UA Levels Research Articles

Recent Progress and Future Perspectives on Anti-Hyperuricemic Agents.

Increased biosynthesis or underexcretion of uric acid (UA or urate) in the body ultimately leads to the development of hyperuricemia. Epidemiological studies indicate that hyperuricemia is closely associated with the occurrence of various diseases such as gout and cardiovascular diseases. Currently, the first-line therapeutic medications used to reduce UA levels primarily include xanthine oxidase (XO) inhibitors, which limit UA production, and urate transporter 1 (URAT1) inhibitors, which decrease urate reabsorption and enhance urate excretion. Despite significant progress in urate-lowering therapies, long-term use of these drugs can cause hepatorenal toxicity as well as cardiovascular complications. Therefore, there is an urgent need for novel anti-hyperuricemic agents with better efficacy and lower toxicity. This perspective mainly focuses on the current research progress and design strategy of anti-hyperuricemic agents, particularly those targeting XO and URAT1. It is our hope that this perspective will provide insights into the challenges and opportunities for anti-hyperuricemic drug discovery.

Protective effect of Huashi Baidu formula against AKI and active ingredients that target SphK1 and PAI-1

BackgroundHuashi Baidu Formula (HBF) is a clinical formula known for its efficacy against coronavirus disease 2019 (COVID-19). HBF may reduce the number of patients with abnormal serum creatinine while improving respiratory symptoms, suggesting that this formula may have potential for treating acute kidney injury (AKI). However, the protective effect of HBF on AKI has not been definitively confirmed, and the mechanism remains unclear. Therefore, the present study explored the renoprotective effects and molecular mechanisms of HBF and screened for its active ingredients to identify new potential applications of renoprotection by HBF.MethodsThe present study first assessed the protective effects of HBF on AKI in a DOX-induced mouse model. Then, RNA-seq and bioinformatics analyses were used to explore the related pathological processes and potential molecular mechanisms, which were subsequently validated using qRT-PCR and Western blotting. Furthermore, candidate compounds with potential binding affinity to two pivotal targets, sphingosine kinase 1 (SphK1) and plasminogen activator inhibitor-1 (PAI-1), were screened from the 29 constituents present in the blood using Microscale Thermophoresis (MST). Finally, to identify the active ingredients, the candidate components were re-screened using the SphK1 kinase activity detection system or the uPA/PAI-1 substrate colorimetric assay system.ResultsIn the DOX-induced AKI mouse model, therapeutic administration of HBF significantly reduced the levels of CRE, BUN, TNF-α, IL-1β, IL-6, and UA in plasma and the levels of MDA, T-CHO, and TG in kidney tissue. Additionally, the levels of TP and Alb in plasma and SOD and CAT in the kidney tissue were significantly increased. Histopathological assessment revealed that HBF reduced tubular vacuolation, renal interstitial inflammatory cell infiltration, tubular atrophy, and positive staining of renal interstitial collagen. RNA-seq and bioinformatics analyses showed that oxidative stress, the immune-inflammatory response, and extracellular matrix (ECM) formation could be the pathological processes that HBF targets to exerts its renoprotective effects. Furthermore, HBF regulated the APJ/SPHK1/NF-κB and APJ/PAI-1/TGFβ signaling axes and reduced the phosphorylation levels of NF-κB p65 and SMAD2 and the expression of cytokines and the ECM downstream of the axis. Finally, six SphK1 inhibitors (paeoniflorin, astragalin, emodin, glycyrrhisoflavone, quercetin, and liquiritigenin) and three PAI-1 inhibitors (glycyrrhisoflavone, licochalcone B, and isoliquiritigenin) were identified as potentially active ingredients in HBF.ConclusionIn brief, our investigation underscores the renoprotective effect of HBF in a DOX-induced AKI model mice, elucidating its mechanisms through distinct pathological processes and identifying key bioactive compounds. These findings offer new insights for broadening the clinical applications of HBF and unravelling its molecular mode of action.

