Publications by authors named "Ying-Xia Li"

34 Publications

Development of FABP4/5 inhibitors with potential therapeutic effect on type 2 Diabetes Mellitus.

Eur J Med Chem 2021 Jul 24;224:113720. Epub 2021 Jul 24.

School of Pharmacy, Fudan University, Shanghai, 201203, China. Electronic address:

Fatty acid-binding protein 4 (FABP4) and fatty acid-binding protein 5 (FABP5) are promising therapeutic targets for the treatment of various metabolic diseases. However, the weak potency, low selectivity over FABP3, or poor pharmacokinetic profiles of currently reported dual FABP4/5 inhibitors impeded further research. Here, we described the characterization of a series of dual FABP4/5 inhibitors with improved metabolic stabilities and physicochemical properties based on our previous studies. Among the compounds, D9 and E1 exhibited good inhibitory activities against FABP4/5 and favorable selectivity over FABP3 in vitro. In cell-based assays, D9 and E1 exerted a decrease of FABP4 secretion, a strong anti-lipolytic effect in mature adipocytes, and suppression of MCP-1 expression in THP-1 macrophages. Moreover, D9 and E1 possessed good metabolic stabilities in mouse hepatic microsomes and acceptable pharmacokinetics profiles in ICR mice. Further in vivo experiments showed that D9 and E1 could potently decrease serum FABP4 levels and ameliorate glucose metabolism disorders in obese diabetic db/db mice. These results demonstrated that D9 and E1 could serve as lead compounds for the development of novel anti-diabetic drugs.
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http://dx.doi.org/10.1016/j.ejmech.2021.113720DOI Listing
July 2021

Response of antimony distribution in street dust to urban road traffic conditions.

J Environ Manage 2021 Oct 9;296:113219. Epub 2021 Jul 9.

State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, 19 Xinjiekouwai Street, Haidian District, Beijing, 100875, China. Electronic address:

Little is known about the relationship between traffic congestion and antimony (Sb) distribution in street dust, which is essential for Sb control and emission reduction in urban areas. Sb concentrations and mass load of the street dust collected in 19 cities of China were determined before investigating the mechanism of traffic influence on Sb distribution through diverse statistical means. The results showed that the Sb concentrations in each city were 1.10-4.76 times higher than the local background values. Sb concentrations in transportation areas were significantly higher than those in residential and industrial areas, and were significantly affected by road network density. The effect of congestion on Sb load of street dust was influenced by vehicle flowrate. Only when the vehicle flowrate was high, the traffic congestion would promote the increase of Sb load obviously. The improved accounting method showed that the Sb dissipation from brake wear in major Chinese cities were higher than that in Stockholm, Sweden, in 2005. The latent path analysis illustrated that a 1% increase in congestion index was correlated with a 0.886% increase in the Sb load. Compared with Switzerland, which has a typical industrialized Sb consumption pattern, China needs to recycle brake pads in addition to taking various measures to alleviate traffic congestion and reduce brake pad wear, despite the fact that the maximum health risk of Sb was far below the safety threshold. This study will provide valuable insights for urban traffic management and brake pad recycling.
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http://dx.doi.org/10.1016/j.jenvman.2021.113219DOI Listing
October 2021

Combined treatment with FABP4 inhibitor ameliorates rosiglitazone-induced liver steatosis in obese diabetic db/db mice.

Basic Clin Pharmacol Toxicol 2021 Sep 15;129(3):173-182. Epub 2021 Jun 15.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.

Rosiglitazone has been reported to exert dual effects on liver steatosis, and it could exacerbate liver steatosis in obese animal models, which was suggested to be closely related to the elevated hepatic expression of FABP4. This study aimed to investigate whether combined treatment with FABP4 inhibitor I-9 could alleviate rosiglitazone-induced liver steatosis in obese diabetic db/db mice. Male C57BL/KsJ-db/db mice were orally treated with rosiglitazone, rosiglitazone combined with I-9 daily for 8 weeks. The liver steatosis was evaluated by triglyceride content and H&E staining. The expression of hepatic lipogenic genes or proteins in liver tissue or in FFA-treated hepatocytes and PMA-stimulated macrophages were determined by real-time quantitative polymerase chain reaction (RT-qPCR) or western blotting. Results showed that combined treatment with I-9 decreased rosiglitazone-induced increase in serum FABP4 level and expression of lipogenic genes in liver, especially FABP4, and ameliorated liver steatosis in db/db mice. Rosiglitazone-induced intracellular TG accumulation and increased expression of FABP4 in the cultured hepatocytes and macrophages were also suppressed by combined treatment. We concluded that combined treatment with FABP4 inhibitor I-9 could ameliorate rosiglitazone-exacerbated elevated serum FABP4 level and ectopic liver fat accumulation in obese diabetic db/db mice without affecting its anti-diabetic efficacy.
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http://dx.doi.org/10.1111/bcpt.13621DOI Listing
September 2021

Lead distribution in urban street dust and the relationship with mining, gross domestic product GDP and transportation and health risk assessment.

Environ Pollut 2020 Jul 2;262:114307. Epub 2020 Mar 2.

