Higher Uric Acid Concentrations Research Articles

Recent Advances in Xanthine Oxidase Inhibitors.

Uric acid is a product of purine nucleotide metabolism, and high concentrations of uric acid can lead to hyperuricemia, gout and other related diseases. Xanthine oxidase, the only enzyme that catalyzes xanthine and hypoxanthine into uric acid, has become a target for drug development against hyperuricemia and gout. Inhibition of xanthine oxidase can reduce the production of uric acid, so xanthine oxidase inhibitors are used to treat hyperuricemia and related diseases, including gout. In recent years, researchers have obtained new xanthine oxidase inhibitors through drug design, synthesis, or separation of natural products. This paper summarizes the research on xanthine oxidase inhibitors since 2015, mainly including natural products, pyrimidine derivatives, triazole derivatives, isonicotinamide derivatives, chalcone derivatives, furan derivatives, coumarin derivatives, pyrazole derivatives, and imidazole derivatives, hoping to provide valuable information for the research and development of novel xanthine oxidase inhibitors.

ZnO Nanocages Decorated with Au@AgAu Yolk-Shell Nanomaterials for SERS-Based Detection of Hyperuricemia.

Surface-enhanced Raman scattering (SERS) is widely recognized as a highly sensitive technology for chemical detection and biological sensing. In SERS-based biomedical applications, developing highly efficient sensing platforms based on SERS plays a pivotal role in monitoring disease biomarker levels and facilitating the early detection of cancer biomarkers. Hyperuricemia, characterized by abnormally high concentrations of uric acid (UA) in the blood, was associated with a range of diseases, such as gouty arthritis, heart disease, and acute kidney injury. Recent reports have demonstrated the correlation between UA concentrations in blood and tears. In this work, we report the fabrication of SERS substrates utilizing ZnO nanocages and yolk-shell-structured plasmonic nanomaterials for the noninvasive detection of UA in tears. This innovative SERS substrate enables noninvasive and sensitive detection of UA to prevent hyperuricemia-related diseases.

An efficient sensor based on anodic activation of graphene oxide for sensitive and selective determination of dopamine in blood serum

A native graphene oxide (NGO) prepared by Hummers modified method was used as the template materials for the fabrication of electrochemically oxidative graphene oxide (OGO) onto a glassy carbon electrode (GCE). The fabrication of OGO-GCE persuaded via anodic reversible potentiodynamic of NGO base surface materials that increases the concentration of oxygen functionalities. The development of a new aldehyde/alcoholic functional group on OGO-GCE characterized by XPS analysis is a marked signal for oxygen richness surface which provoked on the cost of sp2 hybridized function. The EIS data underline that OGO-GCE promote the electron transfer kinetics much more than NGO-GCE by 9 times as estimated by the rate constant calculation. The XPS and EIS data highlight the influence of anodic treatment on increasing the interlayer spacing distance between the resultant OGO. Differential pulse voltammetry (DPV) results were evident for a promising efficiency of OGO-GCE on the simultaneous determination of dopamine (DA), ascorbic acid (AA) and uric acid (UA). In addition, the selectivity of the proposed sensor for DA quantification in the presence of high concentrations of AA and UA was achieved successfully with a detection limit (DL3s) approach to 12 nM. The analytical performance of OGO-GCE on serum blood revealed its potential application for trace DA quantification.

Sleep architecture and vitamin D in hypertensives with obstructive sleep apnea: A polysomnographic study.

Obstructive sleep apnea (OSA) and arterial hypertension (AH) are closely linked disorders with common pathophysiological features. The present study aimed to investigate the relationship between AH and OSA by examining sleep architecture, vitamin D concentration and electrolyte levels in patients with these coexisting conditions. A total of 133 patients suspected of having OSA were recruited for examination. The participants were divided into 2 groups: hypertensives (n = 52); and normotensives (n = 81). One full-night polysomnographic examinations were conducted, followed by the statistical analysis of the collected data. Hypertensive individuals displayed increased apnea-hypopnea index (AHI), oxygen desaturation index (ODI), respiratory arousal index (RAI), and periodic limb movement index (PLMI) as compared to non-hypertensive individuals. Moreover, sleep efficiency (SE), the bruxism arousal index (BAI) and oxygen saturation (SpO2)level were decreased in the hypertensive group. In terms of biochemical parameters, hypertensive individuals exhibited a lower magnesium (Mg) level, and higher levels of C-reactive protein (CRP), uric acid (UA) and glucose. Notably, there were no statistical differences in vitamin D concentration between hypertensive and normotensive individuals. The study explored the potential influence of calcium (Ca), Mg, vitamin D, and UA concentrations on the sleep architecture of patients with comorbid AH and OSA. The findings revealed several notable associations. Firstly, sleep fragmentation correlated with Ca level, suggesting a potential role for both Ca and vitamin D in sleep arousals. Secondly, a higher UA concentration was linked to a higher AHI and increased sleep fragmentation. Additionally, alterations in Mg concentration were observed among hypertensive individuals with OSA. However, further research is needed to fully comprehend the potential impact of these factors on the sleep architecture of hypertensive individuals with apnea.

