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Human milk provides bioactive compounds such as milk fat globules (MFGs), which promote brain development, modulate the immune system, and hold antimicrobial properties. To ensure microbiological safety, donor milk banks apply heat treatments. This study compares the effects of heat treatments and homogenization on MFGs physicochemical properties, bioactivity, and bioavailability. Vat pasteurization (Vat-PT), retort (RTR), and ultra-high temperature (UHT) were performed with or without homogenization. UHT, RTR, and homogenization increased the colloidal dispersion of globules, as indicated by increased zeta potential. The RTR treatment completely inactivated xanthine oxidase activity (a marker of MFG bioactivity), whereas UHT reduced its activity by 93%. Interestingly, Vat-PT resulted in less damage, with 28% activity retention. Sialic acid, an important compound for brain health, was unaffected by processing. Importantly, homogenization increased the in vitro lipolysis of MFG, suggesting that this treatment could increase the digestibility of MFG. In terms of color, homogenization led to higher L* values, indicating increased whiteness due to finer dispersion of the fat and casein micelles (and thus greater light scattering), whereas UHT and RTR increased b* values associated with Maillard reactions. This study highlights the nuanced effects of processing conditions on MFG properties, emphasizing the retention of native characteristics in Vat-PT-treated human milk.

Hypouricemia is defined as a serum uric acid concentration of ≤ 2.0 mg/dL or 119 μmol/L. Hypouricemia may occur secondarily to a number of underlying conditions, including severe hepatocellular disease, neoplasia, defective renal tubular reabsorption of uric acid, inherited metabolic defect in purine metabolism, and drugs. Medications are an important cause of hypouricemia. They can cause hypouricemia by a variety of mechanisms. Drug-induced hypouricemia mostly occurs as overtreatment of hyperuricemia by urate-lowering therapies including xanthine oxidase inhibitors, uricosuric agents and uricases. Drugs not used in the treatment of gout may also lead to a decrease of uric acid levels. In this literature review, medications leading to hypouricemia are summarized with regard to their mechanism of action and clinical significance. [ABSTRACT FROM AUTHOR]

Hyperuricemia is an independent predictor of mortality in patients with chronic heart failure (CHF). To determine whether febuxostat, a urate-lowering agent, may improve clinical outcomes in CHF patients, we conducted a multicenter, prospective, randomized, open-label, blinded endpoint study with a treatment period of 24 weeks. We randomly assigned Japanese outpatients diagnosed with both CHF with reduced left ventricular ejection fraction (LVEF < 40%) and asymptomatic hyperuricemia (serum uric acid [UA] levels > 7.0 mg/dl and < 10.0 mg/dl) to either a febuxostat group (n = 51) or a control group (n = 50). The primary efficacy endpoint was the change in log-transformed plasma B-type natriuretic peptide (BNP) levels from baseline to week 24 (or at discontinuation). The secondary efficacy endpoints were the changes in LV systolic or diastolic function evaluated by echocardiography, New York Heart Association (NYHA) class, hemoglobin, and estimated glomerular filtration rate from baseline to week 24, and the change in log-transformed plasma BNP levels or serum UA levels from baseline to weeks 4, 8, 12, 16 and 20 (BNP) or weeks 4, 8, 12, 16, 20 and 24 (serum UA). The primary safety endpoints were occurrence of all-cause death or major cardiovascular events. The mean age of participants was 70 years; 14% were female. The febuxostat group and the control group did not differ with respect to the primary efficacy endpoint (p = 0.13), although the decrease in log-transformed plasma BNP levels from baseline to each of weeks 4, 8, 12, 16 and 20 was greater in the febuxostat group. There were no significant differences between the two groups in the primary safety endpoints or the secondary efficacy endpoints except reduced serum UA levels in the febuxostat group. Febuxostat did not reduce plasma BNP levels at week 24 in patients with CHF, but it appeared safe with no increase in major cardiovascular events and all-cause or cardiovascular mortality. [ABSTRACT FROM AUTHOR]

Polyphenolic plant compounds possess nutritional and pro-healthy potential, reducing the risk of auto-inflammatory and neoplastic diseases. However, their interference with the progression of thyroid gland dysfunctions has remained largely unaddressed. For this purpose, we combined the analyses of phenolic content and antioxidative activity with the thyroid peroxidase (TPO), lipoxygenase (LOX), xanthine oxidase (XO) and cyclooxygenase-2 (COX-2) activity assays, isobolographic approach and the estimation of thyroid cancer cells' proliferation and motility in vitro. Bioaccessible oatmeal (OM) and wheat flour (WF) compounds activated TPO while inhibiting LOX and XO's in vitro activity. OM extracts also inhibited COX-2 activity. Isobolographic and combination index studies revealed cooperation of compounds from OM and WF. However, the relatively strong inhibitory activity of bioaccessible OM compounds on LOX activity correlated with their mildly cytostatic and relatively distinct pro-invasive effects in the thyroid cancer model in vitro. Collectively, the application of OM and WF products for the prophylactics of inflammatory thyroid diseases should be considered with care, especially in the context of the oncological status of the patient. [ABSTRACT FROM AUTHOR]

