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Cytochrome P450-derived eicosanoids in brain: From basic discovery to clinical translation. 脑细胞色素p450衍生的类二十烷:从基础发现到临床转化。
Advances in pharmacology Pub Date : 2023-01-01 DOI: 10.1016/bs.apha.2022.11.002
Catherine M Davis, Aseel H Ibrahim, Nabil J Alkayed
{"title":"Cytochrome P450-derived eicosanoids in brain: From basic discovery to clinical translation.","authors":"Catherine M Davis,&nbsp;Aseel H Ibrahim,&nbsp;Nabil J Alkayed","doi":"10.1016/bs.apha.2022.11.002","DOIUrl":"https://doi.org/10.1016/bs.apha.2022.11.002","url":null,"abstract":"<p><p>Cytochrome P450 metabolism of arachidonic acid produces epoxyeicosatrienoates (EETs) and hydroxyeicosatetraenoates (HETEs). Both classes of eicosanoids play important and opposing roles in brain function and disease. EETs promote vasodilation and exhibit antiinflammatory and cytoprotective properties; their biological action is blunted by metabolism to less active diols by the enzyme soluble epoxide hydrolase (sEH). EETs levels are dysregulated in disease states, primarily due to increased activity of sEH. Inhibition of sEH is a promising therapeutic approach for multiple brain disorders including stroke, dementia, subarachnoid hemorrhage and epilepsy. In this chapter, we summarize evidence implicating P450 eicosanoids and their synthetic and metabolizing enzymes in brain health and disease, and experimental and clinical studies targeting these pathways for brain disorders. We also discuss the diagnostic utility of quantifying P450 eicosanoids and their enzymes as disease biomarkers. Remarkable progress has been achieved in translating basic science discoveries in this field clinically.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"97 ","pages":"283-326"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9756814","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
Senotherapy for lung diseases. 肺部疾病的药物治疗。
Advances in pharmacology Pub Date : 2023-01-01 DOI: 10.1016/bs.apha.2023.04.001
Peter J Barnes
{"title":"Senotherapy for lung diseases.","authors":"Peter J Barnes","doi":"10.1016/bs.apha.2023.04.001","DOIUrl":"https://doi.org/10.1016/bs.apha.2023.04.001","url":null,"abstract":"<p><p>Increasing evidence suggests that there is acceleration of lung ageing in chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), with the accumulation of senescent cells in the lung. Senescent cells fail to repair tissue damage and release an array of inflammatory proteins, known as the senescence-associated secretory phenotype, which drive further senescence and disease progression. This suggests that targeting cellular senescence with senotherapies may treat the underlying disease process in COPD and IPF and thus reduce disease progression and mortality. Several existing or future drugs may inhibit the development of cellular senescence which is driven by chronic oxidative stress (senostatics), including inhibitors of PI3K-mTOR signalling pathways, antagomirs of critical microRNAs and novel antioxidants. Other drugs (senolytics) selectively remove senescent cells by promoting apoptosis. Clinical studies with senotherapies are already underway in chronic lung diseases.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"98 ","pages":"249-271"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10531294","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: 1
Arsenic and cancer: Evidence and mechanisms. 砷与癌症:证据与机制。
Advances in pharmacology Pub Date : 2023-01-01 Epub Date: 2022-09-27 DOI: 10.1016/bs.apha.2022.08.001
Rachel M Speer, Xixi Zhou, Lindsay B Volk, Ke Jian Liu, Laurie G Hudson
{"title":"Arsenic and cancer: Evidence and mechanisms.","authors":"Rachel M Speer, Xixi Zhou, Lindsay B Volk, Ke Jian Liu, Laurie G Hudson","doi":"10.1016/bs.apha.2022.08.001","DOIUrl":"10.1016/bs.apha.2022.08.001","url":null,"abstract":"<p><p>Arsenic is a potent carcinogen and poses a significant health concern worldwide. Exposure occurs through ingestion of drinking water and contaminated foods and through inhalation due to pollution. Epidemiological evidence shows arsenic induces cancers of the skin, lung, liver, and bladder among other tissues. While studies in animal and cell culture models support arsenic as a carcinogen, the mechanisms of arsenic carcinogenesis are not fully understood. Arsenic carcinogenesis is a complex process due its ability to be metabolized and because of the many cellular pathways it targets in the cell. Arsenic metabolism and the multiple forms of arsenic play distinct roles in its toxicity and contribute differently to carcinogenic endpoints, and thus must be considered. Arsenic generates reactive oxygen species increasing oxidative stress and damaging DNA and other macromolecules. Concurrently, arsenic inhibits DNA repair, modifies epigenetic regulation of gene expression, and targets protein function due its ability to replace zinc in select proteins. While these mechanisms contribute to arsenic carcinogenesis, there remain significant gaps in understanding the complex nature of arsenic cancers. In the future improving models available for arsenic cancer research and the use of arsenic induced human tumors will bridge some of these gaps in understanding arsenic driven cancers.