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Resveratrol reverses TGF-β1-mediated invasion and metastasis of breast cancer cells via the SIRT3/AMPK/autophagy signal axis
Abstract
Resveratrol (Resv) has antitumorigenic and antimetastatic activities; however, the molecular mechanisms underlying the inhibitory effects of Resv on the invasion and metastasis of breast cancer cells are still a subject of debate. In our study, we demonstrated that Resv inhibited tumor cell proliferation and tumor growth. It also suppressed invasion and pulmonary metastasis of breast cancer by reversing the transforming growth factor beta 1 (TGF-β1)-mediated EMT process. Meanwhile, the anticarcinogenic effects of Resv were abolished by the autophagy blocker 3-methyladenine (3-MA) or Beclin 1 small interfering RNA. Moreover, Resv upregulated autophagy-related genes and protein levels and induced the formation of autophagosomes in 4T1 breast cancer cells and xenograft mice, suggesting that autophagy was involved in the anticarcinogenic activities of Resv in bothmodels. In addition, Resv-induced autophagy by increasing the expression of SIRT3 and phosphorylated AMPK. SIRT3 knockdown reduced AMPK phosphorylation and
autophagy-related proteins levels, and suppressed the anticancer effects of Resv, demonstrating that the inhibitory effects of Resv on tumor progression were medi
ated via the SIRT3/AMPK/autophagy pathway. Taken together, our study provided novel insight into the anticancer effects of Resv and revealed that targeting the
SIRT3/AMPK/autophagy pathway can serve as a new therapeutic target against breast cancer.
......
Chemicals and reagents
Recombinant human TGF-β1 protein was bought from Peprotech (Rocky Hill, NJ, USA). Resveratrol (CAS number 501-36-0, purity ≥98.0%), identified as pure trans-resveratrol was supplied by Chengdu DeSiTe Biological Technology Co., Ltd (Chengdu, China).
DOI: 10.1002/ptr.7608
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World Journal of Microbiology and Biotechnology-20 June 2018
期刊名：World Journal of Microbiology and Biotechnology文献编号：DOI 10.1007/s11274-018-2464-1文献地址：https://link.springer.com/article/10.1007%2Fs13318-017-0444-8发表日期：20 June 2018
Abstract
The present study has focused on the effects of hypericin (Hyp) based photodynamic inactivation (PDI) of Escherichia coli (E. coli). To evaluate the efficiency of Hyp based PDI of E. coli, single factor experiments and response surface optimization experiment were conducted to obtain the optimum parameter values (36 µM Hyp, 5.9 J cm−2 light dose: 16.4 mW cm−2, 60 W, 260 s, 590 nm and 68 min incubation time) and finally achieved a 4.1 log CFU mL−1 decrease of E. coli. Cell-Hyp interaction and intracellular reactive oxygen species (ROS) level were detected by fluorescence spectrometric photometer. Data indicated that Hyp possessed a strong ability to bind with cells. In addition, a significant increase was observed in intracellular ROS level after Hyp-based photosensitization treatment. Therefore, Hyp-based photosensitization seems to be a promising method to efficiently inactivate E. coli. It is expected to be a safe, efficient, low cost and practical method which can be applied in the field of food safety.
Hypericin used as a photosensitizer in present study was obtained from Chengdu Desite Biological Technology Co., Ltd. (Chengdu, China).
