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Assessment of nephrotoxicity of herbal medicine containing aristolochic acid in mice
Yi Quan,Long Jin,Kang Luo,Jian Jin,Sun Woo Lim,신유진,Eun Jeong Ko,Byung Ha Chung,Chul Woo Yang 대한내과학회 2020 The Korean Journal of Internal Medicine Vol.35 No.2
Background/Aims: It is undetermined if herbal medicines (HM) containing aristolochic acid (AA)-containing have similar nephrotoxicity to AA itself. Methods: We administered HM containing a high concentration of AA for 5 days (short-term study) or a low concentration of AA for 30 days (long-term study) to C57BL/6 mice; for comparison, same dose of AA compound was used as controls. Results: The nephrotoxicity in the HM- and AA-treated mice was compared in terms of renal function, histopathology, oxidative stress, apoptotic cell death, and mitochondrial damage. Short-term HM treatment resulted in acute kidney injury (marked renal dysfunction, acute tubular necrosis, and neutrophil gelatinase-associated lipocalin [NGAL] expression) in which the severity of renal dysfunction and histopathology was comparable with that induced by the administration of AA alone. Long-term HM treatment resulted in features of chronic kidney disease (CKD, mild renal dysfunction and tubular atrophy and dilatation). No significant differences in these parameters were observed between the HM- and AA-treated mice. HM-induced oxidative stress (8-hydroxy-2’-deoxyguanosine and manganese- dependent superoxide dismutase expression) and apoptotic cell death (terminal deoxynucleotidyl transferase dUTP nick end labelling [TUNEL]-positive cells and active caspase-3 expression) were similar in HM- and AA-treated mice in the short-term and long-term studies. Mitochondrial injury, evaluated by electron microscopy, was also similar in HM- and AA-treated mice in the short-term and long-term studies. Conclusions: The nephrotoxic potential of HM containing AA was similar to that of AA itself.
Small activating RNA induced expression of VHL gene in renal cell carcinoma
Kang, Moo Rim,Park, Ki Hwan,Lee, Chang Woo,Lee, Myeong Youl,Han, Sang-Bae,Li, Long-Cheng,Kang, Jong Soon Elsevier 2018 The international journal of biochemistry & cell b Vol.97 No.-
<P><B>Abstract</B></P> <P>Recent studies have reported that chemically synthesized double-stranded RNAs (dsRNAs), also known as small activating RNA (saRNAs), can specifically induce gene expression by targeting promoter sequences by a mechanism termed RNA activation (RNAa). In the present study, we designed 4 candidate saRNAs targeting the Von Hippel-Lindau (VHL) gene promoter. Among these saRNAs, dsVHL-821 significantly inhibited cell growth by up-regulating VHL at both the mRNA and protein levels in renal cell carcinoma 769-P cells. Functional analysis showed that dsVHL-821 induced apoptosis by increasing p53, decreasing Bcl-xL, activating caspase 3/7 and poly-ADP-ribose polymerase in a dose-dependent manner. Chromatin immunoprecipitation analysis revealed that dsVHL-821 increased the enrichment of Ago2 and RNA polymerase II at the dsVHL-821 target site. In addition, Ago2 depletion significantly suppressed dsVHL-821-induced up-regulation of VHL gene expression and related effects. Single transfection of dsVHL-821 caused long-lasting (14 days) VHL up-regulation. Furthermore, the activation of VHL by dsVHL-821 was accompanied by an increase in dimethylation of histone 3 at lysine 4 (H3K4me2) and acetylation of histone 4 (H4ac) and a decrease in dimethylation of histone 3 at lysine 9 (H3K9me2) and lysine 27 (H3K27me2) in the dsVHL-821 target region. Taken together, these results demonstrate that dsVHL-821, a novel saRNA for VHL, induces the expression of the VHL gene by epigenetic changes, leading to inhibition of cell growth and induction of apoptosis, and suggest that targeted activation of VHL by dsVHL-821 may be explored as a novel treatment of renal cell carcinoma.</P>
Lim, Sun Woo,Jin, Long,Luo, Kang,Jin, Jian,Yang, Chul Woo Nature Publishing Group 2017 Laboratory investigation Vol.97 No.11