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"96 ","pages":"151-202"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9076114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lipid mediators generated by the cytochrome P450-Epoxide hydrolase pathway. 细胞色素p450 -环氧化物水解酶途径产生的脂质介质。
Advances in pharmacology Pub Date : 2023-01-01 DOI: 10.1016/bs.apha.2022.12.004
Timo Frömel, Jiong Hu, Ingrid Fleming
{"title":"Lipid mediators generated by the cytochrome P450-Epoxide hydrolase pathway.","authors":"Timo Frömel,&nbsp;Jiong Hu,&nbsp;Ingrid Fleming","doi":"10.1016/bs.apha.2022.12.004","DOIUrl":"https://doi.org/10.1016/bs.apha.2022.12.004","url":null,"abstract":"<p><p>The cytochrome P450 (CYP) soluble epoxide hydrolase (sEH) pathway generates a large number of biologically active epoxides and diols from a range of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs). While epoxides of arachidonic acid or epoxyeicosatrienoic acids are probably the best studied of these mediators, epoxides of linoleic acid as well as the fish oils; docosahexaenoic acid and eicosapentaenoic acid have also been attributed signaling actions. Cell and tissue levels of the PUFA epoxides are largely determined by the sEH and in many cases inflammation and chronic diseases, e.g., cardiovascular disease, diabetes and Alzheimer's disease, have been associated with increased sEH expression and the accelerated conversion of PUFA epoxides to their corresponding diols. In low concentrations, the diols act to influence stem and progenitor cells as well as brown adipose tissue but in high concentrations, they tend to have pro-inflammatory and cytotoxic effects that promote disease progression. This review outlines some of the actions to the PUFA epoxides and diols in physiology and pathophysiology as well as the beneficial effects associates with sEH inhibition.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"97 ","pages":"327-373"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9663535","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
Preface. 序言
Advances in pharmacology Pub Date : 2023-01-01 DOI: 10.1016/S1054-3589(23)00010-8
Max Costa
{"title":"Preface.","authors":"Max Costa","doi":"10.1016/S1054-3589(23)00010-8","DOIUrl":"10.1016/S1054-3589(23)00010-8","url":null,"abstract":"","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"96 ","pages":"xiii-xiv"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10812264","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
Delivery technology of inhaled therapy for asthma and COPD. 哮喘和慢性阻塞性肺病吸入治疗的给药技术。
Advances in pharmacology Pub Date : 2023-01-01 DOI: 10.1016/bs.apha.2023.03.001
Michael Y T Chow, Harry W Pan, Jenny K W Lam
{"title":"Delivery technology of inhaled therapy for asthma and COPD.","authors":"Michael Y T Chow,&nbsp;Harry W Pan,&nbsp;Jenny K W Lam","doi":"10.1016/bs.apha.2023.03.001","DOIUrl":"https://doi.org/10.1016/bs.apha.2023.03.001","url":null,"abstract":"<p><p>Inhaled therapy is the cornerstone of the management of asthma and chronic obstructive pulmonary disease (COPD). Drugs such as bronchodilators and corticosteroids are administered directly to the airways for local effect and rapid onset of action while systemic exposure and side effects are minimized. There are four major types of inhaler devices used clinically to generate aerosols for inhalation, namely, pressurized metered-dose inhalers (pMDIs), nebulizers, Soft Mist™ inhalers (SMIs) and dry powder inhalers (DPIs). Each of them has its own unique characteristics that can target different patient groups. For instance, patients' inhaler technique is critical for pMDIs and SMIs to achieve proper drug deposition in the lung, which could be challenging for some patients. Nebulizers are designed to deliver aerosols to patients during tidal breathing, but they require electricity to operate and are less portable than other devices. DPIs are the only device that delivers aerosols in dry powder form with better stability, but they rely on patients' inspiration effort for powder dispersion, rendering them unsuitable for patients with compromised lung function. Choosing a device that can cater for the need of individual patient is paramount for effective inhaled therapy. This chapter provides an overview of inhaled therapy for the management of asthma and COPD. The operation principles, merits and limitations of different delivery technologies are examined. Looking ahead, the challenges of delivering novel therapeutics such as biologics through the pulmonary route are also discussed.