In this study, the antioxidant and prooxidant potency of protocatechuic aldehyde (PCA) was evaluated using density functional theory (DFT). The potency of direct scavenging of hydroperoxyl (HOO•) and lipid peroxyl radicals (modeled by vinyl peroxyl, H2C=CHOO•) involved in lipid peroxidation was estimated. The repair of oxidative damage in biomolecules (lipids, proteins and nucleic acids) and the prooxidant ability of PCA phenoxyl radicals were considered. The repairing potency of PCA was investigated for damaged tryptophan, cysteine, leucine, DNA base guanine and linolenic acid. The thermodynamics and kinetics of the single electron transfer (SET) and formal hydrogen atom transfer (fHAT) mechanisms underlying the studied processes were investigated under physiological conditions in aqueous and lipid environments using the SMD/M06-2X/6-311++G(d,p) level of theory. Sequestration of catalytic Fe2+ and Fe3+ ions by PCA, which prevents HO• production via Fenton-like reactions, was modeled. Molecular docking was used to study the inhibitory capability of PCA against xanthine oxidase (XO), one of the enzymes producing reactive oxygen species. The attained results show that PCA has the capability to scavenge lipid peroxyl radicals, repair damaged tryptophan, leucine and guanine, chelate catalytic iron ions and inhibit XO. Thus, PCA could be considered a possible multifunctional antioxidant. [ABSTRACT FROM AUTHOR]

Overproduction of uric acid caused by increased expression and/or enhanced activity of xanthine oxidase (XO) is one of the major etiologies of hyperuricemia, which had a significant sex differences. As an important enzyme involved in production of reactive oxygen species and uric acid, activity of XO is highly correlated with hyperuricemia and its complications. However, the mechanisms underlying XO dysregulation remain unclear, and sex difference in the prevalence of hyperuricemia has been well known. To explore the potential role of intestinal farnesoid X receptor (FXR) on XO regulation and production, and the mechanisms of sex differences in this pathological process. Two hundred and sixty-one dyslipidemia participants and intestine-specific FXR-knockout mice were used to study the relationship between the intestinal FXR and the serum uric acid level. Western blotting, quantitative real-time PCR, and dual-luciferase reporter assay, were applied to clarify the regulatory role of FXR deficiency on XO. Special inhibitors, agonists, siRNA, sex hormones were used to investigate the mechanism of sex difference in FXR deficiency induced hyperuricemia in cell and animal model. Serum fibroblast growth factor 19 (FGF19) levels were lower in hyperuricemia patients in a sex difference manner. Increased local TNFα level driven by intestinal FXR deficiency/inhibition induced overexpression and hyperactivity of intestinal XO, leading to elevated intestinal uric acid synthesis, and subsequently resulting in hyperuricemia. We found that estrogens inhibited XO expression and activity, whereas androgens enhanced XO activity, leading to the sex difference in FXR deficiency induced hyperuricemia. Infliximab treatment eliminated the sex difference in uric acid levels in intestinal FXR-knockout mice. This study demonstrated the role of intestinal FXR in the pathogenesis of hyperuricemia, and partially elucidated the mechanisms underlying the sex differences of hyperuricemia. Intestinal FXR deficiency induces dysregulation of xanthine oxidase and accounts for the sex differences in hyperuricemia. Increased local TNFα level driven by intestinal farnesoid X receptor (FXR) deficiency induces the overexpression and hyperactivity of intestinal xanthine oxidase (XO), leading to elevated intestinal uric acid synthesis, ultimately resulting in hyperuricemia. Estrogens inhibits XO expression and activity, whereas androgens enhance XO activity, contributing to the sex differences of hyperuricemia observed in the intestine-specific FXR knockout(FXRΔIE) mice. [Display omitted] • Intestinal FXR deficiency/inhibition caused hyperuricemia in a sex difference manner. • FXR deficiency upregulated XO gene expression by TNF-α/NF-κB pathway. • FXR deficiency enhanced XO activity by PTEN/PI3K/AKT pathway. • Sex hormones showed different regulation effects on the XO expression and activity. [ABSTRACT FROM AUTHOR]

