Roles of serum uric acid on the association between arsenic exposure and incident metabolic syndrome in an older Chinese population.

Growing evidences showed that heavy metals exposure may be associated with metabolic diseases. Nevertheless, the mechanism underlying arsenic (As) exposure and metabolic syndrome (MetS) risk has not been fully elucidated. So we aimed to prospectively investigate the role of serum uric acid (SUA) on the association between blood As exposure and incident MetS. A sample of 1045 older participants in a community in China was analyzed. We determined As at baseline and SUA concentration at follow-up in the Yiwu Elderly Cohort. MetS events were defined according to the criteria of the International Diabetes Federation (IDF). Generalized linear model with log-binominal regression model was applied to estimate the association of As with incident MetS. To investigate the role of SUA in the association between As and MetS, a mediation analysis was conducted. In the fully adjusted log-binominal model, per interquartile range increment of As, the risk of MetS increased 1.25-fold. Compared with the lowest quartile of As, the adjusted relative risk (RR) of MetS in the highest quartile was 1.42 (95% confidence interval, CI: 1.03, 2.00). Additionally, blood As was positively associated with SUA, while SUA had significant association with MetS risk. Further mediation analysis demonstrated that the association of As and MetS risk was mediated by SUA, with the proportion of 15.7%. Our study found higher As was remarkably associated with the elevated risk of MetS in the Chinese older adults population. Mediation analysis indicated that SUA might be a mediator in the association between As exposure and MetS.

Association between serum uric acid levels with essential hypertension and its metabolic variables in Hospital Universiti Sains Malaysia.

INTRODUCTION: Hyperuricaemia is common in essential hypertension with varying results in different populations. This study sought to ascertain the association between serum uric acid levels and essential hypertension in Hospital Universiti Sains Malaysia (HUSM). MATERIALS AND METHODS: A case-control study design involving 132 subjects (88 subjects of hypertension patients for case group and 44 subjects for control group) aged 18 to 40 years old of both genders was conducted at HUSM primary care clinic and physician clinic from May 2020 to May 2021. Blood samples were collected from each of the case and control subjects and analysed for serum uric acid, urea, creatinine, total cholesterol, triglycerides, LDL and HDL on chemical analyser Architect c8000. The data were analysed by using SPSS Statistics 26.0 version. RESULTS: The proportion of subjects with hyperuricaemia in the case group was 48.9%. A significant difference in the uric acid levels between the case group (390.64±92.65µmol/L) and control group (352.09±86.07µmol/L), (p<0.05) was observed. There was no significant difference in the serum uric acid mean ± SD based on the duration of hypertension (<5 years and ≥5 years), (p=0.331) and stages of hypertension (p>0.05). In case group, significant correlations were established between uric acid and triglycerides (r=0.255, p<0.05), uric acid and HDL (r= -0.223, p<0.05), uric acid and urea (r=0.299, p<0.05), uric acid and creatinine (r=0.486, p<0.01). No correlation among uric acid and total cholesterol levels (p>0.05), uric acid and LDL (p>0.05). Serum uric acid was a vital variable in developing hypertension (p<0.05) but not when adapted for age and body mass index (BMI) (p>0.05). CONCLUSION: Serum uric acid was significantly elevated in essential hypertension. The significant associations were established between uric acid and triglycerides, HDL, urea and creatinine in essential hypertension. Serum uric acid was a vital variable to develop hypertension, but the association was weakened by other co-founders as age and BMI. A large-scale population-based study is required to truly conclude the association between serum uric acid levels and essential hypertension in our population.

Antioxidative effects of molybdenum and its association with reduced prevalence of hyperuricemia in the adult population.

