Tianjin International Joint Academy of Biotechnology & Medicine

Tianjin, China

Tianjin International Joint Academy of Biotechnology & Medicine

Tianjin, China

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Qiao X.-L.,Tianjin Nankai Hospital | Xiao X.-F.,Tianjin University of Traditional Chinese Medicine | Zhou D.-Z.,Tianjin Tasly Pride Pharmaceutical Co. | Ye Z.-L.,Tianjin Tasly Pride Pharmaceutical Co. | And 4 more authors.
Chinese Traditional and Herbal Drugs | Year: 2014

Objective: To establish a UPLC-MS/MS analytical method for the simultaneous analysis of ginsenosides (ginsenosides Rb1, Re, Rg1, Rc, Rd, Rf, Rg3, F2, and notoginsenoside R1) and lignans (gomisin A, schisandrol B, deoxyschizandrin, and schisandrin B) in Yiqi Fumai Injection (freeze-dried) (YFI), and measure the contents of these constituents in YFI. Methods: Quantitative research of 13 components in YFI was done by reversed-phase liquid chromatography on a C18 column using a gradient elution (0.1% formic acid in water and 0.1% formic acid in methanol). A triple quadrupole mass spectrometer operating in positive electrospray ionization mode with multiple reaction monitoring was used. Results: Thirteen components in YFI have good linear relationship, precision, stability, and repeatability according to the requirements of the methodology determination. The recoveries were 98.28%-101.08%. The 13 components in three batches of YFI were determined by UPLC-MS/MS method. Conclusion: The developed UPLC-MS/MS method is simple, sensitive, and accurate, and has good repeatability. The 13 components in YFI could be rapidly and accurately quantified by UPLC-MS/MS, which provides the helpful information for the comprehensive quality evaluation of YFI. ©, 2014, Editorial Office of Chinese Traditional and Herbal Drugs. All right reserved.


PubMed | Nankai University, National University of Singapore, Tianjin International Joint Academy of Biotechnology & Medicine, Sichuan University and University of Sichuan
Type: Journal Article | Journal: Nucleic acids research | Year: 2015

Similarity-based clustering and classification of compounds enable the search of drug leads and the structural and chemogenomic studies for facilitating chemical, biomedical, agricultural, material and other industrial applications. A database that organizes compounds into similarity-based as well as scaffold-based and property-based families is useful for facilitating these tasks. CFam Chemical Family database http://bidd2.cse.nus.edu.sg/cfam was developed to hierarchically cluster drugs, bioactive molecules, human metabolites, natural products, patented agents and other molecules into functional families, superfamilies and classes of structurally similar compounds based on the literature-reported high, intermediate and remote similarity measures. The compounds were represented by molecular fingerprint and molecular similarity was measured by Tanimoto coefficient. The functional seeds of CFam families were from hierarchically clustered drugs, bioactive molecules, human metabolites, natural products, patented agents, respectively, which were used to characterize families and cluster compounds into families, superfamilies and classes. CFam currently contains 11,643 classes, 34,880 superfamilies and 87,136 families of 490,279 compounds (1691 approved drugs, 1228 clinical trial drugs, 12,386 investigative drugs, 262,881 highly active molecules, 15,055 human metabolites, 80,255 ZINC-processed natural products and 116,783 patented agents). Efforts will be made to further expand CFam database and add more functional categories and families based on other types of molecular representations.


PubMed | Tianjin University of Traditional Chinese Medicine, Tsinghua University and Tianjin International Joint Academy of Biotechnology & Medicine
Type: Journal Article | Journal: Acta pharmacologica Sinica | Year: 2016

Nuciferine is an aporphine alkaloid extracted from lotus leaves, which is a raw material in Chinese medicinal herb for weight loss. In this study we used a network pharmacology approach to identify the anti-tumor activity of nuciferine and the underlying mechanisms.The pharmacological activities and mechanisms of nuciferine were identified through target profile prediction, clustering analysis and functional enrichment analysis using our traditional Chinese medicine (TCM) network pharmacology platform. The anti-tumor activity of nuciferine was validated by in vitro and in vivo experiments. The anti-tumor mechanisms of nuciferine were predicted through network target analysis and verified by in vitro experiments.The nuciferine target profile was enriched with signaling pathways and biological functions, including regulation of lipase activity, response to nicotine and regulation of cell proliferation. Target profile clustering results suggested that nuciferine to exert anti-tumor effect. In experimental validation, nuciferine (0.8 mg/mL) markedly inhibited the viability of human neuroblastoma SY5Y cells and mouse colorectal cancer CT26 cells in vitro, and nuciferine (0.05 mg/mL) significantly suppressed the invasion of 6 cancer cell lines in vitro. Intraperitoneal injection of nuciferine (9.5 mg/mL, ip, 3 times a week for 3 weeks) significantly decreased the weight of SY5Y and CT26 tumor xenografts in nude mice. Network target analysis and experimental validation in SY5Y and CT26 cells showed that the anti-tumor effect of nuciferine was mediated through inhibiting the PI3K-AKT signaling pathway and IL-1 levels in SY5Y and CT26 cells.By using a TCM network pharmacology method, nuciferine is identified as an anti-tumor agent against human neuroblastoma and mouse colorectal cancer in vitro and in vivo, through inhibiting the PI3K-AKT signaling pathways and IL-1 levels.


