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1.
Front Immunol ; 15: 1362642, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38745649

RESUMEN

Hyperuricaemia (HUA) is a metabolic disorder characterised by high blood uric acid (UA) levels; moreover, HUA severity is closely related to the gut microbiota. HUA is also a risk factor for renal damage, diabetes, hypertension, and dyslipidaemia; however, current treatments are associated with detrimental side effects. Alternatively, Fangyukangsuan granules are a natural product with UA-reducing properties. To examine their efficacy in HUA, the binding of small molecules in Fangyukangsuan granules to xanthine oxidase (XOD), a key factor in UA metabolism, was investigated via molecular simulation, and the effects of oral Fangyukangsuan granule administration on serum biochemical indices and intestinal microorganisms in HUA-model rats were examined. Overall, 24 small molecules in Fangyukangsuan granules could bind to XOD. Serum UA, creatinine, blood urea nitrogen, and XOD levels were decreased in rats treated with Fangyukangsuan granules compared to those in untreated HUA-model rats. Moreover, Fangyukangsuan granules restored the intestinal microbial structure in HUA-model rats. Functional analysis of the gut microbiota revealed decreased amino acid biosynthesis and increased fermentation of pyruvate into short-chain fatty acids in Fangyukangsuan granule-treated rats. Together, these findings demonstrate that Fangyukangsuan granules have anti-hyperuricaemic and regulatory effects on the gut microbiota and may be a therapeutic candidate for HUA.


Asunto(s)
Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Hiperuricemia , Ácido Úrico , Animales , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Ratas , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Masculino , Ácido Úrico/sangre , Xantina Oxidasa/metabolismo , Ratas Sprague-Dawley
3.
Ann Med ; 56(1): 2332956, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38738384

RESUMEN

PURPOSE: It is unknown whether febuxostat can delay the progression of kidney dysfunction and reduce kidney endpoint events. The aim was to evaluate the renoprotective effect of febuxostat in patients with hyperuricemia or gout by performing a meta-analysis of randomized controlled trials (RCTs). METHODS: MEDLINE, Web of science, EMBASE, ClinicalTrials.gov, and the Cochrane Central Register for Randomized Controlled Trials were searched. The main outcomes included kidney events (serum creatinine doubling or progression to end-stage kidney disease or dialysis). The secondary outcomes were the rate of change in the estimated glomerular filtration rate (eGFR) and changes in the urine protein or urine albumin to creatinine ratio from baseline to the end of follow-up. We used random-effects models to calculate the pooled risk estimates and 95% CIs. RESULTS: A total of 16 RCTs were included in the meta-analysis. In comparison with the control group, the patients who received febuxostat showed a reduced risk of kidney events (RR = 0.56, 95% CI 0.37-0.84, p = 0.006) and a slower decline in eGFR (WMD = 0.90 mL/min/1.73 m2, 95% CI 0.31-1.48, p = 0.003). The pooled results also revealed that febuxostat use reduced the urine albumin to creatinine ratio (SMD = -0.21, 95% CI -0.41 to -0.01, p = 0.042). CONCLUSION: Febuxostat use is associated with a reduced risk of kidney events and a slow decline in eGFR. In addition, the urine albumin to creatinine ratio decreased in febuxostat users. Accordingly, it is an effective drug for delaying the progression of kidney function deterioration in patients with gout.Systematic review registration: PROSPERO CRD42021272591.


Asunto(s)
Febuxostat , Tasa de Filtración Glomerular , Supresores de la Gota , Gota , Hiperuricemia , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Creatinina/orina , Creatinina/sangre , Progresión de la Enfermedad , Febuxostat/uso terapéutico , Febuxostat/farmacología , Tasa de Filtración Glomerular/efectos de los fármacos , Gota/tratamiento farmacológico , Gota/complicaciones , Supresores de la Gota/uso terapéutico , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/complicaciones , Riñón/fisiopatología , Riñón/efectos de los fármacos , Fallo Renal Crónico/prevención & control , Fallo Renal Crónico/complicaciones
4.
PLoS One ; 19(5): e0302386, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38713669