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"98 ","pages":"273-311"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9908280","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: 1
Recent developments in the use of monoclonal antibodies targeting the type 2 cytokines for severe asthma treatment. 针对2型细胞因子的单克隆抗体用于重度哮喘治疗的最新进展。
Advances in pharmacology Pub Date : 2023-01-01 DOI: 10.1016/bs.apha.2023.04.003
Garry M Walsh
{"title":"Recent developments in the use of monoclonal antibodies targeting the type 2 cytokines for severe asthma treatment.","authors":"Garry M Walsh","doi":"10.1016/bs.apha.2023.04.003","DOIUrl":"https://doi.org/10.1016/bs.apha.2023.04.003","url":null,"abstract":"<p><p>Severe or refractory asthma is seen in approximately 5% of asthmatic subjects who have unsatisfactory symptom control despite adherence to high-dose inhaled glucocorticoid therapies resulting in significant morbidity, reduced quality of life with attendant implications for healthcare costs. Marked heterogeneity in symptoms and at the molecular phenotypic level are hallmarks of asthma resulting in the requirement of specifically targeted treatments to block the key pathways of the disease. Monoclonal antibody (mAb)-based biologics targeted at inhibition of the type 2 cytokines IL-4, IL-5 and IL-13 have become established as effective treatments for severe asthma, with significant clinical benefit seen in carefully selected patient populations that take asthma phenotypes and endotypes into account. The further development of reproducible and straightforward discriminatory biomarkers may aid identification of those patients most likely to benefit from treatment with these interventions.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"98 ","pages":"31-54"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10158547","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
Genetic and environmental reprogramming of the sarcoma epigenome. 肉瘤表观基因组的遗传和环境重编程。
Advances in pharmacology Pub Date : 2023-01-01 DOI: 10.1016/bs.apha.2022.10.001
Anne Grand'Maison, Rachael Kohrn, Emmanuel Omole, Mahek Shah, Peter Fiorica, Jennie Sims, Joyce E Ohm
{"title":"Genetic and environmental reprogramming of the sarcoma epigenome.","authors":"Anne Grand'Maison,&nbsp;Rachael Kohrn,&nbsp;Emmanuel Omole,&nbsp;Mahek Shah,&nbsp;Peter Fiorica,&nbsp;Jennie Sims,&nbsp;Joyce E Ohm","doi":"10.1016/bs.apha.2022.10.001","DOIUrl":"https://doi.org/10.1016/bs.apha.2022.10.001","url":null,"abstract":"<p><p>Sarcomas are rare and heterogenous mesenchymal tumors occurring in soft tissue and bone. The World Health Organization Classification of sarcomas comprises more than hundred different entities which are very diverse in their molecular, genetic and epigenetic signatures as they are in their clinical presentations and behaviors. While sarcomas can be associated with an underlying hereditary cancer predisposition, most sarcomas developed sporadically without identifiable cause. Sarcoma oncogenesis involves complex interactions between genetic, epigenetic and environmental factors which are intimately related and intensively studied. Several molecular discoveries have been made over the last decades leading to the development of new therapeutic avenues. Sarcoma research continues its effort toward a more specific and personalized approach to all sarcoma sub-types to improve patient outcomes and this through world-wide collaboration. This chapter on \"Genetic and Environmental Reprogramming of the Sarcoma Epigenome\" provides a comprehensive review of general concepts and epidemiology of sarcoma as well as a detailed description of the genetic, molecular and epigenetic alterations seen in sarcomas, their therapeutic implications and ongoing research. This review also presents evidenced-based data on the environmental and occupational factors possibly involved in the etiology of sarcomas and a brief discussion on the role of the microbiome in sarcoma.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"96 ","pages":"283-317"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10869511","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
