Publications by authors named "Jian-Wen Liu"

56 Publications

Alkaloids from Tabernaemontana divaricata combined with fluconazole to overcome fluconazole resistance in Candida albicans.

Bioorg Chem 2021 02 24;107:104515. Epub 2020 Nov 24.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China. Electronic address:

Nineteen indole alkaloids including eleven new ones, taberdines A-K (1-11), were isolated from Tabernaemontana divaricata. Their structures were assigned by MS, NMR, single crystal X-ray diffractions, and ECD analyses. Alkaloid 1 is an aspidosperma-type monoterpenoid indole alkaloid and possesses a rearranged pyrrolidine moiety due to C-3 degradation, and 4 has a rare 1,3-oxazolidine moiety within iboga-type alkaloids. Alkaloids 2, 4, 6, and 11-19 combined with 5 μg/mL fluconazole exhibited significant activity to reverse fluconazole resistance in Candida albicans strains while no one used alone showed any activities against the resistant strain.
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http://dx.doi.org/10.1016/j.bioorg.2020.104515DOI Listing
February 2021

Bousangine A, a novel C-17-nor aspidosperma-type monoterpenoid indole alkaloid from Bousigonia angustifolia.

Fitoterapia 2020 Apr 4;142:104491. Epub 2020 Feb 4.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China. Electronic address:

Two new monoterpenoid indole alkaloids, bousangines A (1) and B (2), were isolated from the twigs and leaves of Bousigonia angustifolia. Their structures including absolute configurations were elucidated by a combination of MS, NMR, ECD calculation, and single-crystal X-ray diffraction analysis. Bousangine A (1) possessed a rearrangement pentacyclic skeleton derived from aspidosperma-type alkaloids with C-17 degradation. Their antiproliferative activity against several human cancer cell lines were evaluated.
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http://dx.doi.org/10.1016/j.fitote.2020.104491DOI Listing
April 2020

[Clinical application of percutaneous transforaminal endoscope-assisted lumbar interbody fusion].

Zhongguo Gu Shang 2019 Dec;32(12):1138-1143

Depatrment of