Advances in pharmacology最新文献_第8页

Cardioprotective mechanisms of cytochrome P450 derived oxylipins from ω-3 and ω-6 PUFAs. ω-3和ω-6 PUFAs中细胞色素P450衍生的氧化脂质的心脏保护机制。

Advances in pharmacology Pub Date : 2023-01-01 DOI: 10.1016/bs.apha.2023.02.001

Christi Cho, Theresa Aliwarga, Alexandra M Wiley, Rheem A Totah

{"title":"Cardioprotective mechanisms of cytochrome P450 derived oxylipins from ω-3 and ω-6 PUFAs.","authors":"Christi Cho, Theresa Aliwarga, Alexandra M Wiley, Rheem A Totah","doi":"10.1016/bs.apha.2023.02.001","DOIUrl":"https://doi.org/10.1016/bs.apha.2023.02.001","url":null,"abstract":"The seminal discovery that cytochrome P450 enzymes (CYPs) can oxidize polyunsaturated fatty acids (PUFAs) sparked a new area of research aimed at discovering the role of these metabolites in cardiac physiology and pathophysiology. CYPs metabolize arachidonic acid, an ω-6 PUFA, to alcohols and epoxides with the latter providing cardioprotection following myocardial infarction, hypertrophy, and diabetes-induced cardiomyopathy through their anti-inflammatory, vasodilatory and antioxidant properties. Despite their protective properties, the use of EETs as therapeutic agents is hampered mainly by their rapid hydrolysis to less active vicinal diols by soluble epoxide hydrolase (sEH). Several approaches have been investigated to prolong EET signaling effects using small molecule sEH inhibitors, chemically and biologically stable analogs of EETs and more recently, through the development of an sEH vaccine. Alternatively, research investigating the cardioprotective outcomes of ω-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), mainly focused on dietary intake or supplementation studies. EPA and DHA have overlapping but distinct effects on myocardial function and merit separate studies to fully understand their mechanism of cardiac protection. In contrast to EETs, relatively fewer studies examined the protective mechanisms of EPA and DHA derived epoxides to determine if some protective effects are in part due to the CYP mediated downstream metabolites. The actions of CYPs on PUFAs generate potent oxylipins utilizing diverse cardioprotective mechanisms and the extent of their full potential will be important for the future development of therapeutics to prevent or treat cardiovascular disease.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"97 ","pages":"201-227"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9663534","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

Polyadenylation of canonical histone H3.1 in carcinogenesis. 标准组蛋白H3.1的聚腺苷化在癌变中的作用。

Advances in pharmacology Pub Date : 2023-01-01 DOI: 10.1016/bs.apha.2022.08.003

Arul Veerappan, Aikaterini Stavrou, Max Costa

{"title":"Polyadenylation of canonical histone H3.1 in carcinogenesis.","authors":"Arul Veerappan, Aikaterini Stavrou, Max Costa","doi":"10.1016/bs.apha.2022.08.003","DOIUrl":"https://doi.org/10.1016/bs.apha.2022.08.003","url":null,"abstract":"Canonical histone messenger RNAs (mRNAs) are transcribed during S phase and do not terminate with a poly(A) tail at the 3' end. Instead, the histone mRNAs display a stem-loop structure at their 3-end. Stem-loop-binding protein (SLBP) binds the stem-loop and regulates canonical histone mRNA metabolism. We previously demonstrated that exposure to arsenic, an environmental carcinogen, induces polyadenylation of canonical histone H3.1 mRNA, causing transformation of human cells in vitro. Arsenic decreased cellular levels of SLBP by inducing its proteasomal degradation and inhibiting SLBP transcription via epigenetic mechanisms. Similarly, we also reported that nickel and arsenic have similar effects on canonical histone mRNA transcription and translation. Most recently, we further demonstrated that bisphenols' exposure increased polyadenylation of canonical histone H3.1 mRNA possibly through down-regulation of SLBP expression. This facilitates the abnormal stability of at least one canonical histone isoform (H3.1), and also increases H3 protein levels. Excess expression of canonical histones have been shown to increase sensitivity to DNA damage as well as increase the frequency of missing chromosomes and induce genomic instability. Thus, polyadenylation of canonical histone mRNA following arsenic, nickel and bisphenols exposure may contribute to metal and bisphenol-induced carcinogenesis.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"96 ","pages":"267-282"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10268048/pdf/nihms-1907478.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9689452","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