RESUMEN

BACKGROUND: The purpose of this study was to evaluate the relationship between hyperuricemia and the risks of all-cause mortality and cardiovascular disease (CVD) mortality in patients with osteoarthritis (OA). METHODS: A retrospective cohort study was performed on 3,971 patients using data from the National Health and Nutrition Examination Survey database between 1999 and 2018. OA was diagnosed through specific questions and responses. The weighted COX regression models were used to explore the factors associated with all-cause mortality/CVD mortality in OA patients. Subgroup analyses were conducted based on age, gender, hypertension, dyslipidemia, CVD, and chronic kidney disease (CKD). Hazard ratio (HR) and 95% confidence interval (95% CI) were measured as the evaluation indexes. RESULTS: During the duration of follow-up time (116.38 ± 2.19 months), 33.69% (1,338 patients) experienced all-cause mortality, and 11.36% (451 patients) died from CVD. Hyperuricemia was associated with higher risks of all-cause mortality (HR: 1.22, 95% CI: 1.06-1.41, P = 0.008) and CVD mortality (HR: 1.32, 95% CI: 1.02-1.72, P = 0.036) in OA patients. Subgroup analyses showed that hyperuricemia was related to the risk of all-cause mortality in OA patients aged >65 years (HR: 1.17, 95% CI: 1.01-1.36, P = 0.042), in all male patients (HR: 1.41, 95% CI: 1.10-1.80, P = 0.006), those diagnosed with hypertension (HR: 1.17, 95% CI: 1.01-1.37, P = 0.049), dyslipidemia (HR: 1.18, 95% CI: 1.01-1.39, P = 0.041), CVD (HR: 1.30, 95% CI: 1.09-1.55, P = 0.004), and CKD (HR: 1.31, 95% CI: 1.01-1.70, P = 0.046). The association between hyperuricemia and a higher risk of CVD mortality was found in OA patients aged ≤ 65 years (HR: 1.90, 95% CI: 1.06-3.41, P = 0.032), who did not suffer from diabetes (HR: 1.36, 95% CI: 1.01-1.86, P = 0.048), who did not suffer from hypertension (HR: 2.56, 95% CI: 1.12-5.86, P = 0.026), and who did not suffer from dyslipidemia (HR: 2.39, 95% CI: 1.15-4.97, P = 0.020). CONCLUSION: These findings emphasize the importance of monitoring serum uric acid levels in OA patients for potentially reducing mortality associated with the disease.


Asunto(s)
Enfermedades Cardiovasculares , Hiperuricemia , Encuestas Nutricionales , Osteoartritis , Humanos , Hiperuricemia/complicaciones , Hiperuricemia/mortalidad , Hiperuricemia/epidemiología , Masculino , Femenino , Osteoartritis/mortalidad , Osteoartritis/complicaciones , Osteoartritis/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/complicaciones , Factores de Riesgo , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Bases de Datos Factuales , Modelos de Riesgos Proporcionales , Hipertensión/complicaciones , Hipertensión/mortalidad , Hipertensión/epidemiología , Adulto , Dislipidemias/mortalidad , Dislipidemias/complicaciones , Dislipidemias/epidemiología
5.
Adv Rheumatol ; 64(1): 37, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38702826

RESUMEN

OBJECTIVE: It is well-established that patients with a history of gout are more susceptible to experiencing gastrointestinal bleeding. Gout flare during active gastrointestinal bleeding poses a significant challenge due to the gastrointestinal side effects of anti-inflammatory therapy. This study sought to investigate the risk factors associated with gout flares during episodes of gastrointestinal bleeding. METHODS: We conducted a retrospective observational study involving 94 patients who experienced active gastrointestinal bleeding and had a history of gout. This study was conducted at Jinhua Municipal Central Hospital from January 2019 to October 2022. We collected and recorded demographic information and clinical characteristics. RESULTS: Among the gout flare patients, hyperuricemia and intravenous fat emulsion therapy were more prevalent compared to those who remained stable (81.6% vs. 57.8% and 46.9% vs. 24.4%, p < 0.05). Multivariate logistic regression analysis revealed that both hyperuricemia (odds ratio 2.741, 95% CI 1.014-7.413, p = 0.047) and intravenous fat emulsion therapy (odds ratio 2.645, 95% CI 1.046-6.686, p = 0.040) were independent predictors of gout flares. Furthermore, gout attacks occurred sooner in patients receiving intravenous fat emulsion therapy compared to those not receiving it (median: 4 days (interquartile range: 2) vs. median: 5 days (interquartile range: 2.25), p = 0.049). CONCLUSION: Our study revealed a high incidence of gout flares during episodes of active gastrointestinal bleeding, with patients undergoing intravenous fat emulsion therapy and those with hyperuricemia being at increased risk.


Asunto(s)
Emulsiones Grasas Intravenosas , Hemorragia Gastrointestinal , Gota , Hiperuricemia , Humanos , Hiperuricemia/complicaciones , Gota/complicaciones , Gota/tratamiento farmacológico , Masculino , Factores de Riesgo , Femenino , Hemorragia Gastrointestinal/etiología , Estudios de Casos y Controles , Estudios Retrospectivos , Persona de Mediana Edad , Emulsiones Grasas Intravenosas/efectos adversos , Emulsiones Grasas Intravenosas/uso terapéutico , Emulsiones Grasas Intravenosas/administración & dosificación , Brote de los Síntomas , Anciano
6.
Nutr J ; 23(1): 48, 2024 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-38704549

RESUMEN

BACKGROUND: Limited data regarding the correlation between oxidative balance score (OBS) and hyperuricemia highlights the necessity for thorough investigations. This study aims to examine the link between OBS, which incorporates dietary and lifestyle factors, and the occurrence of hyperuricemia. METHODS: We conducted a cross-sectional study involving 13,636 participants from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). The oxidative balance score (OBS) was determined based on four lifestyle factors and sixteen dietary nutrients. We assessed the levels of serum uric acid (SUA) and the occurrence of hyperuricemia as outcomes. Weighted logistic regression and linear models were used for statistical analysis, using Restricted Cubic Splines (RCS) to examine potential nonlinear associations. Subgroup analysis and sensitivity assessments were performed to identify any variations and ensure the robustness of the findings. RESULTS: Higher OBS was consistently correlated with decreased SUA levels and a reduced prevalence of hyperuricemia. RCS highlighted a significant negative nonlinear association, particularly in females. Subgroup analysis revealed gender-based differences and interactive correlation, providing additional insights regarding OBS and hyperuricemia relationship. CONCLUSION: This study underscores a robust negative correlation between OBS and SUA levels as well as the incidence of hyperuricemia, emphasizing the importance of dietary and lifestyle factors. Incorporating RCS, subgroup analysis, and sensitivity assessments enhances the depth of our findings, providing valuable insights for further research.