The relationship between molybdenum and kidney-related disease outcomes, including hyperuricemia, is not well investigated. This study aims to determine whether molybdenum and its antioxidative property are associated with systemic inflammation and kidney-related disease parameters including hyperuricemia. Urinary molybdenum's epidemiological relationship to hyperuricemia and kidney-disease related outcomes was evaluated in 15,370 adult participants in the National Health and Nutrition Examination Survey (NHANES) collected between 1999 and 2016. Individuals' urinary molybdenum levels were corrected to their urinary creatinine concentrations. The association between urinary molybdenum-to-creatinine ratio and kidney-disease related outcomes were assessed by multivariable linear and logistic regression analyses, adjusting for covariates including age, sex, ethnicity, diabetes mellitus, hypertension, body mass index, and estimated glomerular filtration rate. Antimony and tungsten were used as control trace metals. Experimentally, HK-2 cell was used to assess molybdenum's antioxidative properties. HK-2 cells were challenged with H2O2-induced oxidative stress. Oxidative stress was measured using a fluorescent microplate assay for reactive oxygen species (ROS) and antioxidation levels were assessed by measuring the expression of manganese superoxide dismutase. In the adult NHANES population, urinary molybdenum-to-creatinine ratio was significantly associated with decreased serum uric acid (ß, -0.119; 95% CI, -0.148 to -0.090) concentrations, and decreased prevalence of hyperuricemia (OR, 0.73; 95% CI, 0.64-0.83) and gout (OR, 0.71; 95% CI, 0.52-0.94). Higher urinary molybdenum levels were associated with lower levels of systemic oxidative stress (gamma-glutamyltransferase levels; ß, -0.052; 95% CI, -0.067 to -0.037) and inflammation (C-reactive protein levels; ß, -0.184; 95% CI, -0.220 to -0.148). In HK-2 cells under H2O2-induced oxidative stress, molybdenum upregulated manganese superoxide dismutase expression and decreased oxidative stress. Urinary molybdenum levels are associated with decreased prevalence of hyperuricemia and gout in adult population. Molybdenum's antioxidative properties might have acted as an important mechanism for the reduction of systemic inflammation, ROS, and uric acid levels.

The effect of astaxanthin supplementation on inflammatory markers, oxidative stress indices, lipid profile, uric acid level, blood pressure, endothelial function, quality of life, and disease symptoms in heart failure subjects.

BACKGROUND: Heart failure is a chronic and progressive disease where the heart muscle is unable to pump enough blood and oxygen to meet the body's needs. Oxidative stress and inflammation are key elements in the development and progression of heart failure. Astaxanthin, a carotenoid, has strong anti-inflammatory and antioxidant effects that may protect the cardiovascular system. A study will evaluate the effect of astaxanthin supplementation on inflammatory status, oxidative stress, lipid profile, uric acid levels, endothelial function, quality of life, and disease symptoms in people with heart failure. METHODS: The current study is a double-blind controlled randomized clinical trial for 8 weeks, in which people with heart failure were randomly assigned to two groups: intervention (one capsule containing 20 mg of astaxanthin per day, n = 40) and placebo (one capsule containing 20 mg of maltodextrin per day, n = 40) will be divided. At the beginning and end of the intervention, uric acid, lipid profile, oxidative stress indices, inflammatory markers, blood pressure, nitric oxide, and anthropometric factors will be measured, and questionnaires measuring quality of life, fatigue intensity, shortness of breath, and appetite will be completed. SPSS version 22 software will be used for statistical analysis. DISCUSSION: There is a growing global interest in natural and functional food products. This RCT contributes to the expanding body of research on the potential benefits of astaxanthin in heart failure patients, including its antioxidant, lipid-lowering, and anti-inflammatory effects. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20200429047235N3. Registered on 26 March 2024.

Metabolic Profile in Rats during Long-Term Restriction of Motor Activity.

We performed a comprehensive study of protein (total protein, medium-molecular-weight peptides, creatinine, and urea), purine (uric acid), and lipid (cholesterol, triglycerides) metabolism, activity of AST, ALT, and acid phosphatase in blood plasma of white male rats under conditions of restriction of motor activity up to 28 days. Patterns of changes in metabolic profile during hypokinesia were established: prevalence of catabolic processes and atherogenic shifts in the lipid spectrum with maximum manifestation on 14-21 days of the experiment.

Association between serum uric acid to serum creatinine ratio with cardiovascular and all-cause mortality in adults with hypertension.

