Pharmacological research最新文献_第9页

Targeting the autoreactive CD8+ T-cell receptor in type 1 diabetes: Insights from scRNA-seq for immunotherapy 靶向 1 型糖尿病患者的自反应 CD8 T 细胞受体：scRNA-seq对免疫疗法的启示。

IF 9.1 2区医学

Pharmacological research Pub Date : 2024-09-27 DOI: 10.1016/j.phrs.2024.107433

Xiaoyang Lai , Junming Luo , Yue Luo , Yijing Zheng , Huan Yang , Fang Zou

引用次数: 0

The therapeutic potential of bee venom-derived Apamin and Melittin conjugates in cancer treatment: A systematic review 蜂毒衍生的蜂毒素和麦利素共轭物在癌症治疗中的治疗潜力：系统综述

IF 9.1 2区医学

Pharmacological research Pub Date : 2024-09-26 DOI: 10.1016/j.phrs.2024.107430

Lucas Fornari Laurindo , Enzo Pereira de Lima , Lívia Fornari Laurindo , Victória Dogani Rodrigues , Eduardo Federighi Baisi Chagas , Ricardo de Alvares Goulart , Adriano Cressoni Araújo , Elen Landgraf Guiguer , Karina Torres Pomini , Rose Eli Grassi Rici , Durvanei Augusto Maria , Rosa Direito , Sandra Maria Barbalho

{"title":"The therapeutic potential of bee venom-derived Apamin and Melittin conjugates in cancer treatment: A systematic review","authors":"Lucas Fornari Laurindo , Enzo Pereira de Lima , Lívia Fornari Laurindo , Victória Dogani Rodrigues , Eduardo Federighi Baisi Chagas , Ricardo de Alvares Goulart , Adriano Cressoni Araújo , Elen Landgraf Guiguer , Karina Torres Pomini , Rose Eli Grassi Rici , Durvanei Augusto Maria , Rosa Direito , Sandra Maria Barbalho","doi":"10.1016/j.phrs.2024.107430","DOIUrl":"10.1016/j.phrs.2024.107430","url":null,"abstract":"<div><div>The therapeutic potential of bee venom-derived peptides, particularly apamin and melittin, in cancer treatment has garnered significant attention as a promising avenue for advancing oncology. This systematic review examines preclinical studies highlighting the emerging role of these peptides in enhancing cancer therapies. Melittin and apamin, when conjugated with other therapeutic agents or formulated into novel delivery systems, have demonstrated improved efficacy in targeting tumor cells. Key findings indicate that melittin-based conjugates, such as polyethylene glycol (PEG)ylated versions, show potential in enhancing therapeutic outcomes and minimizing toxicity across various cancer models. Similarly, apamin-conjugated formulations have improved the efficacy of established anti-cancer drugs, contributing to enhanced targeting and reduced systemic toxicity. These developments underscore a growing interest in leveraging bee venom-derived peptides as adjuncts in cancer therapy. The integration of these peptides into treatment regimens offers a promising strategy to address current limitations in cancer treatment, such as drug resistance and off-target effects. However, comprehensive validation through clinical trials is essential to confirm their safety and effectiveness in human patients. This review highlights the global emergence of bee venom-derived peptides in cancer treatment, advocating for continued research and development to fully realize their therapeutic potential.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107430"},"PeriodicalIF":9.1,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142351743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The potential role of mitochondria in the microbiota-gut-brain axis: Implications for brain health 线粒体在微生物群-肠-脑轴中的潜在作用：对大脑健康的影响

IF 9.1 2区医学

Pharmacological research Pub Date : 2024-09-25 DOI: 10.1016/j.phrs.2024.107434

Lei Qiao , Ge Yang , Peng Wang , Chunlan Xu

{"title":"The potential role of mitochondria in the microbiota-gut-brain axis: Implications for brain health","authors":"Lei Qiao , Ge Yang , Peng Wang , Chunlan Xu","doi":"10.1016/j.phrs.2024.107434","DOIUrl":"10.1016/j.phrs.2024.107434","url":null,"abstract":"<div><div>Mitochondria are crucial organelles that regulate cellular energy metabolism, calcium homeostasis, and oxidative stress responses, playing pivotal roles in brain development and neurodegeneration. Concurrently, the gut microbiota has emerged as a key modulator of brain physiology and pathology through the microbiota-gut-brain axis. Recent evidence suggests an intricate crosstalk between the gut microbiota and mitochondrial function, mediated by microbial metabolites that can influence mitochondrial activities in the brain. This review aims to provide a comprehensive overview of the emerging role of mitochondria as critical mediators in the microbiota-gut-brain axis, shaping brain health and neurological disease pathogenesis. We discuss how gut microbial metabolites such as short-chain fatty acids, secondary bile acids, tryptophan metabolites, and trimethylamine N-oxide can traverse the blood-brain barrier and modulate mitochondrial processes including energy production, calcium regulation, mitophagy, and oxidative stress in neurons and glial cells. Additionally, we proposed targeting the mitochondria through diet, prebiotics, probiotics, or microbial metabolites as a promising potential therapeutic approach to maintain brain health by optimizing mitochondrial fitness. Overall, further investigations into how the gut microbiota and its metabolites regulate mitochondrial bioenergetics, dynamics, and stress responses will provide valuable insights into the microbiota-gut-brain axis in both health and disease states.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107434"},"PeriodicalIF":9.1,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multitarget ligands that comprise opioid/nonopioid pharmacophores for pain management: Current state of the science 由阿片类/非阿片类药物组成的多靶点配体用于疼痛治疗：科学现状。

