Plasma Uric Acid Levels Research Articles

Association between plasma antioxidant status, oxidative stress and uric acid levels of young ecuadorian adults with overweight and obesity

Association between plasma antioxidant status, oxidative stress and uric acid levels of young ecuadorian adults with overweight and obesity

Efficacy and safety of dapagliflozin add-on to evogliptin plus metformin therapy in patients with type 2 diabetes: A randomized, double-blind, placebo-controlled study.

To evaluate the efficacy and safety of dapagliflozin versus placebo as an add-on in patients with type 2 diabetes who did not achieve adequate glycaemic control with evogliptin and metformin combination. In this multicentre, randomized, double-blind, placebo-controlled Phase 3 trial, patients with glycated haemoglobin (HbA1c) levels ≥7.0% (≥53 mmol/mol) and ≤10.5% (≤91 mmol/mol) who had received stable-dose metformin (≥1000 mg) and evogliptin (5 mg) for at least 8 weeks were randomized to receive dapagliflozin 10 mg or placebo once daily for 24 weeks. Participants continued treatment with metformin and evogliptin. The primary endpoint was change in HbA1c level after 24 weeks of treatment from baseline level. In total, 198 patients were randomized, and 195 patients were included in the efficacy analyses (dapagliflozin: 96, placebo: 99). At Week 24, dapagliflozin significantly reduced HbA1c levels. The least squares mean difference in HbA1c level change from baseline after 24 weeks of treatment was -0.70% (-7.7 mmol/mol)(p < 0.0001). The proportion of participants achieving HbA1c <7.0% (≥53 mmol/mol)was higher in the dapagliflozin group than in the placebo group. Compared to placebo, dapagliflozin significantly reduced fasting plasma glucose, mean daily glucose, 2-h postprandial plasma glucose, fasting insulin, uric acid and gamma-glutamyl transferase levels, homeostatic model assessment for insulin resistance index, body weight, hepatic steatosis index, and albuminuria. Adiponectin level significantly increased from baseline level after 24 weeks of dapagliflozin treatment. Adverse event rates were similar in the two groups. Dapagliflozin add-on to evogliptin plus metformin improved glycaemic control and was well tolerated by the target patients.

Targeting Liver Xor by GalNAc-siRNA Is an Effective Strategy for Hyperuricemia Therapy.

Hyperuricemia, i.e., increased plasma uric acid concentration, is a common problem in clinical practice, leading to gout or nephrolithiasis, and is associated with other disorders, such as metabolic syndrome, cardiovascular disease, and chronic renal disease. Xanthine oxidoreductase (XOR) is a critical rate-limiting enzyme involved in uric acid synthesis and a promising target for hyperuricemia therapy. However, XOR inhibitors currently face clinical problems such as a short half-life and side effects. Here, we found that specifically targeting liver Xor with GalNAc-siRNAs had a good therapeutic effect on hyperuricemia. First, siRNAs were designed to target various sites in the homologous region between Homo sapiens and Mus musculus Xor mRNA and were screened in primary mouse hepatocytes. Then, the siRNAs were modified to increase their stability in vivo and conjugated with GalNAc for liver-specific delivery. The effects of GalNAc-siRNAs were evaluated in three hyperuricemia mouse models, including potassium oxonate and hypoxanthine administration in WT and humanized XDH mice and Uox knockout mice. Febuxostat, a specific XOR inhibitor used for hyperuricemia treatment, was used as a positive control. Targeting liver Xor with GalNAc-siRNAs by subcutaneous administration reduced plasma uric acid levels, uric acid accumulation in the kidney, renal inflammation, and fibrosis, thereby alleviating kidney damage in hyperuricemia mouse models without hepatoxicity. The results demonstrated that targeting liver Xor with GalNAc-siRNAs was a promising strategy for hyperuricemia therapy.