Asunto(s)
Dieta , Hiperuricemia , Estilo de Vida , Encuestas Nutricionales , Ácido Úrico , Humanos , Hiperuricemia/sangre , Hiperuricemia/epidemiología , Femenino , Masculino , Estudios Transversales , Encuestas Nutricionales/métodos , Encuestas Nutricionales/estadística & datos numéricos , Persona de Mediana Edad , Adulto , Ácido Úrico/sangre , Dieta/métodos , Dieta/estadística & datos numéricos , Estrés Oxidativo , Prevalencia , Anciano
7.
Int J Rheum Dis ; 27(5): e15193, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38742430

RESUMEN

OBJECTIVE: Known for anti-inflammatory and antioxidant properties, flavonoid has phytoestrogenic effects, but it is unclear whether its role in hyperuricemia and metabolic syndrome (MetS) differs by gender. Moreover, given the strong association between hyperuricemia and MetS, we aimed to explore whether flavonoid is a protective factor for hyperuricemia, independently of MetS, in different genders. METHODS: Data for 2007-2010 and 2017-2018 were obtained from the National Health and Nutrition Examination Survey (NHANES) and the Food and Nutrient Database for Dietary Studies (FNDDS). To assess the association among flavonoid, hyperuricemia, and MetS, multivariate logistic regression and subgroup analyses were conducted. Besides, to investigate whether the association between flavonoid and hyperuricemia was independent of MetS, multivariate logistic regression models were further conducted to explore the association between flavonoid and MetS among females with hyperuricemia and to investigate the association between flavonoid and hyperuricemia among females after excluding MetS. RESULT: Among 5356 females, anthocyanin intake was inversely associated with the prevalence of hyperuricemia (Q4 vs. Q1: OR 0.49, 95% CI 0.31 to 0.76), and MetS (Q4 vs. Q1: OR 0.68, 95% CI 0.50 to 0.93). Furthermore, subgroup analyses showed the beneficial association between anthocyanin and hyperuricemia among females aged 40 to 59 years and menopausal. However, among 5104 males, no significant association was observed after adjustment for covariates (Q4 vs. Q1: OR 0.81, 95% CI 0.56 to 1.18). While in 372 females with hyperuricemia, no significant association was found between MetS and anthocyanin (Q4 vs. Q1: OR 0.88, 95% CI 0.31 to 2.49). Meanwhile, among 3335 females after excluding MetS, there was still a significant association between anthocyanin and a lower prevalence of hyperuricemia (Q4 vs. Q1: OR 0.38, 95% CI 0.17 to 0.85). CONCLUSION: Dietary anthocyanin is associated with a lower prevalence of hyperuricemia independently of MetS among females. Foods rich in anthocyanin should be emphasized for females, especially those aged 40 to 59 years and menopausal, which may be of potential significance in the prevention of hyperuricemia.


Asunto(s)
Antocianinas , Hiperuricemia , Síndrome Metabólico , Encuestas Nutricionales , Humanos , Hiperuricemia/epidemiología , Hiperuricemia/sangre , Hiperuricemia/diagnóstico , Femenino , Síndrome Metabólico/epidemiología , Síndrome Metabólico/sangre , Síndrome Metabólico/diagnóstico , Prevalencia , Adulto , Persona de Mediana Edad , Antocianinas/administración & dosificación , Factores Sexuales , Masculino , Factores de Riesgo , Estudios Transversales , Estados Unidos/epidemiología , Factores Protectores , Dieta/efectos adversos , Ácido Úrico/sangre , Biomarcadores/sangre , Factores de Tiempo , Análisis Multivariante
8.
J Hazard Mater ; 471: 134312, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38640681

RESUMEN

Previous studies indicated per- and poly-fluoroalkyl substances (PFAS) were related to uric acid and hyperuricemia risk, but evidence for the exposure-response (E-R) curves and combined effect of PFAS mixture is limited. Moreover, the potential mediation effect of kidney function was not assessed. Hence, we conducted a national cross-sectional study involving 13,979 US adults in NHANES 2003-2018 to examine the associations of serum PFAS with uric acid and hyperuricemia risk, and the mediation effects of kidney function. Generalized linear models and E-R curves showed positive associations of individual PFAS with uric acid and hyperuricemia risk, and nearly linear E-R curves indicated no safe threshold for PFAS. Weighted quantile sum regression found positive associations of PFAS mixture with uric acid and hyperuricemia risk, and PFOA was the dominant contributor to the adverse effect of PFAS on uric acid and hyperuricemia risk. Causal mediation analysis indicated significant mediation effects of kidney function decline in the associations of PFAS with uric acid and hyperuricemia risk, with the mediated proportion ranging from 19 % to 57 %. Our findings suggested that PFAS, especially PFOA, may cause increased uric acid and hyperuricemia risk increase even at low levels, and kidney function decline plays a crucial mediation effect.


