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Effects of Polygonum cuspidatum on AMPK-FOXO3α Signaling Pathway in Rat Model of uric Acid-Induced Renal Damage

Chinese Journal of Integrative Medicine 2019年第3期25卷 182-189页

作者： MA Wei-guo WANG Jie BU Xiang-wei ZHANG Hong-hong ZHANG Jian-ping ZHANG Xiao-xu HE Yu-xi WANG Da-li ZHANG Zheng-ju MENG Feng-xian Department of Rheumatology Dongfang Hospital Beijing University of Chinese Medicine Department of Endocrinology Shunyi Branch Beijing Hospital of Traditional Chinese Medicine

Objective: To observe the effects of Chinese medicine(CM) Polygonum cuspidatum(PC) on adenosine 5'-monophosphate-activated protein kinase(AMPK), forkhead box O3α(FOXO3α), Toll-like receptor-4(TLR4), NACHT, LRR and PYD domains-containing protein 3(NLRP3), and monocyte chemoattractant protein-1(MCP-1) expression in a rat model of uric acid-induced renal damage and to determine the molecular mechanism. Methods: A rat model of uric acid-induced renal damage was established, and rats were randomly divided into a model group, a positive drug group, and high-, medium-, and low-dose PC groups(n=12 per group). A normal group(n=6) was used as the control. Rats in the normal and model groups were administered distilled water(10 m L·kg^(–1)) by intragastric infusion. Rats in the positive drug group and the high-, medium-, and low-dose PC groups were administered allopurinol(23.33 mg·kg^(–1)), and 7.46, 3.73, or 1.87 g·kg^(–1)·d^(–1) PC by intragastric infusion, respectively for 6 to 8 weeks. After the intervention, reverse transcription polymerase chain reaction, Western blot, enzyme linked immunosorbent assay, and immunohistochemistry were used to detect AMPK, FOXO3α, TLR4, NLRP3, and MCP-1 m RNA and protein levels in renal tissue or serum. Results: Compared with the normal group, the m RNA transcription levels of AMPK and FOXO3α in the model group were significantly down-regulated, and protein levels of AMPKα1, pAMPKα1 and FOXO3α were significantly down-regulated at the 6 th and 8 th weeks(P<0.01 or P<0.05). The m RNA transcription and protein levels of TLR4, NLRP3 and MCP-1 were significantly up-regulated(P<0.01 or P<0.05). Compared with the model group, at the 6 th week, the mRNA transcription levels of AMPK in the high-and medium-dose groups, and protein expression levels of AMPKα1, p AMPKα1 and FOXO3α in the high-dose PC group, AMPKα1 and p AMPKα1 in the mediumdose PC group, and p AMPKα1 in the low-dose PC group were significantly up-regulated(P<0.01 or P<0.05); the m RNA

关键词： Polygonum cuspidatum Chinese medicine uric acid renal damage AMPK-FOXO3 α pathway

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Determining the role for uric acid in non-alcoholic steatohepatitis development and the utility of urate metabolites in diagnosis:An opinion review

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World Journal of Gastroenterology 2020年第15期26卷 1683-1690页

作者： Paul Brennan Kathleen Clare Jacob George John F Dillon Department of Molecular and Clinical Medicine University of DundeeNinewells Hospital and Medical SchoolDundee DD19SYUnited Kingdom Department of Neurology Queen Elizabeth HospitalGlasgow G514TFUnited Kingdom

There has long been a recognised association between non-alcoholic fatty liver disease(NAFLD)and the composite aspects of the metabolic *** of this association highlighted the supposed co-existence of elevated uric acid levels in those with *** is interest in exploitation of this as a putative diagnostic and prognostic biomarker in *** the increased economic and health burden associated with the NAFLD epidemic,improved methods of population-based,minimally-invasive methods and biomarkers are clearly highly sought and *** this opinion review we review the proposed role of uric acid in the pathogenesis of NAFLD and its potential utilisation in the diagnosis and monitoring of the disease process.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis uric acid Urate Non-invasive fibrosis markers Fatty liver index

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Pharmacologic inducers of the uric acid exporter ABCG2 as potential drugs for treatment of gouty arthritis

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Asian Journal of Pharmaceutical Sciences 2020年第2期15卷 173-180页