IF 9.1 2区医学

Pharmacological research Pub Date : 2024-09-21 DOI: 10.1016/j.phrs.2024.107408

Émile Breault , Michael Desgagné , Jolien De Neve , Jérôme Côté , Thomas M.A. Barlow , Steven Ballet , Philippe Sarret

{"title":"Multitarget ligands that comprise opioid/nonopioid pharmacophores for pain management: Current state of the science","authors":"Émile Breault , Michael Desgagné , Jolien De Neve , Jérôme Côté , Thomas M.A. Barlow , Steven Ballet , Philippe Sarret","doi":"10.1016/j.phrs.2024.107408","DOIUrl":"10.1016/j.phrs.2024.107408","url":null,"abstract":"<div><div>Chronic pain, which affects more than one-third of the world’s population, represents one of the greatest medical challenges of the 21st century, yet its effective management remains sub-optimal. The ‘gold standard’ for the treatment of moderate to severe pain consists of opioid ligands, such as morphine and fentanyl, that target the µ-opioid receptor (MOP). Paradoxically, these opioids also cause serious side effects, including constipation, respiratory depression, tolerance, and addiction. In addition, the development of opioid-use disorders, such as opioid diversion, misuse, and abuse, has led to the current opioid crisis, with dramatic increases in addiction, overdoses, and ultimately deaths. As pain is a complex, multidimensional experience involving a variety of pathways and mediators, dual or multitarget ligands that can bind to more than one receptor and exert complementary analgesic effects, represent a promising avenue for pain relief. Indeed, unlike monomodal therapeutic approaches, the modulation of several endogenous nociceptive systems can often result in an additive or even synergistic effect, thereby improving the analgesic-to-side-effect ratio. Here, we provide a comprehensive overview of research efforts towards the development of dual- or multi-targeting opioid/nonopioid hybrid ligands for effective and safer pain management. We reflect on the underpinning discovery rationale by discussing the design, medicinal chemistry, and <em>in vivo</em> pharmacological effects of multitarget antinociceptive compounds.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107408"},"PeriodicalIF":9.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142293013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

GPR40 agonist ameliorates neurodegeneration and motor impairment by regulating NLRP3 inflammasome in Parkinson’s disease animal models GPR40 激动剂通过调节帕金森病动物模型中的 NLRP3 炎症小体，改善神经退行性变和运动障碍。