High Levels of Uric Acid Upregulate Endothelin Receptors: The Role of MAPK Pathways in an in vitro Study

IntroductionUric acid (UA) is the end product of purine compounds' metabolism. There is overwhelming evidence linking hyperuricemia (high levels of UA) and cerebrovascular diseases, but the effect of high levels of UA on cerebral vessels is not fully understood. The aim of this research is to clarify how UA affect the endothelin (ET) receptor in rat cerebral arteries and the related mechanism.Material and methodsIn an in vitro setting, segments of rat cerebral arteries (n=12) were exposed to high levels of UA, either alone or in conjunction with MAPK pathway inhibitors. ET agonists were used to induce contractions that were then measured with a myograph. ET receptor expression was measured using RT-PCR (n=6), Western Blot (n=3), or immunohistochemistry (n=3) to quantify mRNA and protein levels.ResultsThe study revealed that high levels of UA notably increase ETA and ETB receptor-induced contractions and boost the expression of ET receptors in cerebral arteries when compared to that are fresh or cultured alone, suggesting that UA enhances ETA and ETB receptors. Additionally, the up-regulation of ETB receptors induced by UA was inhibited by the p38 inhibitor SB203580, the JNK inhibitor SP600125, and the ERK1/2 inhibitor U0126. SB203580 significantly blocked the increase in ETA receptor-mediated contractions induced by UA and the upregulation of ETA receptor. Neither SP600125 nor U0126 had such effect.ConclusionsHigh levels of UA stimulate the up-regulation of ET receptors in rat cerebral arteries in vitro through MAPK pathways. This study may offer novel perspectives on hyperuricemia-associated cerebrovascular diseases.

The relationship between the Barthel Index and stroke-associated pneumonia in elderly patients and factors of SAP

BackgroundStroke-associated pneumonia (SAP) is a common complication in stroke patients, and the Barthel Index (BI) is a well-established metric for assessing activities of daily living (ADL). However, the association between BI and SAP in acute ischemic stroke (AIS) patients remains unclear. This study aims to investigate the relationship between BI at admission and SAP, and explore the factors in AIS elderly patients.MethodRetrospective data were collected from ischemic stroke patients hospitalized at the Second Affiliated Hospital of Nanchang University between January 2018 and July 2021, including their basic demographic and laboratory test results. Restricted cubic spline regression, multivariate logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were employed to investigate the relationship between BI and SAP. Additionally, the Shapley Additive exPlanations (SHAP) method was used to identify the factors influencing SAP.ResultsThe study included 7,548 eligible stroke patients with a mean age of 75.1 ± 7.6 years, among which 41.14% were female. The SAP group demonstrated significantly lower BI compared to the non-SAP group (50.86 ± 35.60 vs. 75.27 ± 26.33, P < 0.001). Additionally, a conspicuous trend of decreasing SAP risk across the Q1-4 groups was observed (P < 0.001). The RCS analysis further confirmed a gradual reduction in SAP risk with increasing BI. Based on the clinical model, both the BI (NRI = 0.014, P = 0.005; IDI = 0.04, P < 0.001) and the NIHSS score (NRI = 0.09, P = 0.03; IDI = 0.025, P < 0.001) demonstrated additional predictive value for SAP. Multivariate logistic regression and SHAP analysis identified WBC, CONUT, TG, UA, and RBC levels, as well as the type of health insurance (urban employee basic medical insurance), as important independent predictors of SAP.ConclusionBI at admission constitutes a risk factor for the onset of SAP in elderly patients with AIS, Compared to the NIHSS and mRS score, BI may be a more reliable and practical predictor of SAP.