State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing, 100875, China. Electronic address:

Lead (Pb) is an important pollutant and it is of significance to explore the Pb distribution, influencing factors and health risk. Pb concentration and mass load per unit area in 385 street dust samples collected from 19 cities in China were determined during 2011-2013. The results show that the Pb concentration are 68.8, 105.4, 41.7, 49.7, 75.6, 81.7, 131.9, 67.5, 109.3, 164.1, 74.8, 66.4, 99.8, 58.4, 114.0, 59.6, 103.7, 55.4 and 80.4 for Beijing, Chengdu, Daqing, Harbin, Jilin, Jinan, Kunming, Lanzhou, Luoyang, Panzhihua, Qingdao, Yinchuan, Guangzhou, Tangshan, Xi'an, Guangyuan, Nanjing, Taiyuan and Tianjin, respectively. The Pb pollution level of urban street dust varies among cities in the range of 1.72-5.56 times higher than soil background values. The allometric function can fit the change in Pb concentration with particle size well. The medium-sized (38-120 μm) particles contributed 60.2%-80.4% to the Pb load and should be highlighted when selecting street dust management techniques. Influenced by the distribution of Pb ore, the Pb concentration of urban street dust in China shows obvious regional differences, with value in the south 112% higher than that in the north. Among all kinds of mining types, metal-related mining activities discharge a large amount of Pb dust in the process of crushing and smelting, thus contributing most to the Pb load. The Pb load was also affected by transportation. The relationship between Pb load and gross domestic product (GDP) was described with the environmental Kuznets curve (EKC) model, which indicated that the Pb emissions of most cities were still increasing. Finally, the human health risk assessment model with adjusted parameters showed that the Pb risk of all cities was below the threshold. Despite all this, given the EKC law of Pb emission, long-term follow-up assessments are needed.
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http://dx.doi.org/10.1016/j.envpol.2020.114307DOI Listing
July 2020

Preparation of Syringaldehyde from Lignin by Catalytic Oxidation of Perovskite-Type Oxides.

ACS Omega 2020 Feb 29;5(5):2107-2113. Epub 2020 Jan 29.

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China.

The influence of different reaction conditions on the yield of syringaldehyde was studied by using perovskite oxide as the catalyst. The optimal reaction conditions are as follows: 0.60 g of dealkali lignin, 0.60 g of 5 wt % theta ring-loaded LaFeCuO catalyst, 30 mL of 1.0 mol/L NaOH solution, 160 °C reaction temperature, 0.80 MPa O pressure, and 2.5 h reaction time. Under these conditions, the highest syringaldehyde yield was 10.00%. The recycling performance of the catalyst was studied. It was found by XRD analysis that the catalyst maintained high catalytic activity after four times of use.
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http://dx.doi.org/10.1021/acsomega.9b02379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016912PMC
February 2020

Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes.

Endocrine 2020 03 16;67(3):587-596. Epub 2019 Dec 16.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Purpose: Fatty acid binding protein 4 (FABP4) has been demonstrated to be secreted from adipocytes in an unconventional pathway associated with lipolysis. Circulating FABP4 is elevated in metabolic disorders and has been shown to affect various peripheral cells such as pancreatic β-cells, hepatocytes and macrophages, but its effects on adipocytes remains unclear. The aim of this study was to investigate the effects of exogenous FABP4 (eFABP4) on adipocyte differentiation and function.

Methods: 3T3-L1 pre-adipocytes or mature adipocytes were treated with recombinant FABP4 in the absence or presence of FABP4 inhibitor I-9/p38 MAPK inhibitor SB203580; Meanwhile male C57BL/6J mice were subcutaneously injected twice a day with recombinant FABP4 (0.35 mg/kg) with or without I-9 (50 mg/kg) for 2 weeks. The effects of eFABP4 on differentiation, lipolysis and inflammation were determined by triglyceride measurement or lipolysis assay, western blotting, or RT-qPCR analysis.

Results: eFABP4 treatment significantly reduced intracellular triglyceride content and decreased expression of adipogenic markers peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), intracellular FABP4, and adiponectin in 3T3-L1 cells. Besides, eFABP4 promoted lipolysis and inflammation in differentiated 3T3-L1 adipocytes as well as in adipose tissue of eFABP4-treated C57BL/6J mice, with elevated gene expression of monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, and elevated protein expression of adipose triglyceride lipase (ATGL), phosphorylation of hormone-sensitive lipase (HSL) (Ser-660), p38, and nuclear factor-kappa B (NF-κB). The pro-inflammatory and pro-lipolytic effects of eFABP4 could be reversed by SB203580/I-9.

Conclusions: These findings indicate that eFABP4 interferes with adipocyte differentiation, induces p38/HSL mediated lipolysis and p38/NF-κB mediated inflammation in adipocytes in vitro and in vivo.
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http://dx.doi.org/10.1007/s12020-019-02157-8DOI Listing
March 2020

Effectiveness of electroacupuncture for pain after osteosarcoma post surgery: A study protocol of systematic review of randomized controlled trial.

Medicine (Baltimore) 2019 Nov;98(44):e17381

Department of Anesthesiology.

Background: This study will assess the effectiveness of electroacupuncture (EA) for pain in patients with osteosarcoma post surgery (OSPS).

Methods: In this study, we will comprehensively search the following electronic databases from inception to the present without language restrictions: Cochrane Library, EMBASE, MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, the Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database. Two authors will independently carry out study selection, data extraction, and methodological assessments. RevMan 5.3 software will be used for statistical analysis.

Results: The primary outcome is pain intensity. The secondary outcomes consist of event-free survival, overall survival, quality of life, and adverse events.

Conclusion: The findings of this study will provide helpful evidence of EA treatment for patients with OSPS.

