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Synergistic Effects of Leflunomide and Benazepril in Streptozotocin-Induced Diabetic Nephropathy
Jin, Hua,Piao, Shang Guo,Jin, Ji Zhe,Jin, Ying Shun,Cui, Zhen Hua,Jin, Hai Feng,Zheng, Hai Lan,Li, Jin Ji,Jiang, Yu Ji,Yang, Chul Woo,Li, Can S.Karger 2014 The Nephron Journals Vol.126 No.3
<P>Abstract</P><P><B><I>Background:</I></B> Leflunomide (LEF) and benazepril have renoprotective effects on diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic activities. This study investigated whether combined treatment using LEF and benazepril affords superior protection compared with the respective monotherapies. <B><I>Methods:</I></B> Diabetes was induced with streptozotocin (STZ, 65 mg/kg) by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, diabetic rats were treated daily for 12 weeks with LEF (10 mg/kg), benazepril (10 mg/kg), or a combination of both. Basic parameters (body weight, fasting blood glucose level, and 24 h urinary protein excretion), histopathology, inflammatory [inflammatory cell infiltration (ED-1), monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor-2 (TLR-2)] and glomerulosclerotic factors [transforming growth factor-β<SUB>1</SUB> (TGF-β<SUB>1</SUB>) and connective tissue growth factor (CTGF)], and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG) were studied. <B><I>Results:</I></B> Benazepril or LEF treatment significantly prevented body weight loss and 24 h urinary protein excretion induced by diabetes; combined treatment with LEF and benazepril further improved these parameters compared with giving each drug alone (all p < 0.01). Increased expression of inflammatory (MCP-1 and TLR-2) and glomerulosclerotic (TGF-β<SUB>1</SUB> and CTGF) factors in diabetic rat kidney was reduced by treatment with either LEF or benazepril and was further reduced by the combined administration of the two drugs (p < 0.01). These effects were accompanied by suppression of urinary 8-OHdG excretion. There was no significant between-group difference in blood glucose level. <B><I>Conclusions:</I></B> LEF treatment lessens DN, and combined treatment with LEF and benazepril provides synergistic effects in preventing DN.</P><P>© 2014 S. Karger AG, Basel</P>
Cui, Xiao-Bin,Peng, Hao,Li, Su,Li, Ting-Ting,Liu, Chun-Xia,Zhang, Shu-Mao,Jin, Ting-Ting,Hu, Jian-Ming,Jiang, Jin-Fang,Liang, Wei-Hua,Li, Na,Li, Li,Chen, Yun-Zhao,Li, Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22
Background: A number of studies have identified a shared susceptibility locus in phospholipase C epsilon 1 (PLCE1) for esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA). However, the results of PLCE1 expression in esophageal and gastric cancer remain inconsistent and controversial. Moreover, the effects on clinicopathological features remain undetermined. This study aimed to provide a precise quantification of the association between PLCE1 expression and the risk of ESCC and GCA through meta-analysis. Materials and Methods: Eligible studies were identified from PubMed, Wanfang Data, ISI Web of Science, and the Chinese National Knowledge Infrastructure databases. Using RevMan5.2 software, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were employed to assess the association of PLCE1 expression with clinicopathological features relative to ESCC or GCA. Results: Seven articles were identified, including 761 esophageal and gastric cancer cases and 457 controls. Overall, we determined that PLCE1 expression was associated with tumor progression in both esophageal cancers (pooled OR=5.93; 95%CI=3.86 to 9.11) and gastric cancers (pooled OR=9.73; 95%CI=6.46 to 14.7). Moreover, invasion depth (pooled OR=3.62; 95%CI=2.30 to 5.70) and lymph node metastasis (pooled OR=4.21; 95%CI=2.69 to 6.59) were linked with PLCE1 expression in gastric cancer. However, no significant associations were determined between PLCE1 overexpression and the histologic grade, invasion depth, and lymph node metastasis in esophageal cancer. Conclusions: Our metaanalysis results indicated that upregulated PLCE1 is significantly associated with an increased risk of tumor progression in ESCC and GCA. Therefore, PLCE1 expression can be appropriately regarded as a promising biomarker for ESCC and GCA patients.
