li, Chun Liang

Aims: This study aims to elucidate the relationship between potential MI targets and SFA's mechanism of action, providing a theoretical basis for clinical development of new drugs.

Background: Myocardial infarction (MI) has been identified as one of the major cardiovascular diseases with adverse consequences. Sophora flavescens Aiton (SFA) is indicated for the therapeutic treatment of MI. However, there is no systematic research on the new therapeutic targets for MI and the exact action mechanism of SFA.

Objective: This study explores the potential mechanisms of SFA in treating MI by integrating bioinformatics, network pharmacology analyses and experimental verification.

Methods: New MI targets were predicted using bioinformatics techniques. Network pharmacology and molecular docking jointly served for predicting the key targets and underlying mechanisms of SFA. A machine learning model was developed to identify the core MI targets. Subsequently, H9c2 cardiomyocytes hypoxia model was established for experimental verification.

Results: 140 active components were ascertained in SFA and 59 differentially expressed genes (DEGs) were screened for MI. Eighty-seven shared genes were obtained by WGCAN. Eighty proteins and 413 interactions were identified by PPI network. After building the machine model, three core targets were identified (STAT1, TNFRSF1A and MCL1). According to in vitro experiments, SFA exerts a protective effect relying on three core targets and biological processes, including cell viability, the inflammatory response, and antiapoptotic effects, etc. Conclusion: This study finds new core targets for MI and the therapeutic activity of SFA against MI, of which the experimental verification provides valuable insights into the molecular mechanisms underlying SFA's efficacy in MI treatment and paves the way for targeted drug development strategies.

目的:本研究旨在阐明心肌梗死潜在靶点与SFA作用机制之间的关系,为临床开发新药提供理论依据。背景:心肌梗死(MI)已被确定为心血管疾病的主要不良后果之一。苦参(Sophora flavescens Aiton, SFA)有治疗心肌梗死的作用,但其治疗心肌梗死的新靶点及确切作用机制尚无系统研究。目的:结合生物信息学、网络药理学分析和实验验证,探讨SFA治疗心肌梗死的可能机制。方法:应用生物信息学技术预测新的心肌梗死靶点。网络药理学和分子对接共同预测了SFA的关键靶点和潜在机制。开发了一个机器学习模型来识别核心MI目标。随后,建立H9c2心肌细胞缺氧模型进行实验验证。结果:在SFA中检测到140种有效成分,在MI中筛选到59种差异表达基因(DEGs),通过WGCAN获得87种共享基因。通过PPI网络鉴定出80种蛋白和413种相互作用。建立机器模型后,确定了三个核心靶点(STAT1, TNFRSF1A和MCL1)。体外实验表明,SFA的保护作用依赖于三个核心靶点和生物学过程,包括细胞活力、炎症反应和抗凋亡作用等。结论:本研究发现了心肌梗死的新核心靶点和SFA对心肌梗死的治疗活性,实验验证为SFA治疗心肌梗死的分子机制提供了有价值的见解,为靶向药物的开发策略奠定了基础。
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引用次数: 0
Advancing COVID-19 Treatment: The Role of Non-covalent Inhibitors Unveiled by Integrated Machine Learning and Network Pharmacology. 推进COVID-19治疗:整合机器学习和网络药理学揭示的非共价抑制剂的作用。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-16 DOI: 10.2174/0113816128342951241210175314
Saba Qadir, Fahad M Alshabrmi, Faris F Aba Alkhayl, Aqsa Muzammil, Snehpreet Kaur, Abdur Rehman

Introduction: The COVID-19 pandemic has necessitated rapid advancements in therapeutic discovery. This study presents an integrated approach combining machine learning (ML) and network pharmacology to identify potential non-covalent inhibitors against pivotal proteins in COVID-19 pathogenesis, specifically B-cell lymphoma 2 (BCL2) and Epidermal Growth Factor Receptor (EGFR).

Method: Employing a dataset of 13,107 compounds, ML algorithms such as k-Nearest Neighbors (kNN), Support Vector Machine (SVM), Random Forest (RF), and Naïve Bayes (NB) were utilized for screening and predicting active inhibitors based on molecular features. Molecular docking and molecular dynamics simulations, conducted over a 100 nanosecond period, enhanced the ML-based screening by providing insights into the binding affinities and interaction dynamics with BCL2 and EGFR. Network pharmacology analysis identified these proteins as hub targets within the COVID-19 protein-protein interaction network, highlighting their roles in apoptosis regulation and cellular signaling.