作者： Bojana Ristic Mohd Omar Faruk Sikder Yangzom D.Bhutia Vadivel Ganapathy Department of Cell Biology and Biochemistry Texas Tech University Health Sciences CenterLubbockTX 79430United States

uric acid is the end product of purine catabolism and its plasma levels are maintained below its maximum solubility in water(6–7 mg/dl).The plasma levels are tightly regulated as the balance between the rate of production and the rate of excretion,the latter occurring in urine(kidney),bile(liver)and feces(intestinal tract).Reabsorption in kidney is also an important component of this *** excretion and reabsorption are mediated by specific *** of the balance between production and excretion leads to hyperuricemia,which increases the risk of uric acid crystallization as monosodium urate with subsequent deposition of the crystals in joints causing gouty ***-of-function mutations in the transporters that mediate uric acid excretion are associated with *** ATP-Binding Cassette exporter ABCG2 is important in uric acid excretion at all three sites:kidney(urine),liver(bile),and intestine(feces).Mutations in this transporter cause gout and these mutations occur at significant prevalence in general ***,mutations that are most prevalent result only in partial loss of transport ***,if the expression of these partially defective transporters could be induced,the increased number of the transporter molecules would compensate for the mutation-associated decrease in transport function and hence increase uric acid *** such,pharmacologic agents with ability to induce the expression of ABCG2 represent potentially a novel class of drugs for treatment of gouty arthritis.

关键词： uric acid excretion Intestine ABCG2 Loss-of-function mutations Gouty arthritis Pharmacologic inducers

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Elevated serum uric acid level as a predictor for cardiovascu-lar and all-cause mortality in Chinese patients with high cardiovascular risk

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Journal of Geriatric Cardiology 2008年第1期5卷 15-20页

作者： Yongquan Wu Meijing Li Jue Li Yingyi Luo Yan Xing Dayi Hu Heart Lung and Blood Vessel CenterTongji UniversityShanghai 200092China HeartLung and Blood Vessel CenterTongji UniversityShanghai 200092China HeartLung and Blood Vessel CenterTongji UniversityShanghai 200092China HeartLung and Blood Vessel CenterTongji UniversityShanghai 200092China HeartLung and Blood Vessel CenterTongji UniversityShanghai 200092China HeartLung and Blood Vessel CenterTongji UniversityShanghai 200092China

Objective To assess the predictive value of serum uric acid levels for cardiovascular and all-cause mortality in a large prospective population based *** The study was based on 3648 participants in Shanghai and Beijing,who were inpatients with high cardiovascular(CV) risk at baseLine (2004.7 to 2005.1),and blood was ***-up for death from cardiovascular disease and any cause was complete until January 1,*** The mean follow-up was 1 *** were 303 deaths during follow-up,of which 121 were *** mortality rates were 8.3 % for all patients,6.8% for female patients (116/1715),and 9.7% (187/1933) for male *** men,patients in the lower and higher uric acid groups had increased cardiac and overall mortality risks compared with patients in the normal uric acid *** relation was found in women but not statistically *** adjusting for other conventional risk factors (age,diabetes,hypertension,diuretic use and smoking),baseline uric acid level was still associated with increased risk for death from cardiovascular disease (P=0.005),or death from all causes (P=0.014) Conclusion Our data suggest that abnormal serum uric acid levels are independently and significantly associated with risk of cardiovascular and all-cause mortality.(J Geriatr Cardiol 2008;5:15-20)

关键词： epidemiology uric acid cardiovascular mortality all-cause mortality

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Serum uric acid level in newly diagnosed essential hypertension in a Nepalese population:A hospital based cross sectional study

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Asian Pacific Journal of Tropical Biomedicine 2014年第1期4卷 59-64页

作者： Bibek Poudel Binod Kumar Yadav Arun Kumar Bharat Jha Kanak Bahadur Raut Department of Biochemistry Manipal College of Medical Sciences(MCOMS)Manipal Teaching Hospital(MTH) Research Institute of Clinical Medicine Chonbuk National University Medical School and Hospital Department of Biochemistry Institute of MedicineTribhuvan University Teaching Hospital(Institute of MedicineTUTH) Department of Internal.Medicine Institute of MedicineTribhuvan University Teaching Hospital(Institute of MedicineTUTH)

Objective:To develop the missing link between hyperuricemia and ***:The study was conducted in Department of Biochemistry in collaboration with Nephrology Unit of Internal Medicine *** was defined according to blood pressure readings by definitions of the Seventh Report of the Joint National *** 205newly diagnosed and untreated essential hypertensive cases and age-sex matched nonnotensive controls were enrolled in the *** potential confounding factors of hyperuricemia and hypertension in both cases and controls were *** acid levels in all participants were ***:Renal function between newly diagnosed hypertensive cases and nonnotensive healthy controls were *** mean serum uric acid observed in newly diagnosed hypertensive cases and in nonnotensive healthy controls were(290.05±87.03)μmol/L and(245.24±09.38)μmol/L respectively.A total of 59(28.8%)participants of cases and 28(13.7%)participants of controls had hyperuricemia(odds ratio 2.555(95%CI:1.549-4.213),Puric acid leveb and number of hyperuricemic subjects were found to be significantly higher in cases when compared to controls.