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Nat Biotech| 北京大学谢正伟课题组与合作者创建基于基因指纹和深度学习的药效预测系统（DLEPS）
原文链接：https://www.nature.com/articles/s41587-021-00946-z
北京大学谢正伟团队开发的基于人工智能和基因指纹的药效预测系统在Nature Biotechnology（IF 36.6）上线了，先讲了神经网络结构，然后对性能做了标定；然后展示了在减肥、降尿酸和非酒精性脂肪性肝炎中的应用。里面所有的中药化学对照品来自“成都德思特生物”。
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Journal of separation science-07 January 2020
Comparison of the active components of Aster tataricus from different regions and related processed products by ultra-high performance liquid chromatography with tandem mass spectrometry期刊名：Journal of separation science文献编号：DOI 10.1002/jssc.201900814文献地址：https://onlinelibrary.wiley.com/doi/abs/10.1002/jssc.201900814发表日期：07 January 2020AbstractWe investigated crude Aster tataricus, vinegar‐processed Aster tataricus, honey‐processed Aster tataricus, and steamed Aster tataricus as a case study and developed a comprehensive strategy integrating quantitative analysis and chemical pattern recognition methods for the evaluation and differentiation of Aster tataricus from different regions, as well as related processed products. In the study, 15 batches of raw Aster tataricus collected from seven provinces were analyzed. A sensitive and rapid ultra‐high performance liquid chromatography with tandem mass spectrometry method for simultaneous determination of 15 compounds was established to evaluate the quality of raw and processed Aster tataricus. Furthermore, multivariate statistical techniques were applied to compare the differences among Aster tataricus samples. As a result, the herbs collected from seven provinces were divided into two categories, and chlorogenic acid was the most important component distinguishing between the regions. Moreover, all of the raw and processed samples were classified by partial least squares discriminant analysis based on the 15 analyzed compounds. Results showed that raw Aster tataricus, vinegar‐processed Aster tataricus, honey‐processed Aster tataricus, and steamed Aster tataricus were clustered in four different areas. Shionone, chlorogenic acid and kaempferol were the significant constituents differentiating the raw and differently processed Aster tataricus samples.Luteolin, shionone, quercetin, scopoletin, kaempferol, kaempferol-7-O-β-D-glucopyranoside, isorhamnetin, 7-hydroxycoumarin, methyl caffeate, and protocatechuic acid (purity ≥ 98%) were purchased from Chengdu Desite Biological Technology Co. Ltd. (Sichuan, China)
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Chlorogenic acid ameliorates mice clinical endometritis ...
期刊名：Journal of Pharmacy and Pharmacology期刊网址：https://pubmed.ncbi.nlm.nih.gov/33734387/发表日期：18 March 2021bstract
Objectives Clinical endometritis is a common reproductive disorder in mammals that seriously
endangers animal health and causes economic losses worldwide. This study aims to use lipopoly
saccharide and Trueperella pyogenes exotoxin as modelling reagents (LC) to perfuse the mouse
uterus in order to establish a model of clinical endometritis and to investigate the anti-inflamma
tory and antioxidant effects of chlorogenic acid (CGA).
Methods In this study, five LC uterine perfusions were selected to model clinical endomet
ritis. The anti-inflammatory and antioxidant effects of CGA were clarified. Through HE staining,
proinflammatory cytokines, blood testing, NFκB and Keap1/Nrf2 signalling pathways and other
index changes to explore the protection mechanism of CGA.
Key findings After CGA treatment, the appearance, inflammatory damage and blood indicators of
the mouse uterus returned to normal. Simultaneously, CGA could inhibit the activation of NFκB
and reduce the release of inflammatory cytokines; CGA could also activate Keap1/Nrf2, promote
the dissociation of Keap1 and Nrf2 and significantly increase the expression of the downstream
genes HO-1 and NQO1.
CGA (purity >98.0%) was purchased from Desite Bio (Chengdu, China).
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Drug Metabolism and Disposition Fast Forward. Published
Icotinib induces mechanism-based inactivation of rhCYP3A4/5 possibly via heme destruction by ketene intermediate期刊名：Drug Metabolism and Disposition文献编号：DMD-AR-2021-000369R2文献地址： https://doi.org/10.1124/dmd.121.000369发表日期：July 26, 2021
Abstract
Icotinib (ICT) is an anti-tumor drug approved by China National Medical Products Administration and is found to be effective to conquer non-small cell lung cancer. The present study aimed at the interaction of ICT with CYP3A. ICT exhibited time-, concentration- and NADPH-dependent inhibitory effect on recombinant human CYP3A4/5 (rhCYP3A4/5). About 60% of CYP3A activity was suppressed by ICT at 50 μM after 30 min. The observed enzyme inhibition could not be recovered by dialysis. Nifedipine protected CYP3A from the inactivation by ICT. The inhibitory effects of ICT on CYP3A were neither influenced by GSH/NAL nor by SOD/catalase. Incubation of ICT with human hepatic microsomes produced a ketene reactive intermediate trapped by 4-bromobenzylamine. CYP3A4 dominated the metabolic activation of ICT to the ketene intermediate. Ethyl and vinyl analogs of ICT did not induce inactivation of rhCYP3A4/5, which indicates that acetylenic bioactivation of ICT contributed to the enzyme inactivation. Moreover, the metabolic activation of ICT resulted in heme destruction. In conclusion, this study demonstrated that ICT was a mechanism-based inactivator of rhCYP3A4/5, and heme destruction by the ketene metabolite may be responsible for the observed CYP3A inactivation.
6β-Hydroxytestosterone was purchased from Chengdu De-Si-Te Biological Technology Co., Ltd (Chengdu, China).
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