• In vitro simulated digestion of sage tea did not alter its total polyphenol content. • Sage tea flavonoid and phenolic acid contents were moderately affected. • Antioxidant and antiglycant activities were preserved after in vitro digestion. • Xanthine oxidase inhibition capacity of sage tea was preserved. • Consumption of sage tea may play a protective role against oxidative stress. Sage (Salvia officinalis) is a medicinal plant commonly used in traditional medicine, particularly in the form of herbal tea. Sage tea is used, among others, in cases of dyspepsia, rheumatism, and excessive sweating and is known for its positive effects on oxidative stress. However, the impact of digestion on sage phenolic stability and antiglycoxidant properties is not known. This study aimed to assess the influence of the digestive process on phenolic contents, antiglycoxidant activities, and xanthine oxidase inhibition capacity using an in vitro simulated digestion model. Total polyphenol content was not altered by the digestion process, despite a moderate but significant decrease in total flavonoid and phenolic acid contents. HPLC analysis confirmed a significant drop in luteolin 7- O- glucuronide and rosmarinic acid contents (the main sage polyphenolic compounds) after the intestinal stage. However, simulated digestion did not generally alter antioxidant activities nor antiglycant activity and xanthine oxidase inhibition capacity. Consequently, the present study confirmed the potential bioaccessibility of sage tea polyphenolic compounds and suggested that sage tea could exert beneficial effects in view of its preserved antiglycoxidant properties after in vitro simulated digestion. [ABSTRACT FROM AUTHOR]

An optimal culture medium and highly stable biometabolites are important in industrial production processes. The response surface methodology with a Box–Behnken design was performed to determine the optimal culture medium of an engineered Aspergillus oryzae strain for cordycepin production by submerged fermentation. The influences of glucose, yeast extract, and adenine concentrations on cordycepin production were explored, and their concentrations were used for experimental design. The results reveal that the optimal culture components involved 30.0 g/L of glucose, 9.8 g/L of yeast extract, and 1.5 g/L of adenine. As predicted, the maximum cordycepin concentration (1724.53 ± 18.30 mg/L) was obtained with a short fermentation time (2 days). A significant increase in cordycepin yield (>50% increase) was observed in the culture grown in the optimized culture medium compared to that grown in the basal medium. A xanthine oxidase inhibitory activity assay demonstrated that the cordycepin product had a pharmacological function. It exhibited strong stability under high thermal and acidic conditions, with over 95% product recovery. The findings of this study are valuable for developing cost-effective processes for producing health-benefiting products. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is a potentially fatal acute digestive disease that is widespread globally. Although significant progress has been made in the previous decade, the study of mechanisms and therapeutic strategies is still far from being completed. Xanthine oxidase (XO) is an enzyme that catalyzes hypoxanthine and xanthine to produce urate and is accompanied by the generation of reactive oxygen species (ROS) in purine catabolism. Considerable preclinical and clinical studies have been conducted over many decades to investigate the role of XO in the pathogenesis of AP and its potential targeting therapeutic value. There is no doubt that the ROS generated by irreversibly activated XO participates in the local pancreas and multiple organ failure during AP. However, the optimal timing and doses for therapeutic interventions targeting XO in animal studies and the clinic, as well as the additional molecular mechanisms through which XO contributes to disease onset and progression, including metabolic regulation, remain to be elucidated. This review summarized the benefits and contradictions of using XO inhibitors in animal models, offered mechanisms other than ROS, and discussed the difficulties faced in clinical trials. We hope to provide a perspective on the future worthwhile basic and clinical research on XO by analyzing its chemical and biological characteristics, as well as the progress of its regulatory mechanisms in AP. [ABSTRACT FROM AUTHOR]