关键词： Newly diagnosed hypertension Serum uric acid Hyperuricemia Joint National Committee

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Association between serum uric acid level and the severity of coronaryartery disease in patients with obstructive coronary artery disease

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Chinese Medical Journal 2014年第6期127卷 1039-1045页

作者： Jie Yu Jiangli Han Jieming Mao Lijun Guo Wei Gao Department of Cardiology Peking University Third Hospital Beijing 100191 China Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Ministry of Health and Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Beijing 100191 China. Department of Cardiology Peking University Third Hospital Beijing 100191 China Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Ministry of Health and Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Beijing 100191 China. Email: sister.han@***.

Background Many studies have shown that the serum uric acid(SUA) level is one of the cardiovascular risk factors. The aim of the study is to evaluate the relationship between SUA levels and the severity of coronary artery disease(CAD) assessed by angiography and the Syntax score in patients with obstructive *** Participants who visited our hospital for a coronary angiography, from December 2007 to September 2012, were eligible for this analysis. SUA and other blood parameters after at least 12-hour fast were determined. First, the patients were divided into tertiles according to their Syntax scores(low Syntax score group: Syntax score ≤10.0; moderate Syntax score group: 10.0 18.0). Second, to clarify the association between SUA levels and major adverse cardiovascular events(MACEs), all patients were divided into two subgroups on the basis of SUA levels. The cutoff value of SUA was defined by diagnostic criteria of hyperuricemia. Patients were separated into normal SUA group(n=251, with SUA <416 μmol/L for men and SUA <357 μmol/L for women) and high SUA group(n=96, with SUA ≥416 μmol/L for men and SUA ≥357 μmol/L for women). All participants were followed for a mean of 22.0 months(1–75 months, interquartile range: 28 months) for major adverse cardiovascular events(MACEs), including all-cause death, recurrent nonfatal myocardial infarction(re-MI) and recurrent percutaneous coronary intervention(re-PCI). Results A total of 347 patients were registered for the study. The SUA levels in the high Syntax score group were significantly higher than that of the moderate Syntax score group and the low Syntax score group((392.3±81.6) μmol/L vs.(329.9±71.0) μmol/L, P <0.001;(392.3±81.6) μmol/L vs.(311.4±64.7) μmol/L, P <0.001). The SUA level was positively correlated not only with the Syntax score(r=0.421, P <0.001; 95% CI: 0.333–0.512), but also with the number of diseased vessels(r=0.298, P <0.001; 95% CI: 0.19

关键词： serum uric acid obstructive coronary artery disease Syntax score

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Association between serum uric acid and large-nerve fiber dysfunction in type 2 diabetes:a cross-sectional study

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Chinese Medical Journal 2019年第9期132卷 1015-1022页

作者： Tian-Nan Jiang Yu-Feng Li Li-Li Huo Qian Zhang Lian-Ying Wang Cui-Ling Zhao Li-Ge Liu Department of General Practice School of General Practice and Continuing EducationCapital Medical UniversityBeijing 100069China Department of Internal Medicine Health Care CenterBeijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Endocrinology and Metabolism Beijing Friendship Hospital Pinggu CampusCapital Medical UniversityBeijing 101200China Department of Endocrinology and Metabolism Beijing Jishuitan Hospital4th Medical College of Peking UniversityBeijing 100035China Department of National Clinical Research Center for Digestive Disease Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China

Background:Large-nerve fiber dysfunction,as assessed by vibration perception threshold (VPT) predicts risks of ulceration,amputation,and mortality in *** uric acid (UA) is closely associated with various metabolic disorders,especially ***,we sought to investigate the clinical relevance of UA to large-nerve fiber dysfunction,among patients with type 2 diabetes (T2D).Methods:Medical records of consecutive patients with T2D who were admitted to Beijing Friendship Hospital Pinggu Campus between May 2014 and December 2016 were *** for the 824 eligible patients included in the final analysis were extracted using a structured form.A VPT value ≥15 in either foot was defined as *** compared the clinical characteristics between patients with abnormal VPT and those with normal VPT (VPT value uricemia (males >420 μmol/L;females >360 μmol/L) was associated with a reduced risk of abnormal VPT (odds ratio [OR],0.60;95% confidence interval [CI],0.39–0.91;P<0.05).This association was robust in male patients (OR,0.43;95% CI,0.24–0.76;P<0.01) but not in female patients (OR,0.92;95% CI,0.47–1.82;P = 0.816),even after adjustment for confounding *** the younger male subgroup (age <65 years),VPT values decreased as the UA level increased (P for trend = 0.002),but this trend was not significant in older male subgroup (age ≥65 years;P for trend = 0.400).Conclusions:Low serum UA levels showed a significant association with an incr