IF 9.1 2区医学

Pharmacological research Pub Date : 2024-09-21 DOI: 10.1016/j.phrs.2024.107432

Tae-Young Ha , Jae-Bong Kim , Yeji Kim , Sang Myun Park , Keun-A Chang

{"title":"GPR40 agonist ameliorates neurodegeneration and motor impairment by regulating NLRP3 inflammasome in Parkinson’s disease animal models","authors":"Tae-Young Ha , Jae-Bong Kim , Yeji Kim , Sang Myun Park , Keun-A Chang","doi":"10.1016/j.phrs.2024.107432","DOIUrl":"10.1016/j.phrs.2024.107432","url":null,"abstract":"<div><div>Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra (SN) and accumulation of intracellular α-synuclein (ɑ-syn) aggregates known as Lewy bodies and Lewy neurites. Levels of polyunsaturated fatty acids (PUFAs) have previously been shown to be reduced in the SN of PD patients. G protein-coupled receptor 40 (GPR40) serves as a receptor for PUFAs, playing a role in neurodevelopment and neurogenesis. Additionally, GPR40 has been implicated in several neuropathological conditions, such as apoptosis and inflammation, suggesting its potential as a therapeutic target in PD.</div><div>In this study, we investigated the neuroprotective effects of the GPR40 agonist, TUG469 in PD models. Our results demonstrated that TUG469 reduces the neurotoxicity induced by 6-OHDA in SH-SY5Y cells. In 6-OHDA-induced PD model mice, TUG469 treatment improved motor impairment, preserved dopaminergic fibers and cell bodies in the striatum (ST) or SN, and attenuated 6-OHDA-induced microgliosis and astrogliosis in the brain. Furthermore, in a PD model involving the injection of mouse ɑ-syn fibrils into the brain (mPFFs-PD model), TUG469 treatment reduced the levels of pSer129 ɑ-syn, and decreased microgliosis and astrogliosis. Our investigation also revealed that TUG469 modulates inflammasome activation, apoptosis, and autophagy in the 6-OHDA-PD model, as evidenced by the results of RNA-seq and western blotting analyses.</div><div>In summary, our findings highlight the neuroprotective effects of GPR40 agonists on dopaminergic neurons and their potential as therapeutic agents for PD. These results underscore the importance of targeting GPR40 in PD treatment, particularly in mitigating neuroinflammation and preserving neuronal integrity.</div></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107432"},"PeriodicalIF":9.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824003773/pdfft?md5=d61f4024e64ac4d384eff18a3de75018&pid=1-s2.0-S1043661824003773-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent developments of topoisomerase inhibitors: Clinical trials, emerging indications, novel molecules and global sales 拓扑异构酶抑制剂的最新进展：临床试验、新兴适应症、新型分子和全球销售额

IF 9.1 2区医学

Pharmacological research Pub Date : 2024-09-20 DOI: 10.1016/j.phrs.2024.107431

Andrey D. Bondarev , Jörgen Jonsson , Vladimir N. Chubarev , Vadim V. Tarasov , Francisco Alejandro Lagunas-Rangel , Helgi B. Schiöth

{"title":"Recent developments of topoisomerase inhibitors: Clinical trials, emerging indications, novel molecules and global sales","authors":"Andrey D. Bondarev , Jörgen Jonsson , Vladimir N. Chubarev , Vadim V. Tarasov , Francisco Alejandro Lagunas-Rangel , Helgi B. Schiöth","doi":"10.1016/j.phrs.2024.107431","DOIUrl":"10.1016/j.phrs.2024.107431","url":null,"abstract":"<div><p>The nucleic acid topoisomerases (TOP) are an evolutionary conserved mechanism to solve topological problems within DNA and RNA that have been historically well-established as a chemotherapeutic target. During investigation of trends within clinical trials, we have identified a very high number of clinical trials involving TOP inhibitors, prompting us to further evaluate the current status of this class of therapeutic agents. In total, we have identified 233 unique molecules with TOP-inhibiting activity. In this review, we provide an overview of the clinical drug development highlighting advances in current clinical uses and discussing novel drugs and indications under development. A wide range of bacterial infections, along with solid and hematologic neoplasms, represent the bulk of clinically approved indications. Negative ADR profile and drug resistance among the antibacterial TOP inhibitors and anthracycline-mediated cardiotoxicity in the antineoplastic TOP inhibitors are major points of concern, subject to continuous research efforts. Ongoing development continues to focus on bacterial infections and cancer; however, there is a degree of diversification in terms of novel drug classes and previously uncovered indications, such as glioblastoma multiforme or <em>Clostridium difficile</em> infections. Preclinical studies show potential in viral, protozoal, parasitic and fungal infections as well and suggest the emergence of a novel target, TOP IIIβ. We predict further growth and diversification of the field thanks to the large number of experimental TOP inhibitors emerging.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107431"},"PeriodicalIF":9.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824003761/pdfft?md5=df08da2321b9fa2fc00df15b7f52a32c&pid=1-s2.0-S1043661824003761-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insight of neonicotinoid insecticides: Exploring exposure, mechanisms in non-target organisms, and removal technologies 透视新烟碱类杀虫剂：探索非目标生物的接触、机理和清除技术。

IF 9.1 2区医学

Pharmacological research Pub Date : 2024-09-19 DOI: 10.1016/j.phrs.2024.107415

Yuanyuan Zhang , Wanxuan Zhu , Ying Wang , Xueli Li , Jianxin Lv , Jiaoyang Luo , Meihua Yang

引用次数: 0

TRP channels in cancer: Therapeutic opportunities and research strategies 癌症中的 TRP 通道：治疗机会与研究策略

IF 9.1 2区医学

Pharmacological research Pub Date : 2024-09-19 DOI: 10.1016/j.phrs.2024.107412

Jiahui Xu , Ziming Wang , Yuqing Niu , Yuping Tang , Yuwei Wang , Jumin Huang , Elaine Lai-Han Leung

