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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>
Jin, Hai-Guo,Zhao, Yu-Min,Zhou, Guo-li Asian Australasian Association of Animal Productio 2005 Animal Bioscience Vol.18 No.12
Five China native cattle breeds have been characterized by using 10 microsatellite DNA markers. The studied populations can be divided into five groups: Luxi cattle, Nanyang cattle, Jinnan cattle, Qinchuan cattle and Yanbian cattle. Allele frequencies were calculated and used for the characterization of the breeds and the study of their genetic relationships. Heterozygosity, polymorphism information content, the effective number of alleles was calculated. Nei' standard genetic distance (1978) was calculated and used for a neighbor-joining tree construction. NJ tree showed that Luxi cattle, Nanyang cattle, Jinnan cattle and Qinchuan cattle are closely related, whereas Yanbian cattle are clearly distinct from other four populations. The genetic relationship of five breeds corresponds to their history and geographic origins. This work analyzes the recent origin of these populations and contributes to the knowledge and genetic characterization of China native breeds.
Xin, Jin,Zhang, Li-Chun,Li, Zhao-Zhi,Liu, Xiao-Hui,Jin, Hai-Guo,Yan, Chang-Guo Asian Australasian Association of Animal Productio 2011 Animal Bioscience Vol.24 No.1
The calpain I (CAPN1) gene is an important marker for meat tenderness and marbling score in the bovine, but there were no studies to determine whether the CAPN1 gene had an association with other meat quality traits. In this study, we examined the relation between genetic polymorphisms of the CAPN1 gene and some meat quality traits in Yanbian Yellow Cattle of China. By PCRSSCP and gene sequencing in 321 unrelated Yanbian yellow cattle, twenty seven single nucleotide polymorphisms (SNPs) were detected in CAPN1, two existed SNPs in exon 8 and exon 17 resulted in the change of AA at F311S and M599V, respectively, and the otherpolymorphisms were at intron 7, 8, 14, 16 and 17. There were different preponderant genotypes at the corresponding gene locus and all genotypes were not associated with tenderness but other meat traits. This is the first study of the relationship between CAPN1 and meat quality besides tenderness in Yanbian yellow cattle of China.
Zhou, Guo-li,Zhu, Qi,Jin, Hai-guo,Guo, Shan-li Asian Australasian Association of Animal Productio 2006 Animal Bioscience Vol.19 No.3
Associations were analysed between polymorphisms localized in intron 3 of the growth hormone gene (GH-MspI) and milk production traits of 543 China Holstein cows. A PCR-RFLP method was used for identification of genotypes. The following frequencies of genotypes and alleles were found: 0.77, 0.21 and 0.02 for +/+, +/- and -/-, respectively, and 0.87 and 0.13 for $GH^+$ and $GH^-$, respectively. Significant differences between herds were observed in the frequencies of both genotypes and alleles. The results of least squares analysis showed that in all three lactation phases the GH +/+ cows yielded most milk (p<0.01 for lactation I and p<0.05 for lactations II and III), whereas +/- cows showed higher milk fat content than +/+ individuals (p<0.05 for lactation I and II, and p<0.01 for lactation III). The +/+ cows yielded more fat than +/- individuals (p<0.01 only in lactation I). The +/+ cows yielded more milk protein than +/- individuals (p<0.01 for lactation I, II, and III). The +/+ cows produced milk of higher protein content than that of +/- individuals (p<0.05 only in lactation II). Based on these results, we conclude that the +/+ of GH locus should be the favored genotype in China Holstein cow breeds for use in marker-assisted selection programmes.
( Guo Hong Gong ),( Zhi Ming Zheng ),( Hui Liu,Li Wang ),( Jin Shan Diao ),( Peng Wang ),( Gen Hai Zhao ) 한국미생물 · 생명공학회 2014 Journal of microbiology and biotechnology Vol.24 No.6
An extracellular β-glucosidase from Aspergillus niger Au0847 was purified to homogeneity by precipitation with ammonium sulfate, anion exchange, and gel filtration. The purified protein was composed of two subunits with molecular masses of 110 and 120 kDa. Au0847 β-glucosidase exhibited relatively high thermostability and pH stability, and its highest activity was obtained at 65°C and pH 4.6, respectively. As a potential metalloprotein, its enzymatic activity was potently stimulated by manganese ion and DTT. The β-glucosidase displayed avid affinity and high catalytic efficiency for geniposide. Au0847 β-glucosidase has potential value as an industrial enzyme for the hydrolysis of geniposide to genipin.