Alterations in salivary biochemical composition and redox state disruption induced by the anticonvulsant valproic acid in male rat salivary glands

ObjectiveTo investigate the effects of the anticonvulsant valproic acid (VPA) on salivary glands in male rat using biochemical, functional, histomorphometric, and redox state parameters. Materials and methodsTwenty-four male Wistar rats were randomly distributed into three groups (n = 8 per group): Control (0.9% saline solution), VPA100 (100 mg/kg), and VPA400 (400 mg/kg). After 21 consecutive days of treatment with by intragastric gavage. Pilocarpine-induced saliva was collected to determine salivary flow rate, pH, buffering capacity, and biochemical composition. Analyses of histomorphometric parameters and redox balance markers were performed on the parotid and submandibular glands. ResultsSalivary flow rate, pH, buffering capacity, total protein, potassium, sodium, and chloride were similar between groups. However, phosphate and calcium were reduced in VPA400, while amylase was increased in both VPA100 and VPA400. We did not detect significant differences in the areas of acini, ducts, and connective tissue in the salivary glands between the groups. There were no significant changes in the redox status of the submandibular glands. In turn, in the parotid glands we detected reduced total oxidizing capacity and lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARs) and higher uric acid concentration in both the VPA100 and VPA400 groups, and increased superoxide dismutase (SOD) in the VPA400 group. ConclusionChronic treatment with VPA modified the salivary biochemical composition and caused disruption in the redox state of the parotid gland in rats.

Facile fabrication of Fe-Fe3C nanoparticles decorated with carbon nanotubes for sensitive dopamine detection

In this study, we present an electrochemical sensor with superior sensitivity and selectivity for dopamine (DA) detection. The sensor was created using a nanocomposite of iron-iron carbide nanoparticles decorated with carbon nanotubes (Fe-Fe3C@CNTs) to modify a glassy carbon electrode (GCE). The Fe-Fe3C@CNTs nanocomposite can be synthesized by a facile microwave-assisted synthesis method with just adopting ferrocene and carbon fiber as raw material and heat source, respectively. The electron microscopy (EM) results indicate that the Fe-Fe3C nanoparticles encapsulated with graphitic layer were decorated with CNTs. An investigation of the electrochemical responses of the Fe-Fe3C@CNTs/GCE sensor to DA was performed using both cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Notably, in ideal experimental settings, the sensor demonstrated a minimal limit of detection (LOD) of 0.01 μM within a range of linearity from 0.05 to 40 μM, even under a high concentration of uric acid (UA) interference. Moreover, the utility of the produced Fe-Fe3C@CNTs/GCE sensor was further validated through successful DA testing in urine samples of human.

Hyperuricemia promotes the progression of atherosclerosis by activating endothelial cell pyroptosis via the ROS/NLRP3 pathway.