<P>We previously reported that long-term treatment with a calcineurin inhibitor impairs autophagy process in pancreatic beta cells. This study investigated the effect of Korean red ginseng extract (KRGE) on autophagy modulated by oxidative stress. In mice with tacrolimus (Tac)-induced diabetes mellitus, KRGE alleviated islet dysfunction and decreased oxidative stress and autophagic vacuoles. In vitro, KRGE decreased autophagosome formation and attenuated lysosomal degradation, accompanied by improved beta cell viability and insulin secretion. Addition of 3-methyladenine (3-MA), an inhibitor of autophagosomes, to KRGE further improved cell viability and insulin secretion, and bafilomycin A (BA), an inhibitor of lysosomal function, reduced the effects of KRGE. At the subcellular level, Tac caused mitochondrial dysfunction (impaired mitochondrial oxygen consumption, ATP production, and increased reactive oxygen species production). But KRGE improved these parameters. The effect of KRGE on mitochondrial function enhanced by 3-MA but decreased by BA, suggesting a causal relationship between KRGE effect and autophagy modulation in Tac-induced mitochondrial dysfunction. These findings indicate that KRGE modulates autophagy favorably by reducing Tac-induced oxidative stress, and this effect is closely associated with improvement of mitochondrial function.</P>
( Jing Wang ),( Wei Chen ),( Fang Wang ),( Dong Wu ),( Jia Ming Qian ),( Jun Ren Kang ),( Hai Long Li ),( En Ling Ma ) 한국임상영양학회 2015 Clinical Nutrition Research Vol.4 No.2
Mitochondrial neurogastrointestinal encephalopathy (MNGIE) is characterized by significant gastrointestinal dysmotility. Early and long-term nutritional therapy is highly recommended. We report a case of MNGIE in a patient who was undergoing longterm nutrition therapy. The patient was diagnosed with a serious symptom of fatty liver and hyperlipidemia complications, along with homozygous mutation of the thymidine phosphorylase (TYMP) gene (c.217G > A). To our knowledge, this is the first report of such a case. Herein, we describe preventive measures for the aforementioned complications and mitochondrial disease-specific nutritional therapy.
Shen-Kang protects against tacrolimus-induced renal injury
Long Ye Zhang,Jian Jin,Kang Luo,Shang Guo Piao,Hai Lan Zheng,Ji Zhe Jin,임선우,최범순,양철우,Can Li 대한내과학회 2019 The Korean Journal of Internal Medicine Vol.34 No.5
Background/Aims: Evidence suggests that Shen-Kang (SK), a traditional Chinese herbal medicine, protects against various types of renal injury. In this study, we evaluated whether SK treatment confers renoprotection in a rat model of chronic tacrolimus (TAC) nephropathy. Methods: Rats were treated daily with TAC (1.5 mg/kg, subcutaneously) and SK (450 mg/kg, intravenously) for 4 weeks. The effects of SK on TAC-induced renal injury were assessed by measuring renal function, urine albumin excretion, histopathology, inflammatory cell infiltration, expression of profibrotic (transforming growth factor β1 [TGF-β1] and TGF-β inducible gene-h3 [βig-h3]) and proinflammatory cytokines, oxidative stress, and apoptotic cell death. Results: Administration of SK preserved glomerular integrity (fractional mesangial area and Wilms tumor 1-positive glomeruli), attenuated tubulointerstitial fibrosis, and reduced the number of ectodermal dysplasia 1-positive cells, and this was paralleled by improved urine albumin excretion and renal dysfunction. At the molecular level, SK treatment suppressed expression of TGF-β1/Smad2/3, βig-h3, and proinflammatory cytokines. Oxidative stress and apoptotic cell death were significantly decreased with SK treatment, and apoptosis-related genes were regulated toward cell survival (active caspase-3 and the B-cell lymphoma-2/ Bcl2-associated X [Bcl-2/Bax] ratio). Conclusions: SK protects against TAC-induced renal injury.
Pham, Long Quoc,Sohn, Jong Hwa,Park, Ji Hyun,Kang, Hyun Suk,Lee, Byung Cheol,Kang, Young Soo Elsevier 2011 Radiation physics and chemistry Vol.80 No.5
<P><B>Abstract</B></P><P>Copper nanoparticles with narrow size distribution of 5–7nm were synthesized by using electron beam irradiation. The copper nanoparticles were stable in ambient air for two months. TGA showed that the copper nanoparticles prepared by using electron beam irradiation have the higher wt% of pure copper metal compared with the one prepared by chemical reduction using hydrazine hydrate(N<SUB>2</SUB>H<SUB>4</SUB>·<I>x</I>H<SUB>2</SUB>O). The conductive copper paste with copper nanoparticles prepared by electron beam irradiation showed higher conductivity than the paste with copper nanoparticles prepared by chemical reduction with N<SUB>2</SUB>H<SUB>4</SUB> due to small size, less amount of surfactants on the surface and higher stability against the oxidation in ambient condition. The highest conductivity of copper paste was determined as 170Scm<SUP>−1</SUP> at 90wt% of copper nanoparticles in the paste.</P> <P><B>Research highlights</B></P><P>► Copper nanoparticles were synthesized by electron beam irradiation and chemical reduction. ► The copper nanoparticles synthesized by electron beam irradiation have narrower size distribution of 5–7nm and higher wt% of pure copper metal compared with the one synthesized by chemical reduction. ► Conductive pastes prepared by copper nanoparticles synthesized by electron beam irradiation show higher conductivity.</P>