The serum uric acid to serum creatinine ratio (SUA/sCr) is a standardized index of renal function. More importance was attached to the significance of this ratio in the progression of hypertension. While the association between the prognosis of hypertension and SUA/sCr is unknown. Therefore, we aimed to prospectively examine the associations of serum uric acid to serum creatinine ratio and all-cause and CVD mortality in adults with hypertension. Participants with hypertension from NHANES 1999-2018 (n = 15,269) were included. They were stratified by 1 increment of SUA/sCr ratio and categorized into 6 groups as ≤ 4, > 4 to 5, > 5 to 6, > 6 to 7, > 7 to 8, and > 8. The reason for categorization in 6 groups was to analyze the influence of different ratios on outcomes accurately and provide more precise guidance. The sample size is large enough that even if divided into 6 groups, it does not affect the statistical power. The primary outcomes were all-cause and CVD mortality. Weighted multivariable Cox proportional hazards regression models were used to estimate hazard ratio (HRs) of mortality. Restricted cubic spline regression models were utilized to examine dose-response associations between the serum uric acid to serum creatinine ratio and all-cause and CVD mortality. Relatively comprehensive stratified analyses were conducted to confirm the accuracy and stability of the results. There were 15,269 total participants, 49.4% of whom were men, with an average age of 56.6 years. Weighted multivariable Cox proportional hazards regression models demonstrated participants in the lowest group (≤ 4) had the HRs (95% CIs) of 1.43 (1.18, 1.73) for all-cause mortality and 2.8 (1.92, 4.10) for CVD mortality when compared to the reference group. Participants in the highest group (> 8) had the HRs (95% CIs) of 0.47 (0.25, 0.89) for CVD mortality when compared to the reference group. There were progressively lower risks for all-cause and CVD mortality with the SUA/sCr ratio increased (both P trend < 0.01). The SUA/sCr ratio was (P for nonlinearity < 0.01) nonlinearly correlated with all-cause mortality, with inflection points of 6.25. In addition, the restricted cubic splines results indicated that the SUA/sCr ratio (P for nonlinearity = 0.32) showed linear and negative associations with cardiovascular mortality with inflection points of 6.54. The inverse associations between SUA/sCr ratio and all-cause mortality were consistent across all subgroups except for the subgroup of eGFR < 45 ml/min/1.73 m2 and never smokers (P trend = 0.20 and 0.13, respectively), and the inverse associations between low SUA/sCr ratio and CVD mortality were consistent across all subgroups (P trend < 0.01). Contrary to previous studies, outcomes suggest that lower SUA/sCr ratio was associated with higher risks of all-cause and CVD mortality in adults with hypertension.

Easing the way to achieving target serum urate in people with gout: protocol for a non-inferiority randomised strategy trial using an allopurinol dosing model in Aotearoa/New Zealand (the Easy-Allo Study).

INTRODUCTION: Gout is one of the most common forms of arthritis worldwide. Gout is particularly prevalent in Aotearoa/New Zealand and is estimated to affect 13.1% of Maori men, 22.9% of Pacific men and 7.4% of New Zealand European men. Effective long-term treatment requires lowering serum urate to <0.36 mmol/L. Allopurinol is the most commonly used urate-lowering medication worldwide. Despite its efficacy and safety, the allopurinol dose escalation treat-to-target serum urate strategy is difficult to implement and there are important inequities in allopurinol prescribing in Aotearoa. The escalation strategy is labour intensive, time consuming and costly for people with gout and the healthcare system. An easy and effective way to dose-escalate allopurinol is required, especially as gout disproportionately affects working-age Maori men and Pacific men, who frequently do not receive optimal care. METHODS AND ANALYSIS: A 12-month non-inferiority randomised controlled trial in people with gout who have a serum urate ≥ 0.36 mmol/l will be undertaken. 380 participants recruited from primary and secondary care will be randomised to one of the two allopurinol dosing strategies: intensive nurse-led treat-to-target serum urate dosing (intensive treat-to-target) or protocol-driven dose escalation based on dose predicted by an allopurinol dosing model (Easy-Allo). The primary endpoint will be the proportion of participants who achieve target serum urate (<0.36 mmol/L) at 12 months. ETHICS AND DISSEMINATION: The New Zealand Northern B Health and Disability Ethics Committee approved the study (2022 FULL 13478). Results will be disseminated in peer-reviewed journals and to participants. TRIAL REGISTRATION NUMBER: ACTRN12622001279718p.

Causal relationship analysis between 35 blood/urine metabolites and gastroesophageal reflux disease: A Mendelian randomization combined meta-analysis study.

