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Acta Pharmaceutica Sinica. B

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https://www.readbyqxmd.com/read/30109192/epigenetic-modification-in-histone-deacetylase-deletion-strain-of-calcarisporium-arbuscula-leads-to-diverse-diterpenoids
#1
Jian Bai, Rong Mu, Man Dou, Daojiang Yan, Bingyu Liu, Qian Wei, Jun Wan, Yi Tang, Youcai Hu
Epigenetic modifications have been proved to be a powerful way to activate silent gene clusters and lead to diverse secondary metabolites in fungi. Previously, inactivation of a histone H3 deacetylase in Calcarisporium arbuscula had led to pleiotropic activation and overexpression of more than 75% of the biosynthetic genes and isolation of ten compounds. Further investigation of the crude extract of C. arbuscula ΔhdaA strain resulted in the isolation of twelve new diterpenoids including three cassanes ( 1 - 3 ), one cleistanthane ( 4 ), six pimaranes ( 5 - 10 ), and two isopimaranes ( 11 and 12 ) along with two know cleistanthane analogues...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109191/biocatalytic-access-to-diverse-prenylflavonoids-by-combining-a-regiospecific-c-prenyltransferase-and-a-stereospecific-chalcone-isomerase
#2
Jianhua Li, Ridao Chen, Ruishan Wang, Xiao Liu, Kebo Xie, Dawei Chen, Jungui Dai
Prenylflavonoids are valuable natural products that have diverse biological properties, and are usually generated biologically by multiple metabolic enzymes in nature. In this study, structurally diverse prenylflavonoids were conveniently synthesized by enzymatic catalysis by combining GuILDT, a regiospecific chalcone prenyltransferase, and GuCHI, a stereospecific chalcone isomerase that has promiscuous activity for both chalcones and prenylchalcones as substrates. Our findings provided a new approach for the synthesis of natural/unnatural bioactive prenylflavonoids, including prenylchalcones and optical prenylflavanones with chalcone origins...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109190/genome-wide-characterization-and-analysis-of-bhlh-transcription-factors-in-panax-ginseng
#3
Yang Chu, Shuiming Xiao, He Su, Baosheng Liao, Jingjing Zhang, Jiang Xu, Shilin Chen
Ginseng ( Panax ginseng C.A. Meyer) is one of the best-selling herbal medicines, with ginsenosides as its main pharmacologically active constituents. Although extensive chemical and pharmaceutical studies of these compounds have been performed, genome-wide studies of the basic helix-loop-helix (bHLH) transcription factors of ginseng are still limited. The bHLH transcription factor family is one of the largest transcription factor families found in eukaryotic organisms, and these proteins are involved in a myriad of regulatory processes...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109189/-in-situ-monitoring-of-the-structural-change-of-microemulsions-in-simulated-gastrointestinal-conditions-by-saxs-and-fret
#4
Xia Lv, Shuguang Zhang, Huipeng Ma, Peipei Dong, Xiaodong Ma, Ming Xu, Yan Tian, Zeyao Tang, Jinyong Peng, Haibo Chen, Jianbin Zhang
Microemulsions are promising drug delivery systems for the oral administration of poorly water-soluble drugs. However, the evolution of microemulsions in the gastrointestinal tract is still poorly characterized, especially the structural change of microemulsions under the effect of lipase and mucus. To better understand the fate of microemulsions in the gastrointestinal tract, we applied small-angle X-ray scattering (SAXS) and fluorescence resonance energy transfer (FRET) to monitor the structural change of microemulsions under the effect of lipolysis and mucus...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109188/authentic-compound-free-strategy-for-simultaneous-determination-of-primary-coumarins-in-peucedani-radix-using-offline-high-performance-liquid-chromatography-nuclear-magnetic-resonance-spectroscopy-tandem-mass-spectrometry
#5
Yao Liu, Qingqing Song, Wenjing Liu, Peng Li, Jun Li, Yunfang Zhao, Liang Zhang, Pengfei Tu, Yitao Wang, Yuelin Song
Herein, a strategy is proposed for the simultaneous determination of primary coumarins in Peucedani Radix (Chinese name: Qianhu). The methodology consists of three consecutive steps: 1) Semi-preparative LC in combination with a home-made automated fraction collection module to fragment the universal metabolome standard into ten fractions (Frs. I-X); 2) LC-accurate MS/MS and quantitative 1 H NMR spectroscopy conducted in parallel to acquire the qualitative and quantitative data of each fraction; 3) Robust identification and quantification of components by use of LC coupled to multiple reaction monitoring...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109187/limonoids-from-seeds-of-azadirachta-indica-a-juss-and-their-cytotoxic-activity
#6
Jian Chen, Xiaona Fan, Jianhua Zhu, Liyan Song, Zhiwei Li, Fei Lin, Rongmin Yu, Hanhong Xu, Jiachen Zi
Four new limonoid-type nortriterpenoids, 1-detigloyl-1- O -methacryloylsalannin ( 1 ), 28-deoxo-2,3-dihydronimbolide ( 2 ), 12-acetoxy-3- O -acetyl-7- O -tigloylvilasinin ( 3 ) and 12-acetoxy-3- O -acetyl-7- O -methacryloylvilasinin ( 4 ), along with five known ones, were isolated from seeds of Azadirachta indica A. Juss. Their structures were elucidated by various spectroscopic methods, including UV, IR, MS, NMR, X-ray crystallography, quantum chemical calculation, as well as by comparison of their spectroscopic data with those reported...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109186/synthesis-and-biological-evaluation-of-novel-tricyclic-matrinic-derivatives-as-potential-anti-filovirus-agents
