首页 > 最新文献

Pharmacological Research - Reports最新文献

英文 中文
Doxycycline attenuates cognitive impairment, neuroinflammation and oxidative stress in a mouse model of sepsis-associated encephalopathy 强力霉素减轻脓毒症相关脑病小鼠模型的认知障碍、神经炎症和氧化应激
Pub Date : 2025-12-01 DOI: 10.1016/j.prerep.2025.100072
Maria Laura da Cruz Castro , Flávia Monteiro Ferreira , Camila Francieli Chagas , Sttefany Viana Gomes , Renata Rebeca Pereira , Aline Meireles Coelho , Saulo Fehelberg Pinto Braga , Gabrielly Guimarães Coutinho , Vitória Louise Teixeira e Silva , Sirlaine Pio Gomes da Silva , André Talvani , Allan Jefferson Cruz Calsavara , Daniela Caldeira Costa
Sepsis-associated encephalopathy (SAE), affecting up to 70 % of patients with sepsis, is a diffuse cerebral dysfunction that correlates with higher mortality rates and long-term cognitive impairments such as memory deficits. The pathophysiology of SAE includes neuroinflammation, oxidative stress, apoptosis, microglial activation, blood-brain barrier (BBB) dysfunction, and metabolic disturbances. The compromised BBB during sepsis allows inflammatory mediators to infiltrate, increasing oxidative stress. Studies highlight the role of BBB disruption in SAE, with matrix metalloproteinase 9 (MMP-9) activity increasing BBB permeability. The antibiotic doxycycline inhibits MMP activity and shows promise in protecting BBB integrity by reducing neuroinflammation and oxidative stress. This study evaluates the impact and mechanisms underlying doxycycline treatment on cognitive function in mice with polymicrobial sepsis. Doxycycline treatment improves cognition in the animals and increases brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Doxycycline also inhibits MMP-9, reduces neuroinflammation and attenuates oxidative stress in the brain. In addition, molecular modeling suggests that doxycycline effectively binds to MMP-9. These findings suggest that doxycycline attenuates cognitive deficits, reduces neuroinflammation and oxidative stress, and inhibits MMP-9 in a mouse model of sepsis-associated encephalopathy.
脓毒症相关脑病(SAE)影响高达70% %的脓毒症患者,是一种弥漫性脑功能障碍,与较高的死亡率和长期认知障碍(如记忆缺陷)相关。SAE的病理生理包括神经炎症、氧化应激、细胞凋亡、小胶质细胞激活、血脑屏障(BBB)功能障碍和代谢紊乱。败血症期间受损的血脑屏障允许炎症介质浸润,增加氧化应激。研究强调了血脑屏障破坏在SAE中的作用,基质金属蛋白酶9 (MMP-9)活性增加了血脑屏障的通透性。抗生素强力霉素抑制MMP活性,显示出通过减少神经炎症和氧化应激来保护血脑屏障完整性的希望。本研究评估多西环素治疗对多微生物脓毒症小鼠认知功能的影响及其机制。强力霉素治疗改善了动物的认知能力,增加了海马中的脑源性神经营养因子(BDNF)水平。强力霉素还能抑制MMP-9,减少神经炎症,减轻大脑的氧化应激。此外,分子模型表明强力霉素可以有效地与MMP-9结合。这些研究结果表明,在脓毒症相关脑病小鼠模型中,强力霉素可以减轻认知缺陷,减少神经炎症和氧化应激,并抑制MMP-9。
{"title":"Doxycycline attenuates cognitive impairment, neuroinflammation and oxidative stress in a mouse model of sepsis-associated encephalopathy","authors":"Maria Laura da Cruz Castro ,&nbsp;Flávia Monteiro Ferreira ,&nbsp;Camila Francieli Chagas ,&nbsp;Sttefany Viana Gomes ,&nbsp;Renata Rebeca Pereira ,&nbsp;Aline Meireles Coelho ,&nbsp;Saulo Fehelberg Pinto Braga ,&nbsp;Gabrielly Guimarães Coutinho ,&nbsp;Vitória Louise Teixeira e Silva ,&nbsp;Sirlaine Pio Gomes da Silva ,&nbsp;André Talvani ,&nbsp;Allan Jefferson Cruz Calsavara ,&nbsp;Daniela Caldeira Costa","doi":"10.1016/j.prerep.2025.100072","DOIUrl":"10.1016/j.prerep.2025.100072","url":null,"abstract":"<div><div>Sepsis-associated encephalopathy (SAE), affecting up to 70 % of patients with sepsis, is a diffuse cerebral dysfunction that correlates with higher mortality rates and long-term cognitive impairments such as memory deficits. The pathophysiology of SAE includes neuroinflammation, oxidative stress, apoptosis, microglial activation, blood-brain barrier (BBB) dysfunction, and metabolic disturbances. The compromised BBB during sepsis allows inflammatory mediators to infiltrate, increasing oxidative stress. Studies highlight the role of BBB disruption in SAE, with matrix metalloproteinase 9 (MMP-9) activity increasing BBB permeability. The antibiotic doxycycline inhibits MMP activity and shows promise in protecting BBB integrity by reducing neuroinflammation and oxidative stress. This study evaluates the impact and mechanisms underlying doxycycline treatment on cognitive function in mice with polymicrobial sepsis. Doxycycline treatment improves cognition in the animals and increases brain-derived neurotrophic factor (BDNF) levels in the hippocampus. Doxycycline also inhibits MMP-9, reduces neuroinflammation and attenuates oxidative stress in the brain. In addition, molecular modeling suggests that doxycycline effectively binds to MMP-9. These findings suggest that doxycycline attenuates cognitive deficits, reduces neuroinflammation and oxidative stress, and inhibits MMP-9 in a mouse model of sepsis-associated encephalopathy.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100072"},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145624124","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
Therapeutic potential of Abutilon indicum (L.) Sweet seed extract in PCOS: Insights from mass spectrometry, network pharmacology, and molecular docking 阿布蒂隆的治疗潜力PCOS中的甜籽提取物:来自质谱分析、网络药理学和分子对接的见解
Pub Date : 2025-11-03 DOI: 10.1016/j.prerep.2025.100071
Rejuan Islam , Subhajit Ghosh , Subarna Thakur , Tilak Saha

Background

Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder affecting women of reproductive age and is often associated with metabolic and inflammatory complications. Abutilon indicum (L.) Sweet, a small medicinal shrub widely used in traditional medicine systems, including Traditional Chinese Medicine (TCM), has been employed to manage a variety of health complications. Recent findings suggest that its seed extract may offer therapeutic potential against PCOS. This study aimed to investigate the bioactive constituents and underlying pharmacological mechanisms of the methanolic extract of A. indicum seeds (MEAS) in PCOS using a combination of GC-MS based profiling, network pharmacology, and molecular docking analyses.

