20(S)-protopanaxadiol and oleanolic acid ameliorate cognitive deficits in APP/PS1 transgenic mice by enhancing hippocampal neurogenesis

Kaili Lin,Stephen Cho-Wing Sze,Bin Liu,Zhang Zhang,Zhu Zhang,Peili Zhu,Ying Wang,Qiudi Deng,Ken Kin-Lam Yung,Shiqing Zhang 고려인삼학회 2021 Journal of Ginseng Research Vol.45 No.2

Background: Alzheimer"s disease (AD) is one of the most prevalent neurodegenerative disorders. Enhancing hippocampal neurogenesis by promoting proliferation and differentiation of neural stem cells (NSCs) is a promising therapeutic strategy for AD. 20(S)-protopanaxadiol (PPD) and oleanolic acid (OA) are small, bioactive compounds found in ginseng that can promote NSC proliferation and neural differentiation in vitro. However, it is currently unknown whether PPD or OA can attenuate cognitive deficits by enhancing hippocampal neurogenesis in vivo in a transgenic APP/PS1 AD mouse model. Here, we administered PPD or OA to APP/PS1 mice and monitored the effects on cognition and hippocampal neurogenesis. Methods: We used the Morris water maze, Y maze, and open field tests to compare the cognitive capacities of treated and untreated APP/PS1 mice. We investigated hippocampal neurogenesis using Nissl staining and BrdU/NeuN double labeling. NSC proliferation was quantified by Sox2 labeling of the hippocampal dentate gyrus. We used western blotting to determine the effects of PPD and OA on Wnt/GSK3β/β-catenin pathway activation in the hippocampus. Results: Both PPD and OA significantly ameliorated the cognitive impairments observed in untreated APP/PS1 mice. Furthermore, PPD and OA significantly promoted hippocampal neurogenesis and NSC proliferation. At the mechanistic level, PPD and OA treatments resulted in Wnt/GSK-3β/β-catenin pathway activation in the hippocampus. Conclusion: PPD and OA ameliorate cognitive deficits in APP/PS1 mice by enhancing hippocampal neurogenesis, achieved by stimulating the Wnt/GSK-3β/β-catenin pathway. As such, PPD and OA are promising novel therapeutic agents for the treatment of AD and other neurodegenerative diseases.

Combination of High-Density Lipoprotein Cholesterol and Lipoprotein(a) as a Predictor of Collateral Circulation in Patients With Severe Unilateral Internal Carotid Artery Stenosis or Occlusion

Shuyin Ma,Meijuan Zhang,Huiyang Qu,Yuxuan Cheng,Shuang Du,Jiaxin Fan,Qingling Yao,Xiao Dong Zhang,Mengying Chen,Nan Zhang,Kaili Shi,Yizhou Huang,Shuqin Zhan 대한신경과학회 2022 Journal of Clinical Neurology Vol.18 No.1

Background and Purpose Collateral circulation is considered an important factor affecting the risk of stroke, but the factors that affect collateral circulation remain unclear. This study was performed to identify the factors associated with collateral circulation, especially blood lipids. Methods The study involved patients who had undergone digital subtraction angiography and were confirmed as having severe unilateral stenosis or occlusion of the internal carotid artery (ICA). We classified the collateral circulation status of each patient as good (Grade 3 or 4) or poor (Grade 0, 1, or 2) according to the grading system of the American Society of Interventional and Therapeutic Neuroradiology/American Society of Interventional Radiology. We collected data on patients’ characteristics and identified the factors that affect collateral circulation. Results This study included 212 patients. The multivariate logistic regression analysis showed that the high-density lipoprotein cholesterol (HDL-C) concentration and a complete anterior half of the circle of Willis were independent protective factors for good collateral circulation, whereas elevated lipoprotein(a) [Lp(a)] and serum creatinine concentrations were independent risk factors for good collateral circulation. The area under the receiver operating characteristics curve (AUC) was 0.68 (95% confidence interval [CI], 0.61–0.76) for HDL-C and 0.69 (95% CI, 0.62–0.76) for Lp(a). A binary logistic regression model analysis of the joint factor of HDL-C and Lp(a) yielded an AUC of 0.77 (95% CI, 0.71–0.84). Conclusions In patients with severe unilateral ICA stenosis or occlusion, the combination of HDL-C and Lp(a) is a useful predictor of collateral circulation.