Gastroesophageal reflux disease (GERD) is a common condition worldwide. Despite numerous studies on GERD, the causal relationships between blood/urine metabolites and GERD remain unclear. This study aims to explore the causal relationships between GERD and 35 blood/urine metabolites. In this study, we conducted Mendelian randomization (MR) analyses for 35 blood/urine metabolites with GERD phenotypes from the FinnGen R10 and UKB databases separately. We then performed a meta-analysis of the inverse variance weighted results from the 2 MR analyses and applied multiple corrections to the significant P values from the meta-analysis. Finally, we conducted reverse causality validation for the corrected positive blood/urine metabolite phenotypes with GERD. After conducting MR analysis combined with meta-analysis and performing multiple corrections, we found significant positive causal associations between only 3 blood/urine metabolites and GERD, with no significant reverse associations. Among them, 2 are risk factors for the occurrence of GERD: alanine aminotransferase levels (odds ratio (OR) = 1.120, 95% confidence interval (CI) = 1.064-1.180, P = .0005) and urate levels (OR = 1.095, 95% CI = 1.044-1.147, P = .005). Additionally, sex hormone-binding globulin levels are protective against GERD (OR = 0.928, 95% CI = 0.896-0.961, P = .0009). Elevated levels of the metabolites alanine aminotransferase and urate are associated with an increased risk of GERD, identifying them as risk factors for the condition. In contrast, higher levels of SHBG are linked to a decreased risk of GERD, indicating that SHBG is a protective factor against the disease.

Plantaginis Semen Ameliorates Hyperuricemia Induced by Potassium Oxonate.

Plantaginis semen is the dried ripe seed of Plantago asiatica L. or Plantago depressa Willd., which has a long history in alleviating hyperuricemia (HUA) and chronic kidney diseases. While the major chemical ingredients and mechanism remained to be illustrated. Therefore, this work aimed to elucidate the chemicals and working mechanisms of PS for HUA. UPLC-QE-Orbitrap-MS was applied to identify the main components of PS in vitro and in vivo. RNA sequencing (RNA-seq) was conducted to explore the gene expression profile, and the genes involved were further confirmed by real-time quantitative PCR (RT-qPCR). A total of 39 components were identified from PS, and 13 of them were detected in the rat serum after treating the rat with PS. The kidney tissue injury and serum uric acid (UA), xanthine oxidase (XOD), and cytokine levels were reversed by PS. Meanwhile, renal urate anion transporter 1 (Urat1) and glucose transporter 9 (Glut9) levels were reversed with PS treatment. RNA-seq analysis showed that the PPAR signaling pathway; glycine, serine, and threonine metabolism signaling pathway; and fatty acid metabolism signaling pathway were significantly modified by PS treatment. Further, the gene expression of Slc7a8, Pck1, Mgll, and Bhmt were significantly elevated, and Fkbp5 was downregulated, consistent with RNA-seq results. The PPAR signaling pathway involved Pparα, Pparγ, Lpl, Plin5, Atgl, and Hsl were elevated by PS treatment. URAT1 and PPARα proteins levels were confirmed by Western blotting. In conclusion, this study elucidates the chemical profile and working mechanisms of PS for prevention and therapy of HUA and provides a promising traditional Chinese medicine agency for HUA prophylaxis.

Leech Poecilobdella manillensis protein extract ameliorated hyperuricemia by restoring gut microbiota dysregulation and affecting serum metabolites.

BACKGROUND: Hyperuricemia (HUA) is a public health concern that needs to be solved urgently. The lyophilized powder of Poecilobdella manillensis has been shown to significantly alleviate HUA; however, its underlying metabolic regulation remains unclear. AIM: To explore the underlying mechanisms of Poecilobdella manillensis in HUA based on modulation of the gut microbiota and host metabolism. METHODS: A mouse model of rapid HUA was established using a high-purine diet and potassium oxonate injections. The mice received oral drugs or saline. Additionally, 16S rRNA sequencing and ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry-based untargeted metabolomics were performed to identify changes in the microbiome and host metabolome, respectively. The levels of uric acid transporters and epithelial tight junction proteins in the renal and intestinal tissues were analyzed using an enzyme-linked immunosorbent assay. RESULTS: The protein extract of Poecilobdella manillensis lyophilized powder (49 mg/kg) showed an enhanced anti-trioxypurine ability than that of allopurinol (5 mg/kg) (P < 0.05). A total of nine bacterial genera were identified to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder, which included the genera of Prevotella, Delftia, Dialister, Akkermansia, Lactococcus, Escherichia_Shigella, Enterococcus, and Bacteroides. Furthermore, 22 metabolites in the serum were found to be closely related to the anti-trioxypurine activity of Poecilobdella manillensis powder, which correlated to the Kyoto Encyclopedia of Genes and Genomes pathways of cysteine and methionine metabolism, sphingolipid metabolism, galactose metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. Correlation analysis found that changes in the gut microbiota were significantly related to these metabolites. CONCLUSION: The proteins in Poecilobdella manillensis powder were effective for HUA. Mechanistically, they are associated with improvements in gut microbiota dysbiosis and the regulation of sphingolipid and galactose metabolism.