Prospero Registration Number: PROSPERO CRD42019146696.
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http://dx.doi.org/10.1097/MD.0000000000017381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946390PMC
November 2019

Dimeric 1,4-benzoquinone Derivatives with Cytotoxic Activities from the Marine-Derived Fungus sp. L129.

Mar Drugs 2019 Jun 26;17(7). Epub 2019 Jun 26.

Department of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao University, Qingdao 266021, China.

Two new dimeric 1,4-benzoquinone derivatives, peniquinone A () and peniquinone B (), a new dibenzofuran penizofuran A (), and a new pyrazinoquinazoline derivative quinadoline D (4), together with 13 known compounds (-), were isolated from a marine-derived fungus sp. L129. Their structures, including absolute configurations, were elucidated by extensive spectroscopic data and electronic circular dichroism calculations. Compound exhibited cytotoxicity against the MCF-7, U87 and PC3 cell lines with IC values of 12.39 µM, 9.01 µM and 14.59 µM, respectively, while compound displayed relatively weak cytotoxicity activities against MCF-7, U87 and PC3 cell lines with IC values of 25.32 µM, 13.45 µM and 19.93 µM, respectively. Furthermore, compound showed weak quorum sensing inhibitory activity against CV026 with an MIC value of 20 μg/well.
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http://dx.doi.org/10.3390/md17070383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669556PMC
June 2019

Acrepyrone A, a new -pyrone derivative from an endophytic fungus, SS-g13.

Nat Prod Res 2020 Apr 19;34(8):1091-1096. Epub 2019 Jan 19.

Department of Natural Medicinal Chemistry and Pharmacognosy, School of Pharmacy, Qingdao University, Qingdao, People's Republic of China.

A new -pyrone derivative, acrepyrone A (), and three known sorbicillinoids, trichodimerol (), dihydrotrichodimerol () and tetrahydrotrichodimerol () were isolated from an endophytic fungus, SS-g13, harboured in the roots of the Chinese medicinal plant Their structures were determined by analysing MS, NMR, and ECD data. Compound was evaluated for its cytotoxic effect, antibacterial activity and quorum sensing inhibitory potential.
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http://dx.doi.org/10.1080/14786419.2018.1548462DOI Listing
April 2020

[Comparison of Characteristics and Source Apportionment of Polycyclic Aromatic Hydrocarbons in Different Environmental Media in the Urban Area of Daqing City].

Huan Jing Ke Xue 2017 Dec;38(12):5272-5281

State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing 100875, China.

In order to investigate the various pollution characteristics and sources of polycyclic aromatic hydrocarbons (PAHs) in different environmental media, 23 street dust samples and four soil samples were collected in October 2012 in Daqing City. After extraction by Dionex ASE300 and purification, the content of the US EPA priority pollutants[16 individual PAH and total PAHs (ΣPAHs)] was determined by using gas chromatography-mass spectrometry (GC/MS). The results showed that the range of ΣPAHs content in street dust was 579.5-4656.7 ng·g, and the average content was 1839.7 ng·g. The mass percentage of PAHs in the street dust in different functional areas in Daqing showed a similar mass ratio range, with the average mass percentage of low ring (2-3 rings) PAHs of 37.9%, medium ring (4 rings) PAHs of 37.3%, and high ring (5-6 rings) PAHs of 24.8%. However, low ring PAHs, with mass ratios of 69.3%-99.97%, overwhelmingly dominated the Daqing soil, Daqing lake sediment, Daqing lakes, and Daqing ponds (data from literature). The distribution of ΣPAHs content was not significant among different functional areas and was closely related to the type of the plants around the sampling sites. The isomer ratio method confirmed that the sources of PAHs in the street dust in the study area were mixed sources, including oil spills, fuel oil combustion, and coal/biomass burning. Positive matrix factorization (PMF) results showed that the PAHs in the street dust in the center of Daqing originated from coal combustion, oil spill sources, industrial sources, and traffic sources, with contribution rates of 30.1%, 26.9%, 23.6%, and 19.3%, respectively, which were not exactly the same trend as that in other media.
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http://dx.doi.org/10.13227/j.hjkx.201704266DOI Listing
December 2017

From hit to lead: Structure-based discovery of naphthalene-1-sulfonamide derivatives as potent and selective inhibitors of fatty acid binding protein 4.

Eur J Med Chem 2018 Jun 9;154:44-59. Epub 2018 May 9.

School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address:

Fatty acid binding protein 4 (FABP4) plays a critical role in metabolism and inflammatory processes and therefore is a potential therapeutic target for immunometabolic diseases such as diabetes and atherosclerosis. Herein, we reported the identification of naphthalene-1-sulfonamide derivatives as novel, potent and selective FABP4 inhibitors by applying a structure-based design strategy. The binding affinities of compounds 16dk, 16do and 16du to FABP4, at the molecular level, are equivalent to or even better than that of BMS309403. The X-ray crystallography complemented by the isothermal titration calorimetry studies revealed the binding mode of this series of inhibitors and the pivotal network of ordered water molecules in the binding pocket of FABP4. Moreover, compounds 16dk and 16do showed good metabolic stabilities in liver microsomes. Further extensive in vivo study demonstrated that 16dk and 16do exhibited a dramatic improvement in glucose and lipid metabolism, by decreasing fasting blood glucose and serum lipid levels, enhancing insulin sensitivity, and ameliorating hepatic steatosis in obese diabetic (db/db) mice.
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http://dx.doi.org/10.1016/j.ejmech.2018.05.007DOI Listing
June 2018

Structural characteristics of natural chimeric genes and their implications for gene design.