Dual therapy with phospholipase and metalloproteinase inhibitors from Sinonatrix annularis alleviated acute kidney and liver injury caused by multiple snake venoms

Snakebite envenomation often induces acute kidney injury (AKI) and acute liver injury (ALI), leading to augmented injuries and poor rehabilitation. Phospholipase A2 (PLA2) and metalloproteinase (SVMP) present in venom are responsible for the envenomation-associated events. In this study, mice envenomed with Deinagkistrodon acutus, Naja atra, or Agkistrodon halys pallas venom exhibited typical AKI and ALI symptoms, including significantly increased plasma levels of myoglobin, free hemoglobin, uric acid, aspartate aminotransferase, and alanine aminotransferase and upregulated expression of kidney NGAL and KIM-1. These effects were significantly inhibited when the mice were pretreated with natural inhibitors of PLA2 and SVMP isolated from Sinonatrix annularis (SaPLIγ and SaMPI). The inhibitors protected the physiological structural integrity of the renal tubules and glomeruli, alleviating inflammatory infiltration and diffuse hemorrhage in the liver. Furthermore, the dual therapy alleviated oxidative stress and apoptosis in the kidneys and liver by mitigating mitochondrial damage, thereby effectively reducing the lethal effect of snake venom in the inhibitor-treated mouse model. This study showed that dual therapy with inhibitors of metalloproteinase and phospholipase can effectively prevent ALI and AKI caused by snake bites. Our findings suggest that intrinsic inhibitors present in snakes are prospective therapeutic agents for multi-organ injuries caused by snake envenoming.

Analysis of risk factors affecting moderate and severe prognosis after discharge in patients with acute cerebral infarction

Objective: To investigate risk factors affecting short-term functional prognosis after discharge in patients with acute cerebral infarction and explore the correlation between relevant factors and National Institutes of Health Stroke Scale (NIHSS) scores. Methods: A retrospective analysis of 4,048 patients with acute cerebral infarction hospitalised between January 2014 and November 2018 in Department of Neurology, Renqiu Kangji Xintu Hospital, Hebei were conducted. The enrolled patients, including 2,506 men and 1,542 women, were divided into mild (n=3,696), moderate (n=278) and severe groups (n=74) based on NIHSS score. Baseline data (gender, history of hypertension, diabetes, hyperlipidaemia, drinking, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, lipoprotein (a), urea nitrogen, creatinine) were compared among the three groups, and the relationship between relevant factors and NIHSS scores was studied. Results: Through single factor regression analysis, it was found that age, history of stroke, atrial fibrillation, coronary heart disease, antiplatelet medication usage, systolic blood pressure and uric acid were risk factors for the moderate group. Multivariate logistic regression analysis showed that, after adjusting for confounding factors, age, history of stroke and systolic blood pressure (P&lt;0.01) were independent risk factors for the moderate group. Age (OR=1.089; , history of stroke, atrial fibrillation, diastolic blood pressure, fasting plasma glucose and uric acid (P&lt;0.05) were independent risk factors for the severe group. Conclusion: Age, history of stroke, atrial fibrillation, systolic and diastolic blood pressure, fasting plasma glucose and uric acid levels are independent risk factors affecting the short-term post-discharge functional prognosis of patients with acute cerebral infarction and are related to the NIHSS scores of these patients after discharge.

The impact of chrysanthemi indici flos-enriched flavonoid part on the model of hyperuricemia based on inhibiting synthesis and promoting excretion of uric acid

