Uric acid is the end product of purine metabolism in humans. Hyperuricemia is a metabolic disease caused by the increased formation or reduced excretion of serum uric acid (SUA). Alterations in SUA homeostasis have been linked to a number of diseases, and hyperuricemia is the major etiologic factor of gout and has been correlated with metabolic syndrome, cardiovascular disease, diabetes, hypertension, and renal disease. Oxidative stress is usually defined as an imbalance between free radicals and antioxidants in our body and is considered to be one of the main causes of cell damage and the development of disease. Studies have demonstrated that hyperuricemia is closely related to the generation of reactive oxygen species (ROS). In the human body, xanthine oxidoreductase (XOR) catalyzes the oxidative hydroxylation of hypoxanthine to xanthine to uric acid, with the accompanying production of ROS. Therefore, XOR is considered a drug target for the treatment of hyperuricemia and gout. In this review, we discuss the mechanisms of uric acid transport and the development of hyperuricemia, emphasizing the role of oxidative stress in the occurrence and development of hyperuricemia. We also summarize recent advances and new discoveries in XOR inhibitors.

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Potential underlying molecular mechanisms for uric acid‐induced lipid metabolic disturbances had not been elucidated clearly. This study investigated the effects and underlying mechanisms of uric acid on the development of lipid metabolic disorders. We collected blood samples from 100 healthy people and 100 patients with hyperuricemia for whom serum lipid analysis was performed. Meanwhile, a mouse model of hyperuricemia was generated, and lipidomics was performed on liver tissues, comparing control and hyperuricemia groups, to analyze lipid profiles and key metabolic enzymes. Uric acid directly induced serum lipid metabolic disorders in both humans and mice based on triglycerides, total cholesterol, and low‐density lipoprotein cholesterol. Through lipidomic analysis, 46 lipids were differentially expressed in hyperuricemic mouse livers, and the phosphatidylcholine composition was altered, which was mediated by LPCAT3 upregulation. High‐uric acid levels‐induced p‐STAT3 inhibition and SREBP‐1c activation in vivo and in vitro. Moreover, LPCAT3‐knockdown significantly attenuated uric acid‐induced p‐STAT3 inhibition, SREBP‐1c activation, and lipid metabolic disorders in L02 cells. In conclusion, uric acid induces lipid metabolic disturbances through LPCAT3‐mediated p‐STAT3 inhibition and SREBP‐1c activation. LPCAT3 could be a key regulatory factor linking hyperuricemia and lipid metabolic disorders. These results might provide novel insights into the clinical treatment of hyperuricemia.

We identify 2 high-risk areas for the design of the vascularized PNSF, namely, at the inferior aspect of the sphenoid ostium and the junction of the posterior nasal septum and the choana arch.