Qualitative and quantitative differences in the chemical composition between bee pollen originated from Castanea sativa (Türkiye and Slovenia), Salix spp. (Türkiye and Slovenia), and Quercus spp. (Türkiye) and androecia of Castanea sativa, Salix alba, and Quercus pubescens (apetalous trees) were evaluated for the first time by new high-performance thin-layer chromatography (HPTLC) and ultra-performance liquid chromatography (UPLC) methods using marker compounds. N1,N5,N10-tricaffeoylspermidine was isolated, and its structure was elucidated by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). It was the main and the marker compound common to bee pollen (≈3–41 mg/g) and androecia (≈3–6 mg/g) samples. To the best of our knowledge, this is the first report of the identification of N1,N5,N10-tricaffeoylspermidine in bee pollen originated from Salix spp. and androecia of C. sativa, S. alba, and Q. pubescens. The botanical origins of bee pollen were determined via phytochemical profiling using HPTLC-image analyses showing that bee pollen from the same botanical source had almost identical profiles regardless of collection location, geographical differences, and the bee race. In vitro tests and HPTLC-effect-directed analyses (EDAs) were performed to assess antioxidant and xanthine oxidase (XO) inhibitory activities of bee pollen, androecia, and N1,N5,N10-tricaffeoylspermidine. HPTLC-EDA combined with image analyses was used for comparing the activities of bee pollen, androecia, N1,N5,N10-tricaffeoylspermidine, and also other marker compounds (quercetin, myricitrin, hyperoside, quercitrin, isoquercitrin, and rutin). The remarkable bioactivity of N1,N5,N10-tricaffeoylspermidine was for the first time evaluated by HPTLC-EDA and in vitro tests. This is the first study performing HPTLC-XO inhibitory activity analyses on the HPTLC NH2 F254S plates. Further bioactivity studies on botanically and chemically well-characterized bee pollen samples are needed to aid in the use of bee pollen-containing supplements in the prevention and treatment of diseases. [ABSTRACT FROM AUTHOR]

Many studies have evaluated the roles of free radicals and reactive oxygen species (ROS) in various diseases. To date, however, no systematic review has specifically investigated the involvement of free radicals and ROS in acute otitis media (OM), OM with effusion, and chronic OM. The present study therefore assessed the roles of free radicals and ROS in OM. SCOPUS, PubMed, Cochrane Library, EMBASE, and Google Scholar were comprehensively searched to identify studies assessing the roles of free radicals and ROS in OM. Relevant studies were identified and their findings summarized. The literature search identified 21 studies. A review of their findings showed that the concentrations of hydrogen peroxide (H2O2), lipid hydroperoxide (LPO), and myeloperoxidase (MPO) were elevated in patients with acute OM; that the concentrations of H2O2, LPO, MPO, xanthine oxidase (XO), superoxide dismutase (SOD), glutathione peroxidase (GPX), malondialdehyde (MDA), hydroxyl radical (·OH), and nitrotyrosine were elevated in patients with OM with effusion; and that the levels of nitric oxide (NO), MPO, 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were elevated in patients with chronic OM. Although some studies reported that SOD levels were increased in patients with OM with effusion, decreases in antioxidants such as SOD and catalase, as well as total antioxidant capacity, were observed across all types of OM. Although the levels of free radicals and ROS varied by type of OM, study design, control group selection, sample type, ROS and free radical markers, and antioxidant types, most studies showed increased ROS and decreased antioxidants in OM patients. These findings suggest that levels of free radicals and ROS are strongly associated with the pathophysiology of OM. [ABSTRACT FROM AUTHOR]

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Practical Application Abundant polyphenols in Flos Sophorae Immaturus tea (FSIt) exhibited xanthine oxidase (XO) inhibitory activity. However, the XO inhibitory activity of FSIt was closely related to the processing methods. Herein, organic acids were employed as catalysts for polyphenol conversion during heat treatment and applied to enhance the XO inhibitory activity of FSIt; the potential mechanisms were clarified by polyphenols degradation and conversion analysis, omission experiment, and interaction assay. Results showed that 10% oxalic acid (OA)‐ or 10% lactic acid (LA)‐assisted heat treatment significantly increased the XO inhibition rate from 26.49% to 84.16% and 75.45%, respectively. OA‐assisted presented the high catalytic efficiency of rutin (31.56%), hyperoside (33.21%), and quercitrin (34.14%) to quercetin during heat treatment, as well as kaempferol‐3‐O‐rutinoside (20.04%) to kaempferol and narcissoside (26.04%) to isorhamnetin. The de‐glycosylation of polyphenols was the predominant reason for the enhancement of XO inhibitory activity. Moreover, the synergistic effect of chlorogenic acid and flavonoids also exhibited the ability to improve the XO inhibitory activity of FSIt.Improving the polyphenol composition of FSIt through organic acid‐assisted heat treatment, thereby enhancing its XO inhibitory activity, is a promising approach to deeply understand the relationship between processing methods and bioactivities of products, and further promote innovation in specific functional food processing technology. [ABSTRACT FROM AUTHOR]