Ethnopharmacological relevanceIn recent years, in addition to hypertension, hyperglycemia, and hyperlipidemia, the prevalence of hyperuricemia (HUA) has increased considerably. Being the fourth major health risk factor, HUA can affect the kidneys and cardiovascular system. Chrysanthemi Indici Flos is a flavonoid-containing traditional Chinese patent medicine that exhibits a uric acid (UA)-lowering effect. However, the mechanisms underlying Chrysanthemi Indici Flos-enriched flavonoid part (CYM.E) mediated alleviation of HUA remain unelucidated. Aim of the studyThis study aimed to elucidate the efficacy of CYM.E in preventing and treating HUA and its specific effects on UA-related transport proteins, to explore possible mechanism. MethodsThe buddleoside content in CYM.E was determined through high-performance liquid chromatography. HUA was induced in mice models using adenine and potassium oxonate. Subsequently, mice were administered 10 mg/kg allopurinol, and 30, 60, and 90 mg/kg CYM.E to evaluate the effects of CYM.E on the of HUA mice model. Herein, plasma uric acid (UA), creatinine (CR), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) contents, along with serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities were measured. Additionally, xanthine oxidase (XOD) and adenosine deaminase (ADA) activities in the liver were determined. The histomorphologies of the liver and kidney tissues were examined through hematoxylin and eosin staining. The messenger RNA (mRNA) expression of facilitated glucose transporter 9 (GLUT9), organic anion transporter (OAT)1, OAT3, and adenosine triphosphate binding cassette subfamily G2 (ABCG2) in the kidney was assessed by real-time quantitative polymerase chain reaction. Furthermore, the expression of urate transporter 1 (URAT1), GLUT9, OAT1, and OAT3 in the kidney, OAT4, and ABCG2 proteins was determined by immunohistochemistry and western blotting. ResultsThe buddleoside content in CYM.E was approximately 32.77%. CYM.E improved body weight and autonomous activity in HUA mice. Additionally, it reduced plasma UA, BUN, and CR levels and serum ALT and AST activities, thus improving hepatic and renal functions, which further reduced the plasma UA content. CYM.E reduced histopathological damage to the kidneys. Furthermore, it lowered plasma TC, TG, and LDL-c levels, thereby improving lipid metabolism disorder. CYM.E administration inhibited hepatic XOD and ADA activities and reduced the mRNA expression of renal GLUT9. CYM.E inhibited the protein expression of renal URAT1, GLUT9, and OAT4, and increased the mRNA and protein expression of renal OAT1, OAT3, and ABCG2. Altogether, these results show that CYM.E could inhibit the production and promote reabsorption of UA and its excretion.

SGLT2 Inhibitors and Uric Acid Homeostasis

A relationship between metabolic disorders and hyperuricemia is well established. The nature of the relationship—risk factor, causal agent, or byproduct—remains unclear. Recent studies of sodium–glucose transporter 2 inhibitors (SGLT2i’s) have established that this pharmacological intervention is beneficial to patients with hyperglycemia and type 2 diabetes mellitus (T2D) and also against the common cardio and renal comorbidities associated with diabetes. Hyperuricemia, or high plasma uric acid levels, is one of the comorbidities mitigated with SGLT2i treatment, raising the potential for using SGLT2i’s as part of the treatment for gout and hyperuricemia. However, the mechanisms underlying the lower plasma urate levels and increased uricosuria produced with SGLT2i’s remains poorly understood. Here, we review the renal physiology of glucose and uric acid transport, the renal consequences of hyperglycosuria and diabetes, the benefits and physiology of SGLT2i use, and discuss several potential mechanisms that may be responsible for the favorable uricosuric effect observed in those treated with SGLT2i’s.

Plasma albumin, bilirubin, and uric acid and the subsequent risk of cancer: a case-cohort study in the Japan Public Health Center-based Prospective Study.

Several epidemiologic studies have investigated the circulating levels of albumin, bilirubin, and uric acid (UA) in relation to cancer risk; however, they have provided equivocal evidence. In this prospective case-cohort study, we measured the plasma levels of albumin, bilirubin, and UA and investigated their association with cancer incidence in 3584 case patients and 4270 randomly selected participants with a median follow-up of 15.8years. The adjusted hazard ratios (HRs) and 95% CIs of total cancer for the highest quartile (Q4) versus lowest quartile (Q1) was 0.77 (95% CI, 0.67-0.90; P <.001 for trend) for albumin. This association was attenuated after excluding liver cancer cases with lower plasma albumin levels. Plasma bilirubin levels were positively related to liver cancer but inversely to total cancer after excluding liver cancer with, for Q4 versus Q1, an adjusted HR of 0.86 (95% CI, 0.74-0.99; P=.015 for trend). Plasma UA levels were not dose-responsively associated with total cancer risk. Higher plasma bilirubin levels were associated with a decreased risk of total cancer after excluding liver cancer, which is likely attributed to the antioxidant properties of bilirubin.

Mass Spectrometric Analysis of Purine Intermediary Metabolism Indicates Cyanide Induces Purine Catabolism in Rabbits.