Methodology

Phytochemical profiling of MEAS was performed using GC-MS, followed by ADMET-based screening to identify drug-like compounds. Target genes of MEAS phytochemicals were predicted via STP and SEA servers, while PCOS-related genes were retrieved from OMIM and DisGeNET databases. Common targets were intersected with differentially expressed genes (DEGs) derived from a publicly available PCOS-related gene expression dataset. These genes were further analyzed for protein–protein interaction (PPI), Gene Ontology (GO), and KEGG pathway enrichment. Molecular docking and MM/GBSA calculations were conducted to validate compound–target interactions.

Results

GC-MS analysis of MEAS revealed 19 phytochemical compounds, of which 13 satisfied drug-likeness criteria based on ADMET profiling. Database screening identified 110 targets associated with PCOS. Integration of these targets with DEGs resulted in the identification of 10 key PCOS-related genes, including ESR1, HMOX1, CYP17A1, PTAFR, and TLR2. Pathway enrichment analysis revealed a significant enrichment of inflammation-related pathways, oxidative stress, and insulin resistance. Furthermore, molecular docking and MMGBSA results confirmed that phytocompounds like thymidine, 9,12-octadecadienoic acid (Z, Z)-, methyl ester, 9,12-octadecadienoic acid (Z, Z)-, octadecanoic acid, and 9,12-octadecadienoic acid (Z, Z)-, 2-hydroxy-1-(hydroxymethyl) ethyl have strong binding efficacy with the PCOS-related target proteins.