Hyperuricemia closely correlates with the development of atherosclerosis, but little is known of the mechanism by which atherosclerosis progression occurs in hyperuricemia. Atherosclerosis appears to involve pyroptosis, an emerging mechanism of proinflammatory regulated cell death. This study tested the hypothesis that pyroptosis underlies the relationship between hyperuricemia and atherosclerosis, using ApoE-/- mice (a model of atherosclerosis), human umbilical vein endothelial cells (HUVECs), and human atherosclerotic arterial samples. We found that hyperuricemia can aggravate the aortic atherosclerotic plaque-load in ApoE-/- mice and promote endothelial cell pyroptosis. Additionally, hyperuricemia can increase the levels of serum inflammatory factors (including IL-1β and IL-18). Exposure to lipopolysaccharideplus a high concentration of soluble uric acid (≥12 mg/dL) induced cell pyroptosis in HUVECs, as evidenced by increased expression of pyroptosis-related proteins and elevated release of lactate dehydrogenase (a marker of tissue damage). Further, MCC950, a selective nucleotide-binding oligomerization domain (NOD)-like receptor 3(NLRP3) inflammasome inhibitor, and N-acetyl- l-cysteine, an antioxidant, attenuated HUVEC pyroptosis by inhibiting activation of the NLRP3 inflammasome and production of intracellular reactive oxygen species (ROS). Finally, we detected significantly higher expression of pyroptosis-associated proteins in carotid specimens from patients with hyperuricemia. Collectively, our findings suggest that hyperuricemia can aggravate endothelial cell pyroptosis in aortic atherosclerotic plaques, promoting the development of atherosclerosis. Additionally, a high concentration of soluble uric acid can trigger the activation stage of the NLRP3 inflammasome, mediating endothelial cell pyroptosis, and this process is regulated by the cellular ROS level.

Uric acid The Influence of Ethanol Extract of Sambiloto Leaves and Sambung Nyawa Leaves To Decrease Concentration of Uric Acid

Hyperuricemia is a condition of high concentration of uric acid in the blood that occurs because of a buildup of uric acid in the body. Uric acid is formed as a residue of the protein metabolism of foods containing purine. Some of the active compounds in the sambiloto leave (Andrographis Paniculata (Burm.F.) Nees) and sambung nyawa leave of allegedly being able to decrease the concentration of uric acid. The aims of this research is to know the influence of the difference between the ability of ethanol extract of sambiloto leaves and ethanol extract of sambung nyawa leaves (Gynura Procumbens (Lour.)Merr.) against the concentration of uric acid in vitro as well as know the effective concentration of ethanol extract of sambiloto leaves and extract ethanol of sambung nyawa leaves against a decrease in the concentration of uric acid in vitro. The extraction method used in this research is the method of extraction re-maceration by solvent ethanol 70% in 5 days, the sampling technique used was purposive sampling. The determination of concentration of uric acid is determined out by the Spectrophotometry method ABX Pentra. Series of concentrations used was 250, 500, 750, 1000, 1250, 1500, and 1750 ppm. The results of the research, the ability is effective in decreaced the concentration of uric acid in vitro on the extract of sambiloto leaves and extract of sambung nyawa leaves is 250 ppm. Statistical results showed that there is an influence of the ethanol extracts of sambiloto leaves and ethanol extracts of sambung nyawa leaves against decreasing the concentration of uric acid in vitro. And there is no difference between ethanol extracts of sambiloto leaves with ethanol extracts of sambung nyawa leaves against a decreased in the concentration of uric acid in vitro.

Efficacy of Theobromine and Its Metabolites in Reducing the Risk of Uric Acid Lithiasis

Uric acid lithiasis accounts for about 10% of all types of renal lithiasis. The most common causes of uric acid lithiasis are low urinary pH, followed by high concentration of urinary uric acid, and low diuresis. Treatment of patients consists of alkalinization of urine, reducing the consumption of purine-rich foods, and administration of xanthine oxidase inhibitors, because there are no established therapeutic inhibitors of uric acid crystallization. We recently found that theobromine inhibited uric acid crystallization in vitro, and that the increased urinary level of theobromine following its oral consumption was associated with the prevention of uric acid crystallization. In this study, we evaluated the inhibitory effects of theobromine metabolites and other methylxanthine-related compounds on uric acid crystallization. We also measured the urinary concentrations of theobromine and its metabolites in samples from healthy individuals and patients with uric acid stones and compared the extent of uric acid supersaturation and uric acid crystal formation in these different samples. Theobromine and other methylxanthines that lacked a substituent at position 1 inhibited uric acid crystallization, but other methylxanthines did not have this effect. Individuals with clinical parameters that favored uric acid crystallization did not develop uric acid crystals when theobromine and its metabolites were in the urine at high levels. Thus, theobromine and its metabolites reduced the risk of uric acid lithiasis.

