Androgen receptor and hyaluronan-mediated motility receptor as new molecular targets of baicalein: new molecular mechanisms for its anticancer properties

Mingyue Jiang,Suman Poudel,Kyung Song 대한약학회 2023 Archives of Pharmacal Research Vol.46 No.8

Natural compounds known as phytochemicals have served as valuable resources for the development of new anti-cancer drugs and treatment of malignancies. Among these phytochemicals, baicalein is an emerging anti-tumor flavonoid obtained from Scutellaria baicaleinsis (Lamiaceae), but its underlying mechanisms of action and molecular targets have not yet been completely elucidated. Here, we identified new mechanisms for the anti-tumor activities of baicalein, providing evidence that hyaluronan-mediated motility receptor (HMMR) and androgen receptor (AR) are new molecular targets of baicalein in human cancer cells. We observed that HMMR, known to be highly associated with poor prognosis in a wide range of human cancers, was substantially downregulated by baicalein at mRNA and protein levels. Reporter assays further revealed that the suppression of HMMR by baicalein might occur through a transcriptional regulatory mechanism with the participation of Egr-1, E2F3α, and serum response factor (SRF). We also found that baicalein significantly inhibits androgenic responses in hormone-responsive prostate cancer cells, indicating that this might be attributed to the downregulation of AR promoter activity by baicalein. Additionally, baicalein markedly induced the expression of tumor suppressive miR-30C, which might be partly involved in baicalein-mediated autophagy and anti-cancer effects. Overall, our study sheds light on new diverse mechanisms of the anti-cancer effects exhibited by baicalein, implying that baicalein could be a potential therapeutic agent against human cancers and function as an inhibitor of HMMR and AR.

Transcriptional suppression of androgen receptor by 18β-glycyrrhetinic acid in LNCaP human prostate cancer cells

You Sun,Mingyue Jiang,Pil‑Hoon Park,Kyung Song 대한약학회 2020 Archives of Pharmacal Research Vol.43 No.4

Androgen receptor (AR) plays a pivotal role as atarget for amplification/mutation in pathogenesis and tumorprogression in prostate, and thus, controlling AR activityor expression might be a feasible therapeutic approach forthe treatment of prostate cancer. Here, we report the novelmechanisms by which 18β-glycyrrhetinic acid (GA) targetsAR to stimulate cell death in both hormone-responsive and-refractory prostate cancer cells. We found that miR-488, atumor suppressive microRNA, was markedly induced by GAtreatment, resulting in the down-regulation of AR expressionand inhibition of cellular responses mediated by androgens. Moreover, GA not only suppressed the expression of androgentarget genes (TMPRSS2, PSA, and NKX3.1), but alsoenhanced the suppressive effect of anti-androgens (bicalutamideand flutamide) on LNCaP cell growth. Our data furtherprovides evidence that down-regulation of AR expression byGA may occur through transcriptional suppression at AR promoter region between − 1014 and − 829. Ectopic expressionof SFR and E2F3α reversed the inhibitory effect of GAon AR promoter activity as well as protein expression, suggestingthat GA may target transcription factors SRF andE2F3α to regulate AR expression. Taken together, our studyprovides new insights on AR regulation and GA as a potentialtherapeutic candidate for human prostate cancer.

Performance Evaluations of Four MAF-Based PLL Algorithms for Grid-Synchronization of Three-Phase Grid-Connected PWM Inverters and DGs

Yang Han,Mingyu Luo,Changqing Chen,Aiting Jiang,Xin Zhao,Josep M. Guerrero 전력전자학회 2016 JOURNAL OF POWER ELECTRONICS Vol.16 No.5

The moving average filter (MAF) is widely utilized to improve the disturbance rejection capability of phase-locked loops (PLLs). This is of vital significance for the grid-integration and stable operation of power electronic converters to electric power systems. However, the open-loop bandwidth is drastically reduced after incorporating a MAF into the PLL structure, which makes the dynamic response sluggish. To overcome this shortcoming, some new techniques have recently been proposed to improve the transient response of MAF-based PLLs. In this paper, a comprehensive performance comparison of advanced MAF-based PLL algorithms is presented. This comparison includes HPLL, MPLC-PLL, QT1-PLL, and DMAF-PLL. Various disturbances, such as grid voltage sag, voltage flicker, harmonics distortion, phase-angle and frequency jumps, DC offsets and noise, are considered to experimentally test the dynamic performances of these PLL algorithms. Finally, an improved positive sequence extraction method for a HPLL under the frequency jumps scenario is presented to compensate for the steady-state error caused by non-frequency adaptive DSC, and a satisfactory performance has been achieved.

