Pacific Islands Families Study: Serum Uric Acid in Pacific Youth and the Associations with Free-Sugar Intake and Appendicular Skeletal Muscle Mass DOI Open Access
Shabnam Jalili‐Moghaddam, Gael Mearns, Lindsay D. Plank

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 17(1), P. 54 - 54

Published: Dec. 27, 2024

Background: Fructose (50% of sucrose/sugar) is one component free-sugars and metabolized to uric acid, which a known risk factor for gout metabolic syndrome. Pacific peoples in New Zealand experience higher prevalence gout, type 2 diabetes, overweight/obesity than other ethnic groups. Interestingly, despite having similar body mass index (BMI), they tend have proportion appendicular skeletal muscle (ASMM) less fat Given this context, study aimed evaluate the associations between serum acid (SUA), free-sugar intake, ASMM. Methods: In nested sub-study from Islands Families birth-cohort study, 101 boys 99 girls (all aged 14 15 years) self-reported how often had consumed foods containing sugar past month. Anthropometry, fatness, ASMM by dual-energy X-ray absorptiometry factors, including SUA were measured. Results: Overall, 43% 57% ‘sugary drinks’ twice or more day. When analyzed group, was positively related both (r = 0.593, p < 0.0001). The effect intake on 0.176, 0.013) reduced when considered relationships. Conclusions: This shows high levels adolescents, with positive association genders. Sugary drink associated girls. High people an increased raised make it important work communities reduce added adopt integrated, family-based, culturally centered, life-course approaches prevent chronic diseases, gout.

Language: Английский

Targeting uric acid: a promising intervention against oxidative stress and neuroinflammation in neurodegenerative diseases DOI Creative Commons
Xu Lin, Chengwei Li,

Tiantian Wan

et al.

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 3, 2025

Oxidative stress and neuroinflammation are recognized as key factors in the development of neurodegenerative diseases, yet effective interventions biomarkers to address oxidative these conditions limited. Uric acid (UA), traditionally associated with gout, is now gaining prominence a potential target diseases. Soluble UA stands out one most vital antioxidant compounds produced by human body, accounting for up 55% extracellular capacity neutralize free radicals. While there increasing evidence supporting neuroprotective properties Parkinson's disease Alzheimer's disease, gaps knowledge still exist regarding underlying mechanisms how effectively translate benefits into clinical practice. Moreover, current elevation therapy exhibits unstable properties, individual variability, even adverse effects, limiting its applications. This review consolidates recent advancements understanding exerts effects on diseases emphasizes dual roles managing neuroinflammation. Additionally, elucidates through which confers neuroprotection. Based this, underscores significance biomarker aims provide comprehensive therapeutic target, while also addressing possible challenges implementation.

Language: Английский

Citations

4
Structural Basis for Inhibition of Urate Reabsorption in URAT1 DOI Creative Commons
Junping Fan, Wenjun Xie, Han Ke

et al.

JACS Au, Journal Year: 2025, Volume and Issue: 5(3), P. 1308 - 1319

Published: Feb. 23, 2025

The urate transporter 1 (URAT1) is the primary in kidney responsible for reabsorption and, therefore, crucial homeostasis. Hyperuricemia causes common human disease gout and other pathological consequences. Inhibition of through URAT1 has been shown as a promising strategy alleviating hyperuricemia, clinical preclinical drug candidates targeting are emerging. However, how small molecules inhibit remains undefined, lack accurate complex structures hinders development better therapeutics. Here, we present cryoelectron microscopy humanized rat bound with benzbromarone, lingdolinurad, verinurad, elucidating structural basis recognition inhibition. three reside central cavity different binding modes, locking an inward-facing conformation. This study provides mechanistic insights into modulation sheds light on rational design potential URAT1-specific therapeutics treating hyperuricemia.

Language: Английский

Citations

1
Hyperuricaemia and gout in the Pacific DOI

Baptiste Gérard,

Megan Leask, Tony R. Merriman

et al.

Nature Reviews Rheumatology, Journal Year: 2025, Volume and Issue: unknown

Published: March 11, 2025

Language: Английский

Citations

1
Purine metabolism-associated key genes depict the immune landscape in gout patients DOI Creative Commons

Lin-na Li,

Hao Wang, Lushan Xiao

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 17, 2025

Language: Английский

Citations

0
Suppression of NLRP3 inflammasome by a small molecule targeting CK1α–β-catenin–NF-κB and CK1α–NRF2–mitochondrial OXPHOS pathways during mycobacterial infection DOI Creative Commons
Qing Guan, Huan Xiong,