#5619 THE ASSOCIATION BETWEEN THE LEVELS OF URIC ACID AND RENAL OUTCOMES IN EARLY CKD PATIENTS: A MULTI-CENTER REAL-WORLD DATA ANALYSIS

Abstract Background and Aims It is well known that serum uric acid (SUA) plays an important role both in patients with and without chronic kidney disease (CKD). However, the effect of SUA on renal outcomes of CKD patients, especially with asymptomatic hyperuricemia, remains controversial. Therefore, our study explores the relationship between SUA and adverse events in early CKD (stage 1-3) patients in a real-world setting. Method This multi-center real-world study analyzed the data from Chinese Renal Data System (CRDS). Eligible CKD patients (eGFR) (estimated glomerular filtration rate≥30 mL/min/1.73 m2) were enrolled. The primary endpoint is the decline of renal function defined as at least 40% decrease in eGFR. The secondary endpoints include onset of composite cardiovascular events and all-cause mortality. A multivariable cox regression model were used and the associations between levels of mean SUA and all endpoints were evaluated on a continuous scale with restricted cubic spline (RCS) curves based on Cox proportional hazards models. Kaplan-Meier survival curves were used to illustrate the ability of SUA to predict the end points. Results 25,202 adults (mean [SD] age, 52.59 [17.90] years, 8,212 male [46.1%], 9,604 female [53.9%]) were included in this study. During a median follow-up period of 2.61 years, 3,451 (15.9%) at least 40% decreased in eGFR. After adjustment for confounders, higher uric acid concentrations were independently associated with the higher risk for the decline of renal function [Per SD increment adjusted hazard ratio [aHR]: 1.41, 95%CI 1.36-1.47]; composite cardiovascular events [Per SD increment [aHR]: 1.04, 95%CI 1.01-1.07], all-cause mortality [Per SD increment [aHR]:1.32, 95%CI 1.14-1.54]. RCS curves showed that HRs for renal function progression, all-cause mortality and composite cardiovascular events increased significantly with the increase of SUA concentration in CKD patients. Results were consistent in stratified analyses. The KM curves suggested that patients with asymptomatic hyperuricemia had a substantially worse survival rate for renal function. Conclusion SUA is an independent risk factor for the decline of renal function, cardiovascular events and all-cause mortality in early CKD patients (stage 1-3). Treatment of asymptomatic hyperuricemia may be a potential avenue to improve outcomes in CKD patients.

Association between serum uric acid concentration and radiographic axial spondylarthritis: a cross-sectional study of 202 patients.

Association between serum uric acid concentration and radiographic axial spondylarthritis: a cross-sectional study of 202 patients.

Computational Characterization of the Inhibition Mechanism of Xanthine Oxidoreductase by Topiroxostat.

Xanthine oxidase (XO) is a member of the molybdopterin-containing enzyme family. It interconverts xanthine to uric acid as the last step of purine catabolism in the human body. The high uric acid concentration in the blood directly leads to human diseases like gout and hyperuricemia. Therefore, drugs that inhibit the biosynthesis of uric acid by human XO have been clinically used for many years to decrease the concentration of uric acid in the blood. In this study, the inhibition mechanism of XO and a new promising drug, topiroxostat (code: FYX-051), is investigated by employing molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) calculations. This drug has been reported to act as both a noncovalent and covalent inhibitor and undergoes a stepwise inhibition by all its hydroxylated metabolites, which include 2-hydroxy-FYX-051, dihydroxy-FYX-051, and trihydroxy-FYX-051. However, the detailed mechanism of inhibition of each metabolite remains elusive and can be useful for designing more effective drugs with similar inhibition functions. Hence, herein we present the computational investigation of the structural and dynamical effects of FYX-051 and the calculated reaction mechanism for all of the oxidation steps catalyzed by the molybdopterin center in the active site. Calculated results for the proposed reaction mechanisms for each metabolite's inhibition reaction in the enzyme's active site, binding affinities, and the noncovalent interactions with the surrounding amino acid residues are consistent with previously reported experimental findings. Analysis of the noncovalent interactions via energy decomposition analysis (EDA) and noncovalent interaction (NCI) techniques suggests that residues L648, K771, E802, R839, L873, R880, R912, F914, F1009, L1014, and A1079 can be used as key interacting residues for further hybrid-type inhibitor development.