Targeting the renin angiotensin system for respiratory diseases. 针对呼吸系统疾病的肾素-血管紧张素系统。

Advances in pharmacology Pub Date : 2023-01-01 Epub Date: 2023-03-21 DOI: 10.1016/bs.apha.2023.02.002

Phyllis X L Gan, W Liao, Kira M Linke, D Mei, X D Wu, W S Fred Wong

{"title":"Targeting the renin angiotensin system for respiratory diseases.","authors":"Phyllis X L Gan, W Liao, Kira M Linke, D Mei, X D Wu, W S Fred Wong","doi":"10.1016/bs.apha.2023.02.002","DOIUrl":"10.1016/bs.apha.2023.02.002","url":null,"abstract":"Renin-angiotensin system (RAS) plays an indispensable role in regulating blood pressure through its effects on fluid and electrolyte balance. As an aside, cumulative evidence from experimental to clinical studies supports the notion that dysregulation of RAS contributes to the pro-inflammatory, pro-oxidative, and pro-fibrotic processes that occur in pulmonary diseases like asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute lung injury (ALI). Pharmacological intervention of the various RAS components can be a novel therapeutic strategy for the treatment of these respiratory diseases. In this chapter, we first give a recent update on the RAS, and then compile, review, and analyse recent reports on targeting RAS components as treatments for respiratory diseases. Inhibition of the pro-inflammatory renin, angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and Ang II type 1 receptor (AT1R) axis, and activation of the protective ACE2, AT2R, Ang (1-7), and Mas receptor axis have demonstrated varying degrees of efficacies in experimental respiratory disease models or in human trials. The newly identified alamandine/Mas-related G-protein-coupled receptor member D pathway has shown some therapeutic promise as well. However, our understanding of the RAS ligand-and-receptor interactions is still inconclusive, and the modes of action and signaling cascade mediating the newly identified RAS receptors remain to be better characterized. Clinical data are obviously lacking behind the promising pre-clinical findings of certain well-established molecules targeting at different pathways of the RAS in respiratory diseases. Translational human studies should be the focus for RAS drug development in lung diseases in the next decade.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"98 ","pages":"111-144"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9908278","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

The dark side of NRF2 in arsenic carcinogenesis. NRF2在砷致癌作用中的阴暗面。

Advances in pharmacology Pub Date : 2023-01-01 DOI: 10.1016/bs.apha.2022.08.002

Matthew Dodson, Jinjing Chen, Aryatara Shakya, Annadurai Anandhan, Donna D Zhang

{"title":"The dark side of NRF2 in arsenic carcinogenesis.","authors":"Matthew Dodson, Jinjing Chen, Aryatara Shakya, Annadurai Anandhan, Donna D Zhang","doi":"10.1016/bs.apha.2022.08.002","DOIUrl":"https://doi.org/10.1016/bs.apha.2022.08.002","url":null,"abstract":"Arsenic is an environmental toxicant that significantly enhances the risk of developing disease, including several cancers. While the epidemiological evidence supporting increased cancer risk due to chronic arsenic exposure is strong, therapies tailored to treat exposed populations are lacking. This can be accredited in large part to the chronic nature and pleiotropic pathological effects associated with prolonged arsenic exposure. Despite this fact, several putative mediators of arsenic promotion of cancer have been identified. Among these, the critical transcription factor NRF2 has been shown to be a key mediator of arsenic's pro-carcinogenic effects. Importantly, the dependence of arsenic-transformed cancer cells on NRF2 upregulation exposes a targetable liability that could be utilized to treat arsenic-promoted cancers. In this chapter, we briefly introduce the \"light\" vs \"dark\" side of the NRF2 pathway. We then give a brief overview of arsenic metabolism, and discuss the epidemiological and experimental evidence that support arsenic promotion of different cancers, with a specific emphasis on mechanisms mediated by chronic, non-canonical activation of NRF2 (i.e., the \"dark\" side). Finally, we briefly highlight how the non-canonical NRF2 pathway plays a role in other arsenic-promoted diseases, as well as research directions that warrant further investigation.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"96 ","pages":"47-69"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9076115","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

