Ginsenoside Rg1 activates ligand-independent estrogenic effects via rapid estrogen receptor signaling pathway

Quan-Gui Gao,Li-Ping Zhou,Vien Hoi-Yi Lee,Hoi-Yi Chan,Cornelia Wing-Yin Man,Man-Sau Wong 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.4

Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor(ER) via mitogen-activated protein kinaseemediated pathway. Our study aimed to delineate themechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidneyHEK293 cells were treated with Rg1 (10 12M, 10 8M), 17ß-estradiol (10 8M), or vehicle. Immunoprecipitationwas conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or theirinhibitors were applied. Results: Rg1 rapidly induced ERa translocation to plasma membrane via caveolin-1 and the formation ofsignaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator ofnongenomic activity of ER (MNAR), ERa, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase(MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interferingRNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in thesecells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor(EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). Theincrease in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could beabolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containingsignalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independentlyand exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogenreceptor.

Complex and novel determinants of empathy change in medical students

Gerald Sng Gui Ren,Joshua Tung Yi Min,Yeo Su Ping,Lee Shuh Shing,Ma Thin Mar Win,Hooi Shing Chuan,Dujeepa D. Samarasekera 한국의학교육학회 2016 Korean journal of medical education Vol.28 No.1

Purpose: Physician empathy is a core attribute in medical professionals, giving better patient outcomes. Medical school is an opportune time for building empathetic foundations. This study explores empathy change and focuses on contributory factors. Methods: We conducted a cross-sectional study involving 881 students (63%) from Years 1 to 5 in a Singaporean medical school using the Jefferson Scale of Physician Empathy-Student version (JSPE-S) and a questionnaire investigating the relationship between reported and novel personal-social empathy determinants. Results: Empathy declined significantly between preclinical and clinical years. Female and medical specialty interest respondents had higher scores than their counterparts. Despite strong internal consistency, factor analysis suggested that the JSPE model is not a perfect fit. Year 1 students had highest Perspective Taking scores and Year 2 students had highest Compassionate Care scores. High workload and inappropriate learning environments were the most relevant stressors. Time spent with family, arts, and community service correlated with higher empathy scores, whilst time spent with significant others and individual leisure correlated with lower scores. Thematic analysis revealed that the most common self-reported determinants were exposure to activity (community service) or socialisation, personal and family-related event as well as environment (high work-load). Conclusion: While the empathy construct in multicultural Singapore is congruent with a Western model, important differences remain. A more subtle understanding of the heterogeneity of the medical student experience is important. A greater breadth of determinants of empathy, such as engagement in arts-related activities should be considered.

Ginsenoside Rg1 activates ligand-independent estrogenic effects via rapid estrogen receptor signaling pathway

Gao, Quan-Gui,Zhou, Li-Ping,Lee, Vien Hoi-Yi,Chan, Hoi-Yi,Man, Cornelia Wing-Yin,Wong, Man-Sau The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.4

Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 ($10^{-12}M$, $10^{-8}M$), $17{\beta}$-estradiol ($10^{-8}M$), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied. Results: Rg1 rapidly induced $ER{\alpha}$ translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), $ER{\alpha}$, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.

WASTEWATER TREATMENT CHARACTERISTICS OF MEMBRANE PROCESSES COMBINED WITH VARIOUS BIOREACTORS

( Xia HUANG,Ping GUI,Cheng Wen WANG,Yi QIAN ) 한국물환경학회 1997 제6차 국제수질보전학회 아시아 태평양지역 학술회의 Vol.2 No.-

Nonlinear low-velocity impact response of graphene platelets reinforced metal foams doubly curved shells

Hao-Xuan Ding,Yi-Wen Zhang,Yin-Ping Li,Gui-Lin She 국제구조공학회 2023 Steel and Composite Structures, An International J Vol.49 No.3

Due to the fact that the nonlinear low-velocity impact response of graphene platelets reinforced metal foams (GPLRMF) doubly curved shells have not been investigated in the existing works, this paper aims to solve this issue. Using Reddy's high-order shear deformation theory (HSDT), the nonlinear governing equations of GPLRMF doubly curved shells are obtained by Euler-Lagrange method, discretized by Galerkin principle, and solved by the fourth-order Runge-Kutta method to obtain the impact force and central deflection. The nonlinear Hertz contact law is applied to determine the contact force. Finally, the impacts of graphene platelets (GPLs) distribution pattern, porosity distribution form, porosity coefficient, damping coefficient, impact parameters (radius and initial velocity), GPLs weight fraction, pre-stressing force and different shell types on the low-velocity impact curves are analyzed. It can be found that, among the four shell structures, the impact resistance of spherical shell is the best, while that of cylindrical shell is the worst.

