Advances in pharmacology最新文献_第6页

The landscape of new therapeutic opportunities for IBD. IBD 新疗法的前景。

Advances in pharmacology Pub Date : 2024-01-01 Epub Date: 2024-10-30 DOI: 10.1016/bs.apha.2024.10.011

Andrés Hurtado-Lorenzo, Jennifer L Swantek

{"title":"The landscape of new therapeutic opportunities for IBD.","authors":"Andrés Hurtado-Lorenzo, Jennifer L Swantek","doi":"10.1016/bs.apha.2024.10.011","DOIUrl":"https://doi.org/10.1016/bs.apha.2024.10.011","url":null,"abstract":"This chapter presents an overview of the emerging strategies to address the unmet needs in the management of inflammatory bowel diseases (IBD). IBD poses significant challenges, as over half of patients experience disease progression despite interventions, leading to irreversible complications, and a substantial proportion do not respond to existing therapies, such as biologics. To overcome these limitations, we describe a diverse array of novel therapeutic approaches. In the area of immune homeostasis restoration, the focus is on targeting cytokine networks, leukocyte trafficking, novel immune pathways, and cell therapies involving regulatory T cells and mesenchymal stem cells (MSC). Recognizing the critical role of impaired intestinal barrier integrity in IBD, we highlight therapies aimed at restoring barrier function and promoting mucosal healing, such as those targeting cell proliferation, tight junctions, and lipid mediators. Addressing the challenges posed by fibrosis and fistulas, we describe emerging targets for reversing fibrosis like kinase and cytokine inhibitors and nuclear receptor agonists, as well as the potential of MSC for fistulas. The restoration of a healthy gut microbiome, through strategies like fecal microbiota transplantation, rationally defined bacterial consortia, and targeted antimicrobials, is also highlighted. We also describe innovative approaches to gut-targeted drug delivery to enhance efficacy and minimize side effects. Reinforcing these advancements is the critical role of precision medicine, which emphasizes the use of multiomics analysis for the discovery of biomarkers to enable personalized IBD care. Overall, the emerging landscape of therapeutic opportunities for IBD holds great potential to surpass the therapeutic ceiling of current treatments.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"101 ","pages":"1-83"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611659","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 potential of targeting TREM-1 in IBD. 靶向 TREM-1 在 IBD 中的潜力。

Advances in pharmacology Pub Date : 2024-01-01 Epub Date: 2024-10-24 DOI: 10.1016/bs.apha.2024.10.010

Emilie Vinolo, Marine Maillefer, Lucie Jolly, Nelly Colné, Gregory Meiffren, Kevin Carrasco, Marc Derive

{"title":"The potential of targeting TREM-1 in IBD.","authors":"Emilie Vinolo, Marine Maillefer, Lucie Jolly, Nelly Colné, Gregory Meiffren, Kevin Carrasco, Marc Derive","doi":"10.1016/bs.apha.2024.10.010","DOIUrl":"https://doi.org/10.1016/bs.apha.2024.10.010","url":null,"abstract":"Innate immune dysfunction is a hallmark of the pathogenesis of Inflammatory Bowel Disease, both in Crohn's disease and ulcerative colitis. Despite considerable efforts in research to better understand the pathophysiology of IBD and for the development of new therapeutic modalities for IBD patients, there is no therapy specifically targeting the dysregulations of the innate immune response available today in that field. TREM-1 is exclusively expressed by innate immune cells and is an immune amplifier. Its engagement following the primary activation of Pattern Recognition Receptors, including Toll-Like Receptors, triggers the development of a dysregulated and sustained innate immune response, promoting the perpetuation of the inflammatory response in the mucosa of IBD patients, microscopic mucosal tissue alterations, impaired autophagy, impaired epithelial barrier integrity and function, ulcerations, and mucosal damages. In patients, TREM-1 activation is associated with the active status of the disease as well as with severity. Blocking TREM-1 in experimental colitis attenuates the dysregulated innate immune response leading to improved clinical signs. Anti-TREM-1 approaches have the potential of controlling the pathogenic dysregulation of the immune response in IBD by targeting an upstream amplification loop of the activation of innate immunity.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"101 ","pages":"301-330"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611663","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

TL1A: A model for a precision medicine approach in the treatment of Crohn's disease and ulcerative colitis. TL1A：治疗克罗恩病和溃疡性结肠炎的精准医疗方法模型。

Advances in pharmacology Pub Date : 2024-01-01 Epub Date: 2024-10-24 DOI: 10.1016/bs.apha.2024.10.014