Conclusion

This integrative study elucidates the multi-target pharmacological mechanisms of A. indicum seed constituents in modulating key pathways implicated in PCOS. The findings support the potential application of A. indicum within TCM-based approaches for managing PCOS and its complications.
背景:多囊卵巢综合征(PCOS)是一种影响育龄妇女的广泛内分泌疾病,常伴有代谢和炎症并发症。籼稻(Abutilon indicum)甜是一种小型药用灌木,广泛用于传统医学系统,包括中医(TCM),已被用于管理各种健康并发症。最近的研究结果表明,其种子提取物可能具有治疗多囊卵巢综合征的潜力。本研究旨在采用气相色谱-质谱分析、网络药理学和分子对接分析相结合的方法,探讨a . indicum seeds甲醇提取物(MEAS)在PCOS中的生物活性成分及其药理作用机制。方法采用气相色谱-质谱法对MEAS进行植物化学分析,然后采用基于admet的筛选方法鉴定药物样化合物。通过STP和SEA服务器预测MEAS植物化学物质的靶基因,而从OMIM和DisGeNET数据库检索pcos相关基因。共同靶点与来自公开可用的pcos相关基因表达数据集的差异表达基因(DEGs)相交。进一步分析这些基因的蛋白-蛋白相互作用(PPI)、基因本体(GO)和KEGG途径富集。通过分子对接和MM/GBSA计算来验证化合物与靶标的相互作用。结果gc - ms分析发现19种植物化学成分,其中13种符合ADMET图谱的药物相似标准。数据库筛选鉴定出110个与多囊卵巢综合征相关的靶点。将这些靶标与DEGs整合,鉴定出10个关键的pcos相关基因,包括ESR1、HMOX1、CYP17A1、PTAFR和TLR2。通路富集分析显示炎症相关通路、氧化应激和胰岛素抵抗显著富集。此外,分子对接和MMGBSA结果证实,胸腺嘧啶、9,12-十八烯二烯酸(Z, Z)-、甲酯、9,12-十八烯二烯酸(Z, Z)-、十八烯酸、9,12-十八烯二烯酸(Z, Z)-、2-羟基-1-(羟甲基)乙基等植物化合物与pcos相关靶蛋白具有较强的结合作用。结论本综合研究阐明了籼稻种子成分调控PCOS关键通路的多靶点药理机制。研究结果支持了籼稻在基于tcm的多囊卵巢综合征及其并发症治疗方法中的潜在应用。
{"title":"Therapeutic potential of Abutilon indicum (L.) Sweet seed extract in PCOS: Insights from mass spectrometry, network pharmacology, and molecular docking","authors":"Rejuan Islam ,&nbsp;Subhajit Ghosh ,&nbsp;Subarna Thakur ,&nbsp;Tilak Saha","doi":"10.1016/j.prerep.2025.100071","DOIUrl":"10.1016/j.prerep.2025.100071","url":null,"abstract":"<div><h3>Background</h3><div>Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder affecting women of reproductive age and is often associated with metabolic and inflammatory complications. <em>Abutilon indicum (L.)</em> Sweet, a small medicinal shrub widely used in traditional medicine systems, including Traditional Chinese Medicine (TCM), has been employed to manage a variety of health complications. Recent findings suggest that its seed extract may offer therapeutic potential against PCOS. This study aimed to investigate the bioactive constituents and underlying pharmacological mechanisms of the methanolic extract of <em>A. indicum</em> seeds (MEAS) in PCOS using a combination of GC-MS based profiling, network pharmacology, and molecular docking analyses.</div></div><div><h3>Methodology</h3><div>Phytochemical profiling of MEAS was performed using GC-MS, followed by ADMET-based screening to identify drug-like compounds. Target genes of MEAS phytochemicals were predicted via STP and SEA servers, while PCOS-related genes were retrieved from OMIM and DisGeNET databases. Common targets were intersected with differentially expressed genes (DEGs) derived from a publicly available PCOS-related gene expression dataset. These genes were further analyzed for protein–protein interaction (PPI), Gene Ontology (GO), and KEGG pathway enrichment. Molecular docking and MM/GBSA calculations were conducted to validate compound–target interactions.</div></div><div><h3>Results</h3><div>GC-MS analysis of MEAS revealed 19 phytochemical compounds, of which 13 satisfied drug-likeness criteria based on ADMET profiling. Database screening identified 110 targets associated with PCOS. Integration of these targets with DEGs resulted in the identification of 10 key PCOS-related genes, including ESR1, HMOX1, CYP17A1, PTAFR, and TLR2. Pathway enrichment analysis revealed a significant enrichment of inflammation-related pathways, oxidative stress, and insulin resistance. Furthermore, molecular docking and MMGBSA results confirmed that phytocompounds like thymidine, 9,12-octadecadienoic acid (<em>Z</em>, <em>Z</em>)-, methyl ester, 9,12-octadecadienoic acid (<em>Z</em>, <em>Z</em>)-, octadecanoic acid, and 9,12-octadecadienoic acid (<em>Z</em>, <em>Z</em>)-, 2-hydroxy-1-(hydroxymethyl) ethyl have strong binding efficacy with the PCOS-related target proteins.</div></div><div><h3>Conclusion</h3><div>This integrative study elucidates the multi-target pharmacological mechanisms of <em>A. indicum</em> seed constituents in modulating key pathways implicated in PCOS. The findings support the potential application of <em>A. indicum</em> within TCM-based approaches for managing PCOS and its complications.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100071"},"PeriodicalIF":0.0,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473842","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
Supplemental use of melatonin to protect against oxidative stress induced by intensive athletic training and competition 补充使用褪黑素以防止高强度运动训练和竞争引起的氧化应激
Pub Date : 2025-10-30 DOI: 10.1016/j.prerep.2025.100069
Yupeng Cui , Xiaoyan Liu , Russel J. Reiter
Ample experimental evidence supports the protective effect of melatonin against oxidative damage and fatigue induced by overload athletic training. This article aims to review recent research on the protective effect and mechanisms of melatonin against oxidative stress induced by intensive training and competition, and to provide theoretical support for its application and future research directions. The mechanism of melatonin action involves around direct scavenger of reactive oxygen species, aggregation in mitochondria, and activating signal pathways by binding to receptors. Mitochondria may be one of the most important targets of melatonin in preventing oxidative stress, histiocytic damage and metabolic disorders induced by intensive training. Given the important role of redox signaling agents in activating different signal transduction systems to elicit adaptive changes to exercise stimuli, a phased short-term mode of melatonin supplementation tailored to athletes’ redox status and training load is recommended.
大量实验证据支持褪黑素对过度运动训练引起的氧化损伤和疲劳的保护作用。本文旨在综述褪黑素对高强度训练和竞争引起的氧化应激的保护作用及其机制的最新研究进展,为其应用和未来的研究方向提供理论支持。褪黑素的作用机制包括直接清除活性氧、线粒体聚集以及通过与受体结合激活信号通路。线粒体可能是褪黑素预防氧化应激、组织细胞损伤和高强度训练引起的代谢紊乱的最重要靶点之一。考虑到氧化还原信号剂在激活不同的信号转导系统以引起对运动刺激的适应性变化方面的重要作用,建议根据运动员的氧化还原状态和训练负荷采用分阶段的短期褪黑素补充模式。
{"title":"Supplemental use of melatonin to protect against oxidative stress induced by intensive athletic training and competition","authors":"Yupeng Cui ,&nbsp;Xiaoyan Liu ,&nbsp;Russel J. Reiter","doi":"10.1016/j.prerep.2025.100069","DOIUrl":"10.1016/j.prerep.2025.100069","url":null,"abstract":"<div><div>Ample experimental evidence supports the protective effect of melatonin against oxidative damage and fatigue induced by overload athletic training. This article aims to review recent research on the protective effect and mechanisms of melatonin against oxidative stress induced by intensive training and competition, and to provide theoretical support for its application and future research directions. The mechanism of melatonin action involves around direct scavenger of reactive oxygen species, aggregation in mitochondria, and activating signal pathways by binding to receptors. Mitochondria may be one of the most important targets of melatonin in preventing oxidative stress, histiocytic damage and metabolic disorders induced by intensive training. Given the important role of redox signaling agents in activating different signal transduction systems to elicit adaptive changes to exercise stimuli, a phased short-term mode of melatonin supplementation tailored to athletes’ redox status and training load is recommended.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100069"},"PeriodicalIF":0.0,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473845","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
Controlled release approaches in ocular drug delivery 眼部给药的控释方法
Pub Date : 2025-10-29 DOI: 10.1016/j.prerep.2025.100070
Harshita Krishnatreyya , Hemanga Hazarika
Ocular drug delivery is significant as it delivers drugs to one of the most vital and intricate structures in the human body, the eye, which is currently the site for increased occurrences of diseases like dryness, glaucoma, age related macular degeneration, diabetic retinopathy etc. It is noticeable that drugs delivered at a controlled rate, over prolonged periods of time, are the most effective in treating ocular complications by improving drug therapeutic efficacy and ocular bioavailability. In this article, we provide a summary of the importance of controlled release (CR) systems in ocular delivery, its significance, and the most popular types of CR formulations. Factors to be considered while designing CR drug formulations and the essential mechanisms involved in CR of drugs have been briefed. The significance of diversely sourced biodegradable polymers and the impact of their physicochemical characteristics on drug release is discussed. Previously conducted research on CR formulations, few currently available and marketed ocular CR products and patents; the advantages, disadvantages and challenges of CR systems in ocular tissues are debated. With smarter developments arising to benefit people, there is no definitive endpoint to the progressing research that develops innovative and effective strategies to provide CR of ocular drugs with diminished side effects.
眼部药物输送非常重要,因为它将药物输送到人体最重要、最复杂的结构之一——眼睛,而眼睛目前是干燥、青光眼、年龄相关性黄斑变性、糖尿病视网膜病变等疾病发病率增加的部位。值得注意的是,在一段较长的时间内,以控制的速度给药,通过提高药物治疗效果和眼部生物利用度,对治疗眼部并发症最有效。在这篇文章中,我们总结了控释(CR)系统在眼部给药中的重要性,它的意义,以及最流行的CR制剂类型。简要介绍了设计CR药物配方时应考虑的因素和药物CR的基本机制。讨论了来源多样的生物可降解聚合物的重要性及其物理化学特性对药物释放的影响。以前进行过CR配方的研究,目前市面上的眼用CR产品和专利很少;讨论了眼组织CR系统的优点、缺点和挑战。随着更智能的发展造福于人类,开发创新和有效的策略以提供减少副作用的眼科药物CR的进展研究没有明确的终点。
{"title":"Controlled release approaches in ocular drug delivery","authors":"Harshita Krishnatreyya ,&nbsp;Hemanga Hazarika","doi":"10.1016/j.prerep.2025.100070","DOIUrl":"10.1016/j.prerep.2025.100070","url":null,"abstract":"<div><div>Ocular drug delivery is significant as it delivers drugs to one of the most vital and intricate structures in the human body, the eye, which is currently the site for increased occurrences of diseases like dryness, glaucoma, age related macular degeneration, diabetic retinopathy etc. It is noticeable that drugs delivered at a controlled rate, over prolonged periods of time, are the most effective in treating ocular complications by improving drug therapeutic efficacy and ocular bioavailability. In this article, we provide a summary of the importance of controlled release (CR) systems in ocular delivery, its significance, and the most popular types of CR formulations. Factors to be considered while designing CR drug formulations and the essential mechanisms involved in CR of drugs have been briefed. The significance of diversely sourced biodegradable polymers and the impact of their physicochemical characteristics on drug release is discussed. Previously conducted research on CR formulations, few currently available and marketed ocular CR products and patents; the advantages, disadvantages and challenges of CR systems in ocular tissues are debated. With smarter developments arising to benefit people, there is no definitive endpoint to the progressing research that develops innovative and effective strategies to provide CR of ocular drugs with diminished side effects.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100070"},"PeriodicalIF":0.0,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473841","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
Melatonin alleviates streptozotocin-induced neuropathic pain in rat model: Involvement of noradrenergic receptor pathways 褪黑素减轻链脲佐菌素引起的大鼠神经性疼痛模型:参与去甲肾上腺素能受体通路
Pub Date : 2025-10-19 DOI: 10.1016/j.prerep.2025.100068
Ilhem Dallali , Ahmed Hasan , Feyza Alyu Altınok , Nurcan Bektas Turkmen , Yusuf Ozturk

