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.

Ginseng extract reduces tacrolimus-induced oxidative stress by modulating autophagy in pancreatic beta cells

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>

Growth and Optical Properties of Nanocrystalline/Microcrystalline DiamondMultilayer Films

Jin-Long Luo,Xuan-Tong Ying,Liang-Yao Chen,Pei-Nan Wang 한국물리학회 2005 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.46 No.2

Nanocrystalline/microcrystalline diamond (NCD/MCD) multilayer film with high sp3 bonded carbon concentration and smooth surface has been successfully deposited on silicon substrate. Optimized deposition parameters based on substrate temperature modulation were adopted to grow the NCD/MCD film. The nanocrystallinity, purity and the multilayer structure were characterized by Raman spectroscopy, X-ray diffraction (XRD) and scanning electron microscopy (SEM). The smoothness of the film surface was shown by surface profile measurements and further verified by its high optical transmittance from visible to infrared band. Therefore, this newly proposed NCD/MCD multilayer film would have a variety of optical applications.

Effect of Conversion to CTLA4Ig on Tacrolimus-Induced Diabetic Rats

Jin, Long,Lim, Sun Woo,Jin, Jian,Luo, Kang,Ko, Eun Jeong,Chung, Byung Ha,Lin, Hong Li,Yang, Chul Woo Wolters Kluwer Health, Inc. All rights reserved. 2018 Transplantation Vol.102 No.4

<P>Conclusions CTLA4Ig was not diabetogenic, and conversion to CTLA4Ig reduced TAC-induced pancreatic islet injury.</P>

Profiling of skeletal muscle tissue for long non-coding RNAs related to muscle metabolism in the QingYu pig at the growth inflection point

Luo, Jia,Shen, Linyuan,Gan, Mailin,Jiang, Anan,Chen, Lei,Ma, Jideng,Jin, Long,Liu, Yihui,Tang, Guoqing,Jiang, Yanzhi,Li, Mingzhou,Li, Xuewei,Zhang, Shunhua,Zhu, Li Asian Australasian Association of Animal Productio 2021 Animal Bioscience Vol.34 No.8

Objective: Investigation of muscle growth at different developmental stages is an appropriate strategy for studying the mechanisms underlying muscle development and differences in phenotypes. In particular, the muscle development mechanisms and the difference between the fastest and slowest growth rates. Methods: In this study, we used a growth curve model to fit the growth inflection point (IP) of QingYu pigs and compared differences in the long non-coding RNA (lncRNA) transcriptome of muscle both at the growth IP and plateau phase (PP). Results: The growth curve of the QingYu pig had a good fit (R² = 0.974) relative to a typical S-curve and reached the IP at day 177.96. At the PP, marbling, intramuscular fat, and monounsaturated fatty acids had increased significantly and the percentage of lean muscle and polyunsaturated fatty acids had decreased. A total of 1,199 mRNAs and 62 lncRNAs were differentially expressed at the IP compared with the PP. Additional to gene ontology and Kyoto encyclopedia of genes and genomes pathway analyses, these differentially expressed protein coding genes were principally related to muscle growth and lipid metabolism. Conclusion: Our results suggest that the identified differentially expressed lncRNAs, could play roles in muscle growth, fat deposition and regulation of fatty acid composition at the IP and PP.

Deep Learning in Drebin: Android malware Image Texture Median Filter Analysis and Detection

( Luo Shi-qi ),( Ni Bo ),( Jiang Ping ),( Tian Sheng-wei ),( Yu Long ),( Wang Rui-jin ) 한국인터넷정보학회 2019 KSII Transactions on Internet and Information Syst Vol.13 No.7

This paper proposes an Image Texture Median Filter (ITMF) to analyze and detect Android malware on Drebin datasetsMedian Filter (MF) to reflect the similarity of the malware binary file block. At the same time, using the MAEVS (Malware Activity Embedding in Vector Space) to reflect the potential dynamic activity of malware. In order to ensure the improvement of the classification accuracy, the above-mentioned features(ITMF feature and MAEVS feature)are studied to train Restricted Boltzmann Machine (RBM) and Back Propagation (BP). The experimental results show that the model has an average accuracy rate of 95.43% 1. We design a model of “ITMF” combined with Image Processing of with few false alarms. to Android malicious code, which is significantly higher than 95.2% of without ITMF, 93.8% of shallow machine learning model SVM, 94.8% of KNN, 94.6% of ANN.

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.