20(S)-protopanaxadiol promotes the migration, proliferation, and differentiation of neural stem cells by targeting GSK-3b in the Wnt/ GSK-3b/b-catenin pathway

Kaili Lin,Bin Liu,Sze-Lam Lim,Xiuqiong Fu,Stephen C.-W. Sze,Ken K.-L. Yung,Shiqing Zhang 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.3

Background: Active natural ingredients, especially small molecules, have recently received wide attention as modifiers used to treat neurodegenerative disease by promoting neurogenic regeneration of neural stem cell (NSC) in situ. 20(S)-protopanaxadiol (PPD), one of the bioactive ingredients in ginseng, possesses neuroprotective properties. However, the effect of PPD on NSC proliferation and differentiation and its mechanism of action are incompletely understood. Methods: In this study, we investigated the impact of PPD on NSC proliferation and neuronal lineage differentiation through activation of the Wnt/glycogen synthase kinase (GSK)-3b/b-catenin pathway. NSC migration and proliferation were investigated by neurosphere assay, Cell Counting Kit-8 assay, and EdU assay. NSC differentiation was analyzed by Western blot and immunofluorescence staining. Involvement of the Wnt/GSK3b/b-catenin pathway was examined by molecular simulation and Western blot and verified using gene transfection. Results: PPD significantly promoted neural migration and induced a significant increase in NSC proliferation in a time- and dose-dependent manner. Furthermore, a remarkable increase in antimicrotubule- associated protein 2 expression and decrease in nestin protein expression were induced by PPD. During the differentiation process, PPD targeted and stimulated the phosphorylation of GSK-3b at Ser9 and the active forms of b-catenin, resulting in activation of the Wnt/GSK-3b/b-catenin pathway. Transfection of NSCs with a constitutively active GSK-3b mutant at S9A significantly hampered the proliferation and neural differentiation mediated by PPD. Conclusion: PPD promotes NSC proliferation and neural differentiation in vitro via activation of the Wnt/ GSK-3b/b-catenin pathway by targeting GSK-3b, potentially having great significance for the treatment of neurodegenerative diseases.

20(S)-protopanaxadiol promotes the migration, proliferation, and differentiation of neural stem cells by targeting GSK-3β in the Wnt/GSK-3β/β-catenin pathway

Lin, Kaili,Liu, Bin,Lim, Sze-Lam,Fu, Xiuqiong,Sze, Stephen C.W.,Yung, Ken K.L.,Zhang, Shiqing The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.3

Background: Active natural ingredients, especially small molecules, have recently received wide attention as modifiers used to treat neurodegenerative disease by promoting neurogenic regeneration of neural stem cell (NSC) in situ. 20(S)-protopanaxadiol (PPD), one of the bioactive ingredients in ginseng, possesses neuroprotective properties. However, the effect of PPD on NSC proliferation and differentiation and its mechanism of action are incompletely understood. Methods: In this study, we investigated the impact of PPD on NSC proliferation and neuronal lineage differentiation through activation of the Wnt/glycogen synthase kinase (GSK)-3β/β-catenin pathway. NSC migration and proliferation were investigated by neurosphere assay, Cell Counting Kit-8 assay, and EdU assay. NSC differentiation was analyzed by Western blot and immunofluorescence staining. Involvement of the Wnt/GSK3β/β-catenin pathway was examined by molecular simulation and Western blot and verified using gene transfection. Results: PPD significantly promoted neural migration and induced a significant increase in NSC proliferation in a time- and dose-dependent manner. Furthermore, a remarkable increase in anti-microtubule-associated protein 2 expression and decrease in nestin protein expression were induced by PPD. During the differentiation process, PPD targeted and stimulated the phosphorylation of GSK-3β at Ser9 and the active forms of β-catenin, resulting in activation of the Wnt/GSK-3β/β-catenin pathway. Transfection of NSCs with a constitutively active GSK-3β mutant at S9A significantly hampered the proliferation and neural differentiation mediated by PPD. Conclusion: PPD promotes NSC proliferation and neural differentiation in vitro via activation of the Wnt/GSK-3β/β-catenin pathway by targeting GSK-3β, potentially having great significance for the treatment of neurodegenerative diseases.