Background

Diabetic neuropathic pain is a persistent and debilitating complication of diabetes with limited treatments. Melatonin shows promise in pain modulation, though its underlying antinociceptive mechanisms remain unclear. This study investigated the analgesic efficacy of melatonin in alleviating streptozotocin-induced neuropathic pain in rats and explored the involvement of noradrenergic pathways.

Methods

Neuropathic pain was induced in male Sprague-Dawley rats via a single intravenous injection of streptozotocin (50 mg/kg). Melatonin (50 mg/kg, i.p.) was administered daily for two weeks. Gabapentin (50 mg/kg, i.p.) served as a positive control. Mechanical allodynia and thermal hyperalgesia were assessed using the e-Von Frey and Hargreaves tests, respectively, while locomotor activity was evaluated using an activity cage. To evaluate metabolic effects, blood glucose levels were monitored throughout the study. Adrenergic antagonists’ prazosin (α1, 10 mg/kg), yohimbine (α2, 4 mg/kg), and propranolol (β, 5 mg/kg) were administered prior to the final melatonin dose to assess noradrenergic involvement.

Results

Streptozotocin-induced diabetic rats exhibited pronounced mechanical and thermal hypersensitivity. Subacute melatonin treatment significantly reduced nociceptive responses and improved locomotor activity, showing efficacy comparable to gabapentin. It did not alter blood glucose levels, indicating a neutral metabolic effect. The analgesic effects of melatonin were attenuated by adrenergic antagonists, implicating noradrenergic signaling in its mechanism of action.

