Current Opinion in Pharmacology最新文献_第10页

Targeting fibroblast-like synoviocytes in rheumatoid arthritis 类风湿关节炎靶向成纤维细胞样滑膜细胞

IF 4 3区医学

Current Opinion in Pharmacology Pub Date : 2022-12-01 DOI: 10.1016/j.coph.2022.102304

Vladislav Tsaltskan, Gary S. Firestein

引用次数: 12

Editorial overview – 2022 respiratory issue: Cystic fibrosis pathophysiology, models, and novel therapies 编辑概述- 2022呼吸问题:囊性纤维化病理生理学，模型和新疗法

IF 4 3区医学

Current Opinion in Pharmacology Pub Date : 2022-12-01 DOI: 10.1016/j.coph.2022.102289

Carla M.P. Ribeiro, Martina Gentzsch

引用次数: 0

Ubiquitin proteasome system in immune regulation and therapeutics 泛素蛋白酶体系统在免疫调节和治疗中的应用

IF 4 3区医学

Current Opinion in Pharmacology Pub Date : 2022-12-01 DOI: 10.1016/j.coph.2022.102310

Sameer Ahmed Bhat, Zahra Vasi, Ritika Adhikari, Anish Gudur, Asceal Ali, Liping Jiang, Rachel Ferguson, David Liang, Shafi Kuchay

{"title":"Ubiquitin proteasome system in immune regulation and therapeutics","authors":"Sameer Ahmed Bhat, Zahra Vasi, Ritika Adhikari, Anish Gudur, Asceal Ali, Liping Jiang, Rachel Ferguson, David Liang, Shafi Kuchay","doi":"10.1016/j.coph.2022.102310","DOIUrl":"10.1016/j.coph.2022.102310","url":null,"abstract":"<div>The ubiquitin proteasome system (UPS) is a proteolytic machinery for the degradation of protein substrates that are post-translationally conjugated with ubiquitin polymers through the enzymatic action of ubiquitin ligases, in a process termed ubiquitylation. Ubiquitylation of substrates precedes their proteolysis via proteasomes, a hierarchical feature of UPS. E3-ubiquitin ligases recruit protein substrates providing specificity for ubiquitylation. Innate and adaptive immune system networks are regulated by ubiquitylation and substrate degradation via E3-ligases/UPS. Deregulation of E3-ligases/UPS components in immune cells is involved in the development of lymphomas, neurodevelopmental abnormalities, and cancers. Targeting E3-ligases for therapeutic intervention provides opportunities to mitigate the unintended broad effects of 26S proteasome inhibition. Recently, bifunctional moieties such as PROTACs and molecular glues have been developed to re-purpose E3-ligases for targeted degradation of unwanted aberrant proteins, with a potential for clinical use. Here, we summarize the involvement of E3-ligases/UPS components in immune-related diseases with perspectives.</div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"67 ","pages":"Article 102310"},"PeriodicalIF":4.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9768948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Tapering biologic DMARDs in rheumatoid arthritis 逐渐减少类风湿性关节炎的生物dmard

IF 4 3区医学

Current Opinion in Pharmacology Pub Date : 2022-12-01 DOI: 10.1016/j.coph.2022.102308

Genna Braverman , S. Louis Bridges , Larry W. Moreland

{"title":"Tapering biologic DMARDs in rheumatoid arthritis","authors":"Genna Braverman , S. Louis Bridges , Larry W. Moreland","doi":"10.1016/j.coph.2022.102308","DOIUrl":"10.1016/j.coph.2022.102308","url":null,"abstract":"<div>With the arrival of biologics and the shift toward treat-to-target therapy, the possibility of a sustained clinical response has become an achievable goal for many patients with rheumatoid arthritis (RA). Although biologics have revolutionized the treatment of RA, they are costly, potentially inconvenient, and carry risks of side effects. Whether they can or should be tapered in patients with tight disease control is a matter of clinical uncertainty. The major international rheumatology professional societies have all issued guidelines on this question, but across recommendations, consensus is lacking on how and when to consider therapy de-escalation. Recent evidence suggests that sustained remission or low disease activity is more attainable with dose reduction as opposed to outright discontinuation of biologic therapy, and certain predictors of successful taper have begun to be described. This article will (1) summarize the current evidence base for biologic tapering in RA, (2) outline real-world outcomes findings, (3) review important contextual factors relevant to therapy de-escalation, such as cost-effectiveness considerations and patient perspectives, and (4) conclude by summarizing current guidelines.</div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"67 ","pages":"Article 102308"},"PeriodicalIF":4.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10576425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

Editorial overview: Introduction to the musculoskeletal section of current opinion in pharmacology 编辑综述：药理学当前观点的肌肉骨骼部分介绍。

IF 4 3区医学

Current Opinion in Pharmacology Pub Date : 2022-12-01 DOI: 10.1016/j.coph.2022.102306