[Prevalence and risk factors of hyperuricemia among freshmen at Beijing Sport University from 2021 to 2022].

OBJECTIVE: To investigate the prevalence of hyperuricemia among freshmen enrolled in Beijing Sport University and to explore the influencing factors of hyperuricemia in the college population. METHODS: The study period was from September 2021 to February 2022.3372 freshmen of the class of 2021 from Beijing Sport University in Beijing were selected as the study subjects, and two blood uric acid tests were performed on non-same days to calculate the prevalence of the population and to explore the risk factors of hyperuricemia in the college student population using a case-control method.246 people were selected from the hyperuricemia patients of the population to be included in the case group by convenience sampling, and 211 people were selected from the non-hyperuricemia persons of the population to be included in the control group. They were included in the control group, underwent physical and laboratory examinations, and were retrospectively surveyed with questionnaires that included general information such as age, gender, specialty, place of birth, and diet related to hyperuricemia, awareness of hyperuricemia disease, physical activity level, and sleep. Statistical analysis was performed using chi-square analysis, one-way Logistic regression analysis, and multi-factor logistic regression analysis. RESULTS: The number of patients actually diagnosed with hyperuricemia by two blood uric acid tests on non-same days was 479, with a population prevalence rate of 14.21%. Among them, the number of males in the diseased population was 391(22.39%), and the number of females in the diseased population was 88(5.41%). A total of 457 subjects were enrolled in the case-control study, among them, 246 in the case group(218 males and 28 females, average age 19.74 years), 211 in the control group(177 males and 34 females, average age 19.93 years), and 247 in the case group, 211 in the control group, and 2 groups of subjects were included. A total of 211 subjects, and there was no significant difference between the 2 groups in terms of gender composition and age distribution. One-way logistic regression analysis showed that central obesity(OR=31.52, 95%CI 7.59-130.86), obesity(OR=2.59, 95%CI 1.20-5.58), overweight(OR=1.67, 95%CI 1.08-2.59), frequent consumption of fresh vegetables(OR=0.66, 95%CI 0.43-0.99), and drinking 1500-2000 mL of water per day(OR=0.63, 95%CI 0.41-0.95) were associated with hyperuricemia, and multifactorial Logistic regression analyses were performed to analyze the above factors, and finally central obesity(OR=32.05, 95%CI 7.65-134.20), BMI obesity(OR=3.22, 95%CI 1.44-7.20), and daily water intake of 1500-2000 mL(OR=0.60, 95%CI 0.37-0.95) were included in the model at the level of P=0.05. CONCLUSION: The current high prevalence of hyperuricemia in the college student population, which is more prevalent in male college students. Obesity and central obesity are risk factors for hyperuricemia in young college students, and daily water intake of 1500-2000 mL is a protective factor.

Plasma aldosterone concentrations elevation in hypertensive patients: the dual impact on hyperuricemia and gout.

Background: Prior research has highlighted the association between uric acid (UA) and the activation of the renin-angiotensin-aldosterone system (RAAS). However, the specific relationship between aldosterone, the RAAS's end product, and UA-related diseases remains poorly understood. This study aims to clarify the impact of aldosterone on the development and progression of hyperuricemia and gout in hypertensive patients. Methods: Our study involved 34534 hypertensive participants, assessing plasma aldosterone concentration (PAC)'s role in UA-related diseases, mainly hyperuricemia and gout. We applied multiple logistic regression to investigate the impact of PAC and used restricted cubic splines (RCS) for examining the dose-response relationship between PAC and these diseases. To gain deeper insights, we conducted threshold analyses, further clarifying the nature of this relationship. Finally, we undertook subgroup analyses to evaluate PAC's effects across diverse conditions and among different subgroups. Results: Multivariate logistic regression analysis revealed a significant correlation between the occurrence of hyperuricemia and gout and the elevation of PAC levels. Compared to the first quartile (Q1) group, groups Q2, Q3, and Q4 all exhibited a significantly increased risk of occurrence. Moreover, the conducted RCS analysis demonstrated a significant nonlinear dose-response relationship, especially when PAC was greater than 14 ng/dL, with a further increased risk of hyperuricemia and gout. Finally, comprehensive subgroup analyses consistently reinforced these findings. Conclusion: This study demonstrates a close association between elevated PAC levels and the development of UA-related diseases, namely hyperuricemia and gout, in hypertensive patients. Further prospective studies are warranted to confirm and validate this relationship.

