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BIOSENSORS & BIOELECTRONICS · 2021 · IF 10.618

Continual and accurate home monitoring of uric acid in urine samples with uricase-packaged nanoflowers assisted portable electrochemical uricometer

Xiuguang Xing,Bangben Yao,Qian Wu,Ru Zhang,Li Yao,Jianguo Xu,Guangheng Gao,Wei Chen

A convenient, fast and non-invasive portable electrochemical uricometer (PUM) assisted with the uricase-packaged nanoflowers (NFs) was constructed for continually and accurately monitoring of uric acid (UA) in urine samples at random intervals in just 20 s. Only a small amount of urine (50 μL) was needed for each test. Electrochemical deposition was adopted to modify gold nanoparticles (AuNPs) on screen-printed carbon electrodes (SPCE) and uricase-inorganic hybrid NFs (UOx-NFs) induced by calcium ions (Ca 2+ ) were introduced for UA detection with expected specificity. Cyclic voltammetry (CV) (detection limit of 8.87 μM and liner range of 0–4 mM) and amperometry (detection limit of 0.82 μM and liner range of 0–5 mM) protocols were studied for UA detection, respectively. Finally, the uric acid in urine had be successfully continually monitored from volunteers with various dietary choosing, the results of which can be adopted as the effective evidence for uric acid control.

研究领域: 医学 · 生物传感器 · 电化学分析
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2021 ·Vol. 413 ·期 26 ·6571-6580 · IF 4.157

Study on performance of mimic uricase and its application in enzyme-free analysis

Liu Donghao,Yang Ping,Wang Fangqi,Wang Cong,Chen Li,Ye Sijing,Dramou Pierre,Chen Jianhua,He Hua

Nanozymes were the novel research field to replace natural enzymes because of stability and low cost. However, the research on nanozymes was mainly focused on peroxidase, and there was little research about nanozymes with oxidase-like activity, especially mimic oxidase of small molecules related to human physiology. High levels of uric acid (UA) in the body can cause hyperuricemia and gout. And natural uricase cured this disease because it could oxidize UA. The oxidase-like activity of mixed valence state metal organic frameworks with cerium (MVSM) had been studied, but MVSM was found to have uricase-like activity in this article. The catalytic process of UA with MVSM was studied by a variety of analytical methods, which was similar to the natural uricase except for further oxidation of H 2 O 2 . The catalytic activity constants of MVSM were acquired by the Michaelis-Menten equation. MVSM had a better ability to catalyze UA in in vivo and in vitro experiments. An enzyme-free analysis–based mimic uricase for UA was established. All the experimental results proved that MVSM had a good prospect to replace the natural uricase. Graphical abstract A nanomaterial, mixed valence state Ce-MOF (MVSM), with uricase-like activity has been found in vivo and in vitro. This material has potential to be a fluorescent analysis for detecting uric acid without uricase.

研究领域: 生物化学 · 医学诊断 · 材料科学
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Frontiers in Endocrinology · 2025 · IF 4.6

Uric acid-induced cardiomyocytic polyamines’ insufficience: a potential mechanism mediates cardiomyocytic injury

Cuiting Lin,Qiang Zheng,Haiyan Yu,Ting Wu,Lin Chen,Weihao Lin,Jianxin Pang,Yang Yang

