Advances in pharmacology最新文献

{"title":"Emerging therapeutics for the management of intestinal fibrosis and strictures.","authors":"Yub Raj Neupane, Thanuja Marasarakottige Yogananda, Sri Vishnu Kiran Rompicharla, Florin M Selaru, Laura M Ensign","doi":"10.1016/bs.apha.2024.09.001","DOIUrl":"https://doi.org/10.1016/bs.apha.2024.09.001","url":null,"abstract":"<p><p>Chronic intestinal inflammation in patients with inflammatory bowel disease (IBD) can lead to the development of fibrosis and the formation of strictures. Endoscopic balloon dilation and surgical resection are currently the only available treatments for fibrotic strictures. However, both strategies are associated with potential complications and high rates of stricture recurrence, necessitating additional procedures and/or multiple surgical resections. IBD therapeutic modalities aimed at inflammation, including anti-inflammatory agents, such as corticosteroids, biologics and small molecules, have shown limited efficacy in altering the natural history of strictures, ameliorating fibrosis progression, or preventing recurrences. New and innovative therapeutic approaches targeted at fibrosis are urgently needed. Herein, we provide an overview of emerging therapeutics, including novel drug delivery systems, for the management of intestinal fibrosis and strictures.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"101 ","pages":"107-139"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611648","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}

{"title":"Epigenetic inheritance of phenotypes associated with parental exposure to cocaine.","authors":"Matthew T Rich, Sarah E Swinford-Jackson, R Christopher Pierce","doi":"10.1016/bs.apha.2023.10.004","DOIUrl":"10.1016/bs.apha.2023.10.004","url":null,"abstract":"<p><p>Parental exposure to drugs of abuse induces changes in the germline that can be transmitted across subsequent generations, resulting in enduring effects on gene expression and behavior. This transgenerational inheritance involves a dynamic interplay of environmental, genetic, and epigenetic factors that impact an individual's vulnerability to neuropsychiatric disorders. This chapter aims to summarize recent research into the mechanisms underlying the inheritance of gene expression and phenotypic patterns associated with exposure to drugs of abuse, with an emphasis on cocaine. We will first define the epigenetic modifications such as DNA methylation, histone post-translational modifications, and expression of non-coding RNAs that are impacted by parental cocaine use. We will then explore how parental cocaine use induces heritable epigenetic changes that are linked to alterations in neural circuitry and synaptic plasticity within reward-related circuits, ultimately giving rise to potential behavioral vulnerabilities. This discussion will consider phenotypic differences associated with gestational as well as both maternal and paternal preconception drug exposure and will emphasize differences based on offspring sex. In this context, we explore the complex interactions between genetics, epigenetics, environment, and biological sex. Overall, this chapter consolidates the latest developments in the multigenerational effects and long-term consequences of parental substance abuse.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"99 ","pages":"169-216"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140100820","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}

{"title":"Post-translational mechanisms in psychostimulant-induced neurotransmitter efflux.","authors":"Roxanne A Vaughan, L Keith Henry, James D Foster, Christopher R Brown","doi":"10.1016/bs.apha.2023.10.003","DOIUrl":"10.1016/bs.apha.2023.10.003","url":null,"abstract":"<p><p>The availability of monoamine neurotransmitters in the brain is under the control of dopamine, norepinephrine, and serotonin transporters expressed on the plasma membrane of monoaminergic neurons. By regulating transmitter levels these proteins mediate crucial functions including cognition, attention, and reward, and dysregulation of their activity is linked to mood and psychiatric disorders of these systems. Amphetamine-based transporter substrates stimulate non-exocytotic transmitter efflux that induces psychomotor stimulation, addiction, altered mood, hallucinations, and psychosis, thus constituting a major component of drug neurochemical and behavioral outcomes. Efflux is under the control of transporter post-translational modifications that synergize with other regulatory events, and this review will summarize our knowledge of these processes and their role in drug mechanisms.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"99 ","pages":"1-33"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140100826","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}

