The rising global incidence of diabetes mellitus(DM)and hyperuricemia presents a growing challenge to public health systems worldwide.Urate transporter-1(URAT1),a key renal urate transporter,has emerged as a promising...The rising global incidence of diabetes mellitus(DM)and hyperuricemia presents a growing challenge to public health systems worldwide.Urate transporter-1(URAT1),a key renal urate transporter,has emerged as a promising therapeutic target for managing DM and its associated complications.Growing evidence suggests that URAT1’s role in metabolic disorders extends beyond its function in the kidney.Specifically,URAT1 can influence uric acid metabolism in multiple tissues including neural,hepatic,vascular smooth muscle,cardiac,and adipose tissue,thereby contributing to insulin resistance,inflammation,and end-organ damage.In this review,we comprehensively examine the extra-renal functions of URAT1,focusing on its roles in the hematopoietic system,heart,liver,adipose tissue,and vascular endothelium in the context of DM.This analysis highlights the multi-organ mechanisms through which URAT1 exerts its effects,offering valuable insights into its potential as a therapeutic target for this complex sys-temic metabolic disorder.展开更多
Amid global climate change, rising levels of nitrogen(N) deposition have attracted considerable attention for their potential effects on the carbon cycle of terrestrial ecosystems. The desert steppes are a crucial yet...Amid global climate change, rising levels of nitrogen(N) deposition have attracted considerable attention for their potential effects on the carbon cycle of terrestrial ecosystems. The desert steppes are a crucial yet vulnerable ecosystem in arid areas, but their response to the combination of N addition and precipitation(a crucial factor in arid areas) remains underexplored. This study systematically explored the impact of N addition and precipitation on net ecosystem exchange(NEE) in a desert steppe in northern China. Specifically, we conducted a 2-a experiment from 2022 to 2023 with eight N addition treatments in the Urat desert steppe of Inner Mongolia Autonomous Region, China, to examine changes in NEE and explore its driving factors. The structural equation model(SEM) and multiple regression model were applied to determine the relationship of NEE with plant community characteristics and soil physical-chemical properties. Statistical results showed that N addition has no significant effect on NEE.However, it has a significant impact on the functional traits of desert steppe plant communities. SEM results further revealed that N addition has no significant effect on NEE in the desert steppe, whereas annual precipitation can influence NEE variations. The multiple regression model analysis indicated that plant functional traits play an important role in explaining the changes in NEE, accounting for 62.15% of the variation in NEE. In addition, plant height, as an important plant functional trait indicator, shows stronger reliability in predicting the changes in NEE and becomes a more promising predictor. These findings provide valuable insights into the complex ecological mechanisms governing plant community responses to precipitation and nutrient availability in the arid desert steppes, contributing to the improved monitoring and prediction of desert steppe ecosystem responses to global climate change.展开更多
Gout is caused by the deposition of uric acid as monosodium urate（MSU）. Chronic hyperuricemia is the necessary condition for MSU deposition, which arises from over-production and/or under-excretion of uric acid. Ren...Gout is caused by the deposition of uric acid as monosodium urate（MSU）. Chronic hyperuricemia is the necessary condition for MSU deposition, which arises from over-production and/or under-excretion of uric acid. Renal under-excretion of uric acid accounts for greater than 90% of the patients with hyperuricemia, making URAT1 inhibitors, which act through uricosuric effect a promising class of urate-lowering therapy（ULT）. This review aims at the summary and discussion of the latest development of URAT1 inhibitors for the treatment of hyperuricemia and gout and providing an insight into their structure-activity relationship（SAR）, which will be helpful to the design of URAT1 inhibitors for both academic research and pharmaceutical industry. The current development pipeline of URAT1 inhibitors is promising and encouraging.展开更多
Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseas...Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseases. We aim at identifying Single Nucleotide Polymorphism (SNP) difference of hURAT1 (rs7932775) and ABCG2 (rs3825016) on CKD patient with hyperuricemia and/or gout. Methods: All forty-two CKD patients were divided into two groups: hyperuricemia, and control group. 24 hours urine sample and serum were prepared for testing biochemistry parameters. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used to analyze hURAT1 and ABCG2 single nucleotide polymorphisms in different groups. Results: 17 patients have CT SNP of hURAT1 (rs7932775) and 13 patients have CT SNP of ABCG2 (rs3825016) in hyperuricemia group, while only 5 persons and 6 persons have the same mutations in control group respectively. 7 patients have CT SNP of both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group, while only 2 persons have the same mutations in control group. CT mutation rates of hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 60.7% (17/28) and 50% (13/28) respectively, higher than that of control group (35.7% (5/14) and 42.8% (6/14)). What is more, Double SNP mutations in both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 25% (7/28), higher than that of control group (14.2%, 2/14). Conclusion: There are higher mutation rates of CT SNP in hURAT1 (rs7932775) and/or ABCG2 (rs3825016) in hyperuricemia group. We can conclude that hyperuricemia is a high risk factor in progress of CKD, which is necessary to take measures of decreasing serum uric acid to delay CKD progress.展开更多