The serum uric acid-to-creatinine ratio (UCR) may be a simple method for assessing xanthine oxidase overactivation, which may contribute to an increase in serum uric acid production and oxidative stress. In this study, we investigated the nonlinear association between the UCR and long-term mortality in patients with hypertension. Data were acquired from the National Health and Nutrition Examination Survey database, and a total of 11,346 patients with hypertension were included. We explored the nonlinear link between the UCR and all-cause mortality via spline smoothing, threshold saturation, and log-likelihood ratio tests. The results were validated through a competing risk model. A nonlinear pattern emerged between the UCR and all-cause mortality in hypertensive patients, with an inflection point at 4.3. Below this point, an increased UCR was associated with a decreased mortality risk (OR = 0.80, 95% CI: 0.68–0.94, P = 0.008), whereas above this point, the risk increased (OR = 1.21, 95% CI: 1.07–1.36, P = 0.004). The competing risk model yielded similar findings for cardiovascular and chronic kidney disease-related deaths. In patients with hypertension, the UCR nonlinearly predicted all-cause mortality, with a notable inflection at 4.3. These findings suggest that the UCR is a valuable prognostic indicator for assessing long-term outcomes in patients with hypertension. [ABSTRACT FROM AUTHOR]

Introduction: Hyperuricemia (HUA) refers to the presence of excess uric acid (UA) in the blood, which increases the risk of chronic kidney disease and gout. Probiotics have the potential to alleviate HUA. Methods: This study established a hyperuricemia model using Caenorhabditis elegans (C. elegans), and studied the anti-hyperuricemia activity and potential mechanisms of Weizmannella coagulans BC99 (W. coagulans) at different concentrations (107 CFU/mL BC99, 108 CFU/mL BC99). Subsequently, we utilized UPLC-Q-TOF/MS to investigate the impact of BC99 on endogenous metabolites in C. elegans and identified pathways and biomarkers through differential metabolomics analysis. Results: The results of this study showed that BC99 treatment significantly reduced the expression of P151.2 and T22F3.3 (p < 0.05), reduced the levels of UA and xanthine oxidase (XOD) in nematodes (p < 0.05), while extending their lifespan and movement ability (p < 0.05). Mechanistically, BC99 activates the transcription factors DAF-16 and SKN-1, thereby inducing the expression of stress response genes, enhancing the activity of antioxidant enzymes and tolerance to heat stress in the body, and reducing the production of ROS (p < 0.001). This effect was most significant in the H-BC99 group. Furthermore, non-targeted metabolomics indicated that BC99 predominantly regulated pathways associated with amino acid metabolism (Carnosine), glycerophospholipid metabolism, and purine metabolism. Discussion: These results underscore BC99 as an effective and economical adjunct therapeutic agent for hyperuricemia, providing a scientific basis for further development and application. After intervention, Weizmannella coagulans BC99 can activate transcription factors DAF-16 and SKN-1, thereby inducing the expression of stress response genes, enhancing tolerance to oxidative and thermal stress, and reducing the production of UA. Endogenous disorders in hyperuricemic nematodes can be alleviated by regulating pathways related to amino acid metabolism, glycerophospholipid metabolism, and purine metabolism. [ABSTRACT FROM AUTHOR]

Introduction: Hyperuricemia (HUA) is a metabolic syndrome caused by purine metabolism disorders. Zanthoxyli Pericarpium (ZP) is a medicinal and food homologous plant, and its ripe peel is used to treat diseases and as a spice for cooking. Some studies have shown that ZP can inhibit the formation of xanthine oxidase and reduce the production of uric acid. Methods: Through network pharmacology, ZP's potential targets and mechanisms for HUA treatment were identified. Databases like TCMSP, UniProt, and Swiss Target Prediction were utilized for ZP's active ingredients and targets. HUA-related targets were filtered using GeneCards, Drugbank, and Open Targets. Core targets for ZP's HUA treatment were mapped in a PPI network and analyzed with Cytoscape. GO and KEGG pathway enrichments were conducted on intersected targets via DAVID. Molecular docking and virtual screening were performed to find optimal binding pockets, and ADMET screening assessed compound safety. Molecular dynamics simulations confirmed compound stability in binding sites. Results: We identified 81 ZP active ingredient targets, 140 HUA-related targets, and 6 drug targets, with xanthine dehydrogenase (XDH) as the top core target. Molecular docking revealed ZP's active ingredients had strong binding to XDH. Virtual screening via Protein plus identified 48 compounds near the optimal binding pocket, with 2'-methylacetophenone, ledol, beta-sitosterol, and ethyl geranate as the most promising. Molecular dynamics simulations confirmed binding stability, suggesting ZP's potential in HUA prevention and the need for further experimental validation. Conclusion: Our study provides foundations for exploring the mechanism of the lowering of uric acid by ZP and developing new products of ZP. The role of ZP in the diet may provide a new dietary strategy for the prevention of HUA, and more experimental studies are needed to confirm our results in the future. [ABSTRACT FROM AUTHOR]