Asunto(s)
Fluorocarburos , Hiperuricemia , Riñón , Ácido Úrico , Humanos , Ácido Úrico/sangre , Hiperuricemia/inducido químicamente , Hiperuricemia/sangre , Masculino , Persona de Mediana Edad , Femenino , Adulto , Fluorocarburos/toxicidad , Fluorocarburos/sangre , Estudios Transversales , Riñón/efectos de los fármacos , Riñón/fisiopatología , Contaminantes Ambientales/toxicidad , Contaminantes Ambientales/sangre , Exposición a Riesgos Ambientales/efectos adversos , Encuestas Nutricionales , Anciano
9.
Front Public Health ; 12: 1336674, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38590804

RESUMEN

Background: Hyperuricemia is a common metabolic disorder linked to various health conditions. Its prevalence varies among populations and genders, and high-altitude environments may contribute to its development. Understanding the connection between blood cell parameters and hyperuricemia in high-altitude areas can shed light on the underlying mechanisms. This study aimed to investigate the relationship between blood cell parameters and hyperuricemia in high-altitude areas, with a particular focus on gender differences. Methods: We consecutively enrolled all eligible Tibetan participants aged 18-60 who were undergoing routine medical examinations at the People's Hospital of Chaya County between January and December 2022. During this period, demographic and laboratory data were collected to investigate the risk factors associated with hyperuricemia. Results: Among the participants, 46.09% were diagnosed with hyperuricemia. In the male cohort, significant correlations were found between serum uric acid (SUA) levels and red blood cell (RBC) count, creatinine (Cr). Urea, alanine transaminase (ALT), and albumin (ALB). Notably, RBC exhibited the strongest association. Conversely, in the female cohort, elevated SUA levels were associated with factors such as white blood cell (WBC) count. Urea, ALT, and ALB, with WBC demonstrating the most significant association. Further analysis within the female group revealed a compelling relationship between SUA levels and specific white blood cell subtypes, particularly neutrophils (Neu). Conclusion: This study revealed gender-specific associations between SUA levels and blood cell parameters in high-altitude areas. In males, RBC count may play a role in hyperuricemia, while in females, WBC count appears to be a significant factor. These findings contribute to our understanding of metabolic dynamics in high-altitude regions but require further research for comprehensive mechanistic insights.


Asunto(s)
Hiperuricemia , Humanos , Masculino , Femenino , Hiperuricemia/epidemiología , Altitud , Ácido Úrico , Células Sanguíneas , Urea
10.
Pan Afr Med J ; 47: 49, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38681101

RESUMEN

Introduction: pre-eclampsia (PE) is a multisystemic pregnancy-specific hypertensive disorder associated with significant adverse maternal and perinatal outcomes. Maternal serum uric acid level is hypothesized as a reliable marker for predicting the severity and adverse outcomes of pre-eclampsia and facilitating clinical decisions. This study explored the association between maternal serum uric acid and adverse pregnancy outcomes in pre-eclampsia. Methods: a cross-sectional study involving women diagnosed with pre-eclampsia was conducted at Korle-Bu Teaching Hospital (KBTH), a tertiary hospital in Ghana. Descriptive analyses were performed and multivariable logistic regression model was used to explore the association between maternal serum uric acid levels and pregnancy outcomes using R software. Results: we included 100 women with pre-eclampsia comprising 79% and 21% preterm and term pre-eclampsia respectively and with mean gestational age (GA) at diagnosis of 32.35±2.66 weeks and 35.96±1.94 weeks respectively. The mean maternal age of preterm and term pre-eclampsia groups was 29.81±5.29 years and 29.46±5.78 years respectively. Hyperuricemia (serum uric acid >375 µmol/L) occurred in 61% of the pre-eclamptic women. The mean gestational age (in weeks) at diagnosis was significantly lower in the pre-eclamptic women with hyperuricemia compared with those with normal levels of uric acid (33.51±3.03 versus 34.80±2.71). There was a significant negative association (moderate correlation) between maternal serum uric acid levels and birth weight (R= -0.34, p < 0.001) in pre-eclampsia; the statistical significance was limited to preterm only (Pearson R= -0.39, p-value <0.001) but not term pre-eclampsia. Hyperuricemia was significantly associated with low birth weight [aOR: 3.222 (95% CI: 1.098, 10.393)], caesarean section [aOR: 2.281 (95% CI: 1.084, 7.568)] and severe diastolic pressure at birth [aOR: 3.517 (95% CI: 1.123, 11.939)]. Conclusion: hyperuricemia in pre-eclampsia was significantly associated with both maternal (caesarean section and severe hypertension) and neonatal (low birth weight) adverse outcomes. Hyperuricemia seems clinically useful in predicting pregnancy outcomes, especially in preterm pre-eclampsia. Further longitudinal study is recommended in exploring the clinical significance of maternal uric acid levels and pregnancy outcomes in pre-eclampsia.