{"title":"Chemical mechanisms of DNA damage by carcinogenic chromium(VI).","authors":"Casey Krawic, Anatoly Zhitkovich","doi":"10.1016/bs.apha.2022.07.003","DOIUrl":"10.1016/bs.apha.2022.07.003","url":null,"abstract":"<p><p>Hexavalent chromium is a firmly established human carcinogen with documented exposures in many professional groups. Environmental exposure to Cr(VI) is also a significant public health concern. Cr(VI) exists in aqueous solutions as chromate anion that is unreactive with DNA and requires reductive activation inside the cells to produce genotoxic and mutagenic effects. Reduction of Cr(VI) in cells is nonenzymatic and in vivo principally driven by ascorbate with a secondary contribution from nonprotein thiols glutathione and cysteine. In addition to its much faster rate of reduction, ascorbate-driven metabolism avoids the formation of Cr(V) which is the first intermediate in Cr(VI) reduction by thiols. The end-product of Cr(VI) reduction is Cr(III) which forms several types of Cr-DNA adducts that are collectively responsible for all mutagenic and genotoxic effects in Cr(VI) reactions with ascorbate and thiols. Some Cr(V) forms can react with H₂O₂ to produce DNA-oxidizing peroxo species although this genotoxic pathway is suppressed in cells with physiological levels of ascorbate. Chemical reactions of Cr(VI) with ascorbate or thiols lack directly DNA-oxidizing metabolites. The formation of oxidative DNA breaks in early studies of these reactions was caused by iron contamination. Production of Cr(III)-DNA adducts in cells showed linear dose-dependence irrespective of the predominant reduction pathway and their processing by mismatch repair generated more toxic secondary genetic lesions in euchromatin. Overall, Cr(III)-DNA adduction is the dominant pathway for the formation of genotoxic and mutagenic DNA damage by carcinogenic Cr(VI).</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"96 ","pages":"25-46"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10069994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9239663","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}

{"title":"Bioactive lipids in hypertension.","authors":"John D Imig","doi":"10.1016/bs.apha.2023.01.001","DOIUrl":"10.1016/bs.apha.2023.01.001","url":null,"abstract":"<p><p>Hypertension is a major healthcare issue that afflicts one in every three adults worldwide and contributes to cardiovascular diseases, morbidity and mortality. Bioactive lipids contribute importantly to blood pressure regulation via actions on the vasculature, kidney, and inflammation. Vascular actions of bioactive lipids include blood pressure lowering vasodilation and blood pressure elevating vasoconstriction. Increased renin release by bioactive lipids in the kidney is pro-hypertensive whereas anti-hypertensive bioactive lipid actions result in increased sodium excretion. Bioactive lipids have pro-inflammatory and anti-inflammatory actions that increase or decrease reactive oxygen species and impact vascular and kidney function in hypertension. Human studies provide evidence that fatty acid metabolism and bioactive lipids contribute to sodium and blood pressure regulation in hypertension. Genetic changes identified in humans that impact arachidonic acid metabolism have been associated with hypertension. Arachidonic acid cyclooxygenase, lipoxygenase and cytochrome P450 metabolites have pro-hypertensive and anti-hypertensive actions. Omega-3 fish oil fatty acids eicosapentaenoic acid and docosahexaenoic acid are known to be anti-hypertensive and cardiovascular protective. Lastly, emerging fatty acid research areas include blood pressure regulation by isolevuglandins, nitrated fatty acids, and short chain fatty acids. Taken together, bioactive lipids are key contributors to blood pressure regulation and hypertension and their manipulation could decrease cardiovascular disease and associated morbidity and mortality.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"97 ","pages":"1-35"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10918458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9663538","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}

{"title":"The roles of eicosanoids in myocardial diseases.","authors":"Zuowen He,&nbsp;Dao Wen Wang","doi":"10.1016/bs.apha.2022.11.001","DOIUrl":"https://doi.org/10.1016/bs.apha.2022.11.001","url":null,"abstract":"<p><p>Myocardial disease, the abnormalities of the cardiac muscle, is the leading cause of death in humans. Eicosanoids represent a large spectrum of lipid mediators with critical roles in physiological and pathophysiological conditions. Arachidonic acid (AA) is the major resource of eicosanoids and is metabolized via cyclooxygenases (COXs), lipoxygenases (LOXs), and cytochrome P450 (CYP) enzymes producing a diverse family of lipid mediators called eicosanoids, including prostanoids, leukotrienes (LTs), epoxyeicosatrienoic acids (EETs), dihydroxyeicosatetraenoic acid (diHETEs), eicosatetraenoic acids (ETEs), and lipoxins (LXs). Beyond the well-established roles of eicosanoids in inflammation and vascular biology, a growing body of evidence showed that eicosanoids, especially CYP450 derived eicosanoids EETs, are preventive and therapeutic targets for many of the myocardial diseases. EETs not only ameliorate the cardiac injury and remodeling in different pathological models, but also attenuate subsequent hemodynamic disturbances and cardiac dysfunction. EETs have direct and indirect protective properties in the myocardium, and thus relieve dietetic cardiomyopathy and inflammatory cardiomyopathy. Moreover, EETs are capable to attenuate the ischemic cardiomyopathy, including the myocardial infarction and cardiac ischemic reperfusion injury. Multiple biological events and signaling networks are targeted during the myocardial protection of EETs, these are including mitochondria hemostasis, angiogenesis, oxidative stress, inflammatory response, metabolic regulation, endoplasmic reticulum (ER) stress and cell death. Additionally, eicosanoids from COX and LOX also have important roles in some of the myocardial diseases, such as cardiac hypertrophy and ischemic heart disease. This chapter summarizes the physiological and pathophysiological significance, and the signal mechanisms of the eicosanoids, especially the EETs, in myocardial diseases.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"97 ","pages":"167-200"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9663541","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}