Screening study for genetic polymorphisms affecting pharmacokinetics of talniflumate
Li Hua Jin,김보경,이지현,이기동,곽규범,임성빈 대한임상약리학회 2017 Translational and Clinical Pharmacology Vol.25 No.4
Talniflumate is a phthalidyl ester of niflumic acid, which has potent analgesic and anti-inflammatoryeffects and is widely used to treat inflammatory disorders, such as rheumatoid arthritis. Toscreen the possible genetic factors affecting the pharmacokinetics (PK) of talniflumate, 23 male Koreanvolunteers were enrolled from two separate bioequivalence studies. All subjects received 740mg (two tablets) talniflumate in a standard 2x2 cross-over model in a randomized order. For thegenetic study, PK parameters of the reference drug were used. We used Illumina Human610Quadv1.0 DNA Analysis BeadChip for whole genome single nucleotide polymorphism (SNP) analysisand whole genome genotyping data were processed by linear regression analysis for PK parameters. Whole genome analysis revealed 1498 significant SNPs (P < 0.0001) for Cmax, 65 significant SNPs(P < 0.0001) for Tmax, and 1491 significant SNPs (P < 0.0001) for AUCinf. For clinical pharmacologicalpurposes, we selected SNPs from drug metabolizing enzymes and transporters, and analyzed thePK parameters of various genotypes. Two SNPs (rs11165069 from ABCA4 (p=0.00002); rs17847036from CYP2C9 (p=0.000001)) showed significant associations with talniflumate Cmax. In the Tmaxgroup, two SNPs (rs3787555 from CYP24A1 (p=0.00035); rs2275034 from ABCA4 (p=0.000587))showed significant associations with talniflumate Tmax. In the AUCinf group, two SNPs (rs11165069from ABCA4 (p=0.00002); rs12461006 from SLC1A6 (p=0.00008)) exhibited significant associationswith talniflumate absorption. These results show that genetic factors could affect the PKparameters, and provide information that may be used in the development of personalized talniflumatetherapy.
Immobilization of Lactase onto Various Polymer Nanofibers for Enzyme Stabilization and Recycling
( Li Hua Jin ),( Ye Li ),( Xiang Hao Ren ),( Jung Heon Lee ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.8
Five different polymer nanofibers, namely, polyaniline nanofiber (PANI), magnetically separable polyaniline nanofiber (PAMP), magnetically separable DEAE cellulose fiber (DEAE), magnetically separable CM cellulose fiber (CM), and polystyrene nanofiber (PSNF), have been used for the immobilization of lactase (E.C. 3.2.1.23). Except for CM and PSNF, three polymers showed great properties. The catalytic activities (kcat) of the free, PANI, PAMP, and magnetic DEAE-cellulose were determined to be 4.0, 2.05, 0.59, and 0.042 mM/min·mg protein, respectively. The lactase immobilized on DEAE, PANI, and PAMP showed improved stability and recyclability. PANI- and PAMP-lactase showed only a 0-3% decrease in activity after 3 months of vigorous shaking conditions (200 rpm) and at room temperature (25oC). PANI-, PAMP-, and DEAE-lactase showed a high percentage of conversion (100%, 47%, and 12%) after a 1 h lactose hydrolysis reaction. The residual activities of PANI-, PAMP-, and DEAE-lactase after 10 times of recycling were 98%, 96%, and 97%, respectively.
Jin-Hua Liang,Yun-Ping Zhang,Jun Xia,Chong-Yang Ding,Wei Wu,Li Wang,Lei Cao,Hua-Yuan Zhu,Lei Fan,Tian-Nv Li,Jian-Yong Li,Wei Xu 대한암학회 2019 Cancer Research and Treatment Vol.51 No.4
Purpose The purpose of this study was to investigate the prognostic significance of total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) in patients with follicular lymphoma (FL) at baseline and mid-treatment with 18F-fluorodeoxyglucose positron emission tomography computed tomography (PET-CT) scans. Materials and Methods The study analyzed data from 48 patients with FL who were treated in Jiangsu Province Hospital and reviewed their baseline PET-CT scans. TMTV and TLG were computed by using the absolute value of 2.0, 2.5, and 3.0 thresholding method, respectively. Results Median age was 53 years, 75.0% of patients had stage III to IV disease, 43.8% had a Follicular Lymphoma International Prognostic Index 1 (FLIPI1) score of 3 to 5 and 20.8% had a FLIPI2 score of 3 to 5. Receiver operating characteristic (ROC) curve analysis showed the optimal cut-off values for TMTV3.0 and TLG3.0 were 476.4 (sensitivity, 85.7%; specificity, 78.0%; area under the curve [AUC], 0.760; p=0.003) and 2,676.9 (sensitivity, 71.4%; specificity, 78.0%; AUC, 0.760; p=0.003). On multivariable analysis, TMTV3.0 and TLG3.0 were independent predictors of both progression-free survival (PFS) (hazard ratio [HR], 5.406; 95% confidence interval [CI], 1.326 to 22.040; p=0.019 and HR, 6.502; 95% CI, 1.079 to 39.182; p=0.042) and overall survival (OS) (HR, 4.111; 95% CI, 1.125 to 15.027; p=0.033 and HR, 5.885; 95% CI, 1.014 to 34.148; p=0.049). ROC curve analysis showed the optimal cut-off values for TMTV3.0 and TLG3.0 were 66.3% (sensitivity, 85.7%; specificity, 63.4%; AUC, 0.774; p < 0.001) and 64.5% (sensitivity, 85.7%; specificity, 65.9%; AUC, 0.777; p < 0.001). Conclusion Baseline TMTV and TLG are strong predictors of PFS and OS in FL. Furthermore, interim TMTV (TMTV > 66.3%) and TLG (TLG > 64.5%) reduction are valuable tools for early treatment response assessment in FL patients.