Introduction: Maintaining polyamines homeostasis is essential for cardiovascular health, whereas elevated uric acid levels are recognized as a significant risk factor for the onset and progression of cardiovascular diseases. However, the interaction between uric acid and the regulation of polyamine homeostasis has not been extensively investigated. The objective of this study was to investigate the influence of uric acid on cardiac polyamines regulation and elucidate the role of polyamines in uric acid induced cardiomyocytic injury.Methods: The in vitro experiments utilized H9C2 cardiomyocytes, the hyperuricemic mouse model was established via potassium oxonate and hypoxanthine. Techniques included energy metabolomics, HPLC for polyamine quantification, qPCR, ELISA, immunofluorescence, and mitochondrial membrane potential assessment using JC-1 staining, MTT cell viability analysis. Results: Uric acid treatment can alter ornithine metabolism in cardiomyocytes, revealed a potential of shifting it from the traditional ornithine cycle towards the polyamine cycle. Both ODC1 and SAT1 protein levels were up-regulated in hyperuricemic mice indicated a dysorder of polyamines homostasis. A downregulation tendency of spermidine and spermine levels were observed in cardiomyocytes under uric acid treatment. Notably, exogenous supplementation with spermidine or spermine effectively mitigated the uric acid-induced decline in cardiomyocyte viability and mitochondrial membrane potential.Discussion: Uric acid disrupts polyamine homeostasis, leading to mitochondrial dysfunction and cardiomyocyte damage. Exogenous polyamine supplementation demonstrates therapeutic potential by preserving mitochondrial integrity. These findings unveil a potential mechanism underlying uric acid-induced cardiac injury and propose polyamine replenishment as a viable intervention strategy for hyperuricemia-related cardiovascular complications.

研究领域: 心血管生物学 · 代谢组学 · 分子医学
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Cell Host & Microbe · 2024 · IF 20.6

Alistipes indistinctus-derived hippuric acid promotes intestinal urate excretion to alleviate hyperuricemia

Ying-Xi Xu,Lu-Di Liu,Jiang-Yuan Zhu,Shan-Shan Zhu,Bing-Qi Ye,Jia-Lu Yang,Jing-Yi Huang,Zhi-Hao Huang,Yi You,Wen-Kang Li,Jia-Lin He,Min Xia,Yan Liu

Hyperuricemia induces inflammatory arthritis and accelerates the progression of renal and cardiovascular diseases. Gut microbiota has been linked to the development of hyperuricemia through unclear mechanisms. Here, we show that the abundance and centrality of Alistipes indistinctus are depleted in subjects with hyperuricemia. Integrative metagenomic and metabolomic analysis identified hippuric acid as the key microbial effector that mediates the uric-acid-lowering effect of A. indistinctus. Mechanistically, A. indistinctus-derived hippuric acid enhances the binding of peroxisome-proliferator-activated receptor γ (PPARγ) to the promoter of ATP-binding cassette subfamily G member 2 (ABCG2), which in turn boosts intestinal urate excretion. To facilitate this enhanced excretion, hippuric acid also promotes ABCG2 localization to the brush border membranes in a PDZ-domain-containing 1 (PDZK1)-dependent manner. These findings indicate that A. indistinctus and hippuric acid promote intestinal urate excretion and offer insights into microbiota-host crosstalk in the maintenance of uric acid homeostasis.

CAS / MDL: 52-89-1 7758-11-4
研究领域: 微生物学 · 代谢组学 · 药理学 · 胃肠病学
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Food Science and Human Wellness · 2022 · IF 8.022

Ameliorative effect of Lacticaseibacillus rhamnosus Fmb14 from Chinese yogurt on hyperuricemia

Hongyuan Zhao,Xiaoyu Chen,Fanqiang Meng,Libang Zhou,Xinyi Pang,Zhaoxin Lu,Yingjian Lu

Hyperuricemia is a critical threat to human health, and a high inosine diet can increase the prevalence of it. Lacticaseibacillus rhamnosus Fmb14 was isolated from traditional fermented Chinese yogurt, and its inosine degradation rate reached 36.3 % at 10 9 CFU/mL for 24 h. LC-MS analysis revealed that high concentrations of inosine could activate compensatory metabolic pathways of L. rhamnosus Fmb14 to catalyse inosine as an energy source and produce intracellular folic acid and riboflavin. The contents of folic acid and riboflavin were 6.0 and 4.3 fold increased after inosine treatment in the cell-free extracts (CFE). L. rhamnosus Fmb14 CFE treatment ameliorates hyperuricemia through xanthine oxidase (XOD) inhibition and ATP-binding cassette subfamily G member 2 (ABCG2) promotion, both of which are responsible for uric acid (UA) synthesis and secretion in HepG2 and Caco2 cells, respectively. The in vivo results showed that the serum UA level decreased from 236.28 to 149.28 μmol/L after 8 weeks of oral administration of L. rhamnosus Fmb14 in inosine-induced hyperuricemia model mice. Our results revealed that L. rhamnosus Fmb14 has a potential as a biological therapeutic agent in hyperuricemia prevention.