To study the effect and mechanism of walnut meal polyphenol extract on hyperuricemia (HUA), method of filling the corresponding mold making drug and walnut meal polyphenolic extract, a mouse model of hyperuricemia (HUA) was established by co-administration of 30 g/kg yeast paste by gavage (ig) and 300 mg/kg potassium oxonate by intraperitoneal injection (ip), and by the method of side-administration of the candidate and modeling drug. The serum uric acid (UA) and creatinine (Cr) of mice were detected, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) levels and xanthine oxidase (XOD), aspartate aminotransferase (AST) and alanine transaminase (ALT) activities in mice, hematoxylineosin staining of kidneys for observation and evaluation of pathology, LC-MS technique for liver metabolome, and Illumina technique for intestinal flora in mice. Results showed that, compared to the model group, renal index, serum UA, Cr, IL-6 levels and the activity of XOD, AST and ALT were significantly prevented from increasing in each subject group (P<0.0001 except P<0.05 of UA in low dose group). TNF-α levels were significantly prevented from increasing in the high and medium dose groups (P<0.01), and renal lesions and renal tubular vacuolization were reduced, and the abundance of the dominant intestinal Lactobacillus were increased. There were 20 differential metabolites including biomaker kynurenic acid and lysoPA, which mainly involved in regulating pathways such as TCA cycle, biosynthesis of siderophore group nonribosomal peptides, taurine and hypotaurine metabolism. In summary, the polyphenol extract from walnut meal can significantly prevent hyperuricemia. The mechanism may involve effectively reducing serum XOD activity, preventing the decrease in relative abundance of dominant Lactobacillus in the intestine of mice induced by modeling, regulating liver metabolism, effectively lowering lysoPA (P<0.05), and increasing kynurenic acid (P<0.05). [ABSTRACT FROM AUTHOR]

Marine-derived foods, often called blue foods, are promising sustainable alternatives to conventional food sources owing to their abundant amino acids and high protein content. Current treatments for hyperuricemia, a chronic condition attributed to purine metabolism disorders, are associated with various side effects. Novel peptide xanthine oxidase inhibitors have been discovered in the hydrolyzed products of marine fish and invertebrate proteins, which have demonstrated promising therapeutic potential by reducing uric acid levels in vitro and in vivo. This review explores the potential therapeutic effects of xanthine oxidase inhibitors derived from marine fish and invertebrates, summarizes the methods for extracting bioactive peptides from marine organisms, and emphasizes the impact of different proteases on the structure–activity relationship of bioactive peptides. The hypouricemic effects of these bioactive peptides warrant further verification. There is consensus on the in vitro chemical methods used to verify the xanthine oxidase inhibitory effects of these peptides. Considering several cell and animal model development strategies, this review summarizes several highly recognized modeling methods, proposes strategies to improve the bioavailability of bioactive peptides, and advocates for a diversified evaluation system. Although the screening and evaluation methods for antihyperuricemic peptides have been shown to be feasible across numerous studies, they are not optimal. This review examines the deficiencies in bioavailability, synthesis efficiency, and evaluation mechanisms in terms of their future development and proposes potential solutions to address these issues. This review provides a novel perspective for the exploration and application of marine-derived hypouricemic bioactive peptides. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is characterized by over 5% hepatic fat accumulation without secondary causes. The prevalence of NAFLD has escalated in recent years due to shifts in dietary patterns and socioeconomic status, making it the most prevalent chronic liver disease and a significant public health concern globally. Serum uric acid (SUA) serves as the end product of purine metabolism in the body and is intricately linked to metabolic syndrome. Elevated SUA levels have been identified as an independent risk factor for the incidence and progression of NAFLD. This paper reviews the relationship between SUA and NAFLD, the underlying mechanisms of SUA involved in NAFLD, and the potential benefits of SUA-lowering therapy in treating NAFLD. The aim is to raise awareness of SUA management in patients with NAFLD, and to encourage further investigation into pharmacological interventions in this area. [ABSTRACT FROM AUTHOR]