Anti-fibrotic strategies and pulmonary fibrosis. 抗纤维化策略与肺纤维化。

Advances in pharmacology Pub Date : 2023-01-01 DOI: 10.1016/bs.apha.2023.04.002

Avanka Gunatilaka, Stephanie Zhang, Wan Shun Daniel Tan, Alastair G Stewart

{"title":"Anti-fibrotic strategies and pulmonary fibrosis.","authors":"Avanka Gunatilaka, Stephanie Zhang, Wan Shun Daniel Tan, Alastair G Stewart","doi":"10.1016/bs.apha.2023.04.002","DOIUrl":"https://doi.org/10.1016/bs.apha.2023.04.002","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) results from the dysregulated process of injury and repair, which promotes scarring of the lung tissue and deposition of collagen-rich extracellular matrix (ECM) components, that make the lung unphysiologically stiff. IPF presents a serious concern as its pathogenesis remains elusive, and current anti-fibrotic treatments are only effective in slowing rather than halting disease progression. The IPF disease pathogenesis is incompletely defined, complex and incorporates interplay between different fibrogenesis signaling pathways. Preclinical IPF experimental models used to validate drug candidates present significant limitations in modeling IPF pathobiology, with their limited time frame, simplicity and inaccurate representation of the disease and the mechanical influences of IPF. Potentially more accurate mimetic disease models that capture the cell-cell and cell-matrix interaction, such as 3D cultures, organoids and precision-cut lung slices (PCLS), may yield more meaningful clinical predictions for drug candidates. Recent advances in developing anti-fibrotic compounds have positioned drug towards targeting components of the fibrogenesis signaling pathway of IPF or the extracellular microenvironment. The major goals in this area of research focus on finding ways to reverse or halt the disease progression by utilizing more disease-relevant experimental models to improve the qualification of potential drug targets for treating pulmonary fibrosis.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"98 ","pages":"179-224"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10531298","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

Potential therapeutic targets for the treatment of opioid abuse and pain. 治疗阿片类药物滥用和疼痛的潜在治疗目标。

Advances in pharmacology Pub Date : 2022-01-01 Epub Date: 2021-11-09 DOI: 10.1016/bs.apha.2021.09.002