CAS / MDL: 68-94-0 58-63-9 69-93-2
研究领域: 微生物学 · 药理学 · 分子生物学 · 营养学
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mSphere · 2024 · IF 3.7

Isolation and identification of uric acid-dependent Aciduricibacillus chroicocephali gen. nov., sp. nov. from seagull feces and implications for hyperuricemia treatment

Wenxuan Liu,Fulong Nan,Fengjun Liu,Xiaoli Yang,Zonghui Li,Shasha Jiang,Xianjuan Zhang,Jun Li,Meng Yu,Yunyang Wang,Bin Wang

Hyperuricemia has become the second most prevalent metabolic disease after diabetes, but the limitations of urate-lowering treatment (ULT) drugs and patient nonadherence make ULT far less successful. Thus, more ULT approaches urgently need to be explored. Uric acid-degrading bacteria have potential application value in ULT. In this study, we isolated 44XBT, a uric acid-degrading bacterium, from black-headed gull (Chroicocephalus ridibundus) feces. Using a polyphasic taxonomic approach, strain 44XBT was identified as a novel genus within the family Bacillaceae; subsequently, the name Aciduricibacillus chroicocephali was proposed. Strain 44XBT had a unique uric acid-dependent phenotype and utilized uric acid and allantoin as the sole carbon and nitrogen sources, but not common carbon sources or complex media. In the genome, multiple copies of genes involved in uric acid metabolic pathway (pucL, pucM, uraD, and allB) were found. Six copies of pucL (encoding urate oxidase) were detected. Of these, five pucL copies were in a tandem arrangement and shared 70.42%–99.70% amino acid identity. In vivo experiments revealed that 44XBT reduced serum uric acid levels and attenuated kidney damage in hyperuricemic mice through uric acid catalysis in the gut and gut microbiota remodeling. In conclusion, our findings discover a strain for studying bacterial uric acid metabolism and may provide valuable insights into ULT.

CAS / MDL: 68-94-0
研究领域: 微生物学 · 代谢疾病 · 药理学 · 基因组学
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Small · 2025 · IF 12.1

Albumin Corona-Coated Nanoscale Metal–Organic Framework for Enzyme-Mediated Cascade Metabolization of Uric Acid in Hyperuricemia

Mingchen Lv,Jiaxi Xu,Ran Chen,Wei Hu,Yuxiao Zhou,Min Sun,Zhen Fan,Jianzhong Du

Hyperuricemia, characterized by elevated uric acid levels, is the primary cause of gout. Recombinant uricase is one of the last-resort therapies but generates unwanted pro-inflammatory H 2 O 2 and anti-uricase antibodies. In this work, we developed an albumin corona-coated enzyme-loaded zeolitic imidazolate framework (UCZIF) to sustainably maintain low blood uric acid level without producing H 2 O 2 . The corona coating not only preserves loaded enzymes but also reduces macrophage phagocytosis by 73.4% compared to free uricase. In addition, the uptake level of UCZIF by dendritic cells is reduced by 74.1%, and the maturation of dendritic cells is inhibited by 35.4% compared to free uricase. Animal experiments demonstrate that albumin corona-coated UCZIF effectively lowers blood uric acid level in both acute and diet-induced chronic hyperuricemia models with significantly increasing the half-life of uricase. Furthermore, compared to the generation of anti-uricase antibodies during standalone uricase treatment, the levels of anti-uricase immunoglobulins are significantly reduced by 65.5% (immunoglobulin M) and 76.3% (immunoglobulin G) with repeated administration of albumin corona-coated UCZIF. Overall, this albumin corona-coated nanoscale metal–organic framework offers a promising approach to minimize the immunogenicity induced by exogenous enzymes and further safely reduce uric acid levels in the treatment of hyperuricemia.