Background: Pulmonary tuberculosis (PTB) exacerbation can lead to respiratory failure, multi-organ failure, and symptoms related to central nervous system diseases. The purpose of this study is to screen biomarkers and metabolic pathways that can predict the progression of PTB, and to verify the role of the metabolic enzyme xanthine oxidase (XO) in the progression of PTB. Methods: To explore the biomarkers and mechanisms underlying the progression of PTB, plasma metabolomics sequencing was conducted on patients with severe PTB, non-severe PTB, and healthy individuals. Screening differential metabolites and metabolic pathways that can predict the progression of PTB, and verifying the function and mechanism of action of XO through experiments. Results: The purine metabolism, sphingolipid metabolism, and amino acid metabolism between the three groups differ. In patients with severe PTB, the levels of xanthosine and hypoxanthine are increased, while the levels of D-tryptophan, dihydroceramide and uric acid are decreased. Inhibition of XO activity has been observed to reduce the levels of tumor necrosis factor (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), as well as to suppress the production of reactive oxygen species (ROS) and the activation of the NF-κB pathway, while also promoting the growth of MTB within cells. Conclusion: D-tryptophan, xanthosine, and dihydroceramide can be utilized as biomarkers for progression of PTB, assisting in the evaluation of disease progression, and XO stands out as a potential therapeutic target for impeding the progression of PTB. [ABSTRACT FROM AUTHOR]

Purpose: Preeclampsia (PE) is a common complication of pregnancy that carries significant risks for both the mother and the fetus, and is frequently accompanied by hyperuricemia, yet the exact source of elevated uric acid (UA) levels remains partially elucidated. Several potential origins for increased UA levels include abnormal renal function, increased tissue breakdown, and increased activity of the enzyme Xanthine Oxidase (XO). The aim of the study was to determine serum levels of UA and XO not only in maternal serum, but also in umbilical vein (UV) and umbilical artery (UA) and explore their possible role in PE development. Methods: A prospective case-control pilot study was conducted in women who were found positive for PE with severe features, and had elevated UA levels above 6 mg/dL, with normotensive pregnant women serving as controls. Renal function, UA and XO levels were measured in maternal, UV and UA serums immediately after delivery. They were then compared between PE (n = 21) and control (n = 18) groups, as well as across all mediums (maternal, UV and UA) among the total study sample (N = 39). Diastolic blood pressure (DBP) was also measured immediately following delivery. Results: The mean serum maternal creatinine levels did not differ significantly between groups (0.65 ± 0.03 vs 0.6 ± 0.07, p = 0.13). Both mean maternal serum UA and XO concentrations were higher in PE group than in control (7.3 ± 1.2 vs 4.2 ± 0.9, p < 0.01 and 3.6 ± 3.5 Vs 1.7 ± 0.8, p < 0.01, respectively). The mean UV and UA serum XO concentrations were significantly higher in PE group compared to control (4.2 ± 3.6 vs 2.2 ± 1.4, p < 0.01 and 4.2 ± 3.6 vs 2.1 ± 1.5, p < 0.01, respectively). Polynomial fit correlation test demonstrated a significant association between maternal DBP and UV XO concentration for all the total study participants (p = 0.03). Conclusion: Despite preserved renal functions, UA and XO levels were elevated in women with PE. Importantly, this pattern was found to be applied to the feto-placental unit as well, which may indicate an active involvement of the fetus in the hypoxic process. Further study is needed to clarify the possible role of the feto-placental unit in pregnancies complicated by PE. [ABSTRACT FROM AUTHOR]

Hyperuricemia can lead to various diseases, including diabetes, renal disorders, and gout. Xanthine oxidase (XO), a crucial enzyme, synthesizes uric acid from xanthine; and concurrently generates reactive oxygen species, causing oxidative stress. This study aimed to validate the biological function of perilla seed meal (PSM), a by-product of cold-pressed perilla oil, concerning phytochemical contents, antioxidants, and XO inhibitory activities. PSM extraction employed 70% ethanol, and the solvent partition technique enriched the rosmarinic acid (RA)-rich fraction. Total phenolic and flavonoid contents, along with antioxidant capabilities, were determined. The reducing property of the PSM fraction was confirmed through the FRAP assay, while HPLC quantified RA. In addition, the inhibitory efficiency of the PSM fraction against XO was investigated. The ethyl acetate (EA) fraction exhibited the highest levels of phenolics, flavonoids, and RA. ABTS and DPPH assays revealed the most effective radical scavenging by the EA fraction, with IC50 values of 6.51±0.11 µg/l and 20.43±0.18 µg/l, respectively. Moreover, the EA fraction demonstrated the highest FRAP value of 3778.05±6.8 µM Fe2+/g. The XO inhibition of the EA fraction exhibited significant inhibition compared to the ethanol extract. Mixed-type inhibition of XO was identified in PSM. Our results suggest that PSM exhibits high phytochemical compounds, antioxidant capacities, and XO inhibition, meriting further exploration for clinical applications. [ABSTRACT FROM AUTHOR]

