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.

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.

An Empirical Analysis of Android Apps Bug and Automated Testing Approach for Android Apps

Yi Bie,Sheng Bin,Gengxin Sun,Xicheng Zhou 보안공학연구지원센터 2016 International Journal of Multimedia and Ubiquitous Vol.11 No.9

Android platforms and its applications (apps) have gained tremendous popularity recently, hence the reliability of Android apps is becoming increasingly important. Due to the novelty of the Android platform, apps are prone to errors, which would affect user experience and requires frequent bug fixes. In this paper, an empirical study on bugs in some widely-used open-source Android apps from diverse categories such as media, tools and communication were performed. Based on the findings of the empirical study, an approach for automating the testing process for detecting Android apps GUI bugs was presented. We show how the approach helped to re-discover existing bugs and find new bugs, and how it could be used to prevent certain bug categories. Our empirical study and automated testing approach have the potential to help developers increase the quality of Android apps.

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.

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.

Closed-form solution of axisymmetric deformation of prestressed Föppl-Hencky membrane under constrained deflecting

Yong-Sheng Lian,Jun-Yi Sun,Jiao Dong,Zhou-Lian Zheng,Zhi-Xin Yang 국제구조공학회 2019 Structural Engineering and Mechanics, An Int'l Jou Vol.69 No.6

In this study, the problem of axisymmetric deformation of prestressed Föppl-Hencky membrane under constrained deflecting was analytically solved and its closed-form solution was presented. The small-rotation-angle assumption usually adopted in membrane problems was given up, and the initial stress in membrane was taken into account. Consequently, this closed-form solution has higher calculation accuracy and can be applied for a wider range in comparison with the existing approximate solution. The presented numerical examples demonstrate the validity of the closed-form solution, and show the errors of the contact radius, profile and radial stress of membrane in the existing approximate solution brought by the small-rotation-angle assumption. Moreover, the influence of the initial stress on the contact radius is also discussed based on the numerical examples.

The associations of obesity phenotypes with the risk of hypertension and its transitions among middle-aged and older Chinese adults

Ziyue Sheng,Shang Lou,Jin Cao,Weidi Sun,Yaojia Shen,Yunhan Xu,Ziyang Ren,Wen Liu,Qian Yi,Peige Song 한국역학회 2023 Epidemiology and Health Vol.45 No.-

OBJECTIVES: This study aimed to investigate the associations of obesity phenotypes with hypertension stages, phenotypes, and transitions among middle-aged and older Chinese. METHODS: Using the 2011-2015 waves of the China Health and Retirement Longitudinal Study, we conducted a cross-sectional analysis included 9,015 subjects and a longitudinal analysis included 4,961 subjects, with 4,872 having full data on the hypertension stage and 4,784 having full data on the hypertension phenotype. Based on body mass index and waist circumstance, subjects were categorized into 4 mutually exclusive obesity phenotypes: normal weight with no central obesity (NWNCO), abnormal weight with no central obesity (AWNCO), normal weight with central obesity (NWCO), and abnormal weight with central obesity (AWCO). Hypertension stages were classified into normotension, pre-hypertension, stage 1 hypertension, and stage 2 hypertension. Hypertension phenotypes were categorized as normotension, pre-hypertension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH). The association between obesity phenotypes and hypertension was estimated by logistic regression. A comparison between different sexes was conducted by testing the interaction effect of sex. RESULTS: NWCO was associated with normal→stage 2 (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.11 to 3.42), maintained stage 1 (OR, 1.62; 95% CI, 1.14 to 2.29), and normal→ISH (OR, 1.39; 95% CI, 1.05 to 1.85). AWCO was associated with normal→stage 1 (OR, 1.75; 95% CI, 1.40 to 2.19), maintained stage 1 (OR, 2.77; 95% CI, 2.06 to 3.72), maintained stage 2 (OR, 2.80; 95% CI, 1.50 to 5.25), normal→ISH (OR, 1.56; 95% CI, 1.20 to 2.02), and normal→SDH (OR, 2.54; 95% CI, 1.72 to 3.75). An interaction effect of sex existed in the association between obesity phenotypes and hypertension stages. CONCLUSIONS: This study highlights the importance of various obesity phenotypes and sex differences in hypertension progression. Tailored interventions for different obesity phenotypes may be warranted in hypertension management, taking into account sex-specific differences to improve outcomes.