Yi Chuan 2018 Feb;40(2):135-144

College of Life Science, Shihezi University, Shihezi 832000, China.

The natural chimeric gene is a novel gene fused by two or more independent genes. Its discovery extends the classical gene concept that one gene resides in one chromosomal locus. During tumorigenesis, many chimeric genes lead to tumor-related diseases; therefore, it is one molecular marker for cancer diagnosis. In this review, we summarize the research progress of chimeric genes in terms of their feature, structure, transcription, regulation and function. We pinpoint the difficulties and challenges in the current research work, and discuss the application of chimeric gene in the new gene design.
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http://dx.doi.org/10.16288/j.yczz.17-268DOI Listing
February 2018

[Post-stroke shoulder-hand syndrome treated with acupuncture and rehabilitation: a randomized controlled trial].

Zhongguo Zhen Jiu 2013 Nov;33(11):970-4

Xiamen Municipal Hospital of TCM Affiliated to Fujian University of TCM Xiamen 361009 China.

Objective: To assess the clinical efficacy on post-stroke shoulder-hand syndrome (SHS) treated with acupuncture and rehabilitation and the impacts on patients' nailfold microcirculation.

Methods: One hundred and twenty patients were randomized into an acupuncture rehabilitation group and a simple rehabilitation group, 60 cases in each one. In the simple rehabilitation group, OT (comprehensive rehabilitation therapy) training was adopted. In the acupuncture rehabilitation group, on the basis of the treatment as the simple rehabilitation, acu puncture was added at Taiyuan (LU 9), Zusanli (ST 36), Xuanzhong (GB 39), Waiguan (TE 5), Shousanli (LI 10), Quchi (LI 11) and Jianyu (LI 15). Acupuncture was given once a day, 7 days made one session. Totally, 4 sessions of treatment were required. Fugl-Meyer score, upper limb pain score, the score of nerve function defect and the items of nailfold microcirculation of patients were assessed in the the two groups before and after treatment. The efficacy was compared between the two groups.

Results: (1) The upper limb pain, the systematic motor function of the upper limbs, the nerve function defect, nailfold microcirculation and clinical symptoms were all improved after treatment in either the acupuncture rehabilitation group or the simple rehabilitation group as compared with those before treatment, indicating the significant difference (P<0. 05, P<0. 01). (2) The im provements in the upper limb pain (0. 90+/-0.71 vs 1. 80+/-0. 66), the systematic motor function of the upper limbs (42. 43 13. 57 vs 29. 98+/-15. 11), the nerve function defect (8. 60+/-11. 61 vs 13. 0+/-1. 74), nailfold microcirculation (total score 3. 18+/-1.32 vs 4.34+/-1.23) and clinical symptoms in the acupuncture rehabilitation group after treatment were different significantly as compared with those in the simple rehabilitation group (PO0. 05,P-O. 01), and the results in the acupuncture rehabilitation group were superior to the simple rehabilitation group. (3) In the acupuncture rehabilitation group, the markedly effective rate was 50. 0% (30/60) and the total effective rate was 93.3% (56/60), which was better than 16.7% (10/60) and 63. 3% (38/60) respectively in the simple rehabilitation group (all P<0. 05).

Conclusion: Both the combined therapy of acupuncture and rehabilitation and the simple rehabilitation training are effective in the treatment of post-stroke SHS, and promote the status of nailfold microcirculation, the efficacy of the combined therapy is better than that of the latter.
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November 2013

[Analysis and evaluation of heavy metals along the Chaohe River in Miyun County].

Huan Jing Ke Xue 2013 Sep;34(9):3572-7

State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing 100875, China.

In order to explore the heavy metal concentrations in soils surrounding the Chaohe River, 15 soil samples were collected along the Chaohe River. Results show that average concentrations of As, Cd, Cr, Cu, Hg, Ni, Pb, Zn are 7.94, 0.16, 127.71, 38.45, 0.22, 45.97, 21.98, 81.06 microg x g(-1), respectively. The mean concentrations of 15 samples for most heavy metals are higher than the background values of Beijing soil except Pb. Compared to the heavy metal concentrations in the soil of Shanghai Huangpu River water resource area, the mean concentrations of Cr, Cu and Ni are higher and concentrations of other heavy metals are at a moderate level. Geo-accumulation index method was used to evaluate the pollution status of different heavy metals. Results show that the pollution of Cr and Hg is moderate. The pollution of Cu and Ni is between no to moderate. There is no pollution of As, Cd, Pb and Zn in the study area. Ecological risk index method was also used to evaluate the ecological impact. Results show that the pollution level of Hg is strong and Cu is medium. Other heavy metals are at a slight pollution level. The samplings region as a whole is at a medium ecological pollution level. In a word, Hg, Cr, Ni, and Cu need to be controlled.
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September 2013

Benzbromarone, an old uricosuric drug, inhibits human fatty acid binding protein 4 in vitro and lowers the blood glucose level in db/db mice.

Acta Pharmacol Sin 2013 Nov 30;34(11):1397-402. Epub 2013 Sep 30.

1] Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China [2] Advanced Institute for Translational Medicine, School of Life Science and Technology, Tongji University, Shanghai 200092, China.