Asunto(s)
Biomarcadores , Edad Gestacional , Hiperuricemia , Preeclampsia , Resultado del Embarazo , Ácido Úrico , Humanos , Preeclampsia/sangre , Preeclampsia/epidemiología , Femenino , Embarazo , Estudios Transversales , Ácido Úrico/sangre , Ghana/epidemiología , Adulto , Hiperuricemia/epidemiología , Hiperuricemia/sangre , Recién Nacido , Adulto Joven , Biomarcadores/sangre , Nacimiento Prematuro/epidemiología , Recién Nacido de Bajo Peso , Índice de Severidad de la Enfermedad
11.
Cell Mol Biol (Noisy-le-grand) ; 70(4): 217-224, 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38678602

RESUMEN

This study aimed to experimentally compare the uric acid-lowering effect and renal protection of Yiqing Fang in a rat model of hyperuricemia. Additionally, we used network pharmacology to predict the potential active components, targets, and pathways of Yiqing Fang. Male SD rats were randomly divided into control, model, Yiqing Fang, allopurinol, and probenecid groups. Serum creatinine (Scr), blood urea nitrogen (BUN), serum uric acid (UA), alanine transaminase (ALT), complete blood count, and urinary NAG enzyme levels were measured. Standard pathology and electron microscopy samples were prepared from the left kidney to observe renal pathological changes, renal fibrosis, and collagen III expression levels. In addition, we employed network pharmacology to investigate the molecular mechanisms and pathways of Yiqing Fang. The Yiqing Fang group showed significantly lower levels of Scr, BUN, UA, ALT, urinary NAG enzyme, complete blood count, and liver function tests compared to the model group (P < 0.05). Furthermore, both the Yiqing Fang and allopurinol groups exhibited significant reductions in renal pathological changes compared to the model group, along with decreased expression of collagen III. Network pharmacology analysis identified a total of 27 specific sites related to hyperuricemia. The main active components were predicted to include quercetin, berberine, beta-sitosterol, epimedin C, and dioscin. The primary target sites were predicted to include TNF, IL-6, IL-17, IL-1B, and VEGFA. Yiqing Fang may exert its effects through regulation of drug response, urate metabolism, purine compound absorption, inflammation response, lipopolysaccharide response, cytokine activity, and antioxidant activity. These effects may be mediated through signaling pathways such as IL-17, HIF-1, and AGE-RAGE. Yiqing Fang offers potential as a treatment for hyperuricemia due to its multiple active components, targeting of various sites, and engagement of multiple pathways.


Asunto(s)
Medicamentos Herbarios Chinos , Hiperuricemia , Riñón , Ratas Sprague-Dawley , Ácido Úrico , Animales , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/metabolismo , Masculino , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Ácido Úrico/sangre , Ratas , Modelos Animales de Enfermedad , Farmacología en Red/métodos , Creatinina/sangre , Nitrógeno de la Urea Sanguínea
12.
Eur J Med Chem ; 271: 116407, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38663283

RESUMEN

Xanthine oxidoreductase (XOR) and uric acid transporter 1 (URAT1) are two most widely studied targets involved in production and reabsorption of uric acid, respectively. Marketed drugs almost target XOR or URAT1, but sometimes, single agents might not achieve aim of lowering uric acid to ideal value in clinic. Thus, therapeutic strategies of combining XOR inhibitors with uricosuric drugs were proposed and implemented. Based on our initial work of virtual screening, A and B were potential hits for dual-targeted inhibitors on XOR/URAT1. By docking A/B with XOR/URAT1 respectively, compounds I1-7 were designed to get different degree of inhibition effect on XOR and URAT1, and I7 showed the best inhibitory effect on XOR (IC50 = 0.037 ± 0.001 µM) and URAT1 (IC50 = 546.70 ± 32.60 µM). Further docking research on I7 with XOR/URAT1 led to the design of compounds II with the significantly improved inhibitory activity on XOR and URAT1, such as II11 and II15. Especially, for II15, the IC50 of XOR is 0.006 ± 0.000 µM, superior to that of febuxostat (IC50 = 0.008 ± 0.000 µM), IC50 of URAT1 is 12.90 ± 2.30 µM, superior to that of benzbromarone (IC50 = 27.04 ± 2.55 µM). In acute hyperuricemia mouse model, II15 showed significant uric acid lowering effect. The results suggest that II15 had good inhibitory effect on XOR/URAT1, with the possibility for further investigation in in-vivo models of hyperuricemia.


Asunto(s)
Diseño de Fármacos , Inhibidores Enzimáticos , Transportadores de Anión Orgánico , Proteínas de Transporte de Catión Orgánico , Piridinas , Animales , Piridinas/farmacología , Piridinas/química , Piridinas/síntesis química , Ratones , Humanos , Relación Estructura-Actividad , Transportadores de Anión Orgánico/antagonistas & inhibidores , Transportadores de Anión Orgánico/metabolismo , Proteínas de Transporte de Catión Orgánico/antagonistas & inhibidores , Proteínas de Transporte de Catión Orgánico/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Estructura Molecular , Simulación del Acoplamiento Molecular , Xantina Deshidrogenasa/antagonistas & inhibidores , Xantina Deshidrogenasa/metabolismo , Relación Dosis-Respuesta a Droga , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/metabolismo , Masculino , Ácido Úrico/metabolismo
13.
Nutrients ; 16(7)2024 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-38613119

