scholarly journals Coupling Deep Transcriptome Analysis with Untargeted Metabolic Profiling in Ophiorrhiza pumila to Further the Understanding of the Biosynthesis of the Anti-Cancer Alkaloid Camptothecin and Anthraquinones

2013 ◽  
Vol 54 (5) ◽  
pp. 686-696 ◽  
Author(s):  
Mami Yamazaki ◽  
Keiichi Mochida ◽  
Takashi Asano ◽  
Ryo Nakabayashi ◽  
Motoaki Chiba ◽  
...  
2018 ◽  
Vol 17 (5) ◽  
pp. 1943-1952 ◽  
Author(s):  
Yue-Xiao Xing ◽  
Ming-Hui Li ◽  
Liang Tao ◽  
Ling-Yu Ruan ◽  
Wei Hong ◽  
...  

2019 ◽  
Vol 29 (8) ◽  
pp. 1212-1220
Author(s):  
Junsang Oh ◽  
Eunhyun Choi ◽  
Deok-Hyo Yoon ◽  
Tae-Yong Park ◽  
Bhushan Shrestha ◽  
...  

Biology ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 212
Author(s):  
Kyubin Lee ◽  
You-Jee Jang ◽  
Hyerim Lee ◽  
Eunbin Kim ◽  
Yeojin Kim ◽  
...  

Abeliophyllum distichum Nakai is known as a monotypic genus endemic to South Korea. Currently, several pharmacological studies have revealed that A. distichum extract exhibits diverse biological functions, including anti-cancer, anti-diabetic, anti-hypertensive, and anti-inflammatory activities. In this study, we present the anti-osteoporotic activity of A. distichum extract by inhibiting osteoclast formation. First, we show that the methanolic extract of the leaves of A. distichum, but not extracts of the branches or fruits, significantly inhibits receptor activator of the NF-κB ligand (RANKL)-induced osteoclast differentiation. Second, our transcriptome analysis revealed that the leaf extract (LE) blocks sets of RANKL-mediated osteoclast-related genes. Third, the LE attenuates the phosphorylation of extracellular signal-related kinase. Finally, treatment with the LE effectively prevents postmenopausal bone loss in ovariectomized mice and glucocorticoid-induced osteoporosis in zebrafish. Our findings show that the extract of A. distichum efficiently suppressed osteoclastogenesis by regulating osteoclast-related genes, thus offering a novel therapeutic strategy for osteoporosis.


2018 ◽  
Vol 70 (3) ◽  
pp. 1017-1031 ◽  
Author(s):  
Gilad Gabay ◽  
Adi Faigenboim ◽  
Yardena Dahan ◽  
Yacov Izhaki ◽  
Maxim Itkin ◽  
...  

2019 ◽  
Author(s):  
Chunji Li ◽  
Die Zhao ◽  
Ning Zhang ◽  
Bingxue Li

Background. Salinity stress is one of the most environmental stresses in agricultural regions worldwide. Salinity inhibits shoot and root growth of various crops, which culminate in reductions in the quality and yield. It is of crucial to understand the molecular biological mechanisms of salt stress responses and defenses in order to enhance crops salt-tolerance. Sporobolomyces pararoseus is a member of marine red yeasts. Since marine red yeast has been naturally selected for its long-term survival in high-salt marine ecosystems, some unique salt-tolerant mechanism has been developed. Little research has conducted so far by considering S. pararoseus as model microorganisms to study salt stress tolerance mechanisms. A better understanding of the mechanisms mediating salt stress of S. pararoseus NGR will provide valuable information for enhancing the crops salt-tolerant via genetic engineering. Methods. S. pararoseus NGR (CGMCC 2.5280) cultures were treated with initial NaCl concentrations of 0.75 M throughout 3 days of growth period. Transcriptome analysis was performed using RNA-seq to study the differentially expressed genes (DEGs) between the NaCl-treated cells and the control cells. Metabolome analysis was performed using the LC-MS/MS untargeted metabolic profiling to study the differentially accumulated metabolites between the NaCl-treated cells and the control cells. Co-expression network analysis was carried out using the screening parameters of correlation coefficient = 0.99 and p-value = 0.01. Transcriptome analysis results were confirmed by real-time quantitative PCR (RT-qPCR). Results. After sequencing, de novo assembly and quantitative assessment, 9,533 unigenes were finally generated with an average length of 1,538 bp. A total of 3,849 DGEs were identified in NaCl-treated cultures, including 2,019 up-regulated genes and 1,830 down-regulated genes. Screening of metabolite features with untargeted metabolic profiling of all samples in NaCl-treated and control group, we characterized 4,862 compounds from the LC–MS/MS-based dataset. An integrated analysis of transcriptome and metabolome indicated that amino acid metabolism, carbohydrate metabolism, and lipid metabolism is significantly enriched in response to salt stress. Co-expression network analysis showed that 28 genes and 8 metabolites played an important role in the response of S. pararoseus NGR and defense against salt stress, which provides valuable clues for subsequent validation. Together, our results suggested that the most primary salt-tolerant mechanism of the S. pararoseus NGR is the biosynthesis of carotenoids, and torulene showed the dominated effect among them. Moreover, amino acid metabolism, carbohydrate metabolism and lipid metabolism act as its secondary salt-tolerant mechanism.