#7
Xin Zhang, Qiang Liu, Qianqian Li, Yinghong Li, Zhandong Liu, Hongbin Deng, Sheng Tang, Yanxiang Wang, Youchun Wang, Danqing Song
Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a common chlorinated benzene fragment were designed, synthesized and evaluated for their anti-ebolavirus (EBOV) activities. Structure-activity relationship analysis indicated: (i) 12 N -dichlorobenzyl motif was beneficial for the activity; (ii) the chiral configuration at C5 atom might not affect the activity much. Among the target compounds, compound 7d exhibited the most potent potency against EBOV with an IC50 value of 5.29 μmol/L and an SI value of over 37...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109185/structure-based-design-synthesis-and-biological-evaluation-of-novel-pyrimidinone-derivatives-as-pde9-inhibitors
#8
Xu-Nian Wu, Ya-Dan Huang, Jin-Xuan Li, Yan-Fa Yu, Zhou Qian, Chen Zhang, Yinuo Wu, Hai-Bin Luo
The pathological processes of Alzheimer's disease and type 2 diabetes mellitus have been demonstrated to be linked together. Both PDE9 inhibitors and PPAR γ agonists such as rosiglitazone exhibited remarkable preclinical and clinical treatment effects for these two diseases. In this study, a series of PDE9 inhibitors combining the pharmacophore of rosiglitazone were discovered. All the compounds possessed remarkable affinities towards PDE9 and four of them have the IC50 values <5 nmol/L. In addition, these four compounds showed low cell toxicity in human SH-SY5Y neuroblastoma cells...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109184/development-of-polyvinylpyrrolidone-paclitaxel-self-assemblies-for-breast-cancer
#9
Pallabita Chowdhury, Prashanth K B Nagesh, Sheema Khan, Bilal B Hafeez, Subhash C Chauhan, Meena Jaggi, Murali M Yallapu
The goal of this investigation was to develop and demonstrate a polymer/paclitaxel self-assembly (PTX-SA) formulation. Polymer/PTX-SAs were screened based on smaller size of formulation using dynamic light scattering analysis. Additionally, fluorescence microscopy and flow cytometry studies exhibited that polyvinylpyrrolidone (PVP)-based PTX-SAs (PVP/PTX-SAs) had superior cellular internalization capability in MCF7 and MDA-MB-231 breast cancer cells. The optimized PVP/PTX-SAs exhibited less toxicity to human red blood cells indicating a suitable formulation for reducing systemic toxicity...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109183/gold-nanorods-together-with-hsp-inhibitor-ver-155008-micelles-for-colon-cancer-mild-temperature-photothermal-therapy
#10
Xichuan Tang, Liwei Tan, Kun Shi, Jinrong Peng, Yao Xiao, Wenting Li, Lijuan Chen, Qian Yang, Zhiyong Qian
Enhancing the heat-sensitivity of tumor cells provides an alternative solution to maintaining the therapeutic outcome of photothermal therapy (PTT). In this study, we constructed a therapeutic system, which was composed of methoxy-polyethylene-glycol-coated-gold-nanorods (MPEG-AuNR) and VER-155008-micelles, to evaluate the effect of VER-155008 on the sensitivity of tumor cells to heat, and further investigate the therapeutic outcome of MPEG-AuNR mediated PTT combined with VER-155008- micelles. VER-155008- micelles down-regulate the expression of heat shock proteins and attenuate the heat-resistance of tumor cell...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109182/garlic-derived-compound-s-allylmercaptocysteine-inhibits-hepatocarcinogenesis-through-targeting-lrp6-wnt-pathway
#11
Jia Xiao, Feiyue Xing, Yingxia Liu, Yi Lv, Xiaogang Wang, Ming-Tat Ling, Hao Gao, Songying Ouyang, Min Yang, Jiang Zhu, Yu Xia, Kwok-Fai So, George L Tipoe
Whether and how garlic-derived S -allylmercaptocysteine (SAMC) inhibits hepatocellular carcinoma (HCC) is largely unknown. In the current study, the role of low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6) in HCC progression and the anti-HCC mechanism of SAMC was examined in clinical sample, cell model and xenograft/orthotopic mouse models. We demonstrated that SAMC inhibited cell proliferation and tumorigenesis, while induced apoptosis of human HCC cells without influencing normal hepatocytes...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109181/olmutinib-hm61713-reversed-multidrug-resistance-by-inhibiting-the-activity-of-atp-binding-cassette-subfamily-g-member-2-in-vitro-and-in-vivo
#12
Zhiqiang Zhang, Xiaoran Guo, Kenneth K W To, Zhen Chen, Xiaona Fang, Min Luo, Chunling Ma, Jianhua Xu, Shirong Yan, Liwu Fu
Overexpressing of ATP-binding cassette (ABC) transporters is the essential cause of multidrug resistance (MDR), which is a significant hurdle to the success of chemotherapy in many cancers. Therefore, inhibiting the activity of ABC transporters may be a logical approach to circumvent MDR. Olmutinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which has been approved in South Korea for advanced EGFR T790M-positive non-small cell lung cancer (NSCLC). Here, we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109180/targeting-erk-an-achilles-heel-of-the-mapk-pathway-in-cancer-therapy