Prognostic Value of Right Ventricular Dysfunction in Patients With Decompensated Chronic Heart Failure

Aim To determine the incidence rate and the practical significance of right ventricular dysfunction (RVD) in the development of cardiovascular complications in patients with decompensated chronic heart failure (DCHF).Material and methods This prospective, single-site observational study included 171 patients older than 18 years with NYHA functional class (FC) II-IV chronic heart failure (CHF) who were hospitalized for DCHF. Standard and extended 2D and 3D echocardiography (EchoCG) was performed for all patients on admission. Additionally, functional characteristics of the right ventricle (RV) were evaluated in the 3D mode followed by autonomic 3D processing with a EchoPac station (USA). RVD was taken as a disorder of two or more RV functional parameters according to results of 2D EchoCG, or a reduced RV free wall strain according to results of 2D speckle-tracking EchoCG, or a reduced RV ejection fraction (EF) according to results of 3D EchoCG. Statistical analysis was performed with a SPSS Statistics v. 26.0 software.Results The incidence rate of RVD in general population of patients with DCHF was 75.4 % (n=129). A higher prevalence of RVD was observed in patients with CHF with a low left ventricular (LV) EF (90.1 %). Patients with RVD had a more severe clinical status (significantly higher FC and higher Clinical Condition Scale (CCS) scores), more frequent atrial fibrillation (AF), and higher concentrations of uric acid and total bilirubin. RVD significantly correlated with male sex (odds ratio (OR), 2.05; 95 % confidence interval (CI), 1.01–4.19; р=0.046) and AF (OR, 3.52; 95 % CI, 1.71–7.26; р<0.001). Patients with RVD had lower values of both LV and RV function. Lower LV EF and AF increased the probability of RVD by 1.06 times (95 % CI, 0.90–0.98; р=0.001) and by 2.63 times (95 % CI, 1.08–6.40; р=0.001), respectively. Evaluation of the predictive significance of RV parameters measured by 2D and 3D EchoCG showed only effects of RV EF (2D) and RV global longitudinal strain (GLS) (3D) on all-cause hospitalization. RVD as evaluated by accepted criteria did not influence adverse outcomes.Conclusion The determined incidence, correlations, and the predictive value of RVD in patients with DCHF indicated the appropriateness of assessing the RV function to optimize the management of patients regardless of the CHF phenotype.

The Inter-Trimester Variation and Prognostic Value of Creatinine, Cystatin C and Uric Acid in Preeclamptic Patients: A Retrospective Study

Background: This study aimed to evaluate the clinical significance of maternal serum creatinine, cystatin C, and uric acid levels in relation to fetal death in pregnant women with preeclampsia. Methods: This retrospective study evaluated 708 women with preeclampsia, and 738 healthy pregnant women were selected as control. Medical records were reviewed to collect obstetric, neonatal, and biochemical data, including creatinine, cystatin C, and uric acid concentrations. Results: Maternal serum creatinine, cystatin C, and uric acid concentrations were significantly higher in the preeclamptic group than in the control (p < 0.05). Preeclamptic women in the fetal death group had significantly higher creatinine levels during their second and third trimesters, and higher uric acid concentrations throughout the pregnancy compared to the fetal survival group. Preeclamptic patients were divided into four groups based on quartiles of uric acid levels. The overall fetal survival rate in patients with upper-quartile uric acid concentrations was significantly lower than those with low uric acid levels during pregnancy. Multivariate logistic regression analysis revealed that uric acid concentration was a significant risk factor for fetal death in the first and second trimesters in the preeclamptic group (p < 0.05). Conclusions: In pregnant women with preeclampsia, fetal death was associated with upper-quartile uric acid concentrations in the first and second trimesters. Uric acid levels can be an indicator of fetal death in the early and middle stage of pregnancy.

A Limited Effect of Chronic Renal Insufficiency on the Colon Microbiome.

A Limited Effect of Chronic Renal Insufficiency on the Colon Microbiome.

Enzyme-free and wide-range portable colorimetric sensing system for uric acid and hydrogen peroxide based on copper nanoparticles

Uric acid (UA) is the final product of purine metabolism. A high concentration of UA in body fluid may lead to kidney stones, gout, and some cardiovascular diseases. Therefore, the non-invasive daily monitoring of UA is of great significance for both hyperuricemia patients and fit people. However, most of the current detection methods for UA are enzyme-dependent which limits the application scenarios and lacks portable instruments for on-site detection, including optics and electrochemistry. In this work, an enzyme-free and wide-range colorimetric sensor for UA and H2O2 detection was developed based on a mercaptosuccinic acid (MSA)-modified Cu nanoparticles (CuNPs). Under the action of UA or H2O2, with the cleavage of MSAs on the CuNPs surface, small Cu particles are further aggregated into larger particles with a lightning violet color. With the employment of the multi-channel handheld automatic photometer (MHAP), the concentration of UA and H2O2 can be determined on-site according to the absorbance measurement by the photodiodes. The linear range of UA was 5 μM-4.5 mM with the limit of detection (LOD) of 3.7 μM, while the linear range of H2O2 was 5 mM–500 mM and 5 μM-5 mM with the LOD of 4.3 μM. This approach has been applied to the detection of UA in human urine, providing more possibilities for non-invasive home health monitoring, community medical diagnosis, and broader prospects of on-site disease detection.