Evaluation of Hormonal and Biochemical Profile of Ladakhi Cow during Estrous Cycle: The Future Perspective of Reproductive Management of Ladakhi Cow

The Ladakhi cow is an indigenous breed from Ladakh, India, and has a unique genetic makeup to adapt to high-altitude hypobaric stress. Furthermore, little study is available on examining the Ladakhi cow’s blood biochemicals and reproductive hormonal status during various stages of the estrus cycle. Hence, the current study was conducted on eight reproductively mature Ladakhi cows at the experimental dairy cattle unit in Leh-Ladakh, India, to determine the changes in serum biochemical and hormonal levels during the estrus cycle. The estrus behaviour was initially observed before the blood sampling on days 0 (the day the cow exhibited heat symptoms), 2nd, 8th, 17th, and 21st days. The serum was isolated for biochemical and hormonal profiling as per standard procedures using commercially available kits. The results revealed that serum biochemicals, viz. Ca, Fe, ALT, AST, ALP, TG, TP, Albumin, Glucose, UA, Creatinine, and Urea levels were within the normal range of cows at high altitudes. However, reproductive hormones, e.g. GnRH, FSH, LH, progesterone, estrogen, PGF2α, IGF-1, and Insulin varied from the reference level at different stages of the estrus cycle. This study’s findings have provided new insights into the serum biochemical and hormonal profiling of Ladakhi cows during the estrus cycle and this information may help to develop a reference range and baseline value for the serum biochemicals and hormonal levels of Ladakhi cows for other breeding programs and health monitoring.

Association of serum uric acid levels with risk of epilepsy: A national population-based study

BackgroundUric acid (UA) serves as a crucial endogenous antioxidant in the body, offering protection against oxidative stress, whichmaycontributetoepilepsypathogenesis. The association between serum UA levels and epilepsy remains uncertain. This study aimed to examine the potential connections between serum UA levels and epilepsy in US adults. MethodsUtilizing data from the National Health and Nutrition Examination Survey (NHANES) 2013–2018, a cross-sectional analysis was conducted. Weighted logistic regression analyses were employed to assess the potential link between serum UA levels and the risk of epilepsy. Additionally, sensitivity analyses were conducted to evaluate the reliability of the results. ResultsWe included 15,373 participants, of whom 136 (0.79 %) had epilepsy. Following adjustment for multiple variables, participants with serum UA levels <4.1 mg/dl had an odds ratio of 2.24 (95 % CI: 1.12–4.47, P = 0.023) for epilepsy compared to those with serum UA levels of 5.8–6.5 mg/dl. The results of the sensitivity analyses corroborated the initial findings. ConclusionsOur study revealed a significant association between lower serum UA levels and heightened risks of epilepsy, suggesting that low UA levels may serve as an independent risk factor for epilepsy. A marginal increase in UA levels within the normal range may act as a protective factor against epilepsy.

Efficacy and safety of the urate-lowering agent febuxostat in chronic heart failure patients with hyperuricemia: results from the LEAF-CHF study.

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 24weeks. 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 > 7.0mg/dl and < 10.0mg/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 70years; 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.

The impact of pre-operative uric acid levels on post-operative renal outcomes in off-pump coronary artery bypass grafting patients

Background: Elevated pre-operative uric acid levels significantly impact post-operative renal outcomes in off-pump CABG patients, increasing the risk of acute kidney injury, as evidenced by higher serum creatinine and reduced urine output. Methods: This cross-sectional study was conducted in Department of Cardiac Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka, Bangladesh from January 2021 to December 2022. Total 160 patients undergoing off pump CABG were divided into two groups, group A and group B, each containing 80 patients. In group A, uric acid level was &lt;7 mg/dl for male and &lt;6 mg/dl for female and in group B, it was &gt;7 mg/dl and &gt;6 mg/dL for female. Results: The demographic characteristics, pre-operative serum UA levels and serum creatinine levels between the two groups was not statistically significant. Group A had shorter operative times (mean 265.21±53.33 minutes) compared to Group B (mean 327.04±44.32 minutes), with more patients in Group-B undergoing longer surgeries (&gt;360 minutes). Group-B also had more grafts (mean 4.4 vs 3.6), higher serum creatinine (1.91 vs 1.17 mg/dl), bilirubin (0.8 vs 0.7 mg/dl), and lower urine output (mean 47.52 vs 95.37 ml/hour), all statistically significant (p&lt;0.001). Conclusions: This study concludes that there is significant impact of pre-operative uric acid levels on post-operative renal outcomes in off-pump CABG patients.