Solubility of D(−)-p-Hydroxyphenylglycine dane salt in binary methanol+isopropanol solvent mixtures

Zheng-Ming Yi,Qun-Sheng Li,Wei-Zhong Liu,Xu-Feng Sun 한국화학공학회 2010 Korean Journal of Chemical Engineering Vol.27 No.3

The solubility of D(−)-p-Hydroxyphenylglycine Dane Salt (HPGDane Salt) in binary methanol and isopropanol solvent mixtures was measured using a laser technique with the temperature range from 283.15 K to 323.15 K and mole fraction (x2) range from 0.0000 to 1.0000. The results were correlated with a semi-empirical equation.

Transcriptome analysis reveals distinct innate immunity and ribosomal response at early stage of AcMNPV infection in haemocyte of silkworm resistant and susceptible strains

Li Tao,Qin Sheng,Sun Xia,Zhang Kai-xiang,Ding Xin-yi,Wang Xue-yang,Li Muwang 한국응용곤충학회 2022 Journal of Asia-Pacific Entomology Vol.25 No.3

Baculoviruses are enveloped rod-shaped viruses that with circular double-stranded and large DNA genome. Baculoviruses successfully invade by using the host factors, especially at the process of establishing early infection. In this study, we investigated the different resistant strains of silkworm in response to AcMNPV early infection by RNA-sequencing. Our data revealed that the genes involved in innate immunity and ribosomal proteins were suppressed and cytoskeleton were induced in susceptible strain p50, thus facilitating the viral replication. However, in resistant strain C108, the genes participated in endocytosis and RNA transport were down-regulated, while up-regulation of ribosomal proteins and energy metabolic to inhibit the infection of the virus. These data provide a new sight of the initial host transcriptional responses to viral infection in silkworm.

Association of CDKN2B-AS1 rs1333049 with Brain Diseases: A Case-control Study and a Meta-analysis

Jikuang Zhao,Xizheng Wu,Sheng Nie,Xiang Gao,Jie Sun,Keqin Li,Tiefeng Zhang,Yi Huang 대한정신약물학회 2017 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.15 No.1

Objective: CDKN2B-AS1 polymorphisms were shown to associate with the risk of stroke in European. The goal of this study was to evaluate the contribution of CDKN2B-AS1 rs1333049 to the risk of hemorrhagic stroke (HS) and brain tumor (BT) in Han Chinese. Methods: A total of 142 HSs, 115 BTs, and 494 controls were included in the current association study. The genotyping test was performed using the melting temperature shift method. Results: We failed to validate the association of CDKN2B-AS1 rs1333049 with the risk of brain disease. Significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p=0.027), high-density lipoprotein cholesterol (HDL-C) (p<0.001) and total cholesterol (TC) (p<0.001) were found in HSs in the genotype GG/GC carriers, but not the genotype CC carriers (p>0.05). The meta-analysis of 10 studies among 133,993 individuals concluded that rs1333049 of CDKN2B-AS1 gene was likely to increase a 16% incidence rate of cerebrovascular disease (CD) among various populations (odds ratio 1.16, 95% confidence interval 1.08-1.25; p<0.0001, random-effect method). Conclusion: Our case-control study identified rs1333049 genotypes showed different association with the concentration of the LDL-C, HDL-C and TC in the HS patients. Meta-analysis supported the association between rs1333049 and CD risk in various populations, although we were unable to observe association between rs1333049 and the risk of HSs in Han Chinese.