High step-up isolated forward-flyback DC/DC converter based on resonance with pulse frequency modulation

Zhang, Zhiguo,Liao, Mingyu,Jiang, Dongrong,Yang, Xiaobin,Li, Shan The Korean Institute of Power Electronics 2021 JOURNAL OF POWER ELECTRONICS Vol.21 No.2

A high step-up isolated forward-flyback DC-DC converter with pulse frequency modulation (PFM) is presented in this paper. The proposed converter has features of both a forward and a flyback converter and can deliver energy during the turn-on and turn-off intervals in a switching period. In addition, by utilizing resonance it can achieve zero-voltage switching (ZVS) for the primary switches and zero-current switching (ZCS) for the secondary rectifier diodes. All of the power semiconductors operate under soft switching conditions. The structure of the proposed converter is simple and easily implemented. It also provides a high step-up voltage gain. The current stresses of the power devices in PFM are lower than those in pulse width modulation (PWM). Therefore, the converter efficiency in PFM is higher than that in PWM. The operation principle and characteristic of the presented converter are described in detail, and the converter performances for PWM and PFM are compared. A 160 W hardware prototype has been built, and experimental results verify the validity of the theoretical analysis.

Design of a Beam-coupling System for a Chip-integrated Spectrometer with a Discrete Linear Waveguide

Zhiying Liu,Xin Jiang,Mingyu Li 한국광학회 2020 Current Optics and Photonics Vol.4 No.3

In this study, a beam-coupling system is designed to improve the coupling efficiency of achip-integrated spectrometer when the waveguide is arranged in a linear and discrete manner. In the proposed system the beam is shaped to be anti-Gaussian, to deposit adequate energy in the edge waveguides. The beam is discretely coupled to the corresponding waveguide by a microlens array, to improve the coupling efficiency, and is compressed by a toroidal lens to match the linear discrete waveguides. Based on the findings of this study, the coupling efficiency of the spectrometer is shown to increase by a factor of 2.57. Accordingly, this study provides a reference basis for the improvement of the coupling efficiency of other similar spectrometers.

Investigation of Stereo-dynamic Properties for the Reaction H+HLi by Quasi-classical Trajectory Approach

Wang, Yuliang,Zhang, Jinchun,Jiang, Yanlan,Wang, Kun,Zhou, Mingyu,Liang, Xiaorui Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.9

Quasi-classical trajectory (QCT) calculations of H+HLi reaction have been carried out on a new potential energy surface of the ground state reported by Prudente et al. [Chem. Phys. Lett. 2009, 474, 18]. The four polarization-dependent differential cross sections have been carried out in the center of mass (CM) frame at various collision energies. The reaction probability for the depletion channel has been studied over a wide collision energy range. It has been found that the collision energy decreases remarkably reaction probability, which shows the expected behavior of the title reaction belonging to an exothermic barrierless reaction. The results are in good agreement with previous RMP results. The P(${\theta}_r$), P(${\phi}_r$) and P(${\theta}_r,\;{\phi}_r$) distributions, the k-k'-j' correlation and the angular distribution of product rotational vectors are presented in the form of polar plots. The average rotational alignment factor <$P_2(j{\prime}{\cdot}k)$> as a function of collision energy is also calculated. The results indicate that the collision energy has a great influence on the polarization of the product rotational angular momentum vector j'.