RESUMEN

Resveratrol (RES) has been reported to prevent hyperuricemia (HUA); however, its effect on intestinal uric acid metabolism remains unclear. This study evaluated the impact of RES on intestinal uric acid metabolism in mice with HUA induced by a high-fat diet (HFD). Moreover, we revealed the underlying mechanism through metagenomics, fecal microbiota transplantation (FMT), and 16S ribosomal RNA analysis. We demonstrated that RES reduced the serum uric acid, creatinine, urea nitrogen, and urinary protein levels, and improved the glomerular atrophy, unclear renal tubule structure, fibrosis, and renal inflammation. The results also showed that RES increased intestinal uric acid degradation. RES significantly changed the intestinal flora composition of HFD-fed mice by enriching the beneficial bacteria that degrade uric acid, reducing harmful bacteria that promote inflammation, and improving microbial function via the upregulation of purine metabolism. The FMT results further showed that the intestinal microbiota is essential for the effect of RES on HUA, and that Lactobacillus may play a key role in this process. The present study demonstrated that RES alleviates HFD-induced HUA and renal injury by regulating the gut microbiota composition and the metabolism of uric acid.


Asunto(s)
Microbioma Gastrointestinal , Hiperuricemia , Animales , Ratones , Hiperuricemia/tratamiento farmacológico , Resveratrol/farmacología , Ácido Úrico , Túbulos Renales , Inflamación
14.
BMC Public Health ; 24(1): 1074, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38632558

RESUMEN

BACKGROUND: The prevalence of hyperuricemia in China has been consistently increasing, particularly among the younger generation. The excessive consumption of sugar-sweetened beverages is associated with hyperuricemia. This study examined the knowledge, attitudes, and practices (KAP) of Chinese young adults regarding sugar-sweetened beverage consumption and the correlation with hyperuricemia. METHODS: This cross-sectional investigation was conducted from June 28th, 2023, to July 21st, 2023, and enrolled Chinese young adults. Demographics and KAP were evaluated using a questionnaire (Cronbach's α = 0.787). Factors influencing KAP scores were analyzed using multivariable analyses. RESULTS: A total of 1288 valid questionnaires were analyzed. The median knowledge, attitude, and practice scores were 16 (12,19)/22, 22 (20,24)/30, and 27.5 (23,31.75)/40. The multivariable analysis showed that bachelor's/associate education (OR = 1.912, 95%CI: 1.128-3.239), white collar/employee (OR = 0.147, 95%CI: 0.105-0.206), educator (OR = 0.300, 95%CI: 0.174-0.518), healthcare worker (OR = 0.277, 95%CI: 0.188-0.407), not suffering from hyperuricemia (OR = 0.386, 95%CI: 0.253-0.590), and not having gout (OR = 0.456, 95%CI: 0.282-0.736) were independently associated with knowledge. Age 26-30 (OR = 1.470, 95%CI: 1.052-2.052), age 31-35 (OR = 1.489, 95%CI: 1.097-2.022), age 36-40 (OR = 0.328, 95%CI: 1.010-1.746), age 41-44 (OR = 1.548, 95%CI: 1.091-2.198), and not having hyperuricemia (OR = 0.512, 95%CI: 0.345-0.760) were independently associated with attitude. White collar/employee (OR = 0.386, 95%CI: 0.285-0.521), educator (OR = 0.534, 95%CI: 0.317-0.899), healthcare worker (OR = 0.341, 95%CI: 0.236-0.493), having siblings (OR = 0.725, 95%CI: 0.573-0.917), and not suffering from hyperuricemia (OR = 0.442, 95%CI: 0.296-0.659), were independently associated with practice. CONCLUSION: Chinese young adults display moderate KAP toward sugar-sweetened beverages. Notably, an association was observed between hyperuricemia and each KAP dimension.


Asunto(s)
Hiperuricemia , Bebidas Azucaradas , Humanos , Adulto Joven , Adulto , Hiperuricemia/epidemiología , Estudios Transversales , Encuestas y Cuestionarios , China , Bebidas
15.
Vasc Health Risk Manag ; 20: 195-205, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38633724

RESUMEN

Purpose: The aim of this study was to identify independent risk factors for carotid atherosclerosis (CAS) in a population with hyperuricemia (HUA) and develop a CAS risk prediction model. Patients and Methods: This retrospective study included 3579 HUA individuals who underwent health examinations, including carotid ultrasonography, at the Zhenhai Lianhua Hospital in Ningbo, China, in 2020. All participants were randomly assigned to the training and internal validation sets in a 7:3 ratio. Multivariable logistic regression analysis was used to identify independent risk factors associated with CAS. The characteristic variables were screened using the least absolute shrinkage and selection operator combined with 10-fold cross-validation, and the resulting model was visualized by a nomogram. The discriminative ability, calibration, and clinical utility of the risk model were validated using the receiver operating characteristic curve, calibration curve, and decision curve analysis. Results: Sex, age, mean red blood cell volume, and fasting blood glucose were identified as independent risk factors for CAS in the HUA population. Age, gamma-glutamyl transpeptidase, serum creatinine, fasting blood glucose, total triiodothyronine, and direct bilirubin, were screened to construct a CAS risk prediction model. In the training and internal validation sets, the risk prediction model showed an excellent discriminative ability with the area under the curve of 0.891 and 0.901, respectively, and a high level of fit. Decision curve analysis results demonstrated that the risk prediction model could be beneficial when the threshold probabilities were 1-87% and 1-100% in the training and internal validation sets, respectively. Conclusion: We developed and internally validated a risk prediction model for CAS in a population with HUA, thereby contributing to the CAS early identification.


