Anti-hyperuricemic and nephroprotective effects of Rhizoma Dioscoreae septemlobae extracts and its main component dioscin via regulation of mOAT1, mURAT1 and mOCT2 in hypertensive mice

Junxia Su,Yu-Hui Wei,Minglong Liu,Tianxi Liu,Jianhua Li,Yuanchun Ji,Jianping Liang 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.10

Rhizoma Dioscoreae septemlobae (RDSE) hasbeen widely used for the treatment of hyperuricemia inChina. However, the therapeutic mechanism has beenunknown. This study investigated the antihyperuricemicmechanisms of the extracts obtained from RDSE and itsmain component dioscin (DIS) in hyperuricemic mice. Hyperuricemic mice were induced by potassium oxonate(250 mg/kg). RDSE or DIS was orally administered tohyperuricemic mice at dosages of 319.22, 638.43,1276.86 mg/kg/day for 10 days, respectively. Uric acid orcreatinine in serum and urine was determined by HPLC orHPLC–MS/MS, respectively. The xanthine oxidase (XO)activities in mice liver were examined in vitro. Proteinlevels of organic anion transporter 1 (mOAT1), uratetransporter 1 (mURAT1) and organic cation transporter 2(mOCT2) in the kidney were analyzed by western blotting. The results indicated that uric acid and creatinine in serumwere significantly increased by potassium oxonate, ascompared to that of control mice. Compared saline-treatedgroup, after RDSE treatment in the high and middle dose,the expression of mOAT1 increased 47.98 and 54.48 %,respectively, which accompanied with the decreasedexpression of mURAT1 (47.63 %) in high dose. After DIS treatment in high, middle and low dose, the expression ofmOAT1 increased 23.93, 32.80 and 25.28 % compared tosaline-treated group, respectively, which accompanied withthe decreased expression of mURAT1 (51.07, 51.42 and51.35 %). However, RDSE and DIS displayed a weak XOinhibition activity compared with allopurinol. Therefore,RDSE and DIS processed uricosuric and nephroprotectiveactions by regulation of mOAT1, mURAT1 and mOCT2.

Associations among Genetic Variants and Intracranial Aneurysm in a Chinese Population

Bingyang Li,Chongyu Hu,Junyu Liu,Xin Liao,Jiayu Xun,Manqian Xiao,Junxia Yan 연세대학교의과대학 2019 Yonsei medical journal Vol.60 No.7

Purpose: Genome-wide association studies (GWAS) have revealed that common variants on or near EDNRA, HDAC9, SOX17,RP1, CDKN2B-AS1, and RBBP8 genes are associated with intracranial aneurysm (IA) in European or Japanese populations. However,due to population heterogeneity, whether these loci are associated with IA pathogenesis in Chinese individuals is still unknown. The purpose of this study was to investigate associations among GWAS-identified loci and risk of IA in a Chinese population. Materials and Methods: A total of 765 individuals (including 230 IA patients and 535 controls) were involved in this study. Twelvesingle nucleotide polymorphisms (SNPs) of candidate loci were genotyped using the Sequenom MassARRAY platform. Associationswere analyzed using univariate or multivariate logistic regression analysis. Results: SNPs in CDKN2B-AS1 (especially rs10757272) showed significant associations with IA in dominant and additive models[odds ratio (OR), 2.99 and 1.43; 95% confidence interval (CI), 1.44–6.24 and 1.10–1.86, respectively]. A SNP near HDAC9 (rs10230207)was associated with IA in the dominant model (OR, 1.42; 95% CI, 1.01–1.99). One SNP near RP1 (rs1072737) showed a protectiveeffect on IA in the dominant model (OR, 0.66; 95% CI, 0.46–0.95), while another SNP in RP1 (rs9298506) showed a risk effect onIA in a recessive model (OR, 3.82; 95% CI, 1.84–7.91). No associations were observed among common variants near EDNRA,SOX17, or RBBP8 and IA. Conclusion: These data partially confirmed earlier results and showed that variants in CDKN2B-AS1, RP1, and HDAC9 could begenetic susceptibility factors for IA in a Chinese population.

Polymorphisms of Inflammatory Cytokine Genes and Risk for Intracranial Aneurysm: A Systematic Review and Meta-Analysis

Liming Hu,Bingyang Li,Xin Liao,Junxia Yan 연세대학교의과대학 2020 Yonsei medical journal Vol.61 No.5

Purpose: Inflammatory cytokines are thought to be involved in the pathogenesis of intracranial aneurysm (IA), although results among studies in the literature are inconsistent. This article sought to review studies on the associations among polymorphisms in inflammatory cytokine genes and IA risk and to provide recommendations for future research. Materials and Methods: A systematic search of PubMed, Embase, and Web of Science was conducted up to August 4, 2019. The associations between polymorphisms of inflammatory cytokine genes and IA risk were estimated by pooled odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses were performed according to race. Qualitative systematic review was conducted for variants that were studied in only one study. All analyses were performed using STATA 12.0. Results: 13 studies investigating the associations between polymorphisms in five inflammatory cytokine genes (TNF-α, IL-1α, IL-1β, IL6, and IL-12B) and IA were reviewed. Combined results showed that the A allele of TNF-α rs1800629 polymorphism has a protective effect against IA (dominant model: OR=0.65, 95% CI=0.47–0.89, p=0.007). No associations were identified between polymorphisms in IL-1α rs1800587, IL-1β rs16944, IL6 rs1800795 and rs1800796, or IL-12B rs3212227 and IA risk. Conclusion: This review demonstrated an association between TNF-α rs1800629 polymorphism and IA in Caucasians, illustrating the potentially important role of genes involved in inflammation in IA.