Aim: Fatty acid-binding protein 4 (FABP4) plays an important role in maintaining glucose and lipid homeostasis. The aim of this study was to find new inhibitors of FABP4 for the treatment of type 2 diabetes.

Methods: Human FABP4 protein was expressed, and its inhibitors were detected in 1,8-ANS displacement assay. The effect of the inhibitor on lipolysis activity was examined in mouse 3T3-L1 preadipocytes. The db/db mice were used to evaluate the anti-diabetic activity of the inhibitor. Molecular docking and site-directed mutagenesis studies were carried out to explore the binding mode between the inhibitor and FABP4.

Results: From 232 compounds tested, benzbromarone (BBR), an old uricosuric drug, was discovered to be the best inhibitor of FABP4 with an IC50 value of 14.8 μmol/L. Furthermore, BBR (25 μmol/L) significantly inhibited forskolin-stimulated lipolysis in 3T3-L1 cells. Oral administration of BBR (25 or 50 mg/kg, for 4 weeks) dose-dependently reduced the blood glucose level and improved glucose tolerance and insulin resistance in db/db mice. Molecular docking revealed that the residues Ser55, Asp76, and Arg126 of FABP4 formed important interactions with BBR, which was confirmed by site-directed mutagenesis studies.

Conclusion: BBR is an inhibitor of FABP4 and a potential drug candidate for the treatment of type 2 diabetes and atherosclerosis.
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http://dx.doi.org/10.1038/aps.2013.97DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4651057PMC
November 2013

Synthesis and biological evaluation of oleanolic acid derivatives as PTP1B inhibitors.

Eur J Med Chem 2013 May 14;63:511-22. Epub 2013 Mar 14.

Department of Pharmaceutical Engineering, Northwest University, Xi'an 710069, China.

Twenty-four sugar-substituted oleanolic acid derivatives (1a-1f, 2a-2j, and 3a-3h) were synthesized in a concise and efficient strategy and their effects on the inhibition of protein tyrosine phosphatase 1B (PTP1B) and insulin-sensitizing response were evaluated in vitro. Several derivatives showed moderate to good inhibitory activities against PTP1B, and especially compounds 2f, 2h, 3d and 3e exhibited the most potent inhibitory activities with the IC50 values of 1.91, 12.2, 9.21 and 0.56 μM against PTP1B, respectively. Furthermore, compounds 2g-2h and 3b-3e displayed good insulin-sensitizing activities with the response values ranging from 21.52% to 59.58%. Structure-activity relationship study of these sugar-substituted oleanolic acid derivatives demonstrated that PTP1B inhibitory activity and insulin-sensitizing response were strongly influenced by both the carbohydrate moiety at the C-3 position and the long acidic chain at C-28 position of oleanolic acid.
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http://dx.doi.org/10.1016/j.ejmech.2013.03.001DOI Listing
May 2013

Cryptococcus nanyangensis sp. nov., a new basidiomycetous yeast isolated from the gut of wood-boring larvae.

Curr Microbiol 2012 Nov 12;65(5):617-21. Epub 2012 Aug 12.

College of Life Science and Technology, Nanyang Normal University, 1638 Wolong Road, Nanyang, China.

Two strains of a novel basidiomycetous yeast species were isolated from the gut of wood-boring larvae collected in the Baotianman Nature Reserve, the central China. Sequence analysis of the D1/D2 domains of the large subunit (LSU) rRNA gene and internal transcribed spacer (ITS) regions showed that these yeasts belong to the Bulleromyces clade and formed a cluster together with eleven undescribed Cryptococcus species. The novel species differed from its closest known species, Cryptococcus rajasthanensis, by 3.3 % divergence (15 substitutions and 6 gaps over 630 bases) in the D1/D2 domains, and by 13.4 % divergence (41 substitutions and 27 gaps over 508 bases) in the ITS regions. Physiologically, the fermentation of glucose, galactose, sucrose, trehalose, and raffinose in Durham tubes was observed for the strains of this new yeast. Based on the phenotypical and molecular characteristics presented, the two strains are proposed as a new species, Cryptococcus nanyangensis sp. nov., with the type strain KCY-1(T) (=CICC 1976(T) = CBS 12474(T)).
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http://dx.doi.org/10.1007/s00284-012-0203-7DOI Listing
November 2012

Candida sanyaensis sp. nov., an ascomycetous yeast species isolated from soil.

Antonie Van Leeuwenhoek 2013 Jan 7;103(1):47-52. Epub 2012 Aug 7.

College of Life Science and Technology, Nanyang Normal University, 1638 Wolong Road, Nanyang, 473061, China.

Strains representing a novel ascomycetous yeast species, Candida sanyaensis, were isolated from soil samples collected on Hainan Island and Taiwan Island in China. Analysis of the D1/D2 domains of the large subunit (LUS) rRNA gene and internal transcribed spacer (ITS) regions of these strains showed that this species was related to Candida tropicalis and Candida sojae, their closest relatives. C. sanyaensis differed by three substitutions and one gap from C. tropicalis, and by four substitutions and one gap from C. sojae, in the D1/D2 domain sequences. However, the ITS sequences of C. sanyaensis were quite divergent from the latter two species, showing that it is a genetically separate species. The novel strains were also found to have very similar PCR-fingerprinting profiles which were quite distinct from those of C. tropicalis and C. sojae strains. The type strain of C. sanyaensis is HN-26(T) (= CICC 1979(T) = CBS 12637(T)).
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http://dx.doi.org/10.1007/s10482-012-9785-0DOI Listing
January 2013

[Gene expression of Notch1 and Jagged1 in children with acute leukemia].