The effect of hyperuricemia and its interaction with hypertension towards chronic kidney disease in patients with type 2 diabetes: evidence from a cross- sectional study in Eastern China.

Objectives: This study aimed to explore the synergistic interaction effect between hyperuricemia and hypertension towards chronic kidney disease in patients with type 2 diabetes. Methods: This research originates from a cross-sectional study performed in Zhejiang Province, Eastern China, between March and November 2018. The correlation between serum uric acid levels and the risk of chronic kidney disease was assessed using a restricted cubic spline model. An unconditional multivariable logistic regression model, along with an interaction table, was utilized to explore the potential interaction effect of hyperuricemia and hypertension towards chronic kidney disease. Results: 1,756 patients with type 2 diabetes were included in this study, the prevalence of chronic kidney disease (CKD) was 27.62% in this population. A U-shaped non-linear pattern emerged correlating serum uric acid (SUA) levels and CKD risk, indicating that both low and high SUA levels were linked to an increased CKD risk. This risk achieved its lowest point (nadir) at SUA approximately equals to 285µmol/L (p for trend <0.05). Once adjustments for age, gender, education level, abnormal fasting plasma glucose (FPG), abnormal hemoglobin A1c (HbA1c), abnormal total cholesterol (TC), abnormal high-density lipoprotein cholesterol (HDL-C), alcohol consumption and duration of diabetes were factored in, it was found that patients with both hyperuricemia and hypertension demonstrated a 5.42-fold (95% CI: 3.72-7.90) increased CKD risk compared to the reference group. The additive interaction between hyperuricemia and hypertension was statistically significant, as manifested by the following values: a relative excess risk due to interaction (RERI) of 2.57 (95% CI: 0.71-4.71), an attributable proportion due to interaction (AP) of 0.47 (95% CI: 0.14-0.64), and a synergy index (SI) of 2.39 (95% CI: 1.24-4.58). In contrast, there was no significant interaction effect in multiplicative scale. Conclusion: Hyperuricemia and hypertension may contribute additively to CKD, beyond their isolated impacts. Evaluating the risk of CKD in type 2 diabetes patients necessitates considering this potential interaction.

Serum uric acid concentration in acute pancreatitis is significantly higher than healthy population.

Acute pancreatitis (AP) is a common disease caused by a variety of causes. Is uric acid associated with the onset of AP? The objective of this study was to assess whether uric acid concentration in AP patients was higher than that in healthy population, and whether there were associations between uric acid concentration and serological indicators related to AP. A total of 205 AP patients were included in this study. Two hundred and five people who underwent physical examination in our hospital were randomly selected as controls. We analyzed whether there was difference in uric acid concentrations between the two groups. If the difference was statistically significant, the correlations between uric acid concentration and serological indicators in AP patients was further analyzed. There was significant difference in uric acid concentration (P < 0.001) between AP patients and healthy population. Serum uric acid concentration in AP group was significantly higher than that in control group. Two hundred and five AP patients were divided into mild AP group and non-mild AP group. There was no statistically significant difference in uric acid concentration between the two groups (P = 0.176). There was a low linear correlation between serum uric acid concentration and triglyceride level (r = 0.316, P < 0.001). But there was no linear correlation between serum uric acid concentration and hypersensitive C-reactive protein (r = 0.126, P = 0.072), white blood cell (r = 0.192, P = 0.006), albumin (r = 0.183, P = 0.009), total cholesterol concentration (r = 0.133, P = 0.058), fasting blood-glucose (r = 0.133, P = 0.058) and blood calcium (r = 0.155, P = 0.026). Uric acid concentration in patients with AP was significantly higher than healthy population. There was correlation between uric acid concentration and triglyceride in AP patients.

Baseline and change in serum lipid and uric acid level over time and incident of nonalcoholic fatty liver disease (NAFLD) in Chinese adults.

