Ginsengenin derivatives synthesized from 20(R)-panaxotriol: Synthesis, characterization, and antitumor activity targeting HIF-1 pathway

Guo, Hong-Yan,Xing, Yue,Sun, Yu-Qiao,Liu, Can,Xu, Qian,Shang, Fan-Fan,Zhang, Run-Hui,Jin, Xue-Jun,Chen, Fener,Lee, Jung Joon,Kang, Dongzhou,Shen, Qing-Kun,Quan, Zhe-Shan The Korean Society of Ginseng 2022 Journal of Ginseng Research Vol.46 No.6

Background: Ginseng possesses antitumor effects, and ginsenosides are considered to be one of its main active chemical components. Ginsenosides can further be hydrolyzed to generate secondary saponins, and 20(R)-panaxotriol is an important sapogenin of ginsenosides. We aimed to synthesize a new ginsengenin derivative from 20(R)-panaxotriol and investigate its antitumor activity in vivo and in vitro. Methods: Here, 20(R)-panaxotriol was selected as a precursor and was modified into its derivatives. The new products were characterized by ¹H-NMR, ¹³C-NMR and HR-MS and evaluated by molecular docking, MTT, luciferase reporter assay, western blotting, immunofluorescent staining, colony formation assay, EdU labeling and immunofluorescence, apoptosis assay, cells migration assay, transwell assay and in vivo antitumor activity assay. Results: The derivative with the best antitumor activity was identified as 6,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(2,6,6-trimethyltetrahydro-2H-pyran-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl(tert-butoxycarbonyl)glycinate (A11). The focus of this research was on the antitumor activity of the derivatives. The efficacy of the derivative A11 (IC₅₀ < 0.3 µM) was more than 100 times higher than that of 20(R)- panaxotriol (IC₅₀ > 30 µM). In addition, A11 inhibited the protein expression and nuclear accumulation of the hypoxia-inducible factor HIF-1α in HeLa cells under hypoxic conditions in a dose-dependent manner. Moreover, A11 dose-dependently inhibited the proliferation, migration, and invasion of HeLa cells, while promoting their apoptosis. Notably, the inhibition by A11 was more significant than that by 20(R)-panaxotriol (p < 0.01) in vivo. Conclusion: To our knowledge, this is the first study to report the production of derivative A11 from 20(R)-panaxotriol and its superior antitumor activity compared to its precursor. Moreover, derivative A11 can be used to further study and develop novel antitumor drugs.

Short Low Concentration Cisplatin Treatment Leads to an Epithelial Mesenchymal Transition-like Response in DU145 Prostate Cancer Cells

Liu, Yi-Qing,Zhang, Guo-An,Zhang, Bing-Chang,Wang, Yong,Liu, Zheng,Jiao, Yu-Lian,Liu, Ning,Zhao, Yue-Ran Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.3

Background: Prostate cancer is one of the main causes of cancer death, and drug resistance is the leading reason for therapy failure. However, how this occurs is largely unknown. We therrfore aimed to study the response of DU145 cells to cisplatin. Materials and Methods: Du145 prostate cancer cells were treated with a low dose of cisplatin for 24 h and cell viability and number were determined by MTT assay and trypan blue exclusion assay, respectively. The real time polymerase chain reaction (PCR) was used to assess responses to cisplatin treatment. Results: After 24h $2{\mu}g/ml$ treatment did not result in significant reduction in cell viability or number. However, it led to enhanced cancer cell invasiveness. E-cadherin mRNA was reduced, and vimentin, Snail, Slug, metalloproteinase 9 (MMP9) mRNA expression increased significantly, a feature of epithelial-mesenchymal transition (EMT). Conclusions: Short time low concentration cisplatin treatment leads to elevated invasiveness of DU145 cancer cells and this is possibly due to EMT.