Norikazu Kiguchi, Mei-Chuan Ko

{"title":"Potential therapeutic targets for the treatment of opioid abuse and pain.","authors":"Norikazu Kiguchi, Mei-Chuan Ko","doi":"10.1016/bs.apha.2021.09.002","DOIUrl":"10.1016/bs.apha.2021.09.002","url":null,"abstract":"Although μ-opioid peptide (MOP) receptor agonists are effective analgesics available in clinical settings, their serious adverse effects put limits on their use. The marked increase in abuse and misuse of prescription opioids for pain relief and opioid overdose mortality in the past decade has seriously impacted society. Therefore, safe analgesics that produce potent analgesic effects without causing MOP receptor-related adverse effects are needed. This review highlights the potential therapeutic targets for the treatment of opioid abuse and pain based on available evidence generated through preclinical studies and clinical trials. To ameliorate the abuse-related effects of opioids, orexin-1 receptor antagonists and mixed nociceptin/MOP partial agonists have shown promising results in translational aspects of animal models. There are several promising non-opioid targets for selectively inhibiting pain-related responses, including nerve growth factor inhibitors, voltage-gated sodium channel inhibitors, and cannabinoid- and nociceptin-related ligands. We have also discussed several emerging and novel targets. The current medications for opioid abuse are opioid receptor-based ligands. Although neurobiological studies in rodents have discovered several non-opioid targets, there is a translational gap between rodents and primates. Given that the neuroanatomical aspects underlying opioid abuse and pain are different between rodents and primates, it is pivotal to investigate the functional profiles of these non-opioid compounds compared to those of clinically used drugs in non-human primate models before initiating clinical trials. More pharmacological studies of the functional efficacy, selectivity, and tolerability of these newly discovered compounds in non-human primates will accelerate the development of effective medications for opioid abuse and pain.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"93 1","pages":"335-371"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10948018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54057945","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

Beyond hypertension: Diastolic dysfunction associated with cancer treatment in the era of cardio-oncology. 超越高血压:心脏肿瘤学时代与癌症治疗相关的舒张功能障碍。

Advances in pharmacology Pub Date : 2022-01-01 DOI: 10.1016/bs.apha.2022.02.002

G. Minotti, P. Menna, M. Camilli, E. Salvatorelli, R. Levi

引用次数: 4

Use of engineered cytochromes P450 for accelerating drug discovery and development. 利用工程细胞色素P450加速药物发现和开发。

Advances in pharmacology Pub Date : 2022-01-01 Epub Date: 2022-07-20 DOI: 10.1016/bs.apha.2022.06.001

Raine E S Thomson, Stephlina A D'Cunha, Martin A Hayes, Elizabeth M J Gillam

{"title":"Use of engineered cytochromes P450 for accelerating drug discovery and development.","authors":"Raine E S Thomson, Stephlina A D'Cunha, Martin A Hayes, Elizabeth M J Gillam","doi":"10.1016/bs.apha.2022.06.001","DOIUrl":"https://doi.org/10.1016/bs.apha.2022.06.001","url":null,"abstract":"Numerous steps in drug development, including the generation of authentic metabolites and late-stage functionalization of candidates, necessitate the modification of often complex molecules, such as natural products. While it can be challenging to make the required regio- and stereoselective alterations to a molecule using purely chemical catalysis, enzymes can introduce changes to complex molecules with a high degree of stereo- and regioselectivity. Cytochrome P450 enzymes are biocatalysts of unequalled versatility, capable of regio- and stereoselective functionalization of unactivated CH bonds by monooxygenation. Collectively they catalyze over 60 different biotransformations on structurally and functionally diverse organic molecules, including natural products, drugs, steroids, organic acids and other lipophilic molecules. This catalytic versatility and substrate range makes them likely candidates for application as potential biocatalysts for industrial chemistry. However, several aspects of the P450 catalytic cycle and other characteristics have limited their implementation to date in industry, including: their lability at elevated temperature, in the presence of solvents, and over lengthy incubation times; the typically low efficiency with which they metabolize non-natural substrates; and their lack of specificity for a single metabolic pathway. Protein engineering by rational design or directed evolution provides a way to engineer P450s for industrial use. Here we review the progress made to date toward engineering the properties of P450s, especially eukaryotic forms, for industrial application, and including the recent expansion of their catalytic repertoire to include non-natural reactions.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":" ","pages":"195-252"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40686983","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. 前言。

Advances in pharmacology Pub Date : 2022-01-01 DOI: 10.1016/S1054-3589(22)00070-9

Hiroshi Yamazaki

引用次数: 0

Substance abuse and neurotransmission. 药物滥用与神经传递。

Advances in pharmacology Pub Date : 2022-01-01 Epub Date: 2022-01-17 DOI: 10.1016/bs.apha.2021.10.007

Sarah Davis, Jun Zhu

引用次数: 0