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排序方式: 共有1404条查询结果,搜索用时 15 毫秒
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Dr. Anders Højgaard Hansen Henriette B. Christensen Dr. Sunil K. Pandey Dr. Eugenia Sergeev Alice Valentini Julia Dunlop Domonkos Dedeo Simone Fratta Dr. Brian D. Hudson Prof. Graeme Milligan Prof. Trond Ulven Prof. Elisabeth Rexen Ulven 《ChemMedChem》2021,16(21):3326-3341
Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties. 相似文献
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David Diaz Elisa Lopez-Dolado Sergio Haro Jorge Monserrat Carlos Martinez-Alonso Dimitrios Balomeros Agustín Albillos Melchor Alvarez-Mon 《International journal of molecular sciences》2021,22(2)
Our aim was to investigate the subset distribution and function of circulating monocytes, proinflammatory cytokine levels, gut barrier damage, and bacterial translocation in chronic spinal cord injury (SCI) patients. Thus, 56 SCI patients and 28 healthy donors were studied. The levels of circulating CD14+highCD16−, CD14+highCD16+, and CD14+lowCD16+ monocytes, membrane TLR2, TLR4, and TLR9, phagocytic activity, ROS generation, and intracytoplasmic TNF-α, IL-1, IL-6, and IL-10 after lipopolysaccharide (LPS) stimulation were analyzed by polychromatic flow cytometry. Serum TNF-α, IL-1, IL-6 and IL-10 levels were measured by Luminex and LPS-binding protein (LBP), intestinal fatty acid-binding protein (I-FABP) and zonulin by ELISA. SCI patients had normal monocyte counts and subset distribution. CD14+highCD16− and CD14+highCD16+ monocytes exhibited decreased TLR4, normal TLR2 and increased TLR9 expression. CD14+highCD16− monocytes had increased LPS-induced TNF-α but normal IL-1, IL-6, and IL-10 production. Monocytes exhibited defective phagocytosis but normal ROS production. Patients had enhanced serum TNF-α and IL-6 levels, normal IL-1 and IL-10 levels, and increased circulating LBP, I-FABP, and zonulin levels. Chronic SCI patients displayed impaired circulating monocyte function. These patients exhibited a systemic proinflammatory state characterized by enhanced serum TNF-α and IL-6 levels. These patients also had increased bacterial translocation and gut barrier damage. 相似文献
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Bilal Alashkar Alhamwe Daniel P. Potaczek Sarah Miethe Fahd Alhamdan Lukas Hintz Arslan Magomedov Holger Garn 《International journal of molecular sciences》2021,22(9)
Extracellular vesicles (EVs) are membranous structures, which are secreted by almost every cell type analyzed so far. In addition to their importance for cell-cell communication under physiological conditions, EVs are also released during pathogenesis and mechanistically contribute to this process. Here we summarize their functional relevance in asthma, one of the most common chronic non-communicable diseases. Asthma is a complex persistent inflammatory disorder of the airways characterized by reversible airflow obstruction and, from a long-term perspective, airway remodeling. Overall, mechanistic studies summarized here indicate the importance of different subtypes of EVs and their variable cargoes in the functioning of the pathways underlying asthma, and show some interesting potential for the development of future therapeutic interventions. Association studies in turn demonstrate a good diagnostic potential of EVs in asthma. 相似文献
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Hidetaka Noma Kanako Yasuda Masahiko Shimura 《International journal of molecular sciences》2021,22(7)
Diabetic macular edema (DME) is a critical complication of diabetic retinopathy, a condition that arises from the breakdown of the blood–retinal barrier and the consequent increase in vascular permeability. Over the years, attempts have been made to treat DME by various approaches, including laser photocoagulation, steroid triamcinolone acetonide, and vitrectomy. However, treatment was unsatisfactory until research identified vascular endothelial growth factor (VEGF) as a factor in the pathogenesis of DME. Intraocular anti-VEGF agents show good efficacy in DME. Nevertheless, in some patients the condition recurs or becomes resistant to treatment, suggesting that other factors may be involved. Because inflammation and retinal hypoxia are seen in DME, research has examined the potential role of cytokines and other inflammatory mediators. In this review, we provide an overview of this research and describe feedback mechanisms that may represent a target for novel treatments. 相似文献
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Fang Liu Pengfen Hou Hui Zhang Qingjuan Tang Changhu Xue Robert W. Li 《Comprehensive Reviews in Food Science and Food Safety》2021,20(4):3918-3936
Food additives, often used to guarantee the texture, shelf-life, taste, and appearance of processed foods, have gained widespread attention due to their increased link to the growing incidence of chronic diseases. As one of the most common additives, carrageenans have been used in human diets for hundreds of years. While classified as generally recognized as safe (GRAS) for human consumption, numerous studies since the 1980s have suggested that carrageenans, particularly those with random coil conformations, may have adverse effects on gastrointestinal health, including aggravating intestinal inflammation. While these studies have provided some evidence of adverse effects, the topic is still controversial. Some have suggested that the negative consequence of the consumption of carrageenans may be structure dependent. Furthermore, pre-existing conditions may predispose individuals to varied outcomes of carrageenan intake. In this review, structure–function relationships of various carrageenans in the context of food safety are discussed. We reviewed the molecular mechanisms by which carrageenans exert their biological effects. We summarized the findings associated with carrageenan intake in animal models and clinical trials. Moreover, we examined the interactions between carrageenans and the gut microbiome in the pathogenesis of gastrointestinal disorders. This review argues for personalized guidance on carrageenan intake based on individuals’ health status. Future research efforts that aim to close the knowledge gap on the effect of low-dose and chronic carrageenan intake as well as interactions among food additives should be conducive to the improved safety profile of carrageenans in processed food products. 相似文献
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Alessandra Di Paola Giuseppe Palumbo Pietro Merli Maura Argenziano Chiara Tortora Luisa Strocchio Domenico Roberti Claudia Santoro Silverio Perrotta Francesca Rossi 《International journal of molecular sciences》2021,22(1)
Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibodies-mediated platelet destruction, a prevalence of M1 pro-inflammatory macrophage phenotype and an elevated T helper 1 and T helper 2 lymphocytes (Th1/Th2) ratio, resulting in impairment of inflammatory profile and immune response. Macrophages are immune cells, present as pro-inflammatory classically activated macrophages (M1) or as anti-inflammatory alternatively activated macrophages (M2). They have a key role in ITP, acting both as effector cells, phagocytizing platelets, and, as antigen presenting cells, stimulating auto-antibodies against platelets production. Eltrombopag (ELT) is a thrombopoietin receptor agonist licensed for chronic ITP to stimulate platelet production. Moreover, it improves T and B regulatory cells functions, suppresses T-cells activity, and inhibits monocytes activation. We analyzed the effect of ELT on macrophage phenotype polarization, proposing a new possible mechanism of action. We suggest it as a mediator of macrophage phenotype switch from the M1 pro-inflammatory type to the M2 anti-inflammatory one in paediatric patients with ITP, in order to reduce inflammatory state and restore the immune system function. Our results provide new insights into the therapy and the management of ITP, suggesting ELT also as immune-modulating drug. 相似文献