Advances in pharmacology最新文献_第6页

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":"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.","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, Jiong Hu, Ingrid Fleming","doi":"10.1016/bs.apha.2022.12.004","DOIUrl":"https://doi.org/10.1016/bs.apha.2022.12.004","url":null,"abstract":"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.","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

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, Harry W Pan, 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":"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.","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

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, Rachael Kohrn, Emmanuel Omole, Mahek Shah, Peter Fiorica, Jennie Sims, 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":"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.","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":"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.","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, Clive Page","doi":"10.1016/bs.apha.2023.05.001","DOIUrl":"https://doi.org/10.1016/bs.apha.2023.05.001","url":null,"abstract":"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.","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

Preface. 序言

Advances in pharmacology Pub Date : 2023-01-01 DOI: 10.1016/S1054-3589(23)00031-5

Darryl C Zeldin, John M Seubert

引用次数: 0

Mechanisms of chromate carcinogenesis by chromatin alterations. 染色质改变致铬酸盐癌的机制。

Advances in pharmacology Pub Date : 2023-01-01 DOI: 10.1016/bs.apha.2022.07.001

Hesbon A Zablon, Andrew VonHandorf, Alvaro Puga

{"title":"Mechanisms of chromate carcinogenesis by chromatin alterations.","authors":"Hesbon A Zablon, Andrew VonHandorf, Alvaro Puga","doi":"10.1016/bs.apha.2022.07.001","DOIUrl":"https://doi.org/10.1016/bs.apha.2022.07.001","url":null,"abstract":"In a dynamic environment, organisms must constantly mount an adaptive response to new environmental conditions in order to survive. Novel patterns of gene expression, driven by attendant changes in chromatin architecture, aid in adaptation and survival. Critical mechanisms in the control of gene transcription govern new spatiotemporal chromatin-chromatin interactions that make regulatory DNA elements accessible to the transcription factors that control the response. Consequently, agents that disrupt chromatin structure are likely to have a direct impact on the transcriptional programs of cells and organisms and to drive alterations in fundamental physiological processes. In this regard, hexavalent chromium (Cr(VI)) is of special interest because it interacts directly with cellular proteins, DNA, and other macromolecules, and is likely to upset cell functions that may cause generalized damage to the organism. Here, we will highlight chromium-mediated mechanisms that disrupt chromatin architecture and discuss how these mechanisms are integral to its carcinogenic properties. Emerging evidence indicates that Cr(VI) targets euchromatin, particularly in genomic locations flanking the binding sites of the essential transcription factors CTCF and AP1, and, in so doing, they disrupt nucleosomal architecture. Ultimately, the ensuing changes, if occurring in critical regulatory domains, may establish a new chromatin state, either toxic or adaptive, that will be governed by the corresponding gene transcription changes in key biological processes associated with that state.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"96 ","pages":"1-23"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10869505","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