Risk factors of disease activity and renal damage in patients with systemic lupus erythematosus.

To evaluate the clinical features of patients with Systemic Lupus Erythematosus (SLE) and explore the risk factors of disease activity and renal damage. A retrospective study involving 194 patients were performed. Patients were divided into lupus nephritis (LN) group (63.40%) and non-LN group (36.60%), different disease activity group, and different renal function group according to the clinical data. Multivariate logistic regression analysis showed that albumin (ALB), uric acid (UC), total cholesterol (TC), and anti-dsDNA antibodies were the influencing factors of LN in patients with SLE (P < 0.05); ALB, UC, and complement 3(C3) were the influencing factors of lupus disease activity (P < 0.05); UC, C3, and hemoglobin (HB) were the influencing factors of abnormal renal function in SLE patients. The results of the ROC curve showed that ALB, UA, and TC had certain predictive value for combined LN in patients with SLE, and the predictive value of ALB was greater than that of TC (P < 0.05); ALB, UA, and C3 being predictors of the activity of patients with SLE; BUN, UA, and HB all had certain predictive value for the abnormal renal function in patients with LN. SLE patients have the high incidence of renal impairment. The results of this study suggest that patients with SLE should regularly monitor the levels of ALB, UA, TC, C3, and HB, as well as pay attention to the intervention of hyperlipidemia and hyperuricemia in patients with SLE to better control disease progression.

Integrating network pharmacology and experimental models to investigate the mechanisms of XCHD and YCSLS in preventing HUA progression via TLR4/MYD88/NF-κB signaling

With the alterations in dietary structure and the augmentation of the human living standard, hyperuricemia (HUA) has emerged as a significant factor impacting contemporary human health. It has also been scientifically validated as an independent risk determinant for the progression of renal disease. Existing literature indicates that XCHD (Xiao Chai Hu Decoction) and YCSLS (Yinchen Siling San) possess a capability to ameliorate UA levels and fortify renal function, yet a comprehensive understanding of their mechanisms of action remains elusive. This investigation is designed to elucidate the therapeutic efficacy and mechanistic underpinnings of XCHD/YCSLS on the renal tissues of HUA-afflicted rats, with the objective of fortifying the evidence base to advocate its clinical application. Our preliminary findings substantiated that XCHD and YCSLS impede HUA progression through the inhibition of inflammatory and oxidative stress pathways. Further, we synthesized data from publicly accessible repositories to forecast interactions between XCHD, YCSLS, and their prospective targets in HUA, including the associated signaling pathways. This approach facilitated the identification of shared targets of XCHD/YCSLS, and HUA, and the subsequent correlation analysis of these targets employing KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) methodologies. The findings indicate that the TLR4/MYD88/NF-κB signaling constitutes one of the potential crucial conduits engaged in XCHD and YCSLS-induced HUA mitigation. In conclusion, the analysis of WB and IHC from HUA rat models corroborated that XCHD and YCSLS do indeed attenuate the expression of TLR4/MYD88/NF-κB, reinforcing the hypothesized pivotal role of the its signaling cascade in HUA. This warrants subsequent scholarly exploration.

Effect of hyperuricemia on paroxysmal atrial fibrillation after catheter ablation and influence of alcohol consumption.