Critical Hypermagnesemia in Preeclamptic Women Undera MagnesiumSulfate Regimen: Incidence and Associated Risk Factors.

Magnesium sulfate is used as prophylaxis and treatment of severe preeclampsia/eclampsia, albeit its safety and toxicity are a concern. We designed this study to estimate the incidence of critical hypermagnesemia in severely preeclamptic women undera magnesiumsulfate regimen at 8h following its administration and to identify the associated risk factors as the primary outcomes. Also, secondary outcomes were to compare baseline characteristics, laboratory findings, and maternal-neonatal complications stratified by the baseline serum magnesium (Mg2+) in those women, and to assess the degree of agreement between patellar reflex and serum Mg2+ concentration 8h following magnesiumsulfate administration. We conducted a retrospective study including severely preeclamptic women receiving magnesium sulfate from June 2016 to May 2021. We enrolled 429 women in the study. Two-hundred sixty-one (60.8%) of the included women developed critical hypermagnesemia. Preeclamptic women with high baseline serum Mg2+ concentration demonstrated significantly affected renal functions, hepatic transaminase activities, and low platelet count as well as more reported maternal complications compared to those with low baseline serum Mg2. Multivariable logistic regression revealed that a lower gestational age, a higher uric acid concentration, and a higher baseline serum Mg2+ concentration were independently associated with an increased risk of critical hypermagnesemia. The agreement between deep tendon reflex assessment and serum Mg2+ concentration was slight although not significant. The maternal-neonatal outcomes were non-significant in women with critical hypermagnesemia. More vigilant monitoring through assessment of both serum Mg2+ concentration and deep tendon reflex should be considered especially in high-risk women.

Association between metabolic syndrome and uric acid: a systematic review and meta-analysis

This systematic review and meta-analysis aim to provide the best evidence on the association between metabolic syndrome (MetS) and uric acid (UA) by determining the size of the effect of this biomarker on MetS. The review protocol is registered with PROSPERO (CRD42021231124). The search covered the PubMed and Scopus databases. Methodological quality was assessed with the STROBE tool, overall risk of bias with RevMan (Cochrane Collaboration) and quality of evidence with Grade Pro. Initially, 1582 articles were identified. Then, after excluding duplicates and reviewing titles and abstracts, 1529 articles were excluded from applying the eligibility criteria. We included 43 papers (56 groups) comparing UA concentrations between subjects 91,845 with MetS and 259,931 controls. Subjects with MetS had a higher mean UA of 0.57 mg/dl (95% CI 0.54–0.61) (p < 0.00001). Given the heterogeneity of the included studies, the researchers decided to perform subgroups analysis. Men with MetS have a higher UA concentration mg/dl 0.53 (95% CI 0.45–0.62, p < 0.00001) and women with MetS 0.57 (95% CI 0.48–0.66, p < 0.00001) compared to subjects without MetS. Assessment of UA concentration could provide a new avenue for early diagnosis of MetS, as a new biomarker and the possibility of new therapeutic targets.

A geniposide-phospholipid complex ameliorates posthyperuricemia chronic kidney disease induced by inflammatory reactions and oxidative stress