Purines are the building blocks of DNA/RNA, energy substrates, and cofactors. Purine metabolites, including ATP, GTP, NADH, and coenzyme A, are essential molecules in diverse biological processes such as energy metabolism, signal transduction, and enzyme activity. When purine levels increase, excess purines are either recycled to synthesize purine metabolites or catabolized to the end product uric acid. Purine catabolism increases during states of low oxygen tension (hypoxia and ischemia), but this metabolic pathway is incompletely understood in the context of histotoxic hypoxia (i.e., inhibition of oxygen utilization despite normal oxygen tension). In rabbits exposed to cyanide-a classical histotoxic hypoxia agent-we demonstrated significant increases in several concordant metabolites in the purine catabolic pathway (including plasma levels of uric acid, xanthosine, xanthine, hypoxanthine, and inosine) via mass spectrometry-based metabolite profiling. Pharmacological inhibition of the purine catabolic pathway with oxypurinol mitigated the deleterious effects of cyanide on skeletal muscle cytochrome c oxidase redox state, measured by non-invasive diffuse optical spectroscopy. Finally, plasma uric acid levels correlated strongly with those of lactic acid, an established clinical biomarker of cyanide exposure, in addition to a tissue biomarker of cyanide exposure (skeletal muscle cytochrome c oxidase redox state). Cumulatively, these findings not only shed light on the in vivo role(s) of cyanide but also have implications in the field of medical countermeasure (MCM) development.

Effect of apheresis plasma donation on plasma uric acid levels, the lipid profile, and major plasma proteins in plasma donors in China: A multicenter, prospective cohort study

Abnormal plasma uric acid (UA) levels, the lipid profile, and plasma proteins in blood are associated with a range of adverse health outcomes. This multicenter, prospective cohort study aimed to determine the possible effects of multiple apheresis plasma donations on plasma UA levels, the lipid profile, and major proteins in plasma donors. Participants were enrolled from 1 April 2021 to 31 August 2022. When their plasma UA (men: >420 µmol/L, women: >360 µmol/L) and/or lipid levels (total cholesterol [TC]: ≥6.2 mmol/L, triglycerides [TGs]: ≥2.3 mmol/L, low-density lipoprotein cholesterol: ≥4.1 mmol/L, or high-density lipoprotein cholesterol [HDL-C]: <1.0 mmol/L) were abnormal at their first plasma donation, the enrolled participants were followed up until they had completed 10 plasma donations. A total of 11485 participants were enrolled, of whom 1861 met the inclusion criteria. During the study period, 320 donors completed 10 plasma donations. None of the participants took any corrective medicine for their abnormal index. The measured parameters were significantly different from the first to the tenth plasma donations (donors with asymptomatic hyperuricemia: UA, P < 0.001; donors with asymptomatic hyperlipidemia: HDL-C, P < 0.001; TC, P = 0.025; TGs, P < 0.001; apolipoprotein B, P = 0.025; all of the plasma donors, immunoglobulin G, P < 0.001). The levels of HDL-C, TC, and apolipoprotein B were increased, and the levels of UA, TGs, and immunoglobulin G were decreased over this time. However, immunoglobulin G levels were still in the normal range. Moreover, the changes in these parameters were closely associated with the frequency of plasma donation during the study period. Repeated apheresis plasma donations can reduce plasma UA and TG levels and increase HDL-C levels; and further evaluation of the clinical significance with a larger sample size is required.

PEGylated porcine-human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications.

The growing prevalence of hyperuricemia necessitates the urgent development of more potent treatments. This study aimed to develop, optimize, and evaluate the safety and efficacy of porcine-human recombinant uricase (PHRU) both in vitro and in vivo. The study employed gene editing of PHRU through site-directed mutagenesis, with recombinant proteins expressed in vitro utilizing Escherichia coli. The polyethylene glycol (PEG) approach was employed to augment uricase stability and diminish immunogenicity. The pharmacokinetics and pharmacodynamics of PHRU were tested in vitro and in Sprague Dawley rats. Successful expression of the fusion protein in E. coli and the development of the PEGylated drug were achieved. In vitro experiments confirmed the efficacy of PEG-PHRU in degrading uric acid, with PEGylation not markedly affecting the biological activity of PHRU. Animal studies revealed that PEG-PHRU significantly lowered plasma uric acid levels and mitigated hyperuricemia-induced renal damage in rats. Both drug metabolism and pharmacokinetics exhibited favorable characteristics without observable adverse effects in experimental animals. This novel fusion protein shows the potential for ameliorating hyperuricemia and related renal complications, highlighting it as a promising drug candidate with substantial market applications.