SNPs in the coding region of bovine MGAT2 gene are associated with body weight and weight gain

Lian Qu,Mingjuan Yang,Jinlong Zhu,Junxia Liu,Mijie Li,Liangzhi Zhang,Xianyong Lan,Chuzhao Lei,Chunlei Zhang,Hong Chen 한국유전학회 2011 Genes & Genomics Vol.33 No.3

Monoacylglycerol acyltransferase 2 (MGAT2), as a candidate gene for quantitative traits, relates to dietary fat uptake, lipids synthesis and storage, which plays a major role in the absorption of dietary fat by catalyzing the resynthesis of triacylglycerol in enterocytes. In this study, based on DNA pool sequencing and PCR‐RFLP methods, polymorphisms of the MGAT2 gene were detected in 1145 Chinese indigenous cattle. The results revealed two novel mutations located on exon 1and exon 5 (NM_001099136.1:m.84G>T and 756A>G). Hence, we described the HaeIII forced PCR–RFLP method in exon1 and a MluI PCR–RFLP method in exon5 to detect them. In addition, the associations of these polymorphisms with growth traits were evaluated in Nanyang cattle. The results showed that only HaeIII locus was associated with body weight and average daily gain aged 6 months, and individuals with genotype TT showed significantly higher body weight and average daily gain than those with genotype GG.

Order–disorder structural tailoring and its effects on the chemical stability of (Gd, Nd)2(Zr, Ce)2O7 pyrochlore ceramic for nuclear waste forms

Wang Yan,Wang Jin,Zhang Xue,Li Nan,Wang Junxia,Liang Xiaofeng 한국원자력학회 2022 Nuclear Engineering and Technology Vol.54 No.7

Series of unequal quantity Nd/Ce co-doped ceramic nuclear waste forms, (Gd, Nd)2(Zr, Ce)2O7, were prepared to tailor its ordered pyrochlore or disordered fluorite structure. The phase transition, microtopography, and elemental composition of the ceramic samples were systematically investigated, especially the effect of order-disorder structure on the chemical stability. It was confirmed that unequal quantity of Nd/Ce could synchronously replace the Gd/Zr-sites of Gd2Zr2O7. And the phase transition of order-disorder structure could be successfully tailored by regulating the average cationic radius ratio of (Gd, Nd)2(Zr, Ce)2O7 series. The elements of Gd, Nd, Zr, and Ce are uniformly distributed in the ordered or disordered structures. The MCC-1 leaching results showed that (Gd, Nd)2(Zr, Ce)2O7 pyrochlore ceramic nuclear waste forms had excellent chemical stability, whose elements' normalized leaching rates were as low as 104 -107 g‧m2 ‧d1 after 7 days. In particular, the chemical stability of disordered structure was superior to that of ordered structure. It was proposed that the force constant and the closest packing were changed with the structure transformation resulting the chemical stability difference

Long-term and stable correction of uremic anemia by intramuscular injection of plasmids containing hypoxia-regulated system of erythropoietin expression

Jifeng Sun,Yarong Wang,Jie Yang,Dewei Du,Zhanting Li,Junxia Wei,Angang Yang 생화학분자생물학회 2012 Experimental and molecular medicine Vol.44 No.11

Relative deficiency in production of glycoprotein hormone erythropoietin (Epo) is a major cause of renal anemia. This study planned to investigate whether the hypoxia-regulated system of Epo expression, constructed by fusing Epo gene to the chimeric phosphoglycerate kinase (PGK) hypoxia response elements (HRE) in combination with cytomegalovirus immediate-early (CMV IE) basal gene promoter and delivered by plasmid intramuscular injection, might provide a long-term physiologically regulated Epo secretion expression to correct the anemia in adenine-induced uremic rats. Plasmid vectors (pHRE-Epo) were synthesized by fusing human Epo cDNA to the HRE/CMV promoter. Hypoxia-inducible activity of this promoter was evaluated first in vitro and then in vivo in healthy and uremic rats (n = 30 per group). The vectors (pCMV-Epo) in which Epo expression was directed by a constitutive CMV gene promoter served as control. ANOVA and Student’s t-test were used to analyze between-group differences. A high-level expression of Epo was induced by hypoxia in vitro and in vivo. Though both pHRE-Epo and pCMV-Epo corrected anemia,the hematocrit of the pCMV-Epo-treated rats exceeded the normal (P < 0.05), but that of the pHRE-Epo-treated rats didn’t. Hypoxia-regulated system of Epo gene expression constructed by fusing Epo to the HRE/CMV promoter and delivered by plasmid intramuscular injection may provide a long-term and stable Epo expression and secretion in vivo to correct the anemia in adenine-induced uremic rats.

Melatonin Attenuates Mitochondrial Damage in Aristolochic Acid-Induced Acute Kidney Injury

Sun Jian,Pan Jinjin,Liu Qinlong,Cheng Jizhong,Tang Qing,Ji Yuke,Cheng Ke,wang Rui,Liu Liang,Wang Dingyou,Wu Na,Zheng Xu,Li Junxia,Zhang Xueyan,Zhu Zhilong,Ding Yanchun,Zheng Feng,Li Jia,Zhang Ying,Yua 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.1

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.