Water-soluble coenzyme Q₁₀ provides better protection than lipid-soluble coenzyme Q₁₀ in a rat model of chronic tacrolimus nephropathy

( Sheng Cui ),( Kang Luo ),( Yi Quan ),( Sun Woo Lim ),( Yoo Jin Shin ),( Kyung Eun Lee ),( Hong Lim Kim ),( Eun Jeong Ko ),( Ju Hwan Kim ),( Sang J. Chung ),( Soo Kyung Bae ),( Byung Ha Chung ),( Chu 대한내과학회 2021 The Korean Journal of Internal Medicine Vol.36 No.4

Background/Aims: Coenzyme Q₁₀ (CoQ₁₀), is a promising antioxidant; however, low bioavailability owing to lipid-solubility is a limiting factor. We developed water-soluble CoQ₁₀ (CoQ₁₀-W) and compared its effects with conventional lipid-soluble CoQ₁₀ (CoQ₁₀-L) in an experimental model of chronic tacrolimus (Tac) nephropathy. Methods: CoQ₁₀-W was developed from a glycyrrhizic-carnitine mixed layer CoQ₁₀ micelle based on acyltransferases. Chronic nephropathy was induced in rats with 28-day Tac treatment; they were concomitantly treated with CoQ₁₀-L or CoQ₁₀-W. CoQ₁₀ level in plasma and kidney were measured using liquid chromatography-mass spectrometry. CoQ₁₀-W and CoQ₁₀-L effects on Tac-induced nephropathy were assessed in terms of renal function, histopathology, oxidative stress, and apoptotic cell death. Their effects on cell viability and reactive oxygen species (ROS) production were assessed in cultured proximal tubular cells, human kidney 2 (HK-2) cells. Results: The plasma CoQ₁₀ level was significantly higher in the CoQ₁₀-W group than in the CoQ₁₀-L group. Tac treatment caused renal dysfunction, typical pathologic lesions, and oxidative stress markers. Serum creatinine was restored in the Tac + CoQ₁₀-L or CoQ₁₀-W groups compared with that in the Tac group. CoQ₁₀-W administration reduced oxidative stress and apoptosis markers. Mitochondrial ultrastructure assessment revealed that the addition of CoQ₁₀-L or CoQ₁₀-W with Tac increased mitochondrial size and number than Tac treatment alone. In vitro investigations revealed that both CoQ₁₀-L and CoQ₁₀-W improved cell viability and reduced ROS production in the Tac-induced HK-2 cell injury. Conclusions: CoQ₁₀-W has a better therapeutic effect in Tac-induced renal injury than conventional CoQ₁₀-L, possibly associated with improved CoQ₁₀ bioavailability.

The therapeutic efficacy of water-soluble coenzyme Q10 in an experimental model of tacrolimus-induced diabetes mellitus

Yi Quan,Kang Luo,Sheng Cui,Sun Woo Lim,신유진,Eun Jeong Ko,Ju Hwan Kim,Sang J. Chung,Soo Kyung Bae,Byung Ha Chung,Chul Woo Yang 대한내과학회 2020 The Korean Journal of Internal Medicine Vol.35 No.6

Background/Aims: Coenzyme Q10 (CoQ10) has antioxidant effects and is commercially available and marketed extensively. However, due to its low bioavailability, its effects are still controversial. We developed a water-soluble CoQ10-based micelle formulation (CoQ10-W) and tested it in an experimental model of tacrolimus (TAC)-induced diabetes mellitus (DM). Methods: We developed CoQ10-W from a glycyrrhizic-carnitine mixed layer CoQ10 micelle preparation based on acyltransferases. TAC-induced DM rats were treated with either lipid-soluble CoQ10 (CoQ10-L) or CoQ10-W for 4 weeks. Their plasma and pancreatic CoQ10 concentrations were measured using liquid chromatography- tandem mass spectrometry. The therapeutic efficacies of CoQ10-W and CoQ10-L on TAC-induced DM were compared using functional and morphological parameters and their effects on cell viability and reactive oxygen species (ROS) production were also evaluated in cultured rat insulinoma cells. Results: The plasma CoQ10 level was significantly increased in the CoQ10-W group compared to that in the CoQ10-L group. Intraperitoneal glucose tolerance tests and glucose-stimulated insulin secretion revealed that CoQ10-W controlled hyperglycemia and restored insulin secretion significantly better than CoQ10-L. The TAC-mediated decrease in pancreatic islet size was significantly attenuated by CoQ10-W but not by CoQ10-L. TAC-induced oxidative stress and apoptosis were significantly more reduced by CoQ10-W than CoQ10-L. Electron microscopy revealed that CoQ10-W restored TAC-induced attenuation in the number of insulin granules and the average mitochondrial area, unlike CoQ10-L. In vitro studies showed that CoQ10-L and CoQ10-W both improved cell viability and reduced ROS production in TAC-treated islet cells to a similar extent. Conclusions: CoQ10-W has better therapeutic efficacy than CoQ10-L in TAC-induced DM.

Aero-engine Gas Path Performance Degradation Assessment Based on a Multi-objective Optimized Discrete Feddback Network

Zhi-Quan Cui,Shi-Sheng Zhong,Zhi-Qi Yan 제어·로봇·시스템학회 2021 International Journal of Control, Automation, and Vol.19 No.6

In order to solve the problem of neural network algorithm for aero-engine’s gas path performance evaluation under high-dimensional evaluation index with non-equal weights, the trend analysis method and fault fingerprints are used to mine engine’s gas path performance characteristic parameters. A comprehensive weighting method based on game theory is proposed to optimize the weight value of each gas path performance characteristic parameter. A discrete feedback neural network with single-layer and binary output is established. The original gas path performance evaluation index is equivalently expanded according to the weight ratio, and the gas path state evaluation indexes with different weights are mapped into higher-dimensional equivalent evaluation indexes with equal weights. The network attractor is designed according to the engine gas path performance evaluation levels, and the design of discrete feedback neural network weights is transformed into multi-objective programming problem, and a particle swarm optimization algorithm with adaptive inertia weight is used to improve the efficiency and global search ability of particle swarm optimization. The experimental results shows that the proposed model and algorithm can provide a scientific and reasonable machine learning method for the evaluation of high-dimensional evaluation index with non-equal weights.