Christopher P. Cardozo, Helen Bramlett

引用次数: 0

Novel therapeutic avenues for kisspeptin kisspeptin的新治疗途径

IF 4 3区医学

Current Opinion in Pharmacology Pub Date : 2022-12-01 DOI: 10.1016/j.coph.2022.102319

Jovanna Tsoutsouki , Ali Abbara , Waljit Dhillo

{"title":"Novel therapeutic avenues for kisspeptin","authors":"Jovanna Tsoutsouki , Ali Abbara , Waljit Dhillo","doi":"10.1016/j.coph.2022.102319","DOIUrl":"10.1016/j.coph.2022.102319","url":null,"abstract":"<div>Kisspeptin is a hypothalamic neuropeptide that acts via the hypothalamus to stimulate hypothalamic gonadotrophin-releasing hormone secretion and downstream gonadotrophin release. In health, kisspeptin induces normal puberty and modulates ovulation in healthy women. Hypothalamic kisspeptin expression is reduced in several functional reproductive disorders; thus, treating such conditions with kisspeptin is conceptually attractive. Recent studies have demonstrated that kisspeptin can induce a more physiological degree of oocyte maturation during in vitro fertilisation treatment that can reduce the risk of potentially life-threatening complications such as ovarian hyperstimulation syndrome seen with human chorionic gonadotrophin. Furthermore, chronic use of kisspeptin could potentially restore reproductive health in females with hypothalamic amenorrhoea, treat hyposexual drive disorder in otherwise healthy males and has potential indications in polycystic ovary syndrome, osteoporosis and metabolic dysfunction-associated fatty liver disease. Finally, kisspeptin analogues could potentially overcome some of the pharmacological challenges associated with the natural forms of kisspeptin such as short duration of action and development of tachyphylaxis.</div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"67 ","pages":"Article 102319"},"PeriodicalIF":4.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10576953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

New players of the adipose secretome: Therapeutic opportunities and challenges 脂肪分泌组的新参与者:治疗的机遇和挑战

IF 4 3区医学

Current Opinion in Pharmacology Pub Date : 2022-12-01 DOI: 10.1016/j.coph.2022.102302

Laetitia Coassolo , Niels Banhos Dannieskiold-Samsøe , Meng Zhao , Hobson Allen , Katrin J. Svensson

引用次数: 3

RAD51 paralogs: Expanding roles in replication stress responses and repair RAD51的类似物:在复制应激反应和修复中的扩展作用

IF 4 3区医学

Current Opinion in Pharmacology Pub Date : 2022-12-01 DOI: 10.1016/j.coph.2022.102313

Debanjali Bhattacharya , Satyaranjan Sahoo , Tarun Nagraj , Suruchi Dixit , Harsh Kumar Dwivedi, Ganesh Nagaraju

引用次数: 3

Physiological regulation of leptin as an integrative signal of reproductive readiness 瘦素作为生殖准备综合信号的生理调节

IF 4 3区医学

Current Opinion in Pharmacology Pub Date : 2022-12-01 DOI: 10.1016/j.coph.2022.102321

Maggie C. Evans, Rebecca E. Campbell, Greg M. Anderson

{"title":"Physiological regulation of leptin as an integrative signal of reproductive readiness","authors":"Maggie C. Evans, Rebecca E. Campbell, Greg M. Anderson","doi":"10.1016/j.coph.2022.102321","DOIUrl":"10.1016/j.coph.2022.102321","url":null,"abstract":"<div>Reproductive function is tightly regulated by both environmental and physiological factors. The adipose-derived hormone leptin has been identified as one such critical factor that relays information about peripheral energy availability to the centrally-governed HPG axis to ensure there is sufficient energy availability to support the high energy demands of mammalian reproduction. In the absence of adequate central leptin signaling, reproductive function is suppressed. While leptin levels are predominantly regulated by adiposity, circulating leptin levels are also under the modulatory influence of other factors, such as stress system activation, circadian rhythmicity, and immune activation and the inflammatory response. Furthermore, changes in leptin sensitivity can affect the degree to which leptin exerts its influence on the neuroendocrine reproductive axis. This review will discuss the different mechanisms by which leptin serves to integrate and relay information about metabolic, psychological, environmental and immune conditions to the central neuronal network that governs reproductive function.</div>","PeriodicalId":50603,"journal":{"name":"Current Opinion in Pharmacology","volume":"67 ","pages":"Article 102321"},"PeriodicalIF":4.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10565699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

PRRT for higher-grade neuroendocrine neoplasms: What is still acceptable? PRRT治疗高级别神经内分泌肿瘤:哪些仍可接受?

IF 4 3区医学

Current Opinion in Pharmacology Pub Date : 2022-12-01 DOI: 10.1016/j.coph.2022.102293

Grace Kong , Rodney J. Hicks

引用次数: 3