Observational studies have shown that non-alcoholic fatty liver disease (NAFLD) is strongly associated with metabolic dysfunction. However, there is a paucity of research on whether changes in indicators of serum metabolism contribute to the development of NAFLD. This study was conducted with 4084 participants who underwent healthy physical examinations at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China, in 2022 and 2023. Baseline and follow-up measurements, including anthropometric data, abdominal ultrasound and blood samples were collected. The diagnosis of NAFLD was based on the 2010 Chinese Guidelines on Diagnosis and Treatment of NAFLD. Multiple logistic regression was utilized to analyze the odds ratios (ORs) for the 1-year risk of NAFLD in connection with both baseline metabolic indicators and changes in metabolic indicators observed over the course of 1 year. A total of 3425 study participants who were free of NAFLD at baseline, including 1146 men and 2279 women, were included in the final analysis. The mean age was 34.43 ± 7.20 years. Participants who developed NAFLD were older, male and had higher levels of body mass index (BMI), blood pressure, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free triiodothyronine (fT3), uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and lower levels of high-density lipoprotein cholesterol (HDL-C) and free thyroxine (fT4) (all P values < 0.05). The multivariable model showed that baseline BMI, diastolic blood pressure (DBP), TG, TC, HDL-C, LDL-C, UA, fT4, fT3, ALT and changes in TG, HDL-C, and UA were associated with the 1-year risk of developing NAFLD. The risk of NAFLD increased by 56% [OR 1.56, 95% Confidence Interval (CI) 1.32-1.87] and 40% (OR 1.40, 95% CI 1.19-1.64) for each standard deviation (SD) increase in altered TG values (1.01 mmol/L) and altered UA values (55 µmol/L) respectively. Conversely, for each SD (0.27 mmol/L) increase in HDL-C change, the 1-year risk of incident NAFLD was reduced by 50% (OR 0.50, 95% CI 0.40-0.62). The present study suggested that increases in TG and UA, and decreases in HDL-C, significantly increase the risk of developing NAFLD. Therefore, more attention should be paid to these factors in the management and prevention of NAFLD.

Pharmacological effects of MT-1207 in bilateral renal artery stenosis hypertension and its hypotensive targets validation.

MT-1207 (MT) as a new antihypertensive drug is under clinical trial. However, its hypotensive mechanism has not been experimentally explored, and it is unknown whether MT can be used for bilateral renal artery stenosis hypertension. Using two-kidney two-clip (2K2C) to mimic bilateral renal artery stenosis in rats, a stroke-prone renovascular hypertension model, the present study further verified its antihypertensive effect, cardiovascular and renal protection, mortality reduction and lifespan prolongation, as well as demonstrated its two novel pharmacological effects for uric acid-lowering and cognition-improving. Notably, MT did not aggravate renal dysfunction; instead, it had beneficial effects on reducing serum uric acid level and maintaining serum K+ at a relatively stable level in 2K2C rats. In contrast, angiotensin receptor blocker losartan aggravated renal dysfunction in 2K2C rats. Mechanistically, MT hypotensive effect was dependent on its blockade of α1 and 5-HT2 receptors, since MT pretreatment abolished these receptor agonists-induced blood pressure elevations in vivo. Further evidence showed MT bound to and interacted with these receptor subtypes including α1A, α1B, α1D, 5-HT2A, 5-HT2B, and 5-HT2C receptors known for control of blood pressure. In conclusion, MT may be used for treatment of bilateral renal artery stenosis hypertension, different from losartan that is prohibited for treatment of bilateral renal artery stenosis hypertension. Targets validation of MT hypotensive mechanism and beneficial effects of MT on uric acid and cognitive function provide new insights for this novel multitarget drug, deserving clinical trial attention.

Association of hyperuricemia with coronary heart disease: Protocol for an updated systematic review and dose-response meta-analysis.