Results: The identified inhibitors exhibited strong binding affinities, suggesting potential efficacy in disrupting viral life cycles and impeding disease progression. Comparative analysis with existing literature affirmed the relevance of BCL2 and EGFR in COVID-19 therapy and underscored the novelty of integrating network pharmacology with ML. This multidisciplinary approach establishes a framework for emerging pathogen treatments and advocates for subsequent in vitro and in vivo validation, emphasizing a multi-targeted drug design strategy against viral adaptability.

Conclusion: This study's findings are crucial for the ongoing development of therapeutic agents against COVID-19, leveraging computational and network-based strategies.

导言:COVID-19大流行使得治疗方法的发现取得了快速进展。本研究提出了一种结合机器学习(ML)和网络药理学的综合方法,以确定针对COVID-19发病机制中关键蛋白的潜在非共价抑制剂,特别是b细胞淋巴瘤2 (BCL2)和表皮生长因子受体(EGFR)。方法:利用13107个化合物的数据集,利用k-近邻(kNN)、支持向量机(SVM)、随机森林(RF)和Naïve贝叶斯(NB)等ML算法,基于分子特征筛选和预测活性抑制剂。在100纳秒的时间内进行分子对接和分子动力学模拟,通过深入了解BCL2和EGFR的结合亲和力和相互作用动力学,增强了基于ml的筛选。网络药理学分析发现这些蛋白是COVID-19蛋白相互作用网络中的枢纽靶点,突出了它们在细胞凋亡调节和细胞信号传导中的作用。结果:鉴定出的抑制剂表现出很强的结合亲和力,表明在破坏病毒生命周期和阻碍疾病进展方面的潜在功效。与现有文献的对比分析证实了BCL2和EGFR在COVID-19治疗中的相关性,并强调了将网络药理学与ML相结合的新颖性。这一多学科方法为新兴病原体治疗建立了框架,并倡导后续的体外和体内验证,强调了针对病毒适应性的多靶点药物设计策略。结论:本研究的发现对于利用计算和基于网络的策略正在进行的针对COVID-19治疗药物的开发至关重要。
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引用次数: 0
Selection Criteria for Oils, Surfactants, and Co-Surfactants in Ocular Nanoemulsion Formulation: A Mini Review. 眼用纳米乳液配方中油、表面活性剂和助表面活性剂的选择标准:综述。
IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2025-01-15 DOI: 10.2174/0113816128350573241202105210
Ankita Kishore, Adarsh Jain, Navdeep Asthana, Rhytham Milan, S Mohana Lakshmi, Madhu Gupta, Alok Kumar Mahor, Jovita Kanoujia

The ocular nanoemulsions (NE) are biphasic systems mainly composed of oil and water emulsified by surfactants/cosurfactants. The extensive surface area of ocular NE enhances corneal contact, leading to improved drug penetration and making it a preferable delivery system. They can also increase the solubility of drugs across the ocular barrier with improved residence time. Oils, surfactants, and co-surfactants used in formulating ocular NEs present a significant challenge in developing safe, stable, less irritant, more permeable, improved residence time, and highly bioavailable products. The choice of oil, surfactant, and co-surfactant significantly impacts the development of ocular Nano emulsions (NE) with desirable characteristics, such as small globule size, enhanced penetration, high drug content, and prolonged retention in the eye. This mini-review aims to contribute valuable insights into the selection criteria of oils, surfactants, and co-surfactants for ocular NE. Finally, the correlation between the properties of ocular NEs and the choice of oils, surfactants, and co-surfactants with emphasis on sterilization and stability aspects are considered in short.

眼纳米乳液是一种以油和水为主要成分,经表面活性剂/助表面活性剂乳化而成的双相体系。眼部NE的广泛表面积增强了角膜接触,从而改善了药物渗透,使其成为一种较好的给药系统。它们还可以增加药物在眼屏障中的溶解度,延长停留时间。用于配制眼部NEs的油、表面活性剂和助表面活性剂在开发安全、稳定、低刺激性、高渗透性、延长停留时间和高生物利用度的产品方面面临着重大挑战。油、表面活性剂和助表面活性剂的选择显著影响眼纳米乳液(NE)的形成,这些纳米乳液具有理想的特性,如小球状、增强渗透、高药物含量和在眼内滞留时间长。这篇小型综述旨在为眼部NE的油、表面活性剂和助表面活性剂的选择标准提供有价值的见解。最后,简要讨论了眼用NEs的性能与油、表面活性剂和助表面活性剂的选择之间的关系,重点是灭菌和稳定性方面。
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引用次数: 0
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Current pharmaceutical design
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