{"title":"TRP channels in cancer: Therapeutic opportunities and research strategies","authors":"Jiahui Xu , Ziming Wang , Yuqing Niu , Yuping Tang , Yuwei Wang , Jumin Huang , Elaine Lai-Han Leung","doi":"10.1016/j.phrs.2024.107412","DOIUrl":"10.1016/j.phrs.2024.107412","url":null,"abstract":"<div><p>The influence of gut microbiota on transient receptor potential (TRP) channels has been identified as an important element in the development of gastrointestinal conditions, yet its involvement in cancer progression is not as thoroughly understood. This review explores the multifaceted roles of TRP channels in oncogenesis and emphasizes their significance in cancer progression and therapeutic outcomes. Critical focus was placed on the influence of traditional medicines, such as traditional Chinese medicine (TCM) related aromatic medicines, on TRP channel functions. Moreover, we explored the interplay between the gut microbiota and TRP channels in cancer signaling, highlighting the therapeutic potential of targeting this axis in cancer treatment. The impact of current therapies on TRP channel function was examined, demonstrating the need for a comprehensive understanding of how different modalities affect TRP channels in cancer. Technological advancements, including artificial intelligence (AI) tools and computer-aided drug development (CADD), have been discussed in the context of leveraging TRP channels for innovative cancer therapies. Future directions emphasize the potential applications of TRP channel research in advancing cancer treatment and enhancing patients' well-being.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107412"},"PeriodicalIF":9.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824003578/pdfft?md5=46248b88c7beaa74fe4643d2e77feaf7&pid=1-s2.0-S1043661824003578-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The ZDHHC13/ZDHHC17 subfamily: From biological functions to therapeutic targets of diseases ZDHHC13/ZDHHC17 亚家族：从生物功能到疾病治疗靶点。

IF 9.1 2区医学

Pharmacological research Pub Date : 2024-09-19 DOI: 10.1016/j.phrs.2024.107418

Ying Zhang , Sisi Fan , Lu He , Lanfang Li

引用次数: 0

Astrocyte-derived lactoferrin inhibits neuronal ferroptosis by reducing iron content and GPX4 degradation in APP/PS1 transgenic mice 在 APP/PS1 转基因小鼠体内，源自星形胶质细胞的乳铁蛋白通过降低铁含量和 GPX4 降解抑制神经元铁突变

IF 9.1 2区医学

Pharmacological research Pub Date : 2024-09-19 DOI: 10.1016/j.phrs.2024.107404

Yong-Gang Fan , Ri-Le Ge , Hang Ren , Rong-Jun Jia , Ting-Yao Wu , Xian-Fang Lei , Zheng Wu , Xiao-Bei Zhou , Zhan-You Wang

{"title":"Astrocyte-derived lactoferrin inhibits neuronal ferroptosis by reducing iron content and GPX4 degradation in APP/PS1 transgenic mice","authors":"Yong-Gang Fan , Ri-Le Ge , Hang Ren , Rong-Jun Jia , Ting-Yao Wu , Xian-Fang Lei , Zheng Wu , Xiao-Bei Zhou , Zhan-You Wang","doi":"10.1016/j.phrs.2024.107404","DOIUrl":"10.1016/j.phrs.2024.107404","url":null,"abstract":"<div><p>Increased astrocytic lactoferrin (Lf) expression was observed in the brains of elderly individuals and Alzheimer's disease (AD) patients. Our previous study revealed that astrocytic Lf overexpression improved cognitive capacity by facilitating Lf secretion to neurons to inhibit β-amyloid protein (Aβ) production in APP/PS1 mice. Here, we further discovered that astrocytic Lf overexpression inhibited neuronal loss by decreasing iron accumulation and increasing glutathione peroxidase 4 (GPX4) expression in neurons within APP/PS1 mice. Furthermore, human Lf (hLf) treatment inhibited ammonium ferric citrate (FAC)-induced ferroptosis by chelating intracellular iron. Additionally, machine learning analysis uncovered a correlation between Lf and GPX4. hLf treatment boosted low-density lipoprotein receptor-related protein 1 (LRP1) internalization and facilitated its interaction with heat shock cognate 70 (HSC70), thereby inhibiting HSC70 binds to GPX4, and eventually attenuating GPX4 degradation and FAC-induced ferroptosis. Overall, astrocytic Lf overexpression inhibited neuronal ferroptosis through two pathways: reducing intracellular iron accumulation and promoting GPX4 expression via inhibiting chaperone-mediated autophagy (CMA)-mediated GPX4 degradation. Hence, upregulating astrocytic Lf expression is a promising strategy for combating AD.</p></div>","PeriodicalId":19918,"journal":{"name":"Pharmacological research","volume":"209 ","pages":"Article 107404"},"PeriodicalIF":9.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1043661824003499/pdfft?md5=f4bacab0e0cb1852dc9c6eb5368dfb4e&pid=1-s2.0-S1043661824003499-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0