Evidence regarding the association between hyperuricemia and arrhythmia recurrence after catheter ablation for paroxysmal atrial fibrillation (AF) is scarce. We investigated whether hyperuricemia predicts arrhythmia recurrence after catheter ablation for paroxysmal AF and the relationship between hyperuricemia and alcohol consumption in AF recurrence. Patients who underwent catheter ablation for paroxysmal AF were divided into the hyperuricemia (index serum uric acid [UA] >7.0 mg/dL; n = 114) and control (UA ≤7.0 mg/dL; n = 609) groups and were followed for a median of 24 (12-48) months after ablation. The hyperuricemia group had more patients with an alcohol intake of ≥20 g/day (33.3% vs. 22.7%, p = .017) and a lower incidence of AF-free survival (p = .019). Similarly, those with an alcohol intake of ≥20 g/day had a lower incidence of AF-free survival than other patients. Multivariate Cox regression analysis revealed the following independent predictors of AF recurrence (adjusted hazard ratio, 95% confidence interval): hyperuricemia (1.64, 1.12-2.40), female gender (1.91, 1.36-2.67), brain natriuretic peptide level >100 pg/mL (1.59, 1.14-2.22), and alcohol consumption ≥20 g/day (1.49, 1.03-2.15) (all p < .05). In addition, causal mediation analysis revealed that alcohol consumption of ≥20 g/day directly affected AF recurrence, independent of hyperuricemia. Patients with hyperuricemia may be at a high risk of arrhythmia recurrence after catheter ablation for paroxysmal AF. Although high alcohol consumption may contribute to increased UA levels, the presence of hyperuricemia may independently predict AF recurrence.

Exploring therapeutic mechanisms of Chuan Huang Fang-II in the treatment of acute kidney injury on chronic kidney disease patients from the perspective of lipidomics

Objective This study aims to assess the clinical efficacy and safety of CHF-II in combination with RG for treating AKI on CKD (A on C), and to explore potential therapeutic mechanisms through lipidomics analysis. Methods 98 patients were enrolled and randomly assigned to the RG or RG + CHF groups. Both groups received RG therapy, with RG + CHF group additionally receiving CHF-II treatment over a duration of two weeks. Evaluation endpoints included changes in renal function, blood lipid profiles, urinary AKI biomarkers, and TCM symptoms before and after treatment. Serum samples were collected for lipid metabolite analysis. Results The total clinical effective rate in RG + CHF group was 73.5%, and that of RG group was 40.8%. TCM syndrome scores in RG + CHF group showed a more pronounced decrease (p < 0.05). Scr, BUN, and UA levels decreased while eGFR levels increased in both groups (p < 0.05), with a greater magnitude of change observed in the RG + CHF group. Urinary AKI biomarkers decreased more in RG + CHF group (p < 0.05). No serious adverse events occurred during the trial. 58 different lipid metabolites and 48 lipid biomarkers were identified. According to the KEGG database, the possible metabolic pathways involved triglyceride metabolic pathway and fat digestion and absorption metabolic pathways. Conclusion CHF-II effectively alleviated kidney injury and improved TCM syndrome scores in patients with A on C. Lipid differential metabolites could serve as diagnostic indicators for AKI in patients with CKD. The possible metabolic pathways might be implicated in therapeutic action of CHF-II in the prevention and treatment of patients with A on C.

Epigallocatechin gallate (EGCG) alleviates inflammation and endothelial dysfunction and improves pregnancy outcomes in preeclampsia (PE)-like rats via eNOS/Nrf2/HO-1 pathway