PubMed | Tsinghua University, Tianjin International Joint Academy of Biotechnology &Medicine and Chinese Institute of Materia Medica
Type: | Journal: Scientific reports | Year: 2015

Wu-tou decoction (WTD) has been extensively used for the treatment of rheumatoid arthritis (RA). Due to lack of appropriate methods, pharmacological mechanisms of WTD acting on RA have not been fully elucidated. In this study, a list of putative targets for compositive compounds containing in WTD were predicted by drugCIPHER-CS. Then, the interaction network of the putative targets of WTD and known RA-related targets was constructed and hub nodes were identified. After constructing the interaction network of hubs, four topological features of each hub, including degree, node betweenness, closeness and k-coreness, were calculated and 79 major hubs were identified as candidate targets of WTD, which were implicated into the imbalance of the nervous, endocrine and immune (NEI) systems, leading to the main pathological changes during the RA progression. Further experimental validation also demonstrated the preventive effects of WTD on inflammation and joint destruction in collagen-induced arthritis (CIA) rats and its regulatory effects on candidate targets both in vitro and in vivo systems. In conclusion, we performed an integrative analysis to offer the convincing evidence that WTD may attenuate RA partially by restoring the balance of NEI system and subsequently reversing the pathological events during RA progression.


Tian X.,Tianjin University of Traditional Chinese Medicine | Tian X.,Tianjin International Joint Academy of Biotechnology & Medicine | Liu J.,Tianjin University of Traditional Chinese Medicine | Liu J.,Tianjin International Joint Academy of Biotechnology & Medicine | And 7 more authors.
Mitochondrial DNA | Year: 2015

The giant Asian mantis Hierodula formosana (Mantodea: Mantidae) is widely distributed in Taiwan. In the present study, we investigated the complete mitochondrial genome of H. formosana and the mitogenome is 16 266 bp in length. The circular molecule consists of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes, and a non-coding control region, with an AT content of 75.8%. An extra non-coding region is inserted between trnM and ND2, similar to the other Mantidae species T. tamolana. A preliminary phylogenetic analysis has been carried out with 11 related species and the status of Hierodula formosana is further confirmed. © 2015 Taylor & Francis.


Dong S.,Nankai University | Dong S.,Tianjin International Joint Academy of Biotechnology & Medicine | Yang P.,Nankai University | Yang P.,Tianjin International Joint Academy of Biotechnology & Medicine | And 15 more authors.
Protein and Cell | Year: 2015

Ebola virus (EBOV) is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA (−ssRNA) viruses, EBOV possess a nucleocapsid protein (NP) to facilitate genomic RNA encapsidation to form viral ribonucleoprotein complex (RNP) together with genome RNA and polymerase, which plays the most essential role in virus proliferation cycle. However, the mechanism of EBOV RNP formation remains unclear. In this work, we solved the high resolution structure of core domain of EBOV NP. The polypeptide of EBOV NP core domain (NPcore) possesses an N-lobe and C-lobe to clamp a RNA binding groove, presenting similarities with the structures of the other reported viral NPs encoded by the members from Mononegavirales order. Most strikingly, a hydrophobic pocket at the surface of the C-lobe is occupied by an α-helix of EBOV NPcore itself, which is highly conserved among filoviridae family. Combined with other biochemical and biophysical evidences, our results provides great potential for understanding the mechanism underlying EBOV RNP formation via the mobility of EBOV NP element and enables the development of antiviral therapies targeting EBOV RNP formation. © 2015, The Author(s).