Effects of Amino Acid Supplementation to a Low-Protein Diet on the Growth Performance and Protein Metabolism-related Factors in Broiler Chicks.

A low-protein (LP) diet may alleviate the environmental impact of chicken meat production by reducing nitrogen excretion and ammonia emissions. Thus, this study investigated the effect of a 15% reduced protein diet with or without amino acid (AA) supplementation on the growth performance of broiler chicks from 10 to 35 days of age and the underlying mechanism for loss of skeletal muscle mass. Thirty-six male broiler chicks were allocated to three experimental groups based on body weight: control, LP, and essential AA-supplemented LP (LP+AA). The body weight gain, feed conversion ratio, and weight of breast muscles and legs significantly decreased only in the LP group at the end of the feeding period. Plasma uric acid levels were significantly lower in the LP+AA group than those of the other groups. In the LP group, mRNA levels of microtubule-associated protein 1 light chain 3 isoform B were significantly higher in the pectoralis major, whereas those of atrogin-1, muscle RING-finger protein-1, and myoblast determination protein 1 were significantly higher in the biceps femoris compared to those in the control group. There were no significant differences in insulin-like growth factor 1 mRNA levels in the liver or skeletal muscle between groups. These findings suggested that supplementation with essential AAs ameliorated the impaired effects of an LP diet on growth performance in broiler chicks, and that the transcriptional changes in proteolytic genes in skeletal muscles might be related to the impaired effects of the LP diet.

Effect of short-term moderate intake of ice wine on hepatic glycolipid metabolism in C57BL/6J mice.

As the correlation between high fructose intake and metabolism-related diseases (e.g., obesity, fatty liver, and type 2 diabetes) has been increasingly reported, the health benefits of consuming ice wine high in fructose have been called into question. In this study, 6-week-old male C57BL/6J mice were divided into control (pure water), fructose (130 g L-1 fructose solution), alcohol (11% alcohol solution), low-dose (50% diluted ice wine) and high-dose ice wine (100% ice wine) groups to investigate the effects and mechanisms of short-term (4 weeks) ice wine intake on hepatic glycolipid metabolism in mice. The results showed that short-term consumption of ice wine suppressed the elevation of low-density lipoprotein cholesterol content and did not cause hepatic lipid accumulation compared with those of the fructose group. Meanwhile, ice wine had no significant effect on lipogenesis although it inhibited fatty acid oxidation via the PPARα/CPT-1α pathway. Compared with the control group, ice wine interfered with the elevation of fasting glucose and the insulin resistance index in a dose-dependent manner, and led to an increase in plasma uric acid levels, which may further contribute to the disruption of glucolipid metabolism. Overall, short-term moderate intake of ice wine over a 4-week period may not significantly affect hepatic glycolipid metabolism in C57BL/6J mice for the time being.

The protective role of virgin olive oil and vitamin E on mercury-induced hepatic, renal, testicular and adrenal toxicity in the rabbit (Oryctolagus cuniculus)

This study aimed to strengthen the antioxidant defenses against the toxic effect of mercury, by administering a synthetic antioxidant (vitamin E) and a natural product rich in antioxidant compounds (virgin olive oil) to rabbits. Hepatic and renal biomarker levels, cortisol and testosterone synthesis, mercury concentration, relative weight of organs, and tissue architecture were studied. The results showed a significant decrease in the plasma alkaline phosphatase (ALP), plasma aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), plasma testosterone levels, and relative weight of the liver, testes, and adrenal in the mercury treated group (group M), while the other indices were significantly increased in the m-group compared to the control (group C). However, the group treated with olive oil combined with mercury (group O) showed a significant decrease in the ALP, AST, ALT, testosterone levels, and adrenal relative weight, while plasma creatinine, uric acid levels, mercury concentration in organs, and the kidney relative weight were significantly increased. Vitamin E supplementation (group E) led to a significant decrease in the ALP, testosterone levels, and adrenal relative weight, a significant increase was observed in plasma levels of triglycerides, creatinine, and uric acid. Histological sections of the liver, kidney, testis, and adrenal of group M showed severe tissue damage, while the other groups showed less important tissue alterations demonstrating that supplementation with natural or synthetic antioxidants can protect against the toxicity of heavy metals such as mercury, improving the health of rabbits.