Janine M Bilsborough, Stephan R Targan

{"title":"TL1A: A model for a precision medicine approach in the treatment of Crohn's disease and ulcerative colitis.","authors":"Janine M Bilsborough, Stephan R Targan","doi":"10.1016/bs.apha.2024.10.014","DOIUrl":"https://doi.org/10.1016/bs.apha.2024.10.014","url":null,"abstract":"Inflammatory bowel disease (IBD) is a collective term for chronic inflammatory diseases of the intestinal tract. The term IBD encompasses two main forms, Crohn's disease (CD) and Ulcerative colitis (UC). CD is characterized by inflammation throughout the length of the gut, especially the ileum and colon, and is often complicated with fistulae and/or intestinal strictures. Ulcerative colitis (UC) is inflammatory disease restricted to the colon and rectum. In practice however, IBD is a heterogenous disease with CD and UC representing the extremes of a continuum of diseases with varied clinical presentation, including disease location, severity, and manifestation of extraintestinal diseases. This disease heterogeneity poses a challenge to successful and efficacious therapeutic treatment as the etiology driving disease in individual patients is unknown and likely to be multifactorial, including genetic predisposition, environmental factors such as the microbiota, as well as social behaviors such as smoking and diet. Precision medicine provides a strategy to account for disease heterogeneity and diverse etiology to select for patients most likely to respond to a given therapeutic. In this chapter we present an example of the development of a novel antibody therapeutic, Tulisokibart, as a model for a Precision Medicine approach to the successful treatment of patients with IBD.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"101 ","pages":"287-299"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611666","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

Modulators of nicotine reward and reinforcement. 尼古丁奖赏和强化的调节剂。

Advances in pharmacology Pub Date : 2024-01-01 Epub Date: 2024-02-10 DOI: 10.1016/bs.apha.2023.10.005

Brandon J Henderson, Samuel Tetteh-Quarshie, Nathan A Olszewski

引用次数: 0

Immunity on ice: The impact of methamphetamine on peripheral immunity. 冰上免疫：甲基苯丙胺对外周免疫的影响。

Advances in pharmacology Pub Date : 2024-01-01 Epub Date: 2023-10-24 DOI: 10.1016/bs.apha.2023.09.003

Emily J Miller, Habibeh Khoshbouei

{"title":"Immunity on ice: The impact of methamphetamine on peripheral immunity.","authors":"Emily J Miller, Habibeh Khoshbouei","doi":"10.1016/bs.apha.2023.09.003","DOIUrl":"10.1016/bs.apha.2023.09.003","url":null,"abstract":"Methamphetamine (METH) regulation of the dopamine transporter (DAT) and central nervous system (CNS) dopamine transmission have been extensively studied. However, our understanding of how METH influences neuroimmune communication and innate and adaptive immunity is still developing. Recent studies have shed light on the bidirectional communication between the CNS and the peripheral immune system. They have established a link between CNS dopamine levels, dopamine neuronal activity, and peripheral immunity. Akin to dopamine neurons in the CNS, a majority of peripheral immune cells also express DAT, implying that in addition to their effect in the CNS, DAT ligands such as methamphetamine may have a role in modulating peripheral immunity. For example, by directly influencing DAT-expressing peripheral immune cells and thus peripheral immunity, METH can trigger a feed-forward cascade that impacts the bidirectional communication between the CNS and peripheral immune system. In this review, we aim to discuss the current understanding of how METH modulates both innate and adaptive immunity and identify areas where knowledge gaps exist. These gaps will then be considered in guiding future research directions.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"99 ","pages":"217-250"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140100821","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

Current and emerging therapeutic strategies for perianal fistula in Crohn's disease patients. 克罗恩病患者肛周瘘的现有和新兴治疗策略。

Advances in pharmacology Pub Date : 2024-01-01 Epub Date: 2024-10-24 DOI: 10.1016/bs.apha.2024.10.013

Kailei Ding, Jiayuan Kong, Ling Li, Florin M Selaru, Alyssa Parian, Hai-Quan Mao

引用次数: 0

The pharmacology and neurotoxicology of synthetic cathinones. 合成卡西酮的药理学和神经毒理学。

Advances in pharmacology Pub Date : 2024-01-01 Epub Date: 2023-12-26 DOI: 10.1016/bs.apha.2023.12.001