Zhongguo Dang Dai Er Ke Za Zhi 2012 Feb;14(2):105-9

Department of Pediatrics, Fourth Military Medical University, Xi'an, China.

Objective: To study the gene expression of Notch1 and Jagged1 in children with acute leukemia (AL) and their possible roles in the pathogenesis of AL.

Methods: Mononuclear cells from bone marrow or peripheral blood of 47 children with AL and 20 controls (normal children or children with nonmalignant hematologic disease) were collected from February 2009 to July 2011. A two-step method to semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the gene expression of Notch1 and Jagged1. Of the 47 children with AL, there were 26 cases of B-ALL, 6 cases of T-ALL and 15 cases of AML.

Results: The positive expression rate of Notch1 in the ALL and AML groups was higher than in the control group (P<0.05). The expression level of Notch1 in T-ALL children was higher than in B-ALL children (P<0.01). The positive expression rate of Jagged1 in the ALL and AML groups was not significantly different from the control group, however, the expression level of Jagged1 in the ALL and AML groups was higher than in the control group (P<0.05).

Conclusions: There are significant differences in the gene expression of Notch1 between children with different types of ALL, and a higher expression of Notch1 relates to T-ALL. The activation of Notch1 signal is common in children with AL. The abnormal gene expression of Notch1 in children with AML shows the role of Notch1 in AML. The gene expression of Jagged1 in children with ALL or AML is abnormal, and this needs to be confirmed by further research.
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February 2012

Cyclin D1 inhibits whereas c-Myc enhances the cytotoxicity of cisplatin in mouse pancreatic cancer cells via regulation of several members of the NF-κB and Bcl-2 families.

J Carcinog 2011 30;10:24. Epub 2011 Nov 30.

Department of the University of Minnesota, Hormel Institute, Austin, MN 55912, USA.

Background: Cisplatin (CDDP) is a drug used for treatment of many types of malignancy but pancreatic cancer is relatively resistant to it. This study aims to determine whether and how cyclin D1 (D1) and c-Myc influence the response of pancreatic cancer cells to CDDP.

Materials And Methods: Ela-mycPT mouse pancreatic cancer cells were transfected with D1 or c-myc cDNA and treated with CDDP alone or together with NPCD, an inhibitor of cyclin dependent ckinase (CDK) 4 and 6. Reverse transcription followed by polymerase chain reaction (RT-PCR) and western blot assays were used to determine the mRNA and protein levels of interested genes. Cell viability was determined using 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay.

Results: Treatment of Ela-mycPT1 cells with CDDP caused an increase in c-myc expression but a slightly latent decrease in D1 expression, whereas D1 and c-Myc proteins repressed each other. D1 or c-Myc rendered Ela-mycPT1 cells resistant or sensitive, respectively, to CDDP. D1 induced the expression of several members of the NF-κB family, including RelA, RelB, Nfκb1 and Nfκb2. D1 also induced BIRC5 and several pro-survival members of the Bcl-2 gene family, including Bcl-2 , Mcl-1 and Bad while it decreased the level of the pro-apoptotic Noxa. Inhibition of CDK4 or CDK6 kinase activity by NPCD did not affect these effects of D1. In contrast, c-Myc in Ela-mycPT1 and Ela-mycPT4 cells has the opposite effects to D1 on the expression of most of these apoptosis regulating genes.

Conclusion: Our results suggest that induction of c-Myc and inhibition of D1 may be mechanisms for CDDP to elicit cytotoxicity. On the other hand, D1 induces whereas c-Myc represses the expression of key NF-κB family members to induce and repress, respectively, the expression of BIRC5 and several Bcl-2 family members, in turn inhibiting or enhancing the response to CDDP.
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http://dx.doi.org/10.4103/1477-3163.90437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243339PMC
August 2012

Design, synthesis and biological evaluation of novel glycosylated diphyllin derivatives as topoisomerase II inhibitors.

Eur J Med Chem 2012 Jan 13;47(1):424-31. Epub 2011 Nov 13.

School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.

Recently, a novel glycosylated diphyllin derivative 11 which exhibiting potent anticancer activity by targeting topoisomerase IIα was reported by our group. In order to provide more molecules for structure-activity relationship (SAR) studies, 12 new glycosylated diphyllin analogs have been designed, synthesized, and evaluated for their biological activities. The SAR analysis revealed that (i) the sugar moiety on the diphyllin is essential for the anticancer activity; (ii) equatorial C4'-OH on the sugar is superior to the axial one, and (iii) a proper cyclic lipophilic group at the C4' and C6' of sugar might enhance the anticancer activity.
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http://dx.doi.org/10.1016/j.ejmech.2011.11.011DOI Listing
January 2012

Effects of the novel vascular targeting agent MDS-11P on tumor vascularity and its antitumor activity.

Biochem Pharmacol 2011 Dec 6;82(12):1832-42. Epub 2011 Sep 6.

Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.