Characterization and function of a short peptidoglycan recognition protein from the Chinese oak silkworm, Antheraea pernyi

Li-Shang Dai,Cen Qian, LeiWang,Guo-Qing Wei,Qiu-Ning Liu,Yu Sun,Cong-Fen Zhang,Jun Li,Dong-Ran Liu,Bao-Jian Zhu,Chao-Liang Liu 한국응용곤충학회 2015 Journal of Asia-Pacific Entomology Vol.18 No.4

Peptidoglycan recognition proteins (PGRPs) are conserved proteins in animals from insects to mammals and play an important role in immune response by recognizing peptidoglycan on microbial surfaces. In this study, a PGRP gene from Antheraea pernyi, named Ap-PGRP-A, was isolated and characterized. Sequence analysis revealed that the full-length cDNA of Ap-PGRP-A was 961 bp, containing a 40 bp 5′-untranslated sequence, a 339 bp 3′-untranslated region and an open reading frame of 582 bp. This gene encoded a putative protein of 193 amino acid residues. Phylogenetic analysis indicated that Ap-PGRP-A had the closest protein sequence similarity to Antheraea mylitta PGRP. The recombinant protein was successfully expressed in Escherichia coli cells and a rabbit anti-Ap-PGRP-A antibody was also prepared. Real-time quantitative reverse transcription-PCR analysis showed that Ap-PGRP-A was extensively expressed in the fat body, midgut, hemocyte,malpighian tubule and epidermis of A. pernyi, especially in the fat body and midgut. The expression levels of Ap-PGRP-A were significantly up-regulated by three types of microorganisms, and Ap-PGRP-A expression was more sensitive in response to the Gram-negative bacterium E. coli than the Gram-positive bacterium Bacillus subtilis or the fungus Beauveria bassiana. These data indicate that Ap-PGRP-A may play a role in the innate immune responses of A. pernyi.

Assessment of clinical competency among TCM medical students using standardized patients of traditional Chinese medicine: A 5-year prospective randomized study

Zeng Jinhao,Liang Shuang,Zhang Xiaotong,Yan Ran,Chen Chongli,Wen Lijuan,Xia Ting,Li Wenyuan,Lu Bingqing,Nian Qing,Yang Han,Guo Jing 한국한의학연구원 2022 Integrative Medicine Research Vol.11 No.2

Background: Some Western medicine schools in China established standardized patient (SP) programs for medical education. However, SP programs are rarely applied to the education of traditional Chinese medicine (TCM). In this study, we evaluated the effectiveness of using standardized patient traditional Chinese medicine (SP-TCM) to improve clinical competency among TCM medical students. Methods: This study was a prospective, 2-group, parallel-training randomized trial over the course of 5 years. Data were collected from September 2016 to December 2020. Participants in each year were randomly allocated into the traditional-method training group or the SP-TCM training group (1:1) for a 3-month curriculum. Measurement of clinical competency among all trainees was based on a standardized examination composed of scores of medical record documentation, scores of TCM syndrome differentiation and therapeutic regimen, and checklist assessment from both SP-TCMs and TCM professionals. Feedback was collected using semi-constructive questionnaires from both groups. Results: Compared with those assigned to traditional-method training, those assigned to SP-TCM training demonstrated significantly greater post-training improvement in medical record documentation and TCM syndrome differentiation and therapeutic regimen. Moreover, SP-TCM trainees outscored those assigned to traditional training in the assessment for encounter performance given by independent SP-TCMs and TCM professionals. The SP-TCM method gained higher satisfaction of training efficacy and test performance than the traditional method. Conclusion: This SP-TCM program demonstrated great benefits for improving clinical competency among TCM medical students.

NPC-IGCT Phase Module Clamp Circuit LRC Parameters Design considering FRD snappy Recovery

Yang Ju Zou,Jia Xi Hu,Zhen Yu Ma,Jian Ping Liu,Run Qing Guo,Zhi Xue Zhang 전력전자학회 2019 ICPE(ISPE)논문집 Vol.2019 No.5

In this paper, a method for neutral point clamping-integrated gate commutated thyristor (NPCIGCT) phase module clamp circuit parameters design considering FRD snappy recovery is present. Based on the snappy recovery theory, and analysis of snappy recovery factors, the paper has shown decreasing current commutating slope can attenuated snappy recovery affect effectively. Then, the paper has shown that it is reasonable for decreasing di/dt by increasing inductance of NPC-IGCT phase module clamp circuit, based on the circuit working principle. Then, the new clamp circuit parameters design method which combine multi-objective optimization solution mathematical module of the circuit, fast recovery diode (FRD) snappy recovery, devices overvoltage and loss is shown in paper. A design example and its test results have demonstrated both IGCT and FRD characteristics have been guaranteed and ensuring safety and reliability of the NPC - IGCT phase module.