How graphene crosses a grain boundary on the catalyst surface during chemical vapour deposition growth

Dong, Jichen,Zhang, Leining,Zhang, Kaili,Ding, Feng The Royal Society of Chemistry 2018 Nanoscale Vol.10 No.15

<P>The chemical vapour deposition (CVD) growth of graphene is normally an epitaxial process, where the atomic structure of the adlayer should copy the texture of the substrate. However, it has been widely observed that single crystalline graphene grown on metal foil may cross a grain boundary (GB) of the substrate without forming any line defect, a necessary condition to change its crystalline orientation and maintain the structure registry with the substrate on the other side of the GB. Here, we present a comprehensive theoretical study on graphene growth behavior on polycrystalline metal substrates. Our density functional theory (DFT) calculations reveal that for graphene growth on most metal surfaces, the binding energy difference between the epitaxial and non-epitaxial graphene on the substrate is not large enough to compensate for the formation energy of a GB in graphene and therefore, during the CVD process, the growing graphene can pass through a GB on the metal surface without changing its crystalline orientation. Hence, graphene CVD growth cannot be strictly regarded as an epitaxial process; this conclusion is further verified by atomic simulations. The present study shows that the growth of graphene on a metal catalyst surface should be regarded rather as a quasi-epitaxial process, where a graphene domain is aligned only on the single crystalline metal facet on which it nucleates, but this structural registry with the metal substrate may be lost when the graphene crosses a GB on the metal surface.</P>

Ectopic expression of grape hyacinth R3 MYB repressor MaMYBx affects anthocyanin and proanthocyanidin biosynthesis and epidermal cell differentiation in Arabidopsis

Wang Jiangyu,Zhang Boxiao,Tian Shuting,Zhang Han,Gong Jiaxin,Chen Kaili,Du Lingjuan 한국원예학회 2022 Horticulture, Environment, and Biotechnology Vol.63 No.3

Single-repeat R3 MYB transcription factors regulate multiple developmental and metabolic pathways in plants. The anthocyanin-related R3 MYB repressor MaMYBx was previously identified in grape hyacinth (Muscari spp.), and its ectopic expression reduced the accumulation of anthocyanin in tobacco petals. However, whether the function of MaMYBx is conserved across plant species remains unclear. Here, we report that ectopic expression of MaMYBx regulates anthocyanin and proanthocyanidin (PA) biosynthesis and epidermal cell differentiation in Arabidopsis. MaMYBx overexpression in Arabidopsis decreased the accumulation of anthocyanin and PA by downregulating the late structural genes (AtDFR, AtANS, AtANR, and AtGST), some key regulatory factors of MBW complexes (AtPAP1, AtTT8, and AtGL3) and an R3 MYB gene (AtCPC) involved in flavonoid biosynthesis. In addition, MaMYBx also modulated trichome formation and root hair differentiation by downregulating MBW component genes (AtGL1, AtWER, and AtGL3) and their target gene AtGL2 and by upregulating several R3 MYB genes (AtTRY and AtTCL1). We further found that MaMYBx transgenic plants accumulated less anthocyanin than did wild-type plants under salt, osmotic pressure, cold, and nitrogen stresses. Moreover, the effect was even greater, and significantly less anthocyanin accumulated. In conclusion, these results implied functional conservation of MaMYBx in anthocyanin and PA biosynthesis pathways of Arabidopsis. Therefore, MaMYBx likely represents a new potential gene for the molecular breeding of horticulture and ornamental plants via the regulation of anthocyanin and PA.

Motives of cheating among secondary students: the role of self-efficacy and peer influence

Wong Lok Yan Nora,Kaili Chen Zhang 서울대학교 교육연구소 2010 Asia Pacific Education Review Vol.11 No.4

A survey research study was conducted with a sample of 100 secondary students from a local secondary school about the motives of cheating. The primary focus of this study was the interplay among variables of self-efficacy, peer influence and cheating. The results showed that students with low self-efficacy were more likely to cheat than those who perceived themselves as efficacious. It was further found that peers played a significant role in discouraging cheating by expressing disapproval and informing teachers of dishonest behaviour.