Korean oriental medicine prescription is widely used for the treatment of gouty diseases. In the present study, we investigated anti-inflammatory effects of modified Korean herbal formulation, mixed extract of medicin...Korean oriental medicine prescription is widely used for the treatment of gouty diseases. In the present study, we investigated anti-inflammatory effects of modified Korean herbal formulation, mixed extract of medicinal herbs(MEMH), and its modulatory effects on inflammatory mediators associated with gouty arthritis. Both in vitro and in vivo studies were carried out to assess the anti-inflammatory efficacy of MEMH on monosodium urate(MSU) crystals-induced gouty inflammation. MSU crystals stimulated human chondrosarcoma cell line, SW1353, and human primary chondrocytes were treated with MEMH in vitro. The expression levels of pro-inflammatory mediators and metalloproteases were analyzed. The effect of MEMH on NFκB signaling pathway in SW1353 cells was examined. Effect of MEMH on the mR NA expression level of pro-inflammatory mediators and chemotactic factor from human monocytic cell line, THP-1, was also analyzed. The probable role of MEMH in the differentiation process of osteoblast like cells, SaO S-2, after MSU treatment was also observed. To investigate the effects of MEMH in vivo, MSU crystals-induced ankle arthritic model was established. Histopathological changes in affected joints and plasma levels of pro-inflammatory mediators(IL-1β and TNFα) were recorded. MEMH inhibited NFκB signaling pathway and COX-2 protein expression in chondrocytes. MSU-induced mR NA expressions of pro-inflammatory mediators and chemotactic cytokines were suppressed by MEMH. In MSU crystals-induced ankle arthritic mouse model, administration of MEMH relieved inflammatory symptoms and decreased the plasma levels of IL-1β and TNFα. The results indicated that MEMH can effectively inhibit the expression of inflammatory mediators in gouty arthritis, demonstrating its potential for treating gouty arthritis.展开更多
文摘The rising global incidence of diabetes mellitus(DM)and hyperuricemia presents a growing challenge to public health systems worldwide.Urate transporter-1(URAT1),a key renal urate transporter,has emerged as a promising therapeutic target for managing DM and its associated complications.Growing evidence suggests that URAT1’s role in metabolic disorders extends beyond its function in the kidney.Specifically,URAT1 can influence uric acid metabolism in multiple tissues including neural,hepatic,vascular smooth muscle,cardiac,and adipose tissue,thereby contributing to insulin resistance,inflammation,and end-organ damage.In this review,we comprehensively examine the extra-renal functions of URAT1,focusing on its roles in the hematopoietic system,heart,liver,adipose tissue,and vascular endothelium in the context of DM.This analysis highlights the multi-organ mechanisms through which URAT1 exerts its effects,offering valuable insights into its potential as a therapeutic target for this complex sys-temic metabolic disorder.
基金supported by the Major Science and Technology Project of Inner Mongolia Autonomous Region (2024JBGS0011-02)Foundation for Innovative Research Groups in Basic Research of Gansu Province (25JRRA490)+1 种基金Youth Innovation Promotion Association of the Chinese Academy of Sciences (2022437)National Natural Science Foundation of China (42207538)。
文摘Amid global climate change, rising levels of nitrogen(N) deposition have attracted considerable attention for their potential effects on the carbon cycle of terrestrial ecosystems. The desert steppes are a crucial yet vulnerable ecosystem in arid areas, but their response to the combination of N addition and precipitation(a crucial factor in arid areas) remains underexplored. This study systematically explored the impact of N addition and precipitation on net ecosystem exchange(NEE) in a desert steppe in northern China. Specifically, we conducted a 2-a experiment from 2022 to 2023 with eight N addition treatments in the Urat desert steppe of Inner Mongolia Autonomous Region, China, to examine changes in NEE and explore its driving factors. The structural equation model(SEM) and multiple regression model were applied to determine the relationship of NEE with plant community characteristics and soil physical-chemical properties. Statistical results showed that N addition has no significant effect on NEE.However, it has a significant impact on the functional traits of desert steppe plant communities. SEM results further revealed that N addition has no significant effect on NEE in the desert steppe, whereas annual precipitation can influence NEE variations. The multiple regression model analysis indicated that plant functional traits play an important role in explaining the changes in NEE, accounting for 62.15% of the variation in NEE. In addition, plant height, as an important plant functional trait indicator, shows stronger reliability in predicting the changes in NEE and becomes a more promising predictor. These findings provide valuable insights into the complex ecological mechanisms governing plant community responses to precipitation and nutrient availability in the arid desert steppes, contributing to the improved monitoring and prediction of desert steppe ecosystem responses to global climate change.