Mariana Angoa-Perez, Donald M Kuhn

{"title":"The pharmacology and neurotoxicology of synthetic cathinones.","authors":"Mariana Angoa-Perez, Donald M Kuhn","doi":"10.1016/bs.apha.2023.12.001","DOIUrl":"10.1016/bs.apha.2023.12.001","url":null,"abstract":"The synthetic cathinones are man-made compounds derived from the naturally occurring drug cathinone, which is found in the khat plant. The drugs in this pharmacological class that will be the focus of this chapter include mephedrone, MDPV, methcathinone and methylone. These drugs are colloquially known as \"bath salts\". This misnomer suggests that these drugs are used for health improvement or that they have legitimate medical uses. The synthetic cathinones are dangerous drugs with powerful pharmacological effects that include high abuse potential, hyperthermia and hyperlocomotion. These drugs also share many of the pharmacological effects of the amphetamine class of drugs including methamphetamine, amphetamine and MDMA and therefore have high potential to cause damage to the central nervous system. The synthetic cathinones are frequently taken in combination with other psychoactive drugs such as alcohol, marijuana and the amphetamine-like stimulants, creating a situation where heightened pharmacological and neurotoxicological effects are likely to occur. Despite the structural features shared by the synthetic cathinones and amphetamine-like stimulants, including their actions at monoamine transporters and receptors, the effects of the synthetic cathinones do not always match those of the amphetamines. In particular, the synthetic cathinones are far less neurotoxic than their amphetamine counterparts, they produce a weaker hyperthermia, and they cause less glial activation. This chapter will briefly review the pharmacology and neurotoxicology of selected synthetic cathinones with the aim of delineating key areas of agreement and disagreement in the literature particularly as it relates to neurotoxicological outcomes.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"99 ","pages":"61-82"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140100830","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

Targeting proliferating cell nuclear antigen (PCNA) for cancer therapy. 靶向增殖细胞核抗原（PCNA）治疗癌症。

Advances in pharmacology Pub Date : 2024-01-01 Epub Date: 2024-05-14 DOI: 10.1016/bs.apha.2024.04.002

Caroline K Søgaard, Marit Otterlei

引用次数: 0

Modafinil, an atypical CNS stimulant? 莫达非尼，一种非典型中枢神经兴奋剂？

Advances in pharmacology Pub Date : 2024-01-01 Epub Date: 2023-11-22 DOI: 10.1016/bs.apha.2023.10.006

Melinda Hersey, Gianluigi Tanda

{"title":"Modafinil, an atypical CNS stimulant?","authors":"Melinda Hersey, Gianluigi Tanda","doi":"10.1016/bs.apha.2023.10.006","DOIUrl":"10.1016/bs.apha.2023.10.006","url":null,"abstract":"Modafinil is a central nervous system stimulant approved for the treatment of narcolepsy and sleep disorders. Due to its wide range of biochemical actions, modafinil has been explored for other potential therapeutic uses. Indeed, it has shown promise as a therapy for cognitive disfunction resulting from neurologic disorders like ADHD, and as a smart drug in non-medical settings. The mechanism(s) of actions underlying the therapeutic efficacy of this agent remains largely elusive. Modafinil is known to inhibit the dopamine transporter, thus decreasing dopamine reuptake following neuronal release, an effect shared by addictive psychostimulants. However, modafinil is unique in that only a few cases of dependence on this drug have been reported, as compared to other psychostimulants. Moreover, modafinil has been tested, with some success, as a potential therapeutic agent to combat psychostimulant and other substance use disorders. Modafinil has additional, but less understood, actions on other neurotransmitter systems (GABA, glutamate, serotonin, norepinephrine, etc.). These interactions, together with its ability to activate selected brain regions, are likely one of the keys to understand its unique pharmacology and therapeutic activity as a CNS stimulant. In this chapter, we outline the pharmacokinetics and pharmacodynamics of modafinil that suggest it has an \"atypical\" CNS stimulant profile. We also highlight the current approved and off label uses of modafinil, including its beneficial effects as a treatment for sleep disorders, cognitive functions, and substance use disorders.","PeriodicalId":7366,"journal":{"name":"Advances in pharmacology","volume":"99 ","pages":"287-326"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140100822","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

Targeting glutamate carboxypeptidase II in IBD. 在 IBD 中靶向谷氨酸羧肽酶 II。

Advances in pharmacology Pub Date : 2024-01-01 Epub Date: 2024-10-15 DOI: 10.1016/bs.apha.2024.10.001

Diane E Peters

引用次数: 0