Background and purposeEpigallocatechin gallate (EGCG), a natural antioxidant, has shown protective effect in many diseases. We explore the effect and potential regulatory mechanisms of EGCG in preeclampsia (PE)-like rats. Methods and materialsPE was mimicked in pregnant rats. EGCG was orally administered at a dosage of 25(Low, L) or 50 mg/kg (High, H) from gestational day (GD) 6–17. The blood pressure signatures, heart rates were monitored. The 24-h proteinuria and serum were analyzed. On GD 18, rats were sacrificed, and pups and placentas were weighed. Kidneys and placentas were analyzed using immunohistochemistry (IHC) and hematoxylin-eosin staining (H&E). Placentas were examined using western blot for sFlt1, eNOS, Nrf2, HO-1, SLC7A11. MDA, GSH, GPx and Fe2+ were measured. ResultsEGCG inhibits systolic blood pressure, BUN, CREA, ALT, AST, UA and proteinuria levels in PE-like rats. EGCG enhances the pup weight and crown-rump length and reduces the rate of fetus growth restriction in PE group. Endothelial dysfunction and infiltration of inflammatory cells were found in kidney cortex and placenta tissues in PE group and were inhibited by EGCG treatment. sFlt1 was activated in placentas in PE group and inhibited by EGCG while eNOS/Nrf2/HO-1 were inhibited in PE group and restored by EGCG. MDA and Fe concentrations were elevated in PE group and reduced by EGCG while the GSH level, SLC7A11 and the GPx activity were inhibited in PE group and restored by EGCG. ConclusionEGCG alleviates inflammation, endothelial dysfunction and placental ferroptosis, improves pregnancy outcomes in PE-like rats via eNOS/Nrf2/HO-1.

Association between infertility and risk of cardiovascular diseases in young women

Scientists and medical experts are beginning to understand the significant role that a woman’s past reproductive experiences play in her potential risk of developing heart disease. Reproductive history is seldom considered when assessing the cardiovascular risk. Infertility, high blood pressure, and hypertension are risk factors for heart disease. Additional analyses were conducted to determine whether the apparent increase in risk could be influenced by other risk factors associated with infertility such as irregular menstruation, thyroid conditions, and waist circumference. This study aimed to investigate the association between cardiovascular risk and infertility in women and those who are fertile. The objectives of this study were to estimate the levels of serum creatinine kinase (MB) in both infertile and fertile control groups, as well as to estimate the LDL and HDL levels in the same groups. The study group comprised 78 participants, of which 39 were fertile and 39 were infertile. CK (MB), HDL, LDL, Uric acid, and high sensitivity C reactive Protein (hs-CRP) levels were analyzed. In this study, we discuss how infertility may share common pathways with cardiovascular diseases. Numerous mechanisms may be involved in mediating infertility, including ovulatory abnormalities, endometriosis, and uterine fibroids. For example, in addition to having lower HDL levels, women with polycystic ovary syndrome (PCOS) are more likely to have higher levels of total cholesterol, triglycerides, and LDL. PCOS patients typically exhibit elevated UA levels and hyperuricemia, which are commonly associated with increased androgen levels.

Screening and evaluation of a novel nucleotide-degrading Levilactobacillus brevis grx821 with anti-hyperuricemia ability

Hyperuricemia seriously impacts our health and life quality. Probiotics play a vital role in ameliorating hyperuricemia through decrease urate production by purine substance assimilation. However, most research screened probiotics based on the assimilation of purine nucleoside, ignoring nucleotides. Nucleosides are derived from nucleotides. We hypothesized that lactic acid bacteria with the ability of nucleotides assimilation might be better to reduce intestinal absorption of dietary purine substances. In this study, a total of 235 strains of lactic acid bacteria were isolated from Chinese traditional fermented foods and evaluated for their purine nucleotides assimilation ability. A new potential candidate Levilactobacillus (L.) brevis grx821 isolated from naturally fermented soy whey Suanjiangshui, with a strong ability to degrade purine nucleotides and purine nucleosides, effectively reduced the serum levels of UA and creatinine in hyperuricemia mice by 20.76% and 14.38%. Based on the evaluation of antibiotic susceptibility, production of nitrite and biogenic amines, and hemolytic activity, L. brevis grx821 can be considered safe. L. brevis grx821 showed good gastrointestinal tolerance in vitro and cow milk fermentation characteristics, and could be a promising candidate of dietary supplements for prevention of hyperuricemia. This study suggests a novel way screening potential probiotic candidate for hyperuricemia, which has great guiding significance in the dealing with hyperuricemia.