Conclusions

Melatonin exerts significant antiallodynic and antihyperalgesic effects in diabetic neuropathic rats, likely mediated via noradrenergic receptor pathways. Its neutral impact on glycemic control, combined with potential mood-regulating properties, supports its promise as a therapeutic candidate for managing diabetic neuropathic pain, pending clinical validation.
背景:糖尿病神经性疼痛是糖尿病的一种持续性和衰弱性并发症,治疗方法有限。褪黑素在疼痛调节方面显示出前景,尽管其潜在的抗感觉机制尚不清楚。本研究探讨褪黑素在减轻链脲霉素引起的大鼠神经性疼痛中的镇痛作用,并探讨其去甲肾上腺素能通路的参与。方法单次静脉注射链脲佐菌素(50 mg/kg)诱导雄性Sprague-Dawley大鼠神经性疼痛。每日给予褪黑素(50 mg/kg, i.p),持续两周。加巴喷丁(50 mg/kg, ig)作为阳性对照。分别采用e-Von Frey和Hargreaves试验评估机械异常性痛和热痛感过敏,同时使用活动笼评估运动活动。为了评估代谢影响,在整个研究过程中监测血糖水平。肾上腺素能拮抗剂普拉唑嗪(α 1,10 mg/kg)、柔安宾(α 2,4 mg/kg)和心得安(β, 5 mg/kg)在褪黑素最终剂量之前使用,以评估去甲肾上腺素能的影响。结果链脲佐菌素诱导的糖尿病大鼠表现出明显的机械和热过敏。亚急性褪黑素治疗显著减少伤害反应和改善运动活动,显示出与加巴喷丁相当的疗效。它没有改变血糖水平,表明代谢作用是中性的。褪黑素的镇痛作用被肾上腺素能拮抗剂减弱,提示其作用机制中有去甲肾上腺素能信号。结论:在糖尿病神经病大鼠中,褪黑素可能通过去甲肾上腺素能受体通路发挥显著的抗异动和抗痛觉作用。其对血糖控制的中性影响,结合潜在的情绪调节特性,支持其作为治疗糖尿病神经性疼痛的候选治疗方案,有待临床验证。
{"title":"Melatonin alleviates streptozotocin-induced neuropathic pain in rat model: Involvement of noradrenergic receptor pathways","authors":"Ilhem Dallali ,&nbsp;Ahmed Hasan ,&nbsp;Feyza Alyu Altınok ,&nbsp;Nurcan Bektas Turkmen ,&nbsp;Yusuf Ozturk","doi":"10.1016/j.prerep.2025.100068","DOIUrl":"10.1016/j.prerep.2025.100068","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic neuropathic pain is a persistent and debilitating complication of diabetes with limited treatments. Melatonin shows promise in pain modulation, though its underlying antinociceptive mechanisms remain unclear. This study investigated the analgesic efficacy of melatonin in alleviating streptozotocin-induced neuropathic pain in rats and explored the involvement of noradrenergic pathways.</div></div><div><h3>Methods</h3><div>Neuropathic pain was induced in male Sprague-Dawley rats via a single intravenous injection of streptozotocin (50 mg/kg). Melatonin (50 mg/kg, <em>i.p.</em>) was administered daily for two weeks. Gabapentin (50 mg/kg, <em>i.p.</em>) served as a positive control. Mechanical allodynia and thermal hyperalgesia were assessed using the e-Von Frey and Hargreaves tests, respectively, while locomotor activity was evaluated using an activity cage. To evaluate metabolic effects, blood glucose levels were monitored throughout the study. Adrenergic antagonists’ prazosin (α1, 10 mg/kg), yohimbine (α2, 4 mg/kg), and propranolol (β, 5 mg/kg) were administered prior to the final melatonin dose to assess noradrenergic involvement.</div></div><div><h3>Results</h3><div>Streptozotocin-induced diabetic rats exhibited pronounced mechanical and thermal hypersensitivity. Subacute melatonin treatment significantly reduced nociceptive responses and improved locomotor activity, showing efficacy comparable to gabapentin. It did not alter blood glucose levels, indicating a neutral metabolic effect. The analgesic effects of melatonin were attenuated by adrenergic antagonists, implicating noradrenergic signaling in its mechanism of action.</div></div><div><h3>Conclusions</h3><div>Melatonin exerts significant antiallodynic and antihyperalgesic effects in diabetic neuropathic rats, likely mediated via noradrenergic receptor pathways. Its neutral impact on glycemic control, combined with potential mood-regulating properties, supports its promise as a therapeutic candidate for managing diabetic neuropathic pain, pending clinical validation.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100068"},"PeriodicalIF":0.0,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145361052","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
Curcumin as a modulator of drug metabolism and gene expression: Implications for pharmacogenomics 姜黄素作为药物代谢和基因表达的调节剂:对药物基因组学的影响
Pub Date : 2025-10-03 DOI: 10.1016/j.prerep.2025.100067
Igbayilola Yusuff Dimeji , Hamidu Lawan Jabba , Ngabea Murtala , Adekola Saheed Ayodeji
Curcumin, a polyphenolic chemical derived from Curcuma longa, has long been used as a culinary ingredient and in traditional medicine because of its unique orange--yellow color. Anti-inflammatory, antioxidant, antibacterial, and chemopreventive qualities are only a few of its many pharmacological activities. The increasing relevance of curcumin in pharmacogenomics is examined in this review, with particular attention given to how it affects gene expression and drug metabolism. Curcumin alters important enzymes and pathways, including drug transporters and cytochrome P450s, which impacts how the body breaks down medications. Additionally, it controls transcription factors such as Nrf2 and NF-κB, which affect genes related to inflammation and detoxification. Curcumin is a promising adjuvant in personalized medicine since it can improve therapeutic efficacy and decrease adverse drug reactions through these mechanisms. Its potential application in precision treatment procedures is supported by its capacity to fine-tune metabolic and signalling pathways. This review aims to investigate the possible function of curcumin in pharmacogenomics, namely, in modifying individual reactions to medications depending on genetic variants, as well as how it affects drug metabolism and gene expression.
姜黄素是一种从姜黄中提取的多酚类化学物质,由于其独特的橙黄色,长期以来一直被用作烹饪原料和传统药物。抗炎、抗氧化、抗菌和化学预防只是其众多药理活性中的一小部分。本文综述了姜黄素在药物基因组学中日益增长的相关性,特别关注它如何影响基因表达和药物代谢。姜黄素改变重要的酶和途径,包括药物转运体和细胞色素p450,影响身体如何分解药物。此外,它还控制转录因子如Nrf2和NF-κB,这些转录因子影响与炎症和解毒相关的基因。姜黄素可通过上述机制提高治疗效果,减少药物不良反应,在个体化医疗中具有重要的应用前景。它在精密治疗过程中的潜在应用是由其微调代谢和信号通路的能力支持的。本文旨在探讨姜黄素在药物基因组学中的可能功能,即根据遗传变异改变个体对药物的反应,以及它如何影响药物代谢和基因表达。
{"title":"Curcumin as a modulator of drug metabolism and gene expression: Implications for pharmacogenomics","authors":"Igbayilola Yusuff Dimeji ,&nbsp;Hamidu Lawan Jabba ,&nbsp;Ngabea Murtala ,&nbsp;Adekola Saheed Ayodeji","doi":"10.1016/j.prerep.2025.100067","DOIUrl":"10.1016/j.prerep.2025.100067","url":null,"abstract":"<div><div>Curcumin, a polyphenolic chemical derived from <em>Curcuma longa</em>, has long been used as a culinary ingredient and in traditional medicine because of its unique orange--yellow color. Anti-inflammatory, antioxidant, antibacterial, and chemopreventive qualities are only a few of its many pharmacological activities. The increasing relevance of curcumin in pharmacogenomics is examined in this review, with particular attention given to how it affects gene expression and drug metabolism. Curcumin alters important enzymes and pathways, including drug transporters and cytochrome P450s, which impacts how the body breaks down medications. Additionally, it controls transcription factors such as Nrf2 and NF-κB, which affect genes related to inflammation and detoxification. Curcumin is a promising adjuvant in personalized medicine since it can improve therapeutic efficacy and decrease adverse drug reactions through these mechanisms. Its potential application in precision treatment procedures is supported by its capacity to fine-tune metabolic and signalling pathways. This review aims to investigate the possible function of curcumin in pharmacogenomics, namely, in modifying individual reactions to medications depending on genetic variants, as well as how it affects drug metabolism and gene expression.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100067"},"PeriodicalIF":0.0,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227093","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
Ibuprofen: A review on its synthesis, mechanism of action, pharmacological properties, and environmental impact 布洛芬:对其合成、作用机制、药理性质及环境影响的综述
Pub Date : 2025-09-22 DOI: 10.1016/j.prerep.2025.100066
Irene Ebosereme Ainyanbhor , Great Iruoghene Edo , Ali B.M. Ali , Patrick Othuke Akpoghelie , Morenike Olufunmilayo Akpo , Emad Yousif , Joseph Oghenewogaga Owheruo , Ufuoma Augustina Igbuku , Oluwatobi Victoria Obayomi , Arthur Efeoghene Athan Essaghah , Dilber Uzun Ozsahin , Huzaifa Umar , Dina S. Ahmed , Ahmed A. Alamiery

Background

Ibuprofen, the third most frequently prescribed over-the-counter drug globally, is used for treatment of inflammation, pain and pyrexia.

Objective

This review discusses its synthesis, mechanism of action, pharmacokinetics, pharmacodynamics, derivatives, prospect as well as its environmental impact as an emerging contaminant.

Findings

Its anti-inflammatory property stems from its reduction in synthesis of prostaglandins in inflammatory processes through the inhibition of COX-1 and COX-2 enzyme. However, adverse effect such as gastrointestinal ulceration, myocardial infarction and renal failure has been associated with the use of this drug especially during prolonged usage. Hence, the need for structural modification of this drug reduce or eliminate its adverse effect and also improved efficacy. Research report indicates derivative of ibuprofen from its structural modification results in novel drugs for relief of pain and inflammation with little or no side effects associated with the parent drug. Research also propose the prodrug Ibu-GLVL as a prospective drug for the treatment and management of Alzheimer disease. Despite the classical uses and prospect of this drug, its adverse environmental impact due to observed toxicity in organisms as well as possible contamination of food chain needs to be properly addressed.