{"title":"Prospects for macrolide therapy of asthma and COPD.","authors":"Michael J Parnham, Virginia Norris, Jennifer A Kricker, Thorarinn Gudjonsson, Clive P Page","doi":"10.1016/bs.apha.2023.03.002","DOIUrl":"10.1016/bs.apha.2023.03.002","url":null,"abstract":"<p><p>Macrolide compounds, many of which are derived from natural sources, all share a lactone ring structure, but of varying sizes. Their biological activities differ with structure and size but tend to overlap. Marketed macrolide drugs include immunosuppressives and antibiotics. Some of the latter have been shown to exert anti-inflammatory activities, due to direct effects on inflammatory cells and processes when used for respiratory infections. Consequently, azithromycin is included in clinical guidelines for COPD and asthma treatment, though it has the disadvantage, as an antibiotic, of increasing bacterial resistance. COPD and asthma, however, like several chronic inflammatory diseases involving other organs, are driven to a large extent by epithelial barrier dysfunction. Recently, azithromycin was shown to directly enhance epithelial barrier function and a new class of derivatives, barriolides, is under development with the lead indication COPD. It is thus likely that by circumventing antibiosis and acting on a crucial etiological disease process, this type of agent will open up a new, safer approach to COPD and asthma therapy with macrolides.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"98 ","pages":"83-110"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9908283","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}

{"title":"Epigenomic reprogramming in iAs-mediated carcinogenesis.","authors":"Smitha George, Richard N Cassidy, Wesley N Saintilnord, Yvonne Fondufe-Mittendorf","doi":"10.1016/bs.apha.2022.08.004","DOIUrl":"10.1016/bs.apha.2022.08.004","url":null,"abstract":"<p><p>Arsenic is a naturally occurring metal carcinogen found in the Earth's crust. Millions of people worldwide are chronically exposed to arsenic through drinking water and food. Exposure to inorganic arsenic has been implicated in many diseases ranging from acute toxicities to malignant transformations. Despite the well-known deleterious health effects of arsenic exposure, the molecular mechanisms in arsenic-mediated carcinogenesis are not fully understood. Since arsenic is non-mutagenic, the mechanism by which arsenic causes carcinogenesis is via alterations in epigenetic-regulated gene expression. There are two possible ways by which arsenic may modify the epigenome-indirectly through an arsenic-induced generation of reactive oxygen species which then impacts chromatin remodelers, or directly through interaction and modulation of chromatin remodelers. Whether directly or indirectly, arsenic modulates epigenetic gene regulation and our understanding of the direct effect of this modulation on chromatin structure is limited. In this chapter we will discuss the various ways by which inorganic arsenic affects the epigenome with consequences in health and disease.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"96 ","pages":"319-365"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10869508","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}

