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Proline-derived quinoline formamide compounds as human urate transporter 1 inhibitors with potent uric acid-lowering activities
We report the design and synthesis of a series of proline-derived quinoline formamide compounds as human urate transporter 1 (URAT1) inhibitors via a ligand-based pharmacophore approach. Structure-activity relationship studies reveal that the replacement of the carboxyl group on the polar fragment with trifluoromethanesulfonamide and substituent modification at the 6-position of the quinoline ring greatly improve URAT1 inhibitory activity compared with lesinurad. Compounds 21c, 21e, 24b, 24c, and 23a exhibit potent activities against URAT1 with IC50 values ranging from 0.052 to 0.56 μM. Furthermore, compound 23a displays ...
Source: European Journal of Medicinal Chemistry - March 28, 2024 Category: Chemistry Authors: Shengnan Li Hui Liao Lijun Luo Bingxu Meng Fengxin Zheng Li Sheng Hongyi Zhao Yi Huan Lei Lei Jiayu Zhai Kunlu Zhao Jinhong Tian Ting Wu Gang Li Jianxin Pang Haihong Huang Source Type: research

Hyperuricemia Subtypes Classified According to Renal Uric Acid Handling Manifesting Distinct Phenotypic and Genetic Profiles in People With Gout
ConclusionHyperuricemia subtypes classified according to renal uric acid handling have subtype-specific clinical and genetic features, suggesting subtype-unique pathophysiologic mechanisms. (Source: Arthritis and Rheumatology)
Source: Arthritis and Rheumatology - March 28, 2024 Category: Rheumatology Authors: Han Qi, Mingshu Sun, Robert Terkeltaub, Tony R. Merriman, Haibing Chen, Zhiqiang Li, Aichang Ji, Xiaomei Xue, Wenyan Sun, Can Wang, Xinde Li, Yuwei He, Lingling Cui, Nicola Dalbeth, Changgui Li Tags: Full Length Source Type: research

Exploring the potential of SrTi 0.7 Fe 0.3 O 3 perovskite/chitosan nanosheets for the development of a label-free electrochemical sensing assay for determination of naproxen in human plasma samples
Anal Biochem. 2024 Mar 24:115513. doi: 10.1016/j.ab.2024.115513. Online ahead of print.ABSTRACTNaproxen is a nonsteroidal anti-inflammatory drug used to treat nonrheumatic inflammation, migraine, and gout. Therefore, the determination of naproxen in pharmaceutical and biological samples is of particular importance. In the present work, SrTi0.7Fe0.3O3 perovskite/Chitosan nanosheets were used to modify the surface of a glassy carbon electrode (GCE) for highly sensitive determination of naproxen. To ensure the successful synthesis of the perovskite nanosheets, morphological studies including scanning electron microscopy (SEM)...
Source: Analytical Biochemistry - March 26, 2024 Category: Biochemistry Authors: Roghayeh Mahmoudi-Maleki Mir Reza Majidi Hessamaddin Sohrabi Elham Mahmoudi Homa Fooladvand Ali Coruh Aligholi Niaei Source Type: research

Bispecific antibodies tethering innate receptors induce human tolerant dendritic cells and regulatory T cells
There is an urgent need for alternative therapies targeting human dendritic cells (DCs) that could reverse inflammatory syndromes in many auto-immune and inflammatory diseases and organ transplantations. Here we describe a bispecific antibody (bsAb) strategy tethering two pathogenrecognition receptors at the surface of human DCs. This cross-linking switches DCs into a tolerant profile able to induce regulatory T-cell differentiation. The bsAbs, not parental Abs, induced interleukin 10 and transforming growth factor b1 secretion in monocyte-derived DCs and human peripheral blood mononuclear cells. In addition, they induced ...
Source: Frontiers in Immunology - March 26, 2024 Category: Allergy & Immunology Source Type: research

Effect of uric acid reduction on chronic kidney disease. Systematic review and meta-analysis
Accumulating evidence suggests that hyperuricemia is a pathological factor in the development and progression of chronic kidney disease. However, the potential benefit afforded by the control of uric acid (UA) is controversial. Individual studies show discrepant results, and most existing meta-analysis, especially those including the larger number of studies, lack a placebo or control group as they aim to compare efficacy between drugs. On these grounds, we performed a me-ta-analysis restricted to studies including the action of any anti-gout therapies referenced to a control or placebo arm. This approach allows for a clea...
Source: Frontiers in Pharmacology - March 26, 2024 Category: Drugs & Pharmacology Source Type: research

Did the first description of patients with polymyalgia rheumatica take place in Scotland or in Denmark?
Reumatismo. 2024 Mar 22;76(1). doi: 10.4081/reumatismo.2024.1673.ABSTRACTThe first description of polymyalgia rheumatica (PMR) is generally attributed to Dr. Bruce. In an 1888 article entitled Senile rheumatic gout, he described five male patients aged from 60 to 74 years whom he had visited at the Strathpeffer spa in Scotland. In 1945, Dr. Holst and Dr. Johansen reported on five female patients examined over several months at the Medical Department of Roskilde County Hospital in Denmark. These patients suffered from hip, upper arms, and neck pain associated with elevated ESR and constitutional manifestations such as low-g...
Source: Reumatismo - March 25, 2024 Category: Rheumatology Authors: C Manzo M Isetta A Castagna Source Type: research

Did the first description of patients with polymyalgia rheumatica take place in Scotland or in Denmark?
Reumatismo. 2024 Mar 22;76(1). doi: 10.4081/reumatismo.2024.1673.ABSTRACTThe first description of polymyalgia rheumatica (PMR) is generally attributed to Dr. Bruce. In an 1888 article entitled Senile rheumatic gout, he described five male patients aged from 60 to 74 years whom he had visited at the Strathpeffer spa in Scotland. In 1945, Dr. Holst and Dr. Johansen reported on five female patients examined over several months at the Medical Department of Roskilde County Hospital in Denmark. These patients suffered from hip, upper arms, and neck pain associated with elevated ESR and constitutional manifestations such as low-g...
Source: Pain Physician - March 25, 2024 Category: Anesthesiology Authors: C Manzo M Isetta A Castagna Source Type: research