Conclusion

This review emphasizes the need to develop more sophisticated methods for effective removal of emerging contaminant including ibuprofen in WWTP since most traditional WWTP are ineffective in removal of such contaminant. This will reduce and may eliminate the adverse environmental effect posed by this emerging contaminant due its wide usage across the globe.
布洛芬是全球第三大常用非处方药,用于治疗炎症、疼痛和发热。目的综述其合成、作用机制、药动学、药效学、衍生物、前景以及作为一种新兴污染物对环境的影响。发现其抗炎特性源于其通过抑制COX-1和COX-2酶在炎症过程中减少前列腺素的合成。然而,胃肠道溃疡、心肌梗死和肾功能衰竭等不良反应与该药的使用有关,特别是在长期使用期间。因此,需要对该药物进行结构修饰,减少或消除其不良反应,提高疗效。研究报告指出,通过对布洛芬的结构进行修饰而制成的布洛芬衍生物可制成新型药物,用于缓解疼痛和炎症,并且与原药相比几乎没有副作用。研究还提出前药Ibu-GLVL作为治疗和管理阿尔茨海默病的前瞻性药物。尽管该药物具有经典的用途和前景,但由于观察到其对生物体的毒性以及可能对食物链的污染,其对环境的不利影响需要得到适当解决。结论传统污水处理系统对布洛芬等新兴污染物的去除效果较差,需要开发更先进的方法来有效去除这些污染物。这将减少并可能消除由于这种新兴污染物在全球范围内的广泛使用而造成的不利环境影响。
{"title":"Ibuprofen: A review on its synthesis, mechanism of action, pharmacological properties, and environmental impact","authors":"Irene Ebosereme Ainyanbhor ,&nbsp;Great Iruoghene Edo ,&nbsp;Ali B.M. Ali ,&nbsp;Patrick Othuke Akpoghelie ,&nbsp;Morenike Olufunmilayo Akpo ,&nbsp;Emad Yousif ,&nbsp;Joseph Oghenewogaga Owheruo ,&nbsp;Ufuoma Augustina Igbuku ,&nbsp;Oluwatobi Victoria Obayomi ,&nbsp;Arthur Efeoghene Athan Essaghah ,&nbsp;Dilber Uzun Ozsahin ,&nbsp;Huzaifa Umar ,&nbsp;Dina S. Ahmed ,&nbsp;Ahmed A. Alamiery","doi":"10.1016/j.prerep.2025.100066","DOIUrl":"10.1016/j.prerep.2025.100066","url":null,"abstract":"<div><h3>Background</h3><div>Ibuprofen, the third most frequently prescribed over-the-counter drug globally, is used for treatment of inflammation, pain and pyrexia.</div></div><div><h3>Objective</h3><div>This review discusses its synthesis, mechanism of action, pharmacokinetics, pharmacodynamics, derivatives, prospect as well as its environmental impact as an emerging contaminant.</div></div><div><h3>Findings</h3><div>Its anti-inflammatory property stems from its reduction in synthesis of prostaglandins in inflammatory processes through the inhibition of COX-1 and COX-2 enzyme. However, adverse effect such as gastrointestinal ulceration, myocardial infarction and renal failure has been associated with the use of this drug especially during prolonged usage. Hence, the need for structural modification of this drug reduce or eliminate its adverse effect and also improved efficacy. Research report indicates derivative of ibuprofen from its structural modification results in novel drugs for relief of pain and inflammation with little or no side effects associated with the parent drug. Research also propose the prodrug Ibu-GLVL as a prospective drug for the treatment and management of Alzheimer disease. Despite the classical uses and prospect of this drug, its adverse environmental impact due to observed toxicity in organisms as well as possible contamination of food chain needs to be properly addressed.</div></div><div><h3>Conclusion</h3><div>This review emphasizes the need to develop more sophisticated methods for effective removal of emerging contaminant including ibuprofen in WWTP since most traditional WWTP are ineffective in removal of such contaminant. This will reduce and may eliminate the adverse environmental effect posed by this emerging contaminant due its wide usage across the globe.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100066"},"PeriodicalIF":0.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145121125","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
Veterinary bacteriostatic and ionophore antibiotics in aquatic organisms: A systematic review and scientometric analysis of biomarker and exposure concentrations 水生生物中的兽医抑菌剂和离子载体抗生素:生物标志物和暴露浓度的系统回顾和科学计量分析
Pub Date : 2025-09-16 DOI: 10.1016/j.prerep.2025.100065
Thaís Pereira Nascimento , Andrea Carina Crupkin , Mirta Luján Menone
The intensive use of veterinary antibiotics, particularly bacteriostatic agents and ionophores, represents an increasing ecotoxicological concern for aquatic ecosystems. This study integrates scientometric analysis with a systematic literature review specifically aimed at identifying gaps in experimental research addressing the effects of these pharmaceuticals on aquatic organisms through biomarker-based assessments. A total of 648 publications published between 1968 and 2024 were screened; however, only 20 in vivo studies involving 10 aquatic species (7 vertebrates and 3 invertebrates) met the inclusion criteria, of which 17 investigated bacteriostatic antibiotics and 3 ionophores. Acute exposure designs predominated (35 %), followed by subchronic (30 %), chronic (15 %), and combined acute–chronic (20 %) assays. Reported environmental concentrations ranged from nanograms to hundreds of micrograms per liter, whereas experimental exposures frequently reached milligram-per-liter levels — in some cases exceeding environmental concentrations by several orders of magnitude. Observed effects included oxidative stress, immunological alterations, reproductive impairment, embryotoxicity, and histopathological damage. The findings demonstrate a disproportionate reliance on standard model organisms, particularly Danio rerio, and a notable scarcity of studies involving native or ecologically relevant species. This review highlights a critical need for future research to adopt chronic exposure scenarios, incorporate native species, environmentally relevant concentrations, and apply standardized- sensitive biomarkers. Addressing these gaps is essential to advance the environmental risk assessment of veterinary antibiotics and to support more effective and evidence-based environmental policymaking.
兽医抗生素的大量使用,特别是抑菌剂和离子载体,对水生生态系统的生态毒理学问题日益突出。本研究将科学计量学分析与系统的文献综述相结合,旨在通过基于生物标志物的评估来确定这些药物对水生生物影响的实验研究中的空白。共筛选了1968年至2024年间出版的648种出版物;然而,只有20项涉及10种水生物种(7种脊椎动物和3种无脊椎动物)的体内研究符合纳入标准,其中17项研究抑菌抗生素,3项研究离子载体。急性暴露设计占主导地位(35 %),其次是亚慢性(30 %)、慢性(15 %)和急性-慢性联合(20 %)试验。报告的环境浓度从每升纳克到数百微克不等,而实验暴露经常达到每升毫克的水平——在某些情况下超过环境浓度几个数量级。观察到的影响包括氧化应激、免疫改变、生殖损伤、胚胎毒性和组织病理学损伤。研究结果表明,对标准模式生物的依赖不成比例,特别是达尼欧河,而且涉及本地或生态相关物种的研究明显缺乏。这篇综述强调了未来研究的一个关键需求,即采用慢性暴露情景,纳入本地物种,环境相关浓度,并应用标准化的敏感生物标志物。解决这些差距对于推进兽用抗生素的环境风险评估以及支持更有效和基于证据的环境政策制定至关重要。