#13
REVIEW
Feifei Liu, Xiaotong Yang, Meiyu Geng, Min Huang
The mitogen-activated protein kinases (MAPK) pathway, often known as the RAS-RAF-MEK-ERK signal cascade, functions to transmit upstream signals to its downstream effectors to regulate physiological process such as cell proliferation, differentiation, survival and death. As the most frequently mutated signaling pathway in human cancer, targeting the MAPK pathway has long been considered a promising strategy for cancer therapy. Substantial efforts in the past decades have led to the clinical success of BRAF and MEK inhibitors...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109179/the-application-of-car-t-cell-therapy-in-hematological-malignancies-advantages-and-challenges
#14
REVIEW
Zijun Zhao, Yu Chen, Ngiambudulu M Francisco, Yuanqing Zhang, Minhao Wu
Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive immunotherapy where T lymphocytes are engineered with synthetic receptors known as chimeric antigen receptors (CAR). The CAR-T cell is an effector T cell that recognizes and eliminates specific cancer cells, independent of major histocompatibility complex molecules. The whole procedure of CAR-T cell production is not well understood. The CAR-T cell has been used predominantly in the treatment of hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, and multiple myeloma...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109178/personalized-medicine-in-non-small-cell-lung-cancer-a-review-from-a-pharmacogenomics-perspective
#15
REVIEW
Wenxiao Jiang, Guiqing Cai, Peter C Hu, Yue Wang
Non-small cell lung cancer is a prevalent and rapidly-expanding challenge to modern medicine. While generalized medicine with traditional chemotherapy yielded comparatively poor response rates and treatment results, the cornerstone of personalized medicine using genetic profiling to direct treatment has exalted the successes seen in the field and raised the standard for patient treatment in lung and other cancers. Here, we discuss the current state and advances in the field of personalized medicine for lung cancer, reviewing several of the mutation-targeting strategies that are approved for clinical use and how they are guided by patient genetic information...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109177/taxane-resistance-in-castration-resistant-prostate-cancer-mechanisms-and-therapeutic-strategies
#16
REVIEW
Brandon Bumbaca, Wei Li
Despite its good initial response and significant survival benefit in patients with castration-resistant prostate cancer (CRPC), taxane therapy inevitably encounters drug resistance in all patients. Deep understandings of taxane resistant mechanisms can significantly facilitate the development of new therapeutic strategies to overcome taxane resistance and improve CRPC patient survival. Multiple pathways of resistance have been identified as potentially crucial areas of intervention. First, taxane resistant tumor cells typically have mutated microtubule binding sites, varying tubulin isotype expression, and upregulation of efflux transporters...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109176/targeting-an-oncogenic-kinase-phosphatase-signaling-network-for-cancer-therapy
#17
REVIEW
Xiao-Mei Qi, Fang Wang, Matthew Mortensen, Ryan Wertz, Guan Chen
Protein kinases and phosphatases signal by phosphorylation and dephosphorylation to precisely control the activities of their individual and common substrates for a coordinated cellular outcome. In many situations, a kinase/phosphatase complex signals dynamically in time and space through their reciprocal regulations and their cooperative actions on a substrate. This complex may be essential for malignant transformation and progression and can therefore be considered as a target for therapeutic intervention...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109175/understanding-the-biology-of-her3-receptor-as-a-therapeutic-target-in-human-cancer
#18
REVIEW
Hui Lyu, Amy Han, Erik Polsdofer, Shuang Liu, Bolin Liu
HER3 belongs to the human epidermal growth factor receptor (HER) family which also includes HER1/EGFR/erbB1, HER2/erbB2, and HER4/erbB4. As a unique member of the HER family, HER3 lacks or has little intrinsic tyrosine kinase activity. It frequently co-expresses and forms heterodimers with other receptor tyrosine kinases (RTKs) in cancer cells to activate oncogenic signaling, especially the PI-3K/Akt pathway and Src kinase. Elevated expression of HER3 has been observed in a wide variety of human cancers and associates with a worse survival in cancer patients with solid tumors...
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109174/editorial-preface-for-targeted-cancer-therapy
#19
EDITORIAL
Guan Chen, Wei Li
No abstract text is available yet for this article.
July 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30109173/editor-profiles-guest-editor-of-special-column-on-targeted-cancer-therapy
#20
EDITORIAL
(no author information available yet)
No abstract text is available yet for this article.
July 2018: Acta Pharmaceutica Sinica. B
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