RALY RNA Binding Protein-like Reduced Expression is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

Cui, Zhi-Wen,Xia, Ye,Ye, Yi-Wang,Jiang, Zhi-Mao,Wang, Ya-Dong,Wu, Jian-Ting,Sun, Liang,Zhao, Jun,Fa, Ping-Ping,Sun, Xiao-Juan,Gui, Yao-Ting,Cai, Zhi-Ming Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7

The molecular mechanisms involved in the progression of clear cell renal cell carcinomas (ccRCCs) are still unclear. The aim of this study was to analyse the relationships between expression of RALYL and clinical characteristics. In 41 paired samples of ccRCCs and adjacent normal tissues, we used real-time qPCR to evaluate the expression of RALYL mRNA. RALYL protein levels were determined in 146 samples of ccRCC and 37 adjacent normal tissues by immunohistochemistry. Statistical analysis was used to explore the relationships between expression of RALYL and the clinical characteristics (gender, age, tumor size, T stage, N stage, M stage, survival times and survival outcome) in ccRCC. In addition, these patients were follow-up period 64 months (range: 4~116months) to investigate the influence on prognosis. We found significantly differences between ccRCC tissues and normal tissues (p<0.001, paired-sample t test) in mRNA levels of RALYL. Immunohistochemistry analyses in 146 ccRCC samples and 37 adjacent normal tissues showed significantly lower RALYL protein levels in ccRCC samples (${\chi}^2$-test, p<0.001), inversely correlating with tumour size (p=0.024), T stage (0.005), N stage (p<0.001) as well as M stage (p=0.019), but not age (p=0.357) and gender (p=0.348). Kaplan-Meier survival analysis demonstrated that people with lower level of RALYL expression had a poorer survival rate than those with a higher level of RALYL expression, significantly different by the log-rank test (p=0.011). Cox regression analysis indicated that RALYL expression (p=0.039), N stage (p=0.008) and distant metastasis (p<0.001) were independent prognosis factors for the overall survival of ccRCC patients. We demonstrated that the expression of RALYL was significantly low in ccRCC and correlated with a poor prognosis in a large number of clinical samples. Our findings showed that RALYL may be a potential therapeutic target as well as a poor prognostic factor.

Improved Control Strategy Based on Space Vectors for Suppressing Grid-Side Current Harmonics in Three-Phase Current Source Rectifiers with a Hybrid Switch

Yan Xu,Guang-xiang Lu,Li-jie Jiang,Gui-Ping Yi 전력전자학회 2015 JOURNAL OF POWER ELECTRONICS Vol.15 No.2

This paper analyses the harmonic pollution to power grids caused by several high-power rectifiers, summarizes the requirements for rectifiers in suppressing grid-side current harmonics and optimizes a new-type of current source PWM rectifier with a hybrid switch. The rectifier with a hybrid switch boasts significant current characteristics and cost advantages in the high-power area. To further enhance the working frequency of the current source rectifier with a hybrid switch for suppressing grid-side harmonics and reducing the inductance size, this paper proposes an optimal control strategy based on space vector. It also verifies that the optimal control strategy based on space vector can reduce the total harmonic distortion of the grid-side current of the rectifier with a hybrid switch via circuit simulation and experimental results.

Improved Control Strategy Based on Space Vectors for Suppressing Grid-Side Current Harmonics in Three-Phase Current Source Rectifiers with a Hybrid Switch

Xu, Yan,Lu, Guang-Xiang,Jiang, Li-Jie,Yi, Gui-Ping The Korean Institute of Power Electronics 2015 JOURNAL OF POWER ELECTRONICS Vol.15 No.2

This paper analyses the harmonic pollution to power grids caused by several high-power rectifiers, summarizes the requirements for rectifiers in suppressing grid-side current harmonics and optimizes a new-type of current source PWM rectifier with a hybrid switch. The rectifier with a hybrid switch boasts significant current characteristics and cost advantages in the high-power area. To further enhance the working frequency of the current source rectifier with a hybrid switch for suppressing grid-side harmonics and reducing the inductance size, this paper proposes an optimal control strategy based on space vector. It also verifies that the optimal control strategy based on space vector can reduce the total harmonic distortion of the grid-side current of the rectifier with a hybrid switch via circuit simulation and experimental results.

Anti-inflammatory effect of hispidin on LPS induced macrophage inflammation through MAPK and JAK1/STAT3 signaling pathways

Han Ying-Hao,Chen Dong-Qin,Jin Mei-Hua,Jin Ying-Hua,Li Jing,Shen Gui-Nan,Li Wei-Long,Gong Yi-Xi,Mao Ying-Ying,Xie Dan-Ping,Lee Dong-Seok,Yu Li-Yun,Kim Sun-Uk,김지수,권태호,Cui Yu-Dong,Sun Hu-Nan 한국응용생명화학회 2020 Applied Biological Chemistry (Appl Biol Chem) Vol.63 No.3

Severe inflammatory reactions caused by macrophage activation can trigger a systemic immune response. In the present study, we observed the anti-inflammatory properties of hispidin on LPS induced RAW264.7 macrophage cells. Our results showed that hispidin treatment significantly reduced the production of cellular NO, IL-6 and reactive oxygen species (ROS) while has not inhibitory effect on TNF-α productions. Excitingly, hispidin treatment retains the phagocytosis ability of macrophages which enabling them to perform the function of removing foreign invaders. Signaling studies showed, hispidin treatment dramatic suppressed the LPS induced mitogen activated protein kinases (MAPK) and JAK/STAT activations. In conclusion, our findings suggest that hispidin may be a new therapeutic target for clinical treatment of macrophages-mediated inflammatory responses.