{"title":"The role of oxylipins in NSAID-exacerbated respiratory disease (N-ERD).","authors":"Kimberley Cousins, Chien-Chang Chen, Esha Sehanobish, Elina Jerschow","doi":"10.1016/bs.apha.2022.12.002","DOIUrl":"10.1016/bs.apha.2022.12.002","url":null,"abstract":"<p><p>Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) is characterized by nasal polyp formation, adult-onset asthma, and hypersensitivity to all cyclooxygenase-1 (COX-1) inhibitors. Oxygenated lipids are collectively known as oxylipins and are polyunsaturated fatty acids (PUFA) oxidation products. The most extensively researched oxylipins being the eicosanoids formed from arachidonic acid (AA). There are four major classes of eicosanoids including leukotrienes, prostaglandins, thromboxanes, and lipoxins. In N-ERD, the underlying inflammatory process of the upper and lower respiratory systems begins and occurs independently of NSAID consumption and is due to the overproduction of cysteinyl leukotrienes. Leukotriene mediators all induce edema, bronchoconstriction, and airway mucous secretion. Thromboxane A₂ is a potent bronchoconstrictor and induces endothelial adhesion molecule expression. Elevated Prostaglandin D₂ metabolites lead to vasoconstriction, additionally impaired up-regulation of prostaglandin E₂ leads to symptoms seen in N-ERD as it is essential for maintaining homeostasis of inflammatory responses in the airway and has bronchoprotective and anti-inflammatory effects. A characteristic feature of N-ERD is diminished lipoxin levels, this decreased capacity to form endogenous mediators with anti-inflammatory properties could facilitate local inflammatory response and expose bronchial smooth muscle to relatively unopposed actions of broncho-constricting substances. Treatment options, such as leukotriene modifying agents, aspirin desensitization, biologic agents and ESS, appear to influence eicosanoid pathways, however more studies need to be done to further understand the role of oxylipins. Besides AA-derived eicosanoids, other oxylipins may also pay a role but have not been sufficiently studied. Identifying pathogenic N-ERD mechanism is likely to define more effective treatment targets.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"97 ","pages":"423-444"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10591515/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9663540","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}

{"title":"Role of cytochrome P450-epoxygenase and soluble epoxide hydrolase in the regulation of vascular response.","authors":"Mohammed A Nayeem,&nbsp;Werner J Geldenhuys,&nbsp;Ahmad Hanif","doi":"10.1016/bs.apha.2022.12.003","DOIUrl":"https://doi.org/10.1016/bs.apha.2022.12.003","url":null,"abstract":"<p><p>The role of cytochrome P450-epoxygenase has been seen in cardiovascular physiology and pathophysiology. The aberration in CYP450-epoxygenase genes occur due to genetic polymorphisms, aging, or environmental factors, that increase susceptibility to cardiovascular diseases (CVDs). The actual role played by the CYP450-epoxygenases is the metabolism of arachidonic acid (AA) and linoleic acid (LA) into epoxyeicosatrienoic acids (EETs) and epoxyoctadecaenoic acid (EpOMEs) metabolites (oxylipins) and others, which is involved in vasodilation and myocardial-protection. But the genetic polymorphisms in CYP450-epoxygenases lose their beneficial cardiovascular effects of oxylipins, and the soluble epoxide hydrolase (sEH) antagonizes beneficial oxylipins into diols. Like sEH converts EETs into dihydroxyeicosatrienoic acid (DHETs), EpOMEs into dihydroxyoctadecaenoic acid (DiHOMEs), and reverses its beneficial effects, and the sEH gene (Ephx2) polymorphisms cause the enzyme to become overactive and convert epoxy-fatty acids into diols, making them vulnerable to CVDs, including hypertension. Other, enzymes like ω-hydroxylases (CYP450-4A11 & CYP450-4F2)-derived oxylipins from AA, ω-terminal-hydroxyeicosatetraenoic acids (19-, 20-HETE), lipoxygenase-derived oxylipins, mid-chain hydroxyeicosatetraenoic acids (5-, 11-, 12-, 15-HETEs), and the cyclooxygenase-derived prostanoids (prostaglandins: PGD₂, PGF_2α; thromboxane: Txs, oxylipins) are involved in vasoconstriction, hypertension, inflammation, and cardiac toxicity. Also, there are significant interactions were seen between adenosine receptors [adenosine A_2A receptor (A_2AAR) and adenosine A₁ receptor (A₁AR)] with CYP450-epoxygenases, ω-hydroxylases, sEH, and their derived oxylipins in the regulation of the cardiovascular response. Moreover, polymorphisms exist in CYP450-epoxygenases, ω-hydroxylases, sEH, and the adenosine receptor genes in populations associated with CVDs. This chapter will discuss the role of oxylipins' interactions with adenosine receptors in cardiovascular function/dysfunction in mice and humans.</p>","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"97 ","pages":"37-131"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9663536","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}