Plasma antioxidant potential measured by total radical trapping antioxidant parameter in a cohort of multiple sclerosis patients.

Oxidative injury has been implicated as a mediator of demyelination, axonal damage, and neurodegeneration in multiple sclerosis (MS). There is a high demand for oxidative injury biomarkers. The aim of the study was to evaluate MS patients' plasma antioxidant potential using the total radical trapping parameter (TRAP) assay and examine its usefulness as an MS disease biomarker. A total number of 112 MS patients underwent an analysis of TRAP. In addition, plasma uric acid (UA) levels were analyzed. The neurological and radiological data were collected from patient records from Helsinki University Hospital during 2012-2013 when first-line injectables of moderate-efficacy, natalizumab (NTZ), and fingolimod (FTY) of high efficacy disease modifying therapies and in some cases azathioprine (AZT) were used to treat MS. TRAP values were negatively associated with expanded disability status scale (EDSS) score with p-value .052, β=-28. There was also a negative association in TRAP values between patients with no medication (n=22, TRAP mean 1255μmol/L (95% confidence interval [CI] 1136-1374)) and patients who received NTZ, p-value .020 (n=19, TRAP mean was 991μmol/L (95% CI 849-1133) or FTY treatment, p-value .030 (n=5, TRAP mean 982μmol/L (95% CI 55-1909). Due to a small sample size, these results were not significant after applying a false discovery rate correction at a 0.05 significance level but are worth highlighting. Men in the study had higher TRAP values, p-value=.001 (TRAP mean 1320±293μmol/L) than women (TRAP mean 1082±288μmol/L). UA was positively associated with TRAP values, p-value <.001 and UA levels in men (UA mean 334.5±62.6μmol/L) were higher compared to women (UA mean 240±55.8μmol/L), t-test p-value <.001. The significant difference in TRAP levels between genders, with men showing higher TRAP values than women, may be attributed to the variation in UA levels. Our findings suggest that lower plasma antioxidant potential is linked to more severe disability measured by EDSS scores. Patients treated with NTZ and FTY had reduced antioxidant power, which might be influenced by the active MS disease rather than the treatments themselves. The study reveals a strong positive correlation between UA levels and TRAP, particularly among women. However, men on average had better antioxidant potential than women. Neither the disease type nor the duration influences TRAP levels. While serving as a marker of antioxidant potential, plasma TRAP in MS patients does not reliably reflect overall oxidative stress (OS) and should not be solely used as an indicator of OS.

Egg Quality, Sensory Attributes, and Protein Metabolites of Laying Hens Fed Whole Flaxseed, Fish Oil, and Different Sources of Trace Elements.

This study evaluated the effects of whole flaxseed (WFS), fish oil (FO), and different sources of Se, Zn, and Fe (inorganic, organic, and nano-source) on egg production, quality, sensory attributes, and serum protein metabolites in laying hens. A total of 144 hens were divided into six groups with six replicates of four hens each. Hens were fed six diets as follows: 1) control diet; 2) 7.5%WFS+1.5%FO; 3) 7.5%WFS+1.5%FO+175 mg/kg vitamin E (VE); 4) 7.5%WFS+1.5%FO+175 mg/kg VE + inorganic sources of Se, Zn, and Fe (ISeZnFe); 5) 7.5%WFS+1.5%FO+175 mg/kg VE + organic sources of Se, Zn, and Fe (OSeZnFe); 6) 7.5%WFS+1.5%FO+175 mg/kg VE + nano-source of Se, Zn, and Fe (NSeZnFe) from 40-50 weeks of age. Laying hens fed 7.5% WFS, 1.5% FO, and different sources of trace elements in their diets had no negative effects on laying rate, egg weight, egg mass, feed intake, feed conversion ratio, body weight change, or survival rate compared to that of hens fed the control diet. Dietary treatments did not negatively affect the external and internal egg characteristics or egg sensory attributes. Feeding 7.5%WFS+1.5%FO+VE+ISeZnFe positively influenced yolk color in fresh eggs. Dietary treatments had a significant impact on egg nutritional composition, with the highest levels of macronutrients found in eggs from hens fed the 7.5%WFS+1.5%FO+VE+NSeZnFe treatment. The highest plasma globulin concentrations were observed in hens fed organic and nano-source trace elements. The same diets reduced plasma uric acid levels. Based on these findings, the inclusion of organic or nano-source trace minerals in diets containing WFS and FO positively affected egg quality and hen protein metabolites.