We evaluated reactive oxygen species (ROS) modulation of cutaneous vasodilation during local and whole body passive heating in young and older adults. Cutaneous vascular conductance normalized to maximum vasodilation (%CVCmax) was assessed in young and older adults (10/group) using laser-Doppler flowmetry at four dorsal forearm sites treated with 1) Ringer solution (control), 2) 100 µM apocynin (NADPH oxidase inhibitor), 3) 10 µM allopurinol (xanthine oxidase inhibitor), or 4) 10 µM tempol (superoxide dismutase mimetic), via intradermal microdialysis during local (protocol 1) and whole body heating (protocol 2). In protocol 1, forearm skin sites were set at 33°C during baseline and then progressively increased to 39°C and 42°C (30 min each). In protocol 2, participants were immersed in warm water (35°C, midsternum) with the experimental forearm above water level, and local skin sites were maintained at 34°C. Bath temperature was increased (∼40°C) to clamp core temperature at 38.5°C for 60 min. In protocol 1, there were significant treatment site by age interactions for the 39°C (P = 0.015) and 42°C (P = 0.004) plateaus; however no significant effects were observed after post hoc adjustment. In protocol 2, there was a significant treatment site by age interaction (P < 0.001), where %CVCmax in older adults was 11.0% [7.4, 14.6] higher for apocynin (P < 0.001), 8.9% [5.3, 12.5] higher for allopurinol (P < 0.001), and 4.8% [1.3, 8.4] higher for tempol (P = 0.016) sites relative to the control site. ROS derived from NADPH oxidase and xanthine oxidase attenuate cutaneous vasodilation in older adults during passive whole body heating, but not during local skin heating, with negligible effects on their young counterparts for either heating modality. NEW & NOTEWORTHY: We found that local infusion of apocynin or allopurinol improved cutaneous vasodilator responses to passive whole body heating (but not local skin heating) in healthy older adults. These findings indicate that impaired microvascular responses to whole body heating with primary aging are linked to augmented production of reactive oxygen species (ROS) from NADPH oxidase and xanthine oxidase. This study sheds new light on the specific ROS pathways that modulate age-related changes in cutaneous microvascular responses to heating. [ABSTRACT FROM AUTHOR]

Background/Objectives: Current urate-lowering therapies may cause serious side effects in patients. Thus, alternative treatments are needed to regulate uric acid (UA) levels in patients with hyperuricemia associated with kidney injury, and natural antioxidant sources have demonstrated utility in this field. For the first time, our study evaluated the effects of an extract of Dactylopius opuntiae insects on the levels of xanthine oxidase (XO) enzymes and synthetic free radicals in vitro and in vivo. Methods: Insects were bred and collected, and two different extracts (D1 and D2) were obtained. For both extracts, XO inhibition and radical scavenging assays were performed. Subsequently, serum purine levels and renal markers were quantified in male BALB/c mice who received a hyperuricemia induction using potassium oxonate, hypoxanthine, and gentamicin. Results: The D2 extract contained 18,037.7 µg/mL of carminic acid, inhibited 53.2% of XO activity at one concentration, and showed IC50 values of 18,207.8 and 5729.6 µg/mL against ABTS and DPPH radicals, respectively. D2 administration reduced serum UA and creatinine levels and prevented an increase in kidney weight and reduction in renal antioxidant capacity caused by hyperuricemia induction and allopurinol use in mice. Despite the satisfactory antioxidant results obtained in vitro, the D1 extract killed the animal models due to its citric acid content. Conclusions: The D2 insect extract can be used as an effective urate-lowering therapy when the increased level of serum uric acid is due to kidney damage. [ABSTRACT FROM AUTHOR]

The difference on inhibitory effects of bioflavonoids inhibiting XOD activity assayed by varying test methods cause of us to be further in consideration. The reported test method creating a micro‐environment surrounding XOD in the absence of ⋅O2−, which is seemly different from the assay in vivo. So, the vitro test method for assaying XOD activity is necessary to be improved for selection of potential inhibitors in the presence of ⋅O2−. The inhibitory results demonstrated that bioflavonoids of MY, DMY, QUE and LUT are capable to be on effective IC50 values, but others are not. As well, their resulting inhibitions determined by the improved test method are much less than that reported in the literature, indicating that their chemical affinities with XOD become weaker. Moreover, DMY assayed on the inhibitions of XOD in the improved test method performs to be a better inhibitor, as compared to the assay of the reported test methods. Abasing on the transformation of DMY into MY in the presence of ⋅O2−, the good inhibition of DMY on XOD activity can be explained by the synergistic effect of MY. [ABSTRACT FROM AUTHOR]