Hai-long Piao,Yuan-hu Xuan,Su Hyun Park,제병일,Soon Ju Park,Sung Han Park,김철민,Jin Huang,Guo Kui Wang,김민정,강상모,이인중,Taek-Ryoun Kwon,Yong Hwan Kim,Un-sang Yeo,이기환,손대영,한창덕 한국분자세포생물학회 2010 Molecules and cells Vol.30 No.1
Calcineurin B-like protein-interacting protein kinases (CIPKs) are a group of typical Ser/Thr protein kinases that mediate calcium signals. Extensive studies using Arabi-dopsis plants have demonstrated that many calcium sig-natures that activate CIPKs originate from abiotic stresses. However, there are few reports on the functional demon-stration of CIPKs in other plants, especially in grasses. In this study, we used a loss-of-function mutation to charac-terize the function of the rice CIPK gene OsCIPK31. Expo-sure to high concentrations of NaCl or mannitol effected a rapid and transient enhancement of OsCIPK31 expression. These findings were observed only in the light. However, longer exposure to most stresses resulted in down-regulation of OsCIPK31 expression in both the presence and absence of light. To determine the physiological roles of OsCIPK31 in rice plants, the sensitivity of oscipk31::Ds, which is a transposon Ds insertion mutant, to abiotic stresses was examined during germination and seedling stages. oscipk31::Ds mutants exhibited hypersensitive phenotypes to ABA, salt, mannitol, and glucose. Com-pared with wild-type rice plants, mutants exhibited re-tarded germination and slow seedling growth. In addition, oscipk31::Ds seedlings exhibited enhanced expression of several stress-responsive genes after exposure to these abiotic stresses. However, the expression of ABA meta-bolic genes and the endogenous levels of ABA were not altered significantly in the oscipk31::Ds mutant. This study demonstrated that rice plants use OsCIPK31 to modulate responses to abiotic stresses during the seed germination and seedling stages and to modulate the expression of stress-responsive genes.
Jin, Hai-Rong,Kim, Woo Jean,Song, Jae Sook,Piao, Shuguang,Choi, Min Ji,Tumurbaatar, Munkhbayar,Shin, Sun Hwa,Yin, Guo Nan,Koh, Gou Young,Ryu, Ji-Kan,Suh, Jun-Kyu American Diabetes Association 2011 Diabetes Vol.60 No.3
<P><B>OBJECTIVE</B></P><P>Patients with diabetic erectile dysfunction often have severe endothelial dysfunction and respond poorly to oral phosphodiesterase-5 inhibitors. We examined the effectiveness of the potent angiopoietin-1 (Ang1) variant, cartilage oligomeric matrix protein (COMP)-Ang1, in promoting cavernous endothelial regeneration and restoring erectile function in diabetic animals.</P><P><B>RESEARCH DESIGN AND METHODS</B></P><P>Four groups of mice were used: controls; streptozotocin (STZ)-induced diabetic mice; STZ-induced diabetic mice treated with repeated intracavernous injections of PBS; and STZ-induced diabetic mice treated with COMP-Ang1 protein (days −3 and 0). Two and 4 weeks after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations, Western blot analysis, and cGMP quantification. We also performed a vascular permeability test.</P><P><B>RESULTS</B></P><P>Local delivery of the COMP-Ang1 protein significantly increased cavernous endothelial proliferation, endothelial nitric oxide (NO) synthase (NOS) phosphorylation, and cGMP expression compared with that in the untreated or PBS-treated STZ-induced diabetic group. The changes in the group that received COMP-Ang1 restored erectile function up to 4 weeks after treatment. Endothelial protective effects, such as marked decreases in the expression of p47<SUP>phox</SUP> and inducible NOS, in the generation of superoxide anion and nitrotyrosine, and in the number of apoptotic cells in the corpus cavernosum tissue, were noted in COMP-Ang1–treated STZ-induced diabetic mice. An intracavernous injection of COMP-Ang1 completely restored endothelial cell-cell junction proteins and decreased cavernous endothelial permeability. COMP-Ang1–induced promotion of cavernous angiogenesis and erectile function was abolished by the NOS inhibitor, <I>N</I>-nitro-L-arginine methyl ester, but not by the NADPH oxidase inhibitor, apocynin.</P><P><B>CONCLUSIONS</B></P><P>These findings support the concept of cavernous endothelial regeneration by use of the recombinant Ang1 protein as a curative therapy for diabetic erectile dysfunction.</P>