INTRODUCTION: Hyperuricemia, characterized by elevated serum uric acid levels, has garnered significant attention in cardiovascular research due to its potential association with coronary heart disease (CHD). While some studies suggest hyperuricemia as a risk factor of CHD, others present conflicting findings. A systematic review and dose-response meta-analysis is warranted to comprehensively summarize the previous studies and determine the association between hyperuricemia and CHD, thereby supporting clinical practice and future studies in this field. METHODS: In this study, we will comprehensively search Medline, EMBase, Cochrane Central, ICTRP, and ClinicalTrials.gov, from inception to December 31, 2024. Prospective or retrospective cohort studies and case-control studies investigating the association between hyperuricemia and CHD will be included. Two independent reviewers will conduct study selection, data extraction, and risk of bias assessment. The primary outcome will be the pooled relative risk of CHD associated with hyperuricemia by using random-effect model. Dose-response meta-analysis will be performed with linear and non-linear model to explore the the magnitude and direction of the association between serum uric acid levels and CHD risk. Subgroup analyses will be conducted based on uric acid test approaches and corresponding cut-off values and human races. Sensitivity analyses will assess the robustness of the results with leave-one-out method, while publication bias will be evaluated using funnel plots, Egger's test, and Begg's test. We will further use GRADE to evaluate the quality of the evidences provided by our systematic review. EXPECTED RESULTS: From this systematic review and dose-response meta-analysis, we hope out findings will provide reliable conclusion and data support on the association between hyperuricemia and CHD. The transparent and replicable methodologies outlined in this protocol contribute to advancing understanding of hyperuricemia as a potentially modifiable risk factor for CHD, thus supporting evidence-based strategies for cardiovascular disease management. CONCLUSIONS: This protocol describes a rigorous plan to systematically review and analyze the quantitative association between hyperuricemia and CHD risk. In a word, we will help further clinical practice and scientific studies in this field. TRIAL REGISTRATION: This protocol was registered in PROSPERO CRD42024538553.

Relationship between uric acid to high-density cholesterol ratio (UHR) and circulating α-klotho: evidence from NHANES 2007-2016.

OBJECTIVE: To investigate the relationship between uric acid to high-density lipoprotein cholesterol ratio (UHR) and circulating α-klotho levels in U.S. adults. METHODS: A cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Circulating α-klotho was defined as the dependent variable and UHR was defined as the independent variable. Multivariable linear regression was performed to assess the relationship between the independent and dependent variables. The nonlinear relationship and effect size between UHR and α-klotho were evaluated using smooth curve fitting and threshold effect analysis. Subgroup analysis and sensitivity analysis were conducted to determine the stability of the results. The diagnostic performance of UHR and α-klotho in common elderly diseases was compared using ROC (Receiver Operating Characteristic) analysis. RESULTS: Among 12,849 participants, there was a negative relationship between the UHR and circulating α-klotho. In the fully adjusted overall model, each unit increase in UHR was associated with a decrease of 4.1 pg/mL in α-klotho. The threshold effect analysis showed that before the inflection point of 8.2, each unit increase in UHR was associated with a decrease of 15.0 pg/mL in α-klotho; beyond the inflection point of 8.2, each unit increase in UHR was associated with a decrease of 2.8 pg/mL in α-klotho. Subgroup analyses and sensitivity analysis indicated that the relationship between UHR and α-klotho remained stable across most populations. The ROC diagnostic test indicated that the evaluative efficacy of UHR in diagnosing age-related diseases was comparable to that of α-klotho. CONCLUSION: This study revealed that the UHR was associated with the circulating α-klotho concentration, with a negative association observed in most cases. This finding suggested that the UHR might be a promising indicator for evaluating circulating α-klotho levels.

The SGLT2 inhibitor dapagliflozin ameliorates renal fibrosis in hyperuricemic nephropathy.

Hyperuricemic nephropathy (HN) is a global metabolic disorder characterized by uric acid (UA) metabolism dysfunction, resulting in hyperuricemia (HUA) and tubulointerstitial fibrosis (TIF). Sodium-dependent glucose transporter 2 inhibitor, dapagliflozin, has shown potential in reducing serum UA levels in patients with chronic kidney disease (CKD), though its protective effects against HN remain uncertain. This study investigates the functional, pathological, and molecular changes in HN through histological, biochemical, and transcriptomic analyses in patients, HN mice, and UA-stimulated HK-2 cells. Findings indicate UA-induced tubular dysfunction and fibrotic activation, which dapagliflozin significantly mitigates. Transcriptomic analysis identifies estrogen-related receptor α (ERRα), a downregulated transcription factor in HN. ERRα knockin mice and ERRα-overexpressed HK-2 cells demonstrate UA resistance, while ERRα inhibition exacerbates UA effects. Dapagliflozin targets ERRα, activating the ERRα-organic anion transporter 1 (OAT1) axis to enhance UA excretion and reduce TIF. Furthermore, dapagliflozin ameliorates renal fibrosis in non-HN CKD models, underscoring the therapeutic significance of the ERRα-OAT1 axis in HN and CKD.