The safety, immunological benefi ts, and effi cacy of ginseng in organ transplantation

임선우,Kang Luo,Yi Quan,Sheng Cui,Yoo Jin Shin,Eun Jeong Ko,Byung Ha Chung,양철우 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.3

Korean ginseng (Panax ginseng) is associated with a variety of therapeutic effects, including antioxidative,anti-inflammatory, vasorelaxative, antiallergic, antidiabetic, and anticancer effects. Accordingly, the useof ginseng has reached an all-time high among members of the general public. However, the safety andefficacy of ginseng in transplant recipients receiving immunosuppressant drugs have still not beenelucidated. Transplantation is the most challenging and complex of surgical procedures and may requirecausation for the use of ginseng. In this regard, we have previously examined the safety, immunologicalbenefits, and protective mechanisms of ginseng with respect to calcineurin inhibitor-based immunosuppression,which is the most widely used regimen in organ transplantation. Using an experimentalmodel of calcineurin inhibitor-induced organ injury, we found that ginseng does not affect drug levels inthe peripheral blood and tissue, favorably regulates immune response, and protects against calcineurininhibitor-induced nephrotoxicity and pancreatic islet injury. On the basis of our experimental studies anda review of the related literature, we propose that ginseng may provide benefits in organ transplantrecipients administered calcineurin inhibitors. Through the present review, we aimed to briefly discussour current understanding of the therapeutic benefits of ginseng related to transplant patient survival.

The safety, immunological benefits, and efficacy of ginseng in organ transplantation

Lim, Sun Woo,Luo, Kang,Quan, Yi,Cui, Sheng,Shin, Yoo Jin,Ko, Eun Jeong,Chung, Byung Ha,Yang, Chul Woo The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.3

Korean ginseng (Panax ginseng) is associated with a variety of therapeutic effects, including antioxidative, anti-inflammatory, vasorelaxative, antiallergic, antidiabetic, and anticancer effects. Accordingly, the use of ginseng has reached an all-time high among members of the general public. However, the safety and efficacy of ginseng in transplant recipients receiving immunosuppressant drugs have still not been elucidated. Transplantation is the most challenging and complex of surgical procedures and may require causation for the use of ginseng. In this regard, we have previously examined the safety, immunological benefits, and protective mechanisms of ginseng with respect to calcineurin inhibitor-based immunosuppression, which is the most widely used regimen in organ transplantation. Using an experimental model of calcineurin inhibitor-induced organ injury, we found that ginseng does not affect drug levels in the peripheral blood and tissue, favorably regulates immune response, and protects against calcineurin inhibitor-induced nephrotoxicity and pancreatic islet injury. On the basis of our experimental studies and a review of the related literature, we propose that ginseng may provide benefits in organ transplant recipients administered calcineurin inhibitors. Through the present review, we aimed to briefly discuss our current understanding of the therapeutic benefits of ginseng related to transplant patient survival.

Analysis on Double Rain Belts of a Rainstorm in Liaoning

YANG Qing,YAN Qi,CHEN Li-qiang,GAO Song-ying,LI Shuang,CUI Sheng-quan,LU Bing-hong 한국기상학회 2015 한국기상학회 학술대회 논문집 Vol.2015 No.10

Alleviation of renal ischemia/reperfusion injury by exosomes from induced pluripotent stem cell-derived mesenchymal stem cells

( Sun Woo Lim ),( Kyung Woon Kim ),( Bo Mi Kim ),( Yoo Jin Shin ),( Kang Luo ),( Yi Quan ),( Sheng Cui ),( Eun Jeong Ko ),( Byung Ha Chung ),( Chul Woo Yang ) 대한내과학회 2022 The Korean Journal of Internal Medicine Vol.37 No.2

Background/Aims: Renal ischemia followed by reperfusion (I/R) is a leading cause of acute kidney injury (AKI), which is closely associated with high morbidity and mortality. Studies have shown that induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) exert powerful therapeutic effects in renal ischemia. However, the efficacy of iMSC-derived exosomes (iExo) on I/R injuries remains largely unknown. Methods: Human iPSCs were differentiated into iMSCs using a modified one-step method. Ultrafiltration, combined with purification, was used to isolate iExo from iMSCs. iExo was administered following I/R injury in a mouse model. The effect of iExo on I/R injury was assessed through changes in renal function, histology, and expression of oxidative stress, inflammation, and apoptosis markers. Further, we evaluated its association with the extracellular signal-regulated kinase (ERK) 1/2 signaling pathway. Results: Mice subjected to I/R injury exhibited typical AKI patterns; serum creatinine level, tubular necrosis, apoptosis, inflammatory cytokine production, and oxidative stress were markedly increased compared to sham mice. However, treatment with iExo attenuated these changes, significantly improving renal function and tissue damage, similar to the renoprotective effects of iMSCs on I/R injury. Significant induction of activated ERK 1/2 signaling molecules was observed in mice treated with iExo compared to those in the I/R injury group. Conclusions: The present study demonstrates that iExo administration ameliorated renal damage following I/R, suggesting that iMSC-derived exosomes may provide a novel therapeutic approach for AKI treatment.