{"title":"Veterinary bacteriostatic and ionophore antibiotics in aquatic organisms: A systematic review and scientometric analysis of biomarker and exposure concentrations","authors":"Thaís Pereira Nascimento ,&nbsp;Andrea Carina Crupkin ,&nbsp;Mirta Luján Menone","doi":"10.1016/j.prerep.2025.100065","DOIUrl":"10.1016/j.prerep.2025.100065","url":null,"abstract":"<div><div>The intensive use of veterinary antibiotics, particularly bacteriostatic agents and ionophores, represents an increasing ecotoxicological concern for aquatic ecosystems. This study integrates scientometric analysis with a systematic literature review specifically aimed at identifying gaps in experimental research addressing the effects of these pharmaceuticals on aquatic organisms through biomarker-based assessments. A total of 648 publications published between 1968 and 2024 were screened; however, only 20 in vivo studies involving 10 aquatic species (7 vertebrates and 3 invertebrates) met the inclusion criteria, of which 17 investigated bacteriostatic antibiotics and 3 ionophores. Acute exposure designs predominated (35 %), followed by subchronic (30 %), chronic (15 %), and combined acute–chronic (20 %) assays. Reported environmental concentrations ranged from nanograms to hundreds of micrograms per liter, whereas experimental exposures frequently reached milligram-per-liter levels — in some cases exceeding environmental concentrations by several orders of magnitude. Observed effects included oxidative stress, immunological alterations, reproductive impairment, embryotoxicity, and histopathological damage. The findings demonstrate a disproportionate reliance on standard model organisms, particularly <em>Danio rerio</em>, and a notable scarcity of studies involving native or ecologically relevant species. This review highlights a critical need for future research to adopt chronic exposure scenarios, incorporate native species, environmentally relevant concentrations, and apply standardized- sensitive biomarkers. Addressing these gaps is essential to advance the environmental risk assessment of veterinary antibiotics and to support more effective and evidence-based environmental policymaking.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100065"},"PeriodicalIF":0.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104675","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
Dieckol from brown algae targeting the Hepatocellular Carcinoma pathway: A computational pharmacology study 针对肝癌途径的褐藻Dieckol:一项计算药理学研究
Pub Date : 2025-09-11 DOI: 10.1016/j.prerep.2025.100064
Hamad Hasan , Alzamka M.A. Almabruk , Mustapha Belaidi , Saleh Bufarwa
Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide, underscoring the urgent need for novel, multi-target therapeutics. This study systematically evaluates Dieckol, a phlorotannin from brown algae, using a dry-lab pipeline integrating quantum chemical calculations, transcriptomic data mining, network pharmacology, molecular docking, molecular dynamics (MD), and ADMET-toxicity prediction. Density Functional Theory (DFT) analysis revealed favorable electronic properties for selective bio-interactions, including a narrow HOMO–LUMO gap (0.119 eV) and high electron-accepting capacity. From 313 predicted targets and 7325 HCC-associated genes, 33 overlapping genes were identified, enriched in cell cycle, apoptosis, and oncogenic signaling pathways, particularly hsa05225 (HCC pathway). Protein–protein interaction and drug–target–pathway networks highlighted CDKN1A, TP53, DNMT1, AURKA, and MAPK1 as central targets. Molecular docking demonstrated strong binding affinities with key HCC-related proteins (CDKN1A: −10.3 kcal/mol; TP53: −9.5 kcal/mol), supported by stable MD simulations and favorable MMGBSA binding energies (e.g., DNMT1: −362.9 kcal/mol). Dieckol also modulated immune-infiltration signatures of key genes (e.g., PIK3R1, NRAS, CDKN2A), suggesting immunomodulatory potential. Gene and protein expression analyses validated differential upregulation of hub targets in tumor vs. normal liver tissues. In silico ADME profiling revealed low oral bioavailability, poor GI absorption, and selective CYP2C9 inhibition, while toxicity predictions showed no carcinogenicity or genotoxicity but flagged moderate renal and dermal risks. Collectively, our findings position Dieckol as a promising multi-target agent for HCC intervention, warranting further in vitro and in vivo validation.
肝细胞癌(HCC)是全球癌症死亡的主要原因,强调了对新型多靶点治疗的迫切需要。本研究系统地评估了来自褐藻的一种褐藻色素Dieckol,使用了干法实验室管道,整合了量子化学计算、转录组数据挖掘、网络药理学、分子对接、分子动力学(MD)和admet毒性预测。密度泛函理论(DFT)分析揭示了选择性生物相互作用的良好电子特性,包括窄的HOMO-LUMO间隙(0.119 eV)和高的电子接受容量。从313个预测靶点和7325个HCC相关基因中,鉴定出33个重叠基因,这些基因在细胞周期、凋亡和致癌信号通路中富集,特别是hsa05225 (HCC通路)。蛋白相互作用和药物靶标通路网络突出了CDKN1A、TP53、DNMT1、AURKA和MAPK1作为中心靶点。分子对接显示出与关键hcc相关蛋白的强结合亲和力(CDKN1A:−10.3 kcal/mol; TP53:−9.5 kcal/mol),这得到了稳定的MD模拟和有利的MMGBSA结合能(例如DNMT1:−362.9 kcal/mol)的支持。Dieckol还调节了关键基因(如PIK3R1, NRAS, CDKN2A)的免疫浸润特征,提示免疫调节潜力。基因和蛋白表达分析证实了肿瘤与正常肝组织中hub靶点的差异上调。计算机ADME分析显示口服生物利用度低,胃肠道吸收差,选择性CYP2C9抑制,而毒性预测显示无致癌性或遗传毒性,但显示中度肾脏和皮肤风险。总的来说,我们的研究结果将Dieckol定位为HCC干预的有前途的多靶点药物,需要进一步的体外和体内验证。
{"title":"Dieckol from brown algae targeting the Hepatocellular Carcinoma pathway: A computational pharmacology study","authors":"Hamad Hasan ,&nbsp;Alzamka M.A. Almabruk ,&nbsp;Mustapha Belaidi ,&nbsp;Saleh Bufarwa","doi":"10.1016/j.prerep.2025.100064","DOIUrl":"10.1016/j.prerep.2025.100064","url":null,"abstract":"<div><div><em>Hepatocellular carcinoma</em> (<strong>HCC</strong>) is a leading cause of cancer mortality worldwide, underscoring the urgent need for novel, multi-target therapeutics. This study systematically evaluates Dieckol, a phlorotannin from brown algae, using a dry-lab pipeline integrating quantum chemical calculations, transcriptomic data mining, network pharmacology, molecular docking, molecular dynamics (<strong>MD</strong>), and ADMET-toxicity prediction. Density Functional Theory (<strong>DFT</strong>) analysis revealed favorable electronic properties for selective bio-interactions, including a narrow HOMO–LUMO gap (0.119 eV) and high electron-accepting capacity. From 313 predicted targets and 7325 HCC-associated genes, 33 overlapping genes were identified, enriched in cell cycle, apoptosis, and