The multifunctional RNA-binding protein hnRNPK is critical for the proliferation and differentiation of myoblasts

( Yongjie Xu ),( Rui Li ),( Kaili Zhang ),( Wei Wu ),( Suying Wang ),( Pengpeng Zhang ),( Haixia Xu ) 생화학분자생물학회(구 한국생화학분자생물학회) 2018 BMB Reports Vol.51 No.7

HnRNPK is a multifunctional protein that participates in chromatin remodeling, transcription, RNA splicing, mRNA stability and translation. Here, we uncovered the function of hnRNPK in regulating the proliferation and differentiation of myoblasts. hnRNPK was mutated in the C2C12 myoblast cell line using the CRISPR/Cas9 system. A decreased proliferation rate was observed in hnRNPK-mutated cells, suggesting an impaired proliferation phenotype. Furthermore, increased G2/M phase, decreased S phase and increased sub-G1 phase cells were detected in the hnRNPK-mutated cell lines. The expression analysis of key cell cycle regulators indicated mRNA of Cyclin A2 was significantly increased in the mutant myoblasts compared to the control cells, while Cyclin B1, Cdc25b and Cdc25c were decreased sharply. In addition to the myoblast proliferation defect, the mutant cells exhibited defect in myotube formation. The myotube formation marker, myosin heavy chain (MHC), was decreased sharply in hnRNPK-mutated cells compared to control myoblasts during differentiation. The deficiency in hnRNPK also resulted in the repression of Myog expression, a key myogenic regulator during differentiation. Together, our data demonstrate that hnRNPK is required for myoblast proliferation and differentiation and may be an essential regulator of myoblast function. [BMB Reports 2018; 51(7): 350-355]

Facile Preparation of Novel Hierarchically Porous Carbon at the Molecular Level for Supercapacitor Electrode Application

Kai Li,Wei-Bin Zhang,Zhi-Yun Zhao,Yue Zhao,Xi-Wen Chen,Ling-Bin Kong 성균관대학교(자연과학캠퍼스) 성균나노과학기술원 2018 NANO Vol.13 No.08

Hierarchically porous carbons are obtained by a facile process of carbonizing the precursor of diblock copolymer xPS-b-polymethylmethacrylate (PMMA). In the diblock copolymer, there is a carbon source of cross-linked polystyrene (xPS) and a sacrificial block of PMMA. The atom transfer radical polymerization was used to synthesize the diblock copolymer with controlled molecular weight and narrow polydispersity in dimethylformamide at 120 ℃. The obtained hierarchically porous carbons (HPCs) exhibit remarkable electrochemical properties, such as higher specific capacitance of 204 Fg -1 at the current density of 0.5Ag -1 in 6 mol L -1 aqueous KOH electrolyte. In addition, it also presents an excellent rate performance of 64% capacitance retention as the current density increases to 10Ag -1 and a superior cycling stability of 98% capacitance retention after 5000 cycles at the current density of 1Ag -1.

miR-379 Inhibits Cell Proliferation, Invasion, and Migration of Vascular Smooth Muscle Cells by Targeting Insulin-Like Factor-1

Kai Li,Yong Wang,Anji Zhang,Baixue Liu,Li Jia 연세대학교의과대학 2017 Yonsei medical journal Vol.58 No.1

Purpose: MicroRNAs are small non-coding RNAs that play important roles in vascular smooth muscle cell (VSMC) function. Thisstudy investigated the role of miR-379 on proliferation, invasion, and migration of VSMCs and explored underlying mechanismsthereof. Materials and Methods: MicroRNA, mRNA, and protein levels were determined by quantitative real-time PCR and western blot. The proliferative, invasive, and migratory abilities of VSMCs were measured by CCK-8, invasion, and wound healing assay, respectively. Luciferase reporter assay was used to confirm the target of miR-379. Results: Platelet-derived growth factor-bb was found to promote cell proliferation and suppress miR-379 expression in VSMCs. Functional assays demonstrated that miR-379 inhibited cell proliferation, cell invasion, and migration. Flow cytometry results furthershowed that miR-379 induced apoptosis in VSMCs. TargetScan analysis and luciferase report assay confirmed that insulin-likegrowth factor-1 (IGF-1) 3’UTR is a direct target of miR-379, and mRNA and protein levels of miR-379 and IGF-1 were inversely correlated. Rescue experiments showed that enforced expression of IGF-1 sufficiently overcomes the inhibitory effect of miR-379 on cellproliferation, invasion, and migration in VSMCs. Conclusion: Our results suggest that miR-379 plays an important role in regulating VSMCs proliferation, invasion, and migrationby targeting IGF-1.