关键词： Peripheral neuropathy uric acid Type 2 diabetes

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Determination of Dopamine in Presence of uric Acid at Poly (Eriochrome Black t) Film Modified Graphite Pencil Electrode

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American Journal of Analytical Chemistry 2011年第2期2卷 262-269页

作者： Umesh Chandra B. E. Kumara Swamy Ongera Gilbert Sathish Reddy B. S. Sherigara Department of PG Studies and Research in Industrial Chemistry Kuvempu University

A simple commercial graphite pencil electrode was used to investigate the electrochemical oxidation of dopamine. The electropolymerised film of eriochrome black t was prepared on the surface of graphite pencil electrode by using cyclic voltammetry technique. The prepared electrode exhibits an excellent electrocatalytical activity towards the determination of dopamine. The effects of concentration, pH and scan rate were investigated. Simultaneous detection of dopamine and uric acid was investigated by using both cyclic voltammetric and differential pulse voltammetry technique. The modified electrode was also used for the detection of dopamine in injection.

关键词： Poly (Eriochrome Black T) Graphite Pencil Electrode Dopamine uric Acid Cyclic Voltammetry Differential Pulse Voltammetry

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Correlation between Serum uric Acid Level and Left Ventricular Ejection Fraction in Patients with Congestive Heart Failure

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World Journal of Cardiovascular Diseases 2019年第11期9卷 857-866页

作者： Mohamed A. W. Ezzat Ahmed M. Boghdady Kassem F. A. Ibrahim Lotfy H. Abo Dahab Internal Medicine and Cardiology Department Faculty of Medicine Sohag University Sohag Egypt

Background: One of the risk factors of congestive heart failure that still under investigations is hyperuricemia. It’s still debatable whether it’s an independent risk factor or it’s just a consequence of other disorders associated with cardiovascular diseases like hypertension, diabetes and dyslipidemia. Objective: The aim of our study is to elucidate whether in patients with heart failure serum uric acid level correlates with left ventricular ejection fraction supporting the possibility that the detection of progressive hyperuricemia in these patients may be an indicator of deteriorating cardiac function. Methods: We conducted a prospective study that included 124 studied patients and 26 apparently healthy persons at Coronary care unit and Internal Medicine Department at Sohag University Hospitals. Studied populations were classified into;* Group “I”: newly diagnosed heart failure, * Group “II”: decompensated heart failure on regular treatment, * Group “III”: decompensated heart failure but stopped their treatment from three months, Group “IV”: control group, healthy and age-matched subjects. We studied the association between left ventricular ejection fraction, the severity of congestive heart failure and the serum uric acid levels and the well-known conventional risk factors. Results: The main finding was the significantly higher mean serum uric acid levels in patients with congestive heart failure versus apparently healthy persons with “P value = 0.02”. When we adjusted the serum uric acid with other significant risk factors in the univariate analysis which were age, gender and smoking, serum uric acid was an independent risk factor “P value = 0.04”. There was a significant correlation between serum uric acid level and the severity of congestive heart failure “P value 0.35”. High rates of serum uric acid levels were recorded in patients with reduced ejection fraction. A uric acid level of 8.45 mg/dl was found to be the most appropriate cut-off point with the se

关键词： uric Acid Level Congestive Heart Failure

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Decreasing serum uric acid levels might be associated with improving estimated glomerular filtration rate (eGFR) in Japanese men

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Health 2011年第8期3卷 498-503页

作者： Nobuyuki Miyatake Kenichi Shikata Hirofumi Makino Takeyuki Numata Department of Hygiene Faculty of Medicine Kagawa University Center for Innovative Medicine Okayama University Hospital Department of Medicine and Clinical Science Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences

The link between changes in a subject’s serum uric acid levels and his estimated glomerular filtration rate (eGFR) was evaluated in Japanese men. We used data for 108 Japanese men (45.3 ± 8.0 years) with a 1-year follow up. eGFR was defined by a new equation developed for Japan. eGFR was weakly correlated with serum uric acid levels (r = –0.287, p = 0.0026) at baseline. Subjects were given advice for dietary and life-style improvement. At the 1-year follow up, almost metabolic syndrome components were significantly improved. However, blood sugar and uric acid did not change and eGFR was significantly decreased. The changes in eGFR were weakly correlated with abdominal circum-ference (r = –0.249, p = 0.0094) and uric acid (r = –0.340, p = 0.0003). A decrease in serum uric acid levels may be associated with improving eGFR in Japanese men.

关键词： Abdominal Circumference uric Acid Estimated Glomerular Filtration Rate (eGFR) Metabolic Syndrome Lifestyle Modification

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