Performance Evaluations of Four MAF-Based PLL Algorithms for Grid-Synchronization of Three-Phase Grid-Connected PWM Inverters and DGs

Han, Yang,Luo, Mingyu,Chen, Changqing,Jiang, Aiting,Zhao, Xin,Guerrero, Josep M. The Korean Institute of Power Electronics 2016 JOURNAL OF POWER ELECTRONICS Vol.16 No.5

The moving average filter (MAF) is widely utilized to improve the disturbance rejection capability of phase-locked loops (PLLs). This is of vital significance for the grid-integration and stable operation of power electronic converters to electric power systems. However, the open-loop bandwidth is drastically reduced after incorporating a MAF into the PLL structure, which makes the dynamic response sluggish. To overcome this shortcoming, some new techniques have recently been proposed to improve the transient response of MAF-based PLLs. In this paper, a comprehensive performance comparison of advanced MAF-based PLL algorithms is presented. This comparison includes HPLL, MPLC-PLL, QT1-PLL, and DMAF-PLL. Various disturbances, such as grid voltage sag, voltage flicker, harmonics distortion, phase-angle and frequency jumps, DC offsets and noise, are considered to experimentally test the dynamic performances of these PLL algorithms. Finally, an improved positive sequence extraction method for a HPLL under the frequency jumps scenario is presented to compensate for the steady-state error caused by non-frequency adaptive DSC, and a satisfactory performance has been achieved.

Investigation of Stereo-dynamic Properties for the Reaction H+HLi by Quasi-classical Trajectory Approach

Yuliang Wang,Jinchun Zhang,Yanlan Jiang,Kun Wang,Mingyu Zhou,Xiaorui Liang 대한화학회 2012 Bulletin of the Korean Chemical Society Vol.33 No.9

Quasi-classical trajectory (QCT) calculations of H+HLi reaction have been carried out on a new potential energy surface of the ground state reported by Prudente et al. [Chem. Phys. Lett. 2009, 474, 18]. The four polarization-dependent differential cross sections have been carried out in the center of mass (CM) frame at various collision energies. The reaction probability for the depletion channel has been studied over a wide collision energy range. It has been found that the collision energy decreases remarkably reaction probability, which shows the expected behavior of the title reaction belonging to an exothermic barrierless reaction. The results are in good agreement with previous RMP results. The P(θr), P(φr) and P(θr, φr) distributions, the k−k'− j' correlation and the angular distribution of product rotational vectors are presented in the form of polar plots. The average rotational alignment factor as a function of collision energy is also calculated. The results indicate that the collision energy has a great influence on the polarization of the product rotational angular momentum vector j'.

Structure-Based Design and Synthesis of C-1- and C-4-Modified Analogs of Zanamivir as Neuraminidase Inhibitors

Feng, Enguang,Shin, Woo-Jin,Zhu, Xuelian,Li, Jian,Ye, Deju,Wang, Jiang,Zheng, Mingyue,Zuo, Jian-Ping,No, Kyoung Tai,Liu, Xian,Zhu, Weiliang,Tang, Wei,Seong, Baik-Lin,Jiang, Hualiang,Liu, Hong American Chemical Society 2013 Journal of medicinal chemistry Vol.56 No.3

<P>In order to exploit the 430-cavity in the active sites of neuraminidases, 22 zanamivir analogs with C-1 and C-4 modification were synthesized, and their inhibitory activities against both group-1 (H5N1, H1N1) and group-2 neuraminidases (H3N2) were determined. Compound <B>9f</B> exerts the most potency, with IC<SUB>50</SUB> value of 0.013, 0.001, and 0.09 μM against H3N2, H5N1, and H1N1, which is similar to that of zanamivir (H3N2 IC<SUB>50</SUB> = 0.0014 μM, H5N1 IC<SUB>50</SUB> = 0.012 μM, H1N1 IC<SUB>50</SUB> = 0.001 μM). Pharmacokinetic studies of compound <B>9f</B> in rats showed a much longer plasma half-life (<I>t</I><SUB>1/2</SUB>) than that of zanamivir following administration (po dose). Molecular modeling provided information about the binding model between the new inhibitors and neuraminidase, with the elongated groups at the C-1-position being projected toward the 430-loop region. This study may represent a novel starting point for the future development of improved antiflu agents.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jmcmar/2013/jmcmar.2013.56.issue-3/jm3009713/production/images/medium/jm-2012-009713_0009.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jm3009713'>ACS Electronic Supporting Info</A></P>