Wang J.,Tianjin University of Traditional Chinese Medicine | Wang J.,Tianjin International Joint Academy of Biotechnology & Medicine | Lu C.-S.,Tianjin University of Traditional Chinese Medicine | Lu C.-S.,Tianjin International Joint Academy of Biotechnology & Medicine | And 7 more authors.
Journal of Asian Natural Products Research | Year: 2016

A new saponin, isonarthogenin 3-O-β-d-glucopyranosyl-(1→4)-β-d-galactopyranoside (1), together with twelve known compounds, were isolated from the rhizomes of Polygonatum sibiricum. The structures of these compounds were elucidated by analysis of their 1D/2D NMR and MS data. Among them, phenol compounds 4–7 and 9–10 showed significant inhibitions against the formation of advanced glycosylation end products, with IC50 values of 0.091 ± 0.0021, 0.10 ± 0.041, 0.014 ± 0.0027, 0.11 ± 0.011, 0.13 ± 0.045, and 0.055 ± 0.019 μM, respectively. The results will promote exploiting potential medicinal use of these compounds in the prevention of diabetic complications and supporting Polygonatum sibiricum as a functional food for healthy and medicinal diet. © 2016 Taylor & Francis


PubMed | Tianjin University of Traditional Chinese Medicine and Tianjin International Joint Academy of Biotechnology & Medicine
Type: Journal Article | Journal: Journal of Asian natural products research | Year: 2016

A new saponin, isonarthogenin 3-O--d-glucopyranosyl-(14)--d-galactopyranoside (1), together with twelve known compounds, were isolated from the rhizomes of Polygonatum sibiricum. The structures of these compounds were elucidated by analysis of their 1D/2D NMR and MS data. Among them, phenol compounds 4-7 and 9-10 showed significant inhibitions against the formation of advanced glycosylation end products, with IC50 values of 0.0910.0021, 0.100.041, 0.0140.0027, 0.110.011, 0.130.045, and 0.0550.019M, respectively. The results will promote exploiting potential medicinal use of these compounds in the prevention of diabetic complications and supporting Polygonatum sibiricum as a functional food for healthy and medicinal diet.


PubMed | Nankai University and Tianjin International Joint Academy of Biotechnology & Medicine
Type: Journal Article | Journal: Bioorganic & medicinal chemistry letters | Year: 2013

Captopril is a New Delhi metallo--lactamase-1 (NDM-1) inhibitor with an IC50 value of 7.9M. It is composed of two units: a 3-mercapto-2-methylpropanoyl fragment and a proline residue. In this study, we synthesized simple amide derivatives of 3-mercapto-2-methylpropanoic acid, and then tested them as NDM-1 inhibitors in order to identify the pharmacophore for NDM-1 inhibition. We found that the lead compound 22 had an IC50 value of 1.0M. Further structure simplification provided compounds 31 and 32, which had IC50 values of 15 and 10M, respectively. As compound 32 is a clinically used antidote for metal poisoning, it has great potential to be repurposed to treat bacterial infections.


PubMed | Nankai University, Tianjin International Joint Academy of Biotechnology & Medicine and CAS Institute of Biophysics
Type: Journal Article | Journal: Antimicrobial agents and chemotherapy | Year: 2015

Enterovirus 71 (EV71), a primary pathogen of hand, foot, and mouth disease (HFMD), affects primarily infants and children. Currently, there are no effective drugs against HFMD. EV71 3C protease performs multiple tasks in the viral replication, which makes it an ideal antiviral target. We synthesized a small set of fluorogenic model peptides derived from cleavage sites of EV71 polyprotein and examined their efficiencies of cleavage by EV71 3C protease. The novel peptide P08 [(2-(N-methylamino)benzoyl) (NMA)-IEALFQGPPK(DNP)FR] was determined to be the most efficiently cleaved by EV71 3C protease, with a kinetic constant kcat/Km of 11.8 0.82 mM(-1) min(-1). Compared with literature reports, P08 gave significant improvement in the signal/background ratio, which makes it an attractive substrate for assay development. A Molecular dynamics simulation study elaborated the interactions between substrate P08 and EV71 3C protease. Arg39, which is located at the bottom of the S2 pocket of EV71 3C protease, may participate in the proteolysis process of substrates. With an aim to evaluate EV71 3C protease inhibitors, a reliable and robust biochemical assay with a Z factor of 0.87 0.05 was developed. A novel compound (compound 3) (50% inhibitory concentration [IC50] = 1.89 0.25 M) was discovered using this assay, which effectively suppressed the proliferation of EV 71 (strain Fuyang) in rhabdomyosarcoma (RD) cells with a highly selective index (50% effective concentration [EC50] = 4.54 0.51 M; 50% cytotoxic concentration [CC50] > 100 M). This fast and efficient assay for lead discovery and optimization provides an ideal platform for anti-EV71 drug development targeting 3C protease.

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