研究领域: 生物医学工程 · 药物递送 · 免疫学
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CRYSTAL RESEARCH AND TECHNOLOGY · 2020 ·Vol. 55 ·期 10 ·2000039 · IF 1.169

Morphology Regulation of Monosodium Urate Monohydrate Crystals via Fabricated Uniform Hydrogel Slices

Zeqiu Xia,Lin Wang,Gaohong He,Xiaobin Jiang

Crystal morphology control is a common concern for the crystal engineering and relevant applications. For example, urate crystallization is important for the study of the hyperuricemia induced gout. Herein, biomimetic hydrogel material with uniform surface and vertical structure is fabricated, which possesses hybrid pH-temperature responsibility for high-efficiency interfacial nucleation and concentration regulation functions. The developed hydrogel layers are prepared to slice type as a functional microplatform and then added into the uric acid dihydrate (UAD) crystal solution to induce monosodium urate monohydrate (MSUM) crystallization. With different dosage of the hydrogel slices (HGS) in the solution, diverse crystal morphologies can be obtained in an efficient manner, such as “flower,” “sphere,” “sticky spheres,” which entirely distinguishes from the one prepared via no-HGS. This work explores a new path for revealing the relevant crystallization mechanism and developing crystal morphology control technology with hydrogel interfacial materials.

研究领域: 材料科学 · 晶体工程 · 生物医学工程 · 化学
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Microorganisms · 2023 ·Vol. 11 ·期 8 ·1989 · IF 4.5

Biodegradation of Uric Acid by Bacillus paramycoides-YC02

Xiaoyu Cao,Jingyuan Cai,Yu Zhang,Chao Liu,Meijie Song,Qianqian Xu,Yang Liu,Hai Yan

High serum uric acid levels, known as hyperuricemia (HUA), are associated with an increased risk of developing gout, chronic kidney disease, cardiovascular disease, diabetes, and other metabolic syndromes. In this study, a promising bacterial strain capable of biodegrading uric acid (UA) was successfully isolated fromBaijiucellar mud using UA as the sole carbon and energy source. The bacterial strain was identified asBacillus paramycoides-YC02 through 16S rDNA sequence analysis. Under optimal culture conditions at an initial pH of 7.0 and 38 °C, YC02 completely biodegraded an initial UA concentration of 500 mg/L within 48 h. Furthermore, cell-free extracts of YC02 were found to catalyze and remove UA. These results demonstrate the strong biodegradation ability of YC02 toward UA. To gain further insight into the mechanisms underlying UA biodegradation by YC02, the draft genome of YC02 was sequenced using Illumina HiSeq. Subsequent analysis revealed the presence of gene1779 and gene2008, which encode for riboflavin kinase, flavin mononucleotide adenylyl transferase, and flavin adenine dinucleotide (FAD)-dependent urate hydroxylase. This annotation was based on GO or the KEEG database. These enzymes play a crucial role in the metabolism pathway, converting vitamin B2to FAD and subsequently converting UA to 5-hydroxyisourate (HIU) with the assistance of FAD. Notably, HIU undergoes a slow non-enzymatic breakdown into 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) and (S)-allantoin. The findings of this study provide valuable insights into the metabolism pathway of UA biodegradation byB. paramycoides-YC02 and offer a potential avenue for the development of bacterioactive drugs against HUA and gout.Keywords:uric acid;Bacillus paramycoides-YC02;biodegradation;genomic analysis

CAS / MDL: 69-93-2
研究领域: 微生物学 · 基因组学 · 代谢研究 · 生物技术
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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2020 ·Vol. 412 ·期 26 ·7275-7283 · IF 3.637

An electrochemical biosensor based on multi-wall carbon nanotube–modified screen-printed electrode immobilized by uricase for the detection of salivary uric acid