Vascular disrupting agents show selective effects on tumor established vasculature, and achieve encouraging results in both pre-clinical and clinical experiments. In the present study, we investigated the effects of a new CA4 derivative MDS-11 and its prodrug MDS-11P on vascular disrupting activity in vitro and in vivo. Surface plasmon resonance (SPR) and tubulin polymerization assay showed that MDS-11 interacted with tubulin directly and inhibited tubulin polymerization in a cell free system, and western blot assay further confirmed the action in the cellular level. MDS-11 was found to significantly disrupt the microtubulin skeleton in proliferating HUVECs than quiescent ones determined by confocal microscopy. Furthermore, MDS-11 was found to damage the HUVEC-formed tube quickly, but did not influence structures of microvessels from aortic ring possessing pericytes and smooth muscle cells until 3 h treatment. In A549 xenograft mice, immunohistochemistry staining of tumor sections revealed that a single dose of MDS-11P led to large areas of necrosis within tumor and reduced the number of tumor vessels, which was consolidated by perfused vascular volume assay. Pharmacokinetic studies of MDS-11P indicated that MDS-11P rapidly converted to the active form, MDS-11, and exhibited a much faster elimination in mice. The antitumor analysis using H22 and A549 mice xenograft models revealed that the growth inhibition rates of MDS-11P at 50 mg/kg (twice a day for three weeks) reached 59.4%, 60.5% respectively without obvious weight loss. Taken together, these results suggest that MDS-11 is a potential vascular disrupting agent for further development of antitumor drug.
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http://dx.doi.org/10.1016/j.bcp.2011.08.024DOI Listing
December 2011

[Expression of cdx2 gene in pediatric patients with leukemia and its clinical significance].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2011 Feb;19(1):130-3

Department of Pediatrics, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.

This study was aimed to investigate the expression of cdx2 gene in pediatric patients with acute leukemia and its clinical implication. The bone marrow and peripheral blood were collected from 33 newly diagnosed pediatric patients with acute leukemia, the cdx2 gene expression in each AL subtypes and normal controls was detected by RT-PCR, the relationship between cdx2 expression and response to treatment was observed. The results showed that the expression of cdx2 was positive in 25 out of 30 AL cases (83.3%), to be exact, in 20 of 21 ALL cases (95.2%) and in 5 of 9 AML cases (55.6%), which showed statistical difference (p < 0.05). The cdx2 mRNA could be detected also in 1 of 3 CML cases. However, no expression of cdx2 was observed in all normal control which revealed significant difference between patient group and normal control group. 21 AL patients with cdx2 positive expression (17 ALL and 4 AML patients) and 4 AL patients with cxd2 negative expression (1 ALL and 3 AML patients) all reached complete remission (CR) after treatment, which showed no correlation with CR rate. 8 patients with positive cdx2 expression were followed up. As a result, the cdx2 positive expression at initial diagnosis of patients remained positive at reaching CR, but it gradually turned to negative along with prolonging of CR, while the cdx2 negative expression at initial diagnosis of patients remained negative at CR in bone marrow level. It is concluded that cdx2 positive expression is observed in the majority of pediatric AL patients, even positive rate in ALL patients is higher than that in AML patients, while the cdx2 expression also can be observed in CML patients. The cdx2 positive expression is not related to the CR rate in AL patients.
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February 2011

Effects of an Indolocarbazole-Derived CDK4 Inhibitor on Breast Cancer Cells.

J Cancer 2011 Jan 8;2:36-51. Epub 2011 Jan 8.

1. Hormel Institute, University of Minnesota, Austin, MN 55912, USA.

Introduction: Cyclin D1 (D1) binds to cyclin-dependent kinases (CDK) 4 or 6 to form a holoenzyme that phosphorylates the Rb protein to promote cell cycle progression from G1 to S phase. Therefore, targeting CDK4/6 may be a good strategy for chemotherapy of cancer. We performed a proof-of-principle study to determine the effect of Naphtho [2, 1-α] pyrrolo [3, 4-c] carbazole-5, 7 (6H, 12H)-dione (NPCD), a novel CDK4 inhibitor, on breast cancer cell lines.

Methods: NPCD was synthesized and purified to over 99% purity verified by HPLC. MCF7, MB231, MCF15, T47D and GI101Ap human breast cancer cells were analyzed for the efficacy of NPCD with MTT and clonogenic assays, with FACS and staining for ethidium bromide and acridine orange for cell death and cell cycle profile. Western blot, reverse transcription and PCR were used for studies of gene expression, and co-immunoprecipitation for protein-complex formation.

Results: MTT assay showed that NPCD caused growth arrest and apoptosis of MCF7, MDA-MB231, T47D, MCF15 and GI101Ap cells with an IC50 ranging between 3 to 8 µM given as a single dose. The growth arrest persisted for many days after cessation of the treatment, as shown in a clonogenic assay. NPCD could induce or reduce the D1 and CDK4 protein levels, depending on the cell line, but this effect was not correlated with its efficacy. Phosphorylation of D1 at Thr286 was decreased but it unexpectedly did not correlate with the change in D1 level in the cell lines studied. Phosphorylation of the Rb protein was decreased as expected whereas the p27kip1 protein level was decreased unexpectedly. Protein levels of p21cip1, CDK2 and cyclin E were also decreased in some, but not all, of the cell lines, whereas the mRNA levels of D1, CDK4, cyclin E, CDK2, p27kip1 and p21cip1 were increased in different cell lines.

Conclusions: NPCD can cause long-lasting growth arrest and cell death of breast cancer cell lines at an IC50 of 3-8 µM. Decreased phosphorylation of Rb by D1-CDK4/6 and decreased p27kip1 protein level may be part of the underlying mechanism.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020360PMC
http://dx.doi.org/10.7150/jca.2.36DOI Listing
January 2011

[Epidemic condition and biological characteristics of non-O1/non-O139 Vibrio cholerae in Haizhu District of Guangzhou].