Bi Xie Fen Qing Yin decoction alleviates potassium oxonate and adenine induced-hyperuricemic nephropathy in mice by modulating gut microbiota and intestinal metabolites

This study aimed to evaluate the preventive effect of Bi Xie Fen Qing Yin (BXFQY) decoction on hyperuricemic nephropathy (HN). Using an HN mouse model induced by oral gavage of potassium oxonate and adenine, we found that BXFQY significantly reduced plasma uric acid levels and improved renal function. Further study shows that BXFQY suppressed the activation of the NLRP3 inflammasome and decreased the mRNA expressions of pro-inflammatory and fibrosis-associated factors in renal tissues of HN mice. Also, BXFQY prevented the damage to intestinal tissues of HN mice, indicative of suppressed colonic inflammation and increased gut barrier integrity. By 16 S rDNA sequencing, BXFQY significantly improved gut microbiota dysbiosis of HN mice. On the one hand, BXFQY down-regulated the abundance of some harmful bacteria, like Desulfovibrionaceae, Enterobacter, Helicobacter, and Desulfovibrio. On the other hand, BXFQY up-regulated the contents of several beneficial microbes, such as Ruminococcaceae, Clostridium sensu stricto 1, and Streptococcus. Using gas or liquid chromatography-mass spectrometry (GC/LC-MS) analysis, BXFQY reversed the changes in intestinal bacterial metabolites of HN mice, including indole and BAs. The depletion of intestinal flora from HN or HN plus BXFQY mice confirmed the significance of gut microbiota in BXFQY-initiated treatment of HN. In conclusion, BXFQY can alleviate renal inflammation and fibrosis of HN mice by modulating gut microbiota and intestinal metabolites. This study provides new insight into the underlying mechanism of BXFQY against HN.

Sodium butyrate alleviates fructose-induced non-alcoholic fatty liver disease by remodeling gut microbiota to promote γ-amino butyric acid production

Sodium butyrate (NaB) can regulate lipid metabolism and inhibit hepatic steatosis. This study aimed to investigate whether NaB can alleviate fructose-induced hepatic steatosis via remodeling the gut microbiota and evaluate the anti-fatty liver mechanisms. The results showed that NaB and NaB-remodeled gut microbiota significantly alleviated fructose-induced hepatic steatosis and increased plasma uric acid and fructose levels. Furthermore, both NaB and NaB-remodeled gut microbiota increased the abundance of Lactobacillus and altered the levels of plasma amino acids (upregulating gamma-amino butyric acid (GABA) and downregulating L-glutamic acid and L-arginine) in fructose-exposed mice. The correlation analysis showed that GABA levels positively correlated with Lactobacillus abundance, and increased GABA levels might promote the reduction of the hepatic triglyceride content. Further studies confirmed that GABA significantly reduced lipid deposition in mouse hepatocytes induced via fructose pretreatment in vitro. These findings suggested that NaB could ameliorate fructose-induced hepatic steatosis by regulating gut microbiota.

