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
Vascular inflammatory aging is strongly associated with multimorbidity,including immunosenescence.Here,bioinformatic analysis indicated elevated expression of the lysozyme(LYZ)gene in age-dependent vascular diseases.L...Vascular inflammatory aging is strongly associated with multimorbidity,including immunosenescence.Here,bioinformatic analysis indicated elevated expression of the lysozyme(LYZ)gene in age-dependent vascular diseases.Lyzl deficiency led to vascular inflammatory aging,including damage to indicators related to oxidative stress,vascular function,and inflammation in the serum and vascular tissues of wild-type(WT)and Lyz1^(-/-)mice.The 16S ribosomal RNA sequencing of intestinal contents revealed increased Bifidobacterium and its metabolism of acetate,butyrate,omega-muricholic acid,propionate,and valeric acid in Lyz1^(-/-)mice compared with that in WT mice.Additionally,RNA sequencing of vascular tissues identified differentially expressed genes in Lyz1^(-/-)mice compared with those in WT mice,as well as enrichment of the common phosphatidylinositol 3-kinase(Pl3K)-Akt signaling pathway.Vascular inflammatory aging phenotypes were detected in the blood vessels of antibiotic-treated and germ-free mice,and the PI3K-Akt signaling pathway was inhibited.Importantly,intravenous LYZ administration worsened the pathological conditions,whereas oral LYZ administration successfully restored the gut microbial balance and reversed the vascular inflammatory aging phenotypes.Collectively,this study establishes LYZ as a novel biomarker for age-related vascular diseases and the gut microbiota-PI3K-Akt axis as a promising therapeutic target.展开更多
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 the National Natural Sciences Foundation of China(82305072,82305064,and 82300345)the Natural Science Foundation of Jiangsu Province(BK20230184)+6 种基金the Science and Technology Development project of Jiangsu Provincial Administration of Traditional Chinese Medicine(YB2020043)the Wuxi Municipal Health Commission Scientific Research Fund Youth Project(Q202106 and Q202225)The Taihu Lake Talent Project of Wuxi Science and Technology Bureau(K20221027)the Medical Key Discipline Program of Wuxi Health Commission(HB2023044 and HB2023051)the Chongqing Natural Science Foundation(CSTB2024NSCQMSX0368)the high-level hospital clinical research fees of Fu Wai Hospital,CAMS(grant 2023-GSP-QN-23)the Doctoral Talent Startup Fund of Affiliated Hospital of Jiangnan University.
文摘Vascular inflammatory aging is strongly associated with multimorbidity,including immunosenescence.Here,bioinformatic analysis indicated elevated expression of the lysozyme(LYZ)gene in age-dependent vascular diseases.Lyzl deficiency led to vascular inflammatory aging,including damage to indicators related to oxidative stress,vascular function,and inflammation in the serum and vascular tissues of wild-type(WT)and Lyz1^(-/-)mice.The 16S ribosomal RNA sequencing of intestinal contents revealed increased Bifidobacterium and its metabolism of acetate,butyrate,omega-muricholic acid,propionate,and valeric acid in Lyz1^(-/-)mice compared with that in WT mice.Additionally,RNA sequencing of vascular tissues identified differentially expressed genes in Lyz1^(-/-)mice compared with those in WT mice,as well as enrichment of the common phosphatidylinositol 3-kinase(Pl3K)-Akt signaling pathway.Vascular inflammatory aging phenotypes were detected in the blood vessels of antibiotic-treated and germ-free mice,and the PI3K-Akt signaling pathway was inhibited.Importantly,intravenous LYZ administration worsened the pathological conditions,whereas oral LYZ administration successfully restored the gut microbial balance and reversed the vascular inflammatory aging phenotypes.Collectively,this study establishes LYZ as a novel biomarker for age-related vascular diseases and the gut microbiota-PI3K-Akt axis as a promising therapeutic target.