Asunto(s)
Enfermedades de las Arterias Carótidas , Hiperuricemia , Humanos , Glucemia , Estudios Retrospectivos , Calibración
16.
Lipids Health Dis ; 23(1): 116, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38643110

RESUMEN

BACKGROUND: Insufficient attention has been given to examining the correlation between body composition and hyperuricemia, leading to inconsistent findings. The primary objective of this research is to explore the association between lean body mass index (LMI), visceral fat mass index (VFMI), and hyperuricemia. A specific emphasis will be placed on assessing the link between the ratio of lean body mass to visceral fat mass (LMI/VFMI) and hyperuricemia. METHODS: The present study employed a cross-sectional design and involved a total of 9,646 individuals who participated in the National Health and Nutrition Examination Survey (NHANES). To explore the associations among the variables, logistic and linear regressions were employed. Additionally, subgroup analyses and sensitivity analyses were conducted based on various characteristics. RESULTS: The results showed that LMI was positively associated with hyperuricemia (for Per-SD: OR = 1.88, 95%CI: 1.75, 2.01; for quartiles [Q4:Q1]: OR = 5.37, 95%CI: 4.31, 6.69). Meanwhile, VFMI showed a positive association with hyperuricemia (for Per-SD: OR = 2.02, 95%CI: 1.88, 2.16; for quartiles [Q4:Q1]: OR =8.37, 95%CI: 6.70, 10.47). When considering the effects of In LMI/VFMI, an L-shaped negative association with hyperuricemia was observed (for Per-SD: OR = 0.45, 95%CI: 0.42, 0.49; for quartiles [Q4:Q1]: OR = 0.16, 95%CI: 0.13, 0.20). Subgroup and sensitivity analyses demonstrated the robustness of this association across different subgroups. Additionally, the segmented regression analysis indicated a saturation effect of 5.64 for the In LMI/VFMI with hyperuricemia (OR = 0.20, 95%CI: 0.17, 0.24). For every 2.72-fold increase of In LMI/VFMI, the risk of hyperuricemia was reduced by 80%. CONCLUSION: The LMI/VFMI ratio is non-linearly associated with serum uric acid. Whether this association is causal needs to be confirmed in further longitudinal studies or Mendelian randomization.


Asunto(s)
Hiperuricemia , Humanos , Estudios Transversales , Encuestas Nutricionales , Grasa Intraabdominal , Ácido Úrico , Composición Corporal , Índice de Masa Corporal
17.
Medicine (Baltimore) ; 103(17): e37713, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38669360

RESUMEN

Previous research has suggested that the monocyte-to-high-density lipoprotein ratio (MHR), an emerging inflammatory biomarker, holds promise in predicting the prevalence of various cardiovascular and metabolic diseases. However, earlier investigations were constrained by the relatively modest sample sizes. This study endeavored to expand the sample size and conduct a more comprehensive exploration of the potential relationship between MHR and hyperuricemia. This cross-sectional study incorporated data from participants of the 2009 to 2018 National Health and Nutrition Examination Survey (NHANES) with complete and qualifying information. MHR was determined by calculating the ratio between monocyte count and high-density lipoprotein levels. Various statistical methodologies such as weighted multivariate logistic regression, subgroup analysis, smoothed curve fitting, and threshold analysis, have been used to explore the correlation between hyperuricemia and MHR. The study included a cohort of 17,694 participants, of whom 3512 were diagnosed with hyperuricemia. MHR levels were notably higher in the hyperuricemia group than in the normal group, aligning with an elevated body mass index (BMI). A comprehensive multivariate logistic analysis, accounting for all relevant adjustments, revealed a notable positive correlation between MHR and hyperuricemia (P < .001, OR = 1.98, 95% CI: 1.54-2.54). Subgroup analysis indicated that the MHR exhibited an enhanced predictive capacity for identifying hyperuricemia risk, particularly in females (P < .05). Curvilinear and threshold analyses revealed a nonlinear association between MHR and hyperuricemia prevalence, with a notable inflection point at 0.826. In the US population, a clear positive correlation was observed between the MHR and prevalence of hyperuricemia. Importantly, the MHR is a more robust predictor of hyperuricemia risk in females. Further investigations are required to confirm these findings.