Prognostic Significance of Overexpression of EZH2 and H3k27me3 Proteins in Gastric Cancer

He, Long-Jun,Cai, Mu-Yan,Xu, Guo-Liang,Li, Jian-Jun,Weng, Zi-Jin,Xu, Da-Zhi,Luo, Guang-Yu,Zhu, Sen-Lin,Xie, Dan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

The enhancer of zeste homolog 2 (EZH2) methyl transferase and histone 3 lysine 27 (H3K27me3) protein can repress gene transcription, and their aberrant expression has been observed in various human cancers. This study determined their expression levels in gastric cancer tissues with reference to clinicopathological features and patient survival. We collected 117 gastric cancer and corresponding normal tissues for immunohistochemistry analysis. In gastric cancers, 82/117 (70.1%) were positive for EZH2 and 66/117 (56.4%) for H3K27me3 proteins in contrast to only 5.41% and 7.25% of normal gastric mucosa specimens, respectively. Kaplan-Meier survival data showed the average overall and disease-free survival of EZH2 high expression patients was 25.2 and 20.2 months, respectively, shorter than that with EZH2 low expression (40.5 and 35.9 months). The average overall survival and disease-free survival of high H3K27me3 expression patients was 23.4 and 17.4 months, shorter than without H3K27me3 expression (37.6 and 34.5 months). The average overall survival and disease-free survival of patients with both EZH2 and H3K27me3 expression was 18.8 and 12.9 months, respectively, shorter than that with either alone (34.7 and 31.2 months) or with low levels of both (43.9 and 39.9 months). Multivariate Cox regression analysis showed that H3K27me3 and EZH2 expression, tumor size differentiation and clinical stage were all independent prognostic factors for predicting patient survival. This study demonstrated that detection of both EZH2 and H3K27me3 proteins can predict poor survival of gastric cancer patients, superior to single protein detection. In addition, H3K27me3 and EZH2 protein expression could predict lymph node metastasis.

ONYX-I: Efficacy of Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir in South Korean and Taiwanese Patients with HCV Genotype 1b Infection and without Cirrhosis

( Jeong Heo ),( Wan-Long Chuang ),( Yan Luo ),( Mong Cho ),( Chi-Jen Chu ),( Kwang-Hyub Han ),( Jia-Horng Kao ),( Seung Woon Paik ),( Chun-Yen Lin ),( Jin-Woo Lee ),( Cheng-Yuan Peng ),( Young-Suk Lim 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Background: Approximately 45-50% of Hepatitis C virus (HCV) infections in South Korea and Taiwan are genotype (GT) 1b. Previous phase 3 studies demonstrated that the direct-acting antiviral (DAA) regimen of ombitasvir (OBV), ritonavir-boosted paritaprevir (PTV/r; identified by Abbvie and Enanta) and dasabuvir (DSV) was well tolerated and achieved sustained virologic response at post-treatment week 12 (SVR12) in 99% of treatment-naive and 100% of treatment- experienced patients with HCV GT1b. ONYX-I (NCT02517515) was designed to evaluate efficacy and safety in Asian patients with HCV GT1b infection without cirrhosis. Methods: Treatment-naive and IFN-based therapy-experienced patients with HCV GT1b infection in South Korea, Taiwan, and China were randomized 1:1 to receive either OBV/PTV/r (25 mg/150 mg/100 mg once daily) and DSV (250 mg twice daily) or placebo for 12 weeks during the double-blind (DB) period. Patients in the placebo arm subsequently received OBV/PTV/r + DSV for 12 weeks during the open-label period. Patients will be followed for 48 weeks after last dose of study drugs. The primary objectives are to compare the SVR12 rates for the treatment-naive and -experienced patients to corresponding historical SVR rates of telaprevir + peg-interferon and ribavirin therapy, and assess the safety of the OBV/PTV/r + DSV regimen. Presented are results from the South Korean and Taiwanese populations. Results: In both South Korea and Taiwan, 120 patients were randomized and treated. Of South Korean patients, 45% were male, 33% were treatment-experienced and 89% had F0-F1 fibrosis. Of Taiwanese patients, 39% were male, 33% were treatment-experienced, and 87% had F0-F1 fibrosis. Safety data and SVR at post-treatment week 4 will be presented. Conclusions: The ONYX-I study is evaluating the safety and efficacy of DAA regimen, OBV/PTV/r + DSV, in Southeast Asian patients without cirrhosis infected with HCV GT1b. Resultant data may help inform treatment guidelines for HCV GT1b in this population.

Numerical simulations of interactions between solitary waves and elastic seawalls on rubble mound breakwaters

Lou, Yun-Feng,Luo, Chuan,Jin, Xian-Long Techno-Press 2015 Structural Engineering and Mechanics, An Int'l Jou Vol.53 No.3

Two dimensional numerical models and physical models have been developed to study the highly nonlinear interactions between waves and breakwaters, but several of these models consider the effects of the structural dynamic responses and the shape of the breakwater axis on the wave pressures. In this study, a multi-material Arbitrary Lagrangian Eulerian (ALE) method is developed to simulate the nonlinear interactions between nonlinear waves and elastic seawalls on a coastal rubble mound breakwater, and is validated experimentally. In the experiment, a solitary wave is generated and used with a physical breakwater model. The wave impact is validated computationally using a breakwater - flume coupling model that replicates the physical model. The computational results, including those for the wave pressure and the water-on-deck, are in good agreement with the experimental results. A local breakwater model is used to discuss the effects of the structural dynamic response and different design parameters of the breakwater on wave loads, together with pressure distribution up the seawall. A large-scale breakwater model is used to numerically study the large-scale wave impact problem and the horizontal distribution of the wave pressures on the seawalls.