Shi Weishan,Li Jing,Wu Jie,Wei Qianying,Chen Cuili,Bao Ning,Yu Chunmei,Gu Haiying

The amounts of uric acid (UA) in non-invasive biological samples, such as saliva, are critical for diagnosis and therapy of gout, hyperuricemia, Lesch–Nyhan syndrome, and several other diseases. Here, disposable UA biosensors were fabricated with the screen printing technique on the substrate of flexible PET. The working electrode was modified with carbon nanotubes followed by uricase for UA detection with excellent selectivity. The biosensor showed good electrocatalytic activity toward UA with high sensitivity, low detection limit, and wide linear range, which covers the full range of UA levels in human saliva. We demonstrate that UA can be directly detected in human saliva with the biosensor and the experimental data were consistent with the clinical analysis. This study indicated that the non-invasive biosensor is an attractive and possible approach for the monitoring of salivary UA. A disposable uric acid biosensor modified with carbon nanotubes followed by uricase was fabricated on flexible PET and applied for the monitoring of salivary uric acid in human saliva

研究领域: 生物化学 · 纳米技术 · 分析化学 · 医学诊断
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES · 2020 · IF 3.004

An LC-MS/MS- and hURAT1 cell-based approach for screening of uricosuric agents

Chen Sun,Mingyu Zhang,Yanhong Zhao,Jianxin Pang,Ying Peng,Jiang Zheng

Urate anion exchanger 1 (URAT1) expressed in the proximal renal tubules is responsible for about 90% of the reabsorption of uric acid. URAT1 is identified as an important target of uricosuric drugs. Here we present an LC-MS/MS-based approach, combined with URAT1-transgenic MDCK cells, for the assessment of uric acid. Cell lysis was executed with 50 mM NaOH to release uric acid. 1,3- 15 N 2 uric acid was employed as the internal standard. The harvested uric acid, along with the stable isotope-labeled uric acid, was analyzed by LC-MS/MS in multiple reactions monitoring and negative modes. Validation, i.e. determination of selectivity, precision, accuracy, extraction recovery, and matrix effect, and feasibility was evaluated by use of the approach developed. The linearity was observed in the range of 1.0–250 μM (r = 0.9960) with limit of detection of 50 nM and limit of quantitation of 200 nM. The precision and accuracy were found to be RSD ≤ 20% and 80–120% of the nominal value, respectively. Uric acid uptake showed concentration and time dependency in URAT1-transgenic cells. The observed inhibitory effects of three URAT1-targeted uricosuric drugs were consistent with those reported in literature. The stable isotope dilution-based approach was proven to be selective, sensitive, and convenient, which is a good in vitro model for URAT1-targeted drug candidate screening.

研究领域: 药理学 · 分析化学 · 医学
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Journal of Functional Foods · 2019 · IF 3.197

Molecular mechanism underlying the ability of caffeic acid to decrease uric acid levels in hyperuricemia rats

Yin Wan,Fen Wang,Bin Zou,Yuefeng Shen,Yizhen Li,Axi Zhang,Guiming Fu

The mechanism underlying the reduction in uric acid levels in hyperuricemia rats by caffeic acid was investigated in this study. Different doses of caffeic acid (25, 50, and 100 mg/kg) were administered to hyperuricemia rats induced by the intraperitoneal injection of potassium oxonate. In vivo study showed that caffeic acid can down-regulate the transcription levels of URAT1 and GLUT9 mRNA and up-regulate the transcription levels of OAT1, UAT, and ABCG2 mRNA. In vitro study indicated caffeic acid competitively binds with xanthine oxidase to inhibit its activity, and the IC 50 value was 53.45 µM. It was concluded that caffeic acid decreases serum uric acid levels in hyperuricemia rats by binding with xanthine oxidase and inhibiting its catalytic activity and by regulating the mRNA transcription of the renal uric acid transporters.

研究领域: 药理学 · 生物化学 · 分子生物学
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