Asunto(s)
Hiperuricemia , Lipoproteínas HDL , Monocitos , Encuestas Nutricionales , Humanos , Hiperuricemia/epidemiología , Hiperuricemia/sangre , Femenino , Monocitos/metabolismo , Masculino , Estudios Transversales , Persona de Mediana Edad , Lipoproteínas HDL/sangre , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Factores de Riesgo , Estados Unidos/epidemiología , Anciano
18.
Mymensingh Med J ; 33(2): 402-410, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38557518

RESUMEN

Stroke is the second-leading cause of death and also a leading cause of combined death and disability. In Bangladesh, stroke prevalence is 11.39 per 1000 population, but highest prevalence of stroke is 14.71 per 1000 population in the Mymensingh division. Hyperuricemia has been reported as an independent risk factor for stroke in different studies and a significant association between serum uric acid and dyslipidemia has also been stated. On the contrary, some studies suggest that uric acid has a neuroprotective role. This cross-sectional study was completed in the Medicine Department of Mymensingh Medical College Hospital, Mymensingh, Bangladesh from March 2021 to January 2023. In this cross-sectional study, 352 adult acute ischemic stroke patients were included from the Medicine Department of Mymensingh Medical College Hospital. Serum uric acid and fasting serum lipid levels were measured within 48 hours of admission. The mean age ±SD of the respondents was 61.9±12.8 years. Hyperuricemia was found among 18.2% of respondents, whose mean ±SD serum uric acid was 5.7±1.9 mg/dl. Dyslipidemia was present in 88.4% of patients. The mean ±SD of the National Institutes of Health Stroke Scale (NIHSS) score was 12.0±5.9. Most of the patients (65.6%) were suffering from moderate stroke, followed by moderate to severe stroke (15.1%), severe stroke (10.8%) and minor stroke (8.5%). After multiple linear regressions, the independent variables age, gender, serum uric acid and total cholesterol were found to be significant predictors of the NIHSS score of the respondents. In conclusion, the majority of acute ischemic stroke patients have an association with dyslipidemia, but only around one-fifth of patients have hyperuricemia. There is a significant association of high serum uric acid and high serum total cholesterol with stroke severity (NIHSS score). But low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and, triglycerides have no association with stroke severity.


Asunto(s)
Isquemia Encefálica , Dislipidemias , Hiperuricemia , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Adulto , Humanos , Ácido Úrico , Isquemia Encefálica/complicaciones , Estudios Transversales , Hiperuricemia/complicaciones , Hiperuricemia/epidemiología , Accidente Cerebrovascular/epidemiología , Triglicéridos , HDL-Colesterol , Factores de Riesgo , Dislipidemias/complicaciones , Dislipidemias/epidemiología , Hospitales
19.
BMC Med Imaging ; 24(1): 78, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38570748

RESUMEN

BACKGROUND: To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia. METHODS: A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON, n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment. RESULTS: The HUA, AP, and AP + EM group MKOS and MKIS values gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MKOS and MKIS values were positively correlated with Masson's trichrome staining results (r = 0.687, P < 0.001 and r = 0.604, P = 0.001, respectively). The MDOS and FAIS were negatively correlated with Masson's trichrome staining (r = -626, P < 0.0014 and r = -0.468, P = 0.01, respectively). CONCLUSION: DKI may be a non-invasive method for monitoring renal interstitial fibrosis induced by hyperuricemia.


Asunto(s)
Hiperuricemia , Ratas , Animales , Hiperuricemia/diagnóstico por imagen , Riñón/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Imagen de Difusión por Resonancia Magnética/métodos , Fibrosis
20.
J Orthop Surg Res ; 19(1): 215, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561771

RESUMEN

OBJECTIVE: To study the correlation between achilles tendon rupture (ATR) and hyperuricemia, also verify the known risk factors for ATR. METHODS: A retrospective review of 488 subjects was performed (182 with Achilles tendon rupture, 306 controls with ankle sprains). Demographic variables and risk factors for rupture were tabulated and compared. The baseline data and related indicators were compared, and the risk factors of ATR were analyzed by constructing a binary logistic regression model. RESULTS: Univariate logistic analysis showed that BMI, smoking, and hyperuricemia were risk factors for the development of ATR (OR = 1.65, 95%CI 1.13-2.42, P = 0.01; OR = 1.47, 95%CI 1.00-2.24, P < 0.05; OR = 2.85, 95%CI 1.84-4.42, P < 0.01). Multifactorial analysis showed that BMI ≥ 25 kg/m2, smoking, and hyperuricemia were independent risk factors for the development of ATR (OR = 1.66, 95%CI 1.11-2.49, P = 0.01; OR = 2.15, 95%CI 1.28-3.60, P < 0.01; OR = 3.06, 95%CI 1.92-4.89, P < 0.01). Among the blood biochemical indicators, total cholesterol (TC) and uric acid (UA) were independent risk factors for the occurrence of ATR (OR = 1.54, 95% CI 1.12-2.12, P = 0.01; OR = 1.01, 95% CI 1.01-1.01, P < 0.01). CONCLUSION: Our study confirmed that, as in previous results, higher BMI, smoking, and total cholesterol are risk factors for ATR, Hyperuricemia may contribute to the development of ATR, and adjunctive tests for TC and UA in the blood biochemistry may be helpful in predicting the risk of ATR.


Asunto(s)
Tendón Calcáneo , Traumatismos del Tobillo , Hiperuricemia , Humanos , Masculino , Estudios de Casos y Controles , Hiperuricemia/complicaciones , Factores de Riesgo , Colesterol , Traumatismos del Tobillo/complicaciones , Rotura/etiología
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