Does Serum Uric Acid to Creatinine Ratio Predict Mortality Risk in Patients With Heart Failure?

Previous studies have established a positive correlation between serum uric acid to creatinine (SUA/Cr) ratio and cardiovascular disease, but the relationship between SUA/Cr ratio and the prognosis of heart failure (HF) remains unknown. This study investigated the potential of SUA/Cr ratio as a prognostic predictor for patients with HF. This single-center prospective cohort study enrolled 2,122 patients with HF between March 2013 and June 2017. All patients were divided into 3 groups according to SUA/Cr ratio tertiles and were followed up with until December 31, 2022. The association between SUA/Cr ratio and the prognosis of HF was assessed using the Cox proportional hazards model. The mean (SD) age and mean (SD) SUA/Cr ratio of the study cohort (66% male) were 59.3 (14.7) years and 4.71 (2.09), respectively. During a median follow-up period of 15 months (range, 11-26 months), 390 end-point events were observed. Prognosis analysis revealed that a high SUA/Cr ratio was associated with an increased mortality risk of HF (hazard ratio, 1.62 [95% CI, 1.26-2.09]; P < .001) compared with the SUA/Cr ratio in the lowest tertile. After adjusting for covariates, the hazard ratio for mortality risk of HF was 1.71 (95% CI, 1.23-2.37; P = .001). Subgroup analysis showed that mortality risk increased in direct proportion with the SUA/Cr ratio in female patients, patients with a history of hypertension and β-blocker use, and patients with UA levels below 428 μmol/L and creatinine levels less than 97 mg/dL. Stratification by age; by history of diabetes, hyperlipidemia, and smoking; and by level of fasting plasma glucose, however, had no obvious effect on the association between SUA/Cr ratio and HF prognosis. Patients with higher SUA/Cr ratios had reduced left ventricular ejection fraction and increased left ventricular end-diastolic diameter. A high SUA/Cr ratio was an independent risk factor for the mortality risk of HF.

Mediation effect of metabolic factors and inflammation on the association of serum uric acid with serum proprotein convertase subtilisin/kexin type 9 levels

Mediation effect of metabolic factors and inflammation on the association of serum uric acid with serum proprotein convertase subtilisin/kexin type 9 levels

Effect of Extraction effectivity of Senna alata L. Leaves on the Total Phenolic, Antioxidative, Antimicrobial and Antigoat Activity

Phytochemicals from natural product such as part of plants have been widely used as a potential source of herbal medication due to their bioactivity. Ketepeng cina (Senna alata L) is a small shrub that lives in tropical and subtropical regions and commonly used as medicinal plant to cure various diseases from infectious microbes. The current research was aimed to evaluate the extraction effectivity of Senna alata L leaves and the influence of the parameter to the total phenolic content, antioxidative, antimicrobial and antigout activity. Extraction of Senna alata L leaves was conducted by several methods, i.e maceration, ultrasonication and hot water extraction. The study revealed that each method give different yield of extraction and the most effective among those method is maceration, which produce highest yields of extracts (19.4%). Ultrasonic-assisted extraction (UAE) method also resulted in high yield but lower than that of maceration. The maceration method increases the yield by about 170% compared to hot water method. The extracts obtained from maceration method contain highest content of total phenolic (278.39mg GAE/g dry mass), thus demonstrate highest antioxidant activity (IC50 25.68mg/L), but lowest anti uric activity (reducing uric acid level by 85.25%). Maceration method was able to increase total phenolic content by about 128% and improve antioxidant activity by about 41%, compared to hot water method. However, UAE was excellent in producing phytochemicals which were responsible in anti uric activity, thus have the highest percentage in reducing UA level (90.72%), or increases by about 6.4%. compared to hot water method.

Clinical study on the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy.