Xiangyu Song

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 28, 2025

Introduction Pyroptosis is an important inflammatory form of cell death and Mycobacterium tuberculosis ( M.tb ) chronic infection triggers excessive pyroptosis macrophages. Our previous research has confirmed that a small compound pyrvinium pamoate (PP) could inhibit pathological changes mycobacterial burden in -infected mice, but the potential mechanism PP for inhibiting -induced inflammation remains unexplored. Methods The effects on NLRP3-ASC-Casp1 inflammasome assembly activation, gasdermin D (GSDMD) mediated cytokines expression were assessed human THP-1-derived macrophages after H37Rv/H37Ra/ Salmonella typhimurium S. or LPS treatment by Transcriptome sequencing, RT-qPCR, Co-immunoprecipitation Western Blot (WB) analysis. lactate dehydrogenase (LDH) release assay was used to evaluate CC50 THP-1 cells. Results We found / significantly activate GSDMD-mediated (IL-1β IL-18) macrophages, whereas suppress these dose dependent manner. Regarding PP-inhibition mechanism, we further this inhibitory activity through PP-targeting casein kinase 1A1 (CK1α)–β-catenin–NF-κB pathway CK1α–NRF2–mitochondrial oxidative phosphorylation (OXPHOS) pathway. In addition, CK1α specific inhibitor D4476 siRNA reverse bacteria-induced responses Conclusions This study reveals previously unreported can NLRP3 GSDMD–IL-1β via targeting suppressing CK1α–β-catenin–NF-κB OXPHOS pathways, suggesting holds great promise as host directed therapy (HDT) drug mycobacterial-induced response.

Language: Английский

Citations

0
Identification of pathogenic variants in the ABCG2 gene in patients with severe familial hyperuricemia and gout DOI
Yu Toyoda, Kateřina Pavelcová, Jana Mašínová

et al.

Molecular and Cellular Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Language: Английский

Citations

0
Plasma Fetuin-B Levels are Associated with Nervous Symptoms and Conduction Velocity in Patients with Painful DPN DOI Creative Commons
Ke Lin, Xiaocui Wang, Tao Gu

et al.

Diabetes Metabolic Syndrome and Obesity, Journal Year: 2025, Volume and Issue: Volume 18, P. 785 - 793

Published: March 1, 2025

To assess the plasma concentrations of novel hepatokine fetuin-B in individuals with type 2 diabetes or without diabetic peripheral neuropathy (DPN), and to evaluate relationship among levels, nervous function, metabolic parameters. A total 333 participants were recruited divided into three groups: DPN, painful DPN (pDPN), non-DPN. Metabolic parameters, neuropathy-associated indices, general biochemical parameters also measured. Compared non-DPN group, including age, SBP, BUN, Cr, ALT, significantly higher pDPN groups, FPG, HbA1c, TC, TG, LDL, UA levels group. The symptom score (NSS), disability (NDS), Douleur Neuropathique en 4 Questions (DN4) highest followed by lowest Moreover, fetuin B showed same trends as indices. Additionally, oxidative stress markers a decrease antioxidant capacity (TAC) an increase malondialdehyde (MDA) across all most pronounced changes observed patients. Bivariate correlation analysis that positively correlated NSS, NDS, DN4, MDA negatively associated TAC after adjusting for age sex. Furthermore, nerve conduction velocity, MLT, MRT, SRS, SLT, decreasing tertiles levels. current study suggests circulating may be progression highlights effects hepatokine-mediated liver-to-peripheral system crosstalk DPN.

Language: Английский

Citations

0
Exploring the Causal Association between Soy Products Intake and Gout by Bidirectional Mendelian Randomization Analysis DOI

彤 张

Hans Journal of Food and Nutrition Science, Journal Year: 2025, Volume and Issue: 14(02), P. 240 - 253

Published: Jan. 1, 2025

Language: Английский

Citations

0
GLUT2/SLC2A2 is a bi-directional urate transporter DOI Creative Commons
Yu Toyoda,

Ryuichiro Shigesawa,

Tony R. Merriman

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108485 - 108485

Published: April 1, 2025

Language: Английский

Citations

0
Comparison of Pathophysiological Mechanisms Among Crystal-Induced Arthropathies DOI Open Access

M. Zangari,

Roberto Luisetto,

Roberto Pilot

et al.

Gout Urate and Crystal Deposition Disease, Journal Year: 2025, Volume and Issue: 3(2), P. 7 - 7

Published: April 10, 2025

Monosodium urate, calcium pyrophosphate, and basic phosphate crystals are the most common types of found in joints. Each type crystal has been associated with onset different joint diseases. However, mechanisms identified for one often generalized to others; thus, overlooking specific distinct molecular cellular responses activated by each crystal. This review describes similarities differences main molecules underlying diseases three crystals. Specifically, current knowledge on properties formation, induction resolution inflammation, involved pain processing senescence, role mitochondria genomic instability elucidated. A more complete detailed study induced is necessary advance our understanding pathogenesis help identify innovative opportunities prevention treatment deposition disease.

Language: Английский

Citations

0