Uric acid as a predictor of the development of non-alcoholic fatty liver disease in patients with arterial hypertension

Introduction. Currently, increased uric acid (UA) levels are considered an independent risk factor for the development of non-alcoholic fatty liver disease. Oxidative stress, chronic systemic inflammation, and insulin resistance characteristic of non-alcoholic fatty liver disease (NAFLD) may represent possible mechanisms for the association between the development of hyperuricemia and NAFLD.Aim. To clarify the meaning and nature of the relationship between an increase in the level of UA concentration and the development of NAFLD, as well as to evaluate the relationship between uric acid and the risk of cardiovascular complications in patients with hypertension and NAFLD.Materials and methods. A cross-sectional comparative study was conducted, which involved 120 patients aged from 45 to 65 with hypertension of 1–2 degrees, 1–2 stages (with and without NAFLD (FLI &gt; 60). During the examination, a clinical examination was carried out: analysis of anamnesis data, anthropometry. Lipids and uric acid in blood plasma were also analyzed.Results. In the group of comorbid patients, there were significantly more patients with excess of the reference values of UA levels in the blood plasma (OR = 2.25: 95% CI 1.08–4.71). ROC analysis showed that with an uric acid level of 369.5 µmol/l, a high risk of developing NAFLD is predicted. The UA/Cr index in patients with hypertension and NAFLD was statistically significantly higher than in patients in the control group. Increase in the MK/Kr index by 1 USD increases the chances of developing NAFLD by 1.54 times (95% CI: 1.11–2.13). Also, an increase in the concentration of sUA level by 1 µmol/l increases the chances of an increase in the 10-year risk of cardiovascular events to 5.0% or more by 0.6%.Conclusions. With an uric acid level of 369.5 µmol/l, a high risk of developing NAFLD in the study group is predicted. Increase in UA/creatinine index by 1 USD increases the chances of developing NAFLD by 1.54 times. In addition, an increase in the concentration of sUA in the blood plasma by 1 µmol/l increases the chances of an increase in the 10-year risk of cardiovascular events to 5.0% or more by 0.6% in patients with hypertension and NAFLD.

Microvesicle-associated and circulating microRNAs in diabetic dyslipidemia: miR-218, miR-132, miR-143, and miR-21, miR-122, miR-155 have biomarker potential

BackgroundCirculating MicroRNAs (miRNAs) carried by microvesicles (MVs) have various physiological and pathological functions by post-transcriptional regulation of gene expression being considered markers for many diseases including diabetes and dyslipidemia. We aimed to identify new common miRNAs both in MVs and plasma that could be predictive biomarkers for diabetic dyslipidemia evolution.MethodsFor this purpose, plasma from 63 participants in the study (17 type 2 diabetic patients, 17 patients with type 2 diabetes and dyslipidemia, 14 patients with dyslipidemia alone and 15 clinically healthy persons without diabetes or dyslipidemia) was used for the analysis of circulating cytokines, MVs, miRNAs and MV-associated miRNAs.ResultsThe results uncovered three miRNAs, miR-218, miR-132 and miR-143, whose expression was found to be significantly up-regulated in both circulating MVs and plasma from diabetic patients with dyslipidemia. These miRNAs showed significant correlations with important plasma markers, representative of this pathology. Thus, MV/plasma miR-218 was negatively correlated with the levels of erythrocyte MVs, plasma miR-132 was positively connected with MV miR-132 and negatively with uric acid and erythrocyte plasma levels, and plasma miR-143 was negatively related with creatinine levels and diastolic blood pressure. Also, three miRNAs common to MV and plasma, namely miR-21, miR-122, and miR-155, were identified to be down-regulated and up-regulated, respectively, in diabetic dyslipidemia. In addition, MV miR-21 was positively linked with cholesterol plasma levels and plasma miR-21 with TNFα plasma levels, MV miR-122 was negatively correlated with LDL-c levels and plasma miR-122 with creatinine and diastolic blood pressure and positively with MV miR-126 levels, MV miR-155 was positively associated with cholesterol and total MV levels and negatively with HDL-c levels, whereas plasma miR-155 was positively correlated with Il-1β plasma levels and total MV levels and negatively with MV miR-223 levels.ConclusionsIn conclusion, miR-218, miR-132, miR-143, and miR-21, miR-122, miR-155 show potential as biomarkers for diabetic dyslipidemia, but there is a need for more in-depth studies. These findings bring new information regarding the molecular biomarkers specific to diabetic dyslipidemia and could have important implications for the treatment of patients affected by this pathology.