Hyperuricemia is a common metabolic disease and is one of the factors that could induce chronic kidney disease (CKD). Geniposide (GEN) is a typical natural iridoid glucoside compound with a series of biological activities, but the poor bioavailability of GEN limits its clinical application. In this context, the pharmacological activity of the geniposide-phospholipid complex (GEN-PLC) in ameliorating posthyperuricemia CKD was evaluated by in vitro and in vivo experiments in this study. In vitro cell experiments showed that GEN-PLC treatment markedly decreased inflammatory cytokine levels and reactive oxygen species levels compared with those of GEN in uric acid-treated HKC cells. In vivo research results confirmed that a high concentration of uric acid could cause CKD by increasing inflammatory cytokines and reactive oxygen species in hyperuricemic mice. At the same time, GEN-PLC could regulate the PI3K/AKT/NF-κB and Keap1/Nrf2/HO-1 signaling pathways to effectively inhibit the inflammatory response and oxidative stress, thereby ameliorating posthyperuricemia CKD, and the therapeutic effect was better than that of GEN. In addition, the preparation technology of GEN-PLC was optimized, and the physiochemical analysis explained the intermolecular interactions of the two components. Based on the research results, GEN-PLC could enhance the bioavailability of GEN and become a promising candidate for clinical drug development.

PB2053: PRIMARY ARTERIAL HYPERTENSION IN MYELOPROLIFERATIVE NEOPLASMS: A SYSTEMATIC REVIEW

Background: Patients diagnosed with myeloproliferative neoplasms (MPNs) are prone to experience thrombotic events and often experience a high burden of cardiovascular comorbidities. Primary arterial hypertension (HTN) remains one of the most common comorbidities in the elderly. However, the impact of HTN on MPNs is unclear. Aims: Report on the occurrence of HTN in MPNs. Describe its epidemiology, influence on development of thrombosis, HTN treatment strategies. Methods: Systematic search in PubMed/Medline, Web of Science and SCOPUS, from the inception of these databases to retrieve relevant English-written articles. Eligibility criteria: 1. Confirmed MPNs diagnosis, 2. Confirmed HTN diagnosis, 3. Studies reported on the epidemiology of HTN in MPNs, impact of HTN on the development of thrombosis or on the therapeutic options used to treat HTN in MPNs. We excluded studies investigating secondary HTN, e.g., drug-induced HTN. Results: The systematic search resulted in 590 potentially relevant manuscripts. After removal of duplicates and screening of abstracts/titles (n=503), 87 manuscripts were selected for full-text review. After applying the eligibility criteria and full-text evaluation, 25 articles were excluded and the remaining 62 were entered into the qualitative/quantitative analysis. HTN emerged as the most common comorbidity in MPNs, affecting 41-63% of primary myelofibrosis (PMF), 40-64% of essential thrombocythemia (ET), 46-90% of polycythemia vera (PV) cases. In PV, the presence of HTN was associated with decreased serum free epinephrine and aldosterone levels, reduced retinal microperfusion, elevated kidney arteries resistance, JAK2-V617F mutation and high-risk PV. In PMF, it was linked with high uric acid concentrations and elevated risk of thrombosis (OR=1.96). PV subjects with HTN were non-dippers, suffered from systolic/diastolic dysfunction as assessed by cardiac ultrasound, displayed elevated cell-free hemoglobin and nitrite/nitrate ratio, and an increased risk of thrombosis (HR=1.77). HTN in ET was associated with overall thrombosis, especially arterial thrombosis (HR=1.91-3.8). The cardio-IPSET score was superior in predicting thrombosis in ET patients with HTN. Individuals with MPNs and HTN exhibited signs of carotid artery injury, end-organ damage, increased albumin-to-creatinine ratio, P-selectin concentrations and were prone to develop kidney dysfunction. Moreover, stroke was more common in MPNs with concomitant HTN (HR=4.24) and HTN was a predictor of ischemic stroke recurrence in MPNs. The risk of thrombosis in MPNs was higher if HTN was also associated with other cardiovascular risk factors, i.e., dyslipidemia, diabetes or smoking. The risk of cerebral venous sinus thrombosis was lower in MPNs with co-occurring HTN. In terms of treatment options for patients with HTN and MPNs, angiotensin-converting enzyme inhibitors (ACEI), e.g., lisinopril, and calcium-channel blockers (CCB - nifedipine for hypertensive emergencies) have been successfully used. The recommendation to avoid the use of diuretics in patients with elevated blood viscosity, e.g., PV, remains unaltered. Summary/Conclusion: Our findings suggest that HTN is the most common comorbidity in MPNs and is associated with development of thrombosis, end-organ damage, i.e., retinal and kidney dysfunction. Integration of HTN in the current scores employed to predict the development of thrombosis and stratify MPNs subjects in warranted. Screening for HTN in MPNs is urgently needed. Accurate management strategies based on the use ACEI and CCB need further exploration in MPNs with associated HTN.