Objective: To explore the difference in intestinal microecology between patients with preeclampsia and pregnant women at different stages of pregnancy. Methods: From January 2020 to January 2022, clinical data, including blood routine, lipid profile, and renal function indicators, were gathered from a cohort consisting of 5 cases of preeclampsia and 34 cases of non-preeclampsia. The non-preeclampsia group was further categorized into 6 cases in the First trimester, 13 cases in the Second trimester, and 15 cases in the Third trimester. The data collection took place at the Obstetrics Department of the Maternal and Child Health Hospital of Hubei Province. Additionally, fecal samples were obtained from each subject for 16S rDNA gene sequencing and subsequent analysis. The clinical data and composition characteristics of the gut microbiota in each group were analyzed, and the correlation between gut microbiota and clinical data was analyzed by the Spearman correlation analysis method. Results: In comparison to pregnant women without preeclampsia, preeclampsia patients exhibited a statistically significant elevation in blood routine parameters (WBC, N, L, and PLT count), a rise in lipid-related indicators (TC, TG, and LDL-C levels), a reduction in HDL-C levels, and an increase in renal function-related indicators (Cr, BUN, UA and Pro levels). Compared with non-preeclampsia pregnant women, preeclampsia women exhibited an augmented diversity of gut microbiota. Differences in gut microbiota composition between the two groups were observed at the gate and genus levels. Moreover, there are significant differences in the composition of gut microbiota between the preeclampsia group and the third-trimester group in terms of genus and species, and this difference is mainly caused by Prevotella and s_ Bacteroides_ Uniformis and Ruminococcus_ bromii. In addition, actinobacteria, bifidobacterium at the genus level, and Ruminococcus_bromii at the species level are positively correlated with clinically relevant indicators (excluding HDL-C). Conclusion: There are significant differences in gut microbiota between preeclampsia pregnant women and late pregnancy pregnant without preeclampsia, including Prevotella and Bacteroides_ Uniformis, and Ruminococcus_ bromii. In addition, these differential bacteria are correlated with most clinical indicators. However, additional comprehensive analysis is required to ascertain the functional correlation between these bacteria and clinical indicators.

Investigation of Chemical Compounds and Effect of Astragalus Galactites (Pall.) on MSU Crystal-Induced Acute Gouty Arthritis in Rats

The objective of the present investigation is to identify the biologically active components of Astragalus galactites (AG) and examine their effect on rats of acute gouty arthritis induced by crystals of the compound monosodium urate (MSU). Analyses of AG chemical constituents and their antioxidant activity were performed using both UV spectrophotometric and HPLC methods. Twenty-five adult Wistar rat males in total were assigned at random to a choice of five groups: AG 160 mg/kg, AG 330 mg/kg, MSU group, control group, and normal group. We reported the contents of Formononetin 1.97 µg/mL, Astragaloside IV 0.56 mg/mL, and total flavonoid 0.22±0.07% in the aerial part of our sample AG. In the DPPH scavenging assay, methanol and ethanol extracts established antioxidant properties with an IC50 concentration of 91.04 µg/mL and 93.13 µg/mL, respectively. In the ABTS scavenging assay, IC50 concentrations of 387.2 µg/mL (methanol extract) and 436.2 µg/mL (ethanol extract) were also shown. This investigation also looked at the histopathological characteristics related to MSU-induced gouty arthritis in order to assess the preventive effects of the AG plant on inflammatory mediator levels. In the AG 330 mg/kg group, the level of PGE2 significantly reduced (p&lt;0.001). Our results showed that the AG 330 mg/kg group was relatively effective in the treatment of gouty arthritis compared to other groups, which appears to be mediated by inhibiting the release of cytokines that pro-inflammation. The main compounds of the AG medicine plant, flavonoids and saponins, are acutely anti-gout due to the resulting decrease in PGE2 levels. We have hypothesized that it is able to treat acute gouty arthritis by reducing levels of UA and PGE2, providing an anti-inflammatory effect. This study contributes to the body of evidence that AG can be utilized in preventing and treating hyperuricemia.