oncogenic signaling pathways, particularly hsa05225 (HCC pathway). Protein–protein interaction and drug–target–pathway networks highlighted CDKN1A, TP53, DNMT1, AURKA, and MAPK1 as central targets. Molecular docking demonstrated strong binding affinities with key HCC-related proteins (CDKN1A: −10.3 kcal/mol; TP53: −9.5 kcal/mol), supported by stable MD simulations and favorable MMGBSA binding energies (e.g., DNMT1: −362.9 kcal/mol). Dieckol also modulated immune-infiltration signatures of key genes (e.g., PIK3R1, NRAS, CDKN2A), suggesting immunomodulatory potential. Gene and protein expression analyses validated differential upregulation of hub targets in tumor vs. normal liver tissues. In silico ADME profiling revealed low oral bioavailability, poor GI absorption, and selective CYP2C9 inhibition, while toxicity predictions showed no carcinogenicity or genotoxicity but flagged moderate renal and dermal risks. Collectively, our findings position Dieckol as a promising multi-target agent for HCC intervention, warranting further in <em>vitro</em> and in <em>vivo</em> validation.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100064"},"PeriodicalIF":0.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145104676","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
Long term monitoring of serum valproate assays using patient median values show stable test results over a period of more than 20 years 长期监测使用患者中位值的血清丙戊酸测定显示稳定的测试结果超过20年
Pub Date : 2025-09-08 DOI: 10.1016/j.prerep.2025.100063
Anders Larsson, Anna-Karin Hamberg, Jonathan Cedernaes, Mathias Karlsson
Monitoring assay performance using traditional internal quality control (IQC), and external quality assurance (EQA) methods has limitations, particularly regarding sample commutability. This study investigates the use of patient-derived valproate data, specifically median and quartile values, as a complementary approach to quality control in a clinical laboratory setting. A retrospective analysis was performed on 13,336 routine serum valproate results collected between January 2004 and December 2024 at Akademiska Hospital, Uppsala. Valproate was analyzed using immunoassays on the Architect ci8200 platform until 2020, after which testing was transferred to the Roche Cobas Pro c503. Annual patient medians and quartiles were calculated, and seasonal patterns were evaluated. Method transfer and performance were assessed using internal controls and patient data. The number of annual test requests declined modestly over the study period. Median valproate concentrations remained stable across the 21-year period, with minimal variability in interquartile ranges. The 0.10 and 0.90 percentiles showed slightly higher fluctuation, likely due to sample timing variation rather than analytical drift. Seasonal analysis revealed no clinically relevant variation. The method transfer in 2021 did not introduce observable shifts in patient medians, supporting good method comparability. Longitudinal monitoring of patient median and quartile valproate concentrations provides a robust, clinically meaningful tool for supplementary assay performance surveillance. This approach is particularly suitable for therapeutic drug monitoring, where treatment protocols and target ranges are stable over time.
使用传统的内部质量控制(IQC)和外部质量保证(EQA)方法监测检测性能具有局限性,特别是在样品可交换性方面。本研究调查了丙戊酸盐患者来源数据的使用,特别是中位数和四分位数值,作为临床实验室环境中质量控制的补充方法。回顾性分析了2004年1月至2024年12月在乌普萨拉Akademiska医院收集的13336例丙戊酸常规血清结果。在Architect ci8200平台上使用免疫分析法分析丙戊酸盐,直到2020年,之后测试转移到罗氏Cobas Pro c503。计算年度患者中位数和四分位数,并评估季节性模式。使用内部控制和患者数据评估方法转移和性能。在研究期间,年度测试请求的数量略有下降。丙戊酸盐浓度中位数在21年间保持稳定,在四分位数范围内变化最小。0.10和0.90百分位数显示出稍高的波动,可能是由于样本时间变化而不是分析漂移。季节分析显示无临床相关的变化。2021年的方法转移没有引入可观察到的患者中位数变化,支持良好的方法可比性。纵向监测患者丙戊酸盐浓度中位数和四分位数提供了一个强大的,有临床意义的辅助检测性能监测工具。这种方法特别适用于治疗性药物监测,治疗方案和靶标范围随着时间的推移是稳定的。
{"title":"Long term monitoring of serum valproate assays using patient median values show stable test results over a period of more than 20 years","authors":"Anders Larsson,&nbsp;Anna-Karin Hamberg,&nbsp;Jonathan Cedernaes,&nbsp;Mathias Karlsson","doi":"10.1016/j.prerep.2025.100063","DOIUrl":"10.1016/j.prerep.2025.100063","url":null,"abstract":"<div><div>Monitoring assay performance using traditional internal quality control (IQC), and external quality assurance (EQA) methods has limitations, particularly regarding sample commutability. This study investigates the use of patient-derived valproate data, specifically median and quartile values, as a complementary approach to quality control in a clinical laboratory setting. A retrospective analysis was performed on 13,336 routine serum valproate results collected between January 2004 and December 2024 at Akademiska Hospital, Uppsala. Valproate was analyzed using immunoassays on the Architect ci8200 platform until 2020, after which testing was transferred to the Roche Cobas Pro c503. Annual patient medians and quartiles were calculated, and seasonal patterns were evaluated. Method transfer and performance were assessed using internal controls and patient data. The number of annual test requests declined modestly over the study period. Median valproate concentrations remained stable across the 21-year period, with minimal variability in interquartile ranges. The 0.10 and 0.90 percentiles showed slightly higher fluctuation, likely due to sample timing variation rather than analytical drift. Seasonal analysis revealed no clinically relevant variation. The method transfer in 2021 did not introduce observable shifts in patient medians, supporting good method comparability. Longitudinal monitoring of patient median and quartile valproate concentrations provides a robust, clinically meaningful tool for supplementary assay performance surveillance. This approach is particularly suitable for therapeutic drug monitoring, where treatment protocols and target ranges are stable over time.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"4 ","pages":"Article 100063"},"PeriodicalIF":0.0,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145048817","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
期刊
Pharmacological Research - Reports
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1