2019 ◽  
Author(s):  
Chunji Li ◽  
Die Zhao ◽  
Ning Zhang ◽  
Bingxue Li

Background. Salinity stress is one of the most environmental stresses in agricultural regions worldwide. Salinity inhibits shoot and root growth of various crops, which culminate in reductions in the quality and yield. It is of crucial to understand the molecular biological mechanisms of salt stress responses and defenses in order to enhance crops salt-tolerance. Sporobolomyces pararoseus is a member of marine red yeasts. Since marine red yeast has been naturally selected for its long-term survival in high-salt marine ecosystems, some unique salt-tolerant mechanism has been developed. Little research has conducted so far by considering S. pararoseus as model microorganisms to study salt stress tolerance mechanisms. A better understanding of the mechanisms mediating salt stress of S. pararoseus NGR will provide valuable information for enhancing the crops salt-tolerant via genetic engineering. Methods. S. pararoseus NGR (CGMCC 2.5280) cultures were treated with initial NaCl concentrations of 0.75 M throughout 3 days of growth period. Transcriptome analysis was performed using RNA-seq to study the differentially expressed genes (DEGs) between the NaCl-treated cells and the control cells. Metabolome analysis was performed using the LC-MS/MS untargeted metabolic profiling to study the differentially accumulated metabolites between the NaCl-treated cells and the control cells. Co-expression network analysis was carried out using the screening parameters of correlation coefficient = 0.99 and p-value = 0.01. Transcriptome analysis results were confirmed by real-time quantitative PCR (RT-qPCR). Results. After sequencing, de novo assembly and quantitative assessment, 9,533 unigenes were finally generated with an average length of 1,538 bp. A total of 3,849 DGEs were identified in NaCl-treated cultures, including 2,019 up-regulated genes and 1,830 down-regulated genes. Screening of metabolite features with untargeted metabolic profiling of all samples in NaCl-treated and control group, we characterized 4,862 compounds from the LC–MS/MS-based dataset. An integrated analysis of transcriptome and metabolome indicated that amino acid metabolism, carbohydrate metabolism, and lipid metabolism is significantly enriched in response to salt stress. Co-expression network analysis showed that 28 genes and 8 metabolites played an important role in the response of S. pararoseus NGR and defense against salt stress, which provides valuable clues for subsequent validation. Together, our results suggested that the most primary salt-tolerant mechanism of the S. pararoseus NGR is the biosynthesis of carotenoids, and torulene showed the dominated effect among them. Moreover, amino acid metabolism, carbohydrate metabolism and lipid metabolism act as its secondary salt-tolerant mechanism.


2022 ◽  
Author(s):  
Kosuke Yoshida ◽  
Akira Yokoi ◽  
Tomofumi Yamamoto ◽  
Yusuke Hayashi ◽  
Jun Nakayama ◽  
...  

Purpose: Uterine leiomyosarcoma is among the most aggressive gynecological malignancies. No effective treatment strategies have been established. This study aimed to identify novel therapeutic targets for uterine leiomyosarcoma based on transcriptome analysis and assess the preclinical efficacy of novel drug candidates. Experimental Design: Transcriptome analysis was carried out using fresh-frozen samples of six uterine leiomyosarcomas and three myomas. The Ingenuity Pathway Analysis was then used to identify potential therapeutic target genes for uterine leiomyosarcoma. Moreover, our results were validated using three independent datasets, including 40 uterine leiomyosarcomas. Then, the inhibitory effects of several selective inhibitors for the candidate genes were examined using the SK-UT-1, SK-LMS-1, and SKN cell lines. Results: We identified 512 considerably dysregulated genes in uterine leiomyosarcoma compared with myoma. The Ingenuity Pathway Analysis showed that the function of several genes, including CHEK1 and PLK1, were predicted to be activated in uterine leiomyosarcoma. Through an in vitro drug screening, PLK1 or CHEK1 inhibitors (BI 2536 or prexasertib) were found to exert a superior anti-cancer effect against cell lines at low nanomolar concentrations and induced cell cycle arrest. In SK-UT-1 tumor-bearing mice, BI 2536 monotherapy demonstrated a marked tumor regression. Moreover, the prexasertib and cisplatin combination therapy also reduced tumorigenicity and prolonged survival. Conclusion: We identified the upregulated expression of PLK1 and CHEK1; their kinase activity was considered to be activated in uterine leiomyosarcoma. BI 2536 and prexasertib demonstrate a significant anti-cancer effect; thus, cell cycle-related kinases may represent a promising therapeutic strategy for treating uterine leiomyosarcoma.


2018 ◽  
Vol 241 ◽  
pp. 7-13 ◽  
Author(s):  
Jin Jeon ◽  
Jae Kwang Kim ◽  
HyeRan Kim ◽  
Yeon Jeong Kim ◽  
Yun Ji Park ◽  
...  

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