Zhonghua Yu Fang Yi Xue Za Zhi 2010 Dec;44(12):1087-90

Department of Detection, Haizhu District Center for Disease Control and Prevention, Guangzhou 510288, China.

Objective: To understand the epidemic condition, distribution and biological characteristics of non-O1/non-O139 Vibrio cholerae from 2001 to 2009 in Haizhu District, to provide a scientific basis for the prevention and control of acute diarrhea.

Methods: Referring to the detecting method written in "Cholera control handbook" in the fifth edition, 764 specimens from outside environment (including the water in the Pearl River, drinking water, water for breeding fish, aquatic products and delicatessen foods), 189 specimens of healthy population and 3398 intestinal samples of patients with diarrhea, summing up to 4351 specimens for non-O1/non-O139 Vibrio cholerae test.

Results: 4,351 specimens were detected of 101 strains of non O1/non O139 Vibrio cholerae, the total detection rate was 2.32%; 66 strains were identified by serotyping and grouped into 26 different serotypes, the typing rate was 65.3%. The strains VBO9, VBO38 and VBO76 were the dominant bacteria.Nine strains of the same type of non-O1/non-O139 Vibrio cholerae were found from external environments also from patients with diarrhea, suggesting that there might be a correlation between the two.

Conclusion: Non-O1/non-O139 Vibrio cholerae have diversified serotypes, causing certain infection rate among the population in this region. These bacteria exist extensively in external environment and they are the potential hazard to the citizens.
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December 2010

[A case report of childhood histocytic sarcoma].

Zhongguo Dang Dai Er Ke Za Zhi 2010 May;12(5):405-6

Department of Pediatrics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

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May 2010

D11, a novel glycosylated diphyllin derivative, exhibits potent anticancer activity by targeting topoisomerase IIα.

Invest New Drugs 2011 Oct 25;29(5):800-10. Epub 2010 Mar 25.

Division of Antitumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.

Glycosylated natural products are reliable platforms for the development of anticancer drugs, simply due to the important features added by sugar appendages to the shape and the stereoelectronic properties of natural scaffolds. Herein, we indentified D11, a novel diphyllin glycoside with acetylated D-quinovose sugar moiety, as a potent topoisomerase IIα (Topo IIα) inhibitior. This peculiar sugar moiety endows D11 an optimal conformation with a high binding affinity for Topo IIα via hydrogen bonding to the entrance of ATPase pocket, thereby helping achieve more potent Topo II inhibition activity compared to the aglycon diphyllin. Further biochemical insights manifested that D11 significantly inhibited Topo IIα ATPase-catalyzed ATP hydrolysis in an ATP-dependent, but a DNA-independent manner. All these underlie the consequent superiority of D11 in the in vitro proliferation inhibition, apoptosis induction and the in vivo remarkable antitumor potency in xenograft mouse model. Moreover, D11 treatment also displayed no obvious body weight loss and other apparent toxicities, indicative of the restricted side effects by the virtue of sugar attachment. Taken together, a defined glycosylated manipulation of diphyllin may be a promising alternative approach in the development of novel Topo II inhibitors.
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http://dx.doi.org/10.1007/s10637-010-9425-3DOI Listing
October 2011

[Investigation of heavy metal and polycyclic aromatic hydrocarbons contamination in street dusts in urban Beijing].

Huan Jing Ke Xue 2010 Jan;31(1):159-67

State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing 100875, China.

This paper investigated the contamination levels of heavy metal and polycyclic aromatic hydrocarbons (PAHs) in street dusts in different functional areas in urban Beijing. Results show that the mean concentrations of Cd, Hg, Cr, Cu, Ni, Pb and Zn in street dusts in Beijing are 710 ng/g, 307 ng/g, 85.0 microg/g, 78.3 microg/g, 41.1 microg/g, 69.6 microg/g and 248.5 microg/g, respectively, which are significantly lower than those in most cities around the world and Shenyang, Shanghai in China. The mean concentration of Sigma 16PAHs in street dusts in Beijing is 0.398 microg/g, which is also lower than those of Handan, Tianjin and Shanghai. Non-parametric Friedman test demonstrates significant differences of heavy metal contents on street dusts from different functional zones. Street dusts in residential area and parks have lower heavy metal and PAHs concentrations than the street dusts from areas of high traffic density. The concentrations of heavy metals follow the order Zn > Cr > Cu > Pb > Ni > Cd > Hg, which is consistent with the situation in other cities around the world. The geoaccumulation index analysis shows that street dust in urban Beijing is moderately polluted by Cd, Zn and Cu, little polluted by Cr and Pb and practically unpolluted by Ni. The contamination levels of Sigma 16PAHs on street dusts vary greatly in different functional zones with parks little polluted, residential areas moderately to strongly polluted and traffic related areas strongly polluted to extremely polluted. Mass loading of heavy metals and PAHs is largely associated with street dusts of size range < 300 microm. Therefore, the urban sweeping vehicles should update the dust sweeping devices to remove not only the fine particle but also the coarser particles.
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January 2010

Synthesis of the C-terminal penta- peptide of the peptaibol culicinins.

J Pept Sci 2009 May;15(5):366-8

Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.

The synthesis of the C-terminal pentapeptide of culicinins has been achieved using [4 + 1] protocol and reduction-coupling strategy.
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http://dx.doi.org/10.1002/psc.1124DOI Listing
May 2009
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