基金Supported by Key Projects of Tianjin Science and Technology Support Plan(16YFZCSY00910)Natural Science Foundation of Shandong Province(ZR2015BM028)
文摘Gout is caused by the deposition of uric acid as monosodium urate（MSU）. Chronic hyperuricemia is the necessary condition for MSU deposition, which arises from over-production and/or under-excretion of uric acid. Renal under-excretion of uric acid accounts for greater than 90% of the patients with hyperuricemia, making URAT1 inhibitors, which act through uricosuric effect a promising class of urate-lowering therapy（ULT）. This review aims at the summary and discussion of the latest development of URAT1 inhibitors for the treatment of hyperuricemia and gout and providing an insight into their structure-activity relationship（SAR）, which will be helpful to the design of URAT1 inhibitors for both academic research and pharmaceutical industry. The current development pipeline of URAT1 inhibitors is promising and encouraging.
文摘Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseases. We aim at identifying Single Nucleotide Polymorphism (SNP) difference of hURAT1 (rs7932775) and ABCG2 (rs3825016) on CKD patient with hyperuricemia and/or gout. Methods: All forty-two CKD patients were divided into two groups: hyperuricemia, and control group. 24 hours urine sample and serum were prepared for testing biochemistry parameters. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used to analyze hURAT1 and ABCG2 single nucleotide polymorphisms in different groups. Results: 17 patients have CT SNP of hURAT1 (rs7932775) and 13 patients have CT SNP of ABCG2 (rs3825016) in hyperuricemia group, while only 5 persons and 6 persons have the same mutations in control group respectively. 7 patients have CT SNP of both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group, while only 2 persons have the same mutations in control group. CT mutation rates of hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 60.7% (17/28) and 50% (13/28) respectively, higher than that of control group (35.7% (5/14) and 42.8% (6/14)). What is more, Double SNP mutations in both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 25% (7/28), higher than that of control group (14.2%, 2/14). Conclusion: There are higher mutation rates of CT SNP in hURAT1 (rs7932775) and/or ABCG2 (rs3825016) in hyperuricemia group. We can conclude that hyperuricemia is a high risk factor in progress of CKD, which is necessary to take measures of decreasing serum uric acid to delay CKD progress.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(Nos.2014R1A1A4A03009388&2014R1A1A2055560)a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI)+2 种基金funded by the Ministry of Health&Welfare,Republic of Korea(No.HI12C1265)Hallym University Research Fund
文摘Korean oriental medicine prescription is widely used for the treatment of gouty diseases. In the present study, we investigated anti-inflammatory effects of modified Korean herbal formulation, mixed extract of medicinal herbs(MEMH), and its modulatory effects on inflammatory mediators associated with gouty arthritis. Both in vitro and in vivo studies were carried out to assess the anti-inflammatory efficacy of MEMH on monosodium urate(MSU) crystals-induced gouty inflammation. MSU crystals stimulated human chondrosarcoma cell line, SW1353, and human primary chondrocytes were treated with MEMH in vitro. The expression levels of pro-inflammatory mediators and metalloproteases were analyzed. The effect of MEMH on NFκB signaling pathway in SW1353 cells was examined. Effect of MEMH on the mR NA expression level of pro-inflammatory mediators and chemotactic factor from human monocytic cell line, THP-1, was also analyzed. The probable role of MEMH in the differentiation process of osteoblast like cells, SaO S-2, after MSU treatment was also observed. To investigate the effects of MEMH in vivo, MSU crystals-induced ankle arthritic model was established. Histopathological changes in affected joints and plasma levels of pro-inflammatory mediators(IL-1β and TNFα) were recorded. MEMH inhibited NFκB signaling pathway and COX-2 protein expression in chondrocytes. MSU-induced mR NA expressions of pro-inflammatory mediators and chemotactic cytokines were suppressed by MEMH. In MSU crystals-induced ankle arthritic mouse model, administration of MEMH relieved inflammatory symptoms and decreased the plasma levels of IL-1β and TNFα. The results indicated that MEMH can effectively inhibit the expression of inflammatory mediators in gouty arthritis, demonstrating its potential for treating gouty arthritis.