Novel treatments against airway inflammation in COPD based on drug repurposing. 基于药物再利用的新型COPD气道炎症治疗方法。
Advances in pharmacology Pub Date : 2023-01-01 Epub Date: 2023-05-08 DOI: 10.1016/bs.apha.2023.04.005
Rui Chen, Yuting Cui, Judith C W Mak
{"title":"Novel treatments against airway inflammation in COPD based on drug repurposing.","authors":"Rui Chen, Yuting Cui, Judith C W Mak","doi":"10.1016/bs.apha.2023.04.005","DOIUrl":"10.1016/bs.apha.2023.04.005","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a major cause of death and reduces quality of life that contributes to a health problem worldwide. Chronic airway inflammation is a hallmark of COPD, which occurs in response to exposure of inhaled irritants like cigarette smoke. Despite accessible to the most up-to-date medications, none of the treatments is currently available to decrease the disease progression. Therefore, it is believed that drugs which can reduce airway inflammation will provide effective disease modifying therapy for COPD. There are many broad-range anti-inflammatory drugs including those that inhibit cell signaling pathways like inhibitors of p38 mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), and phosphoinositide-3-kinase (PI3K), are now in phase III development for COPD. In this chapter, we review recent basic research data in the laboratory that may indicate novel therapeutic pathways arisen from currently used drugs such as selective monoamine oxidase (MAO)-B inhibitors and drugs targeting peripheral benzodiazepine receptors [also known as translocator protein (TSPO)] to reduce airway inflammation. Considering the impact of chronic airway inflammation on the lives of COPD patients, the potential pharmacological candidates for new anti-inflammatory targets should be further investigated. In addition, it is crucial to consider the phenotypes/molecular endotypes of COPD patients together with specific outcome measures to target novel therapies. This review will enhance our knowledge on how cigarette smoke affects MAO-B activity and TSPO activation/inactivation with specific ligands through regulation of mitochondrial function, and will help to identify new potential treatment for COPD in future.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"98 ","pages":"225-247"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9908282","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
Phosphodiesterase inhibitors and lung diseases. 磷酸二酯酶抑制剂与肺部疾病
Advances in pharmacology Pub Date : 2023-01-01 DOI: 10.1016/bs.apha.2023.05.001
Ivana Stolfa, Clive Page
{"title":"Phosphodiesterase inhibitors and lung diseases.","authors":"Ivana Stolfa,&nbsp;Clive Page","doi":"10.1016/bs.apha.2023.05.001","DOIUrl":"https://doi.org/10.1016/bs.apha.2023.05.001","url":null,"abstract":"<p><p>Phosphodiesterase enzymes (PDE) have long been known as regulators of cAMP and cGMP, second messengers involved in various signaling pathways and expressed in a variety of cell types implicated in respiratory diseases such as airway smooth muscle and inflammatory cells making them a key target for the treatment of lung diseases as chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, and pulmonary hypertension (PH). The first reported PDE inhibitor was the xanthine, theophylline, described as a non-specific PDE inhibitor and whilst this drug is effective, it also has a range of unwanted side effects. In an attempt to improve the therapeutic window of xanthines, a number of selective PDE inhibitors have been developed for the treatment of respiratory diseases with only the selective PDE 4 inhibitor, roflumilast, being approved for the treatment of severe COPD. However, roflumilast also has a very narrow therapeutic window due to a number of important doses limiting side effects, particularly in the gastrointestinal tract. However, there continues to be research carried out in this field to identify improved selective PDE inhibitors, both by targeting other PDE subtypes (e.g., PDE 7 found in a number of inflammatory and immune cells) and through development of selective PDE inhibitors for pulmonary administration to reduce systemic exposure and improve the side effect profile. This approach has been exemplified by the development of ensifentrine, a dual PDE 3-PDE 4 inhibitor, an inhaled drug that has recently completed two successful Phase III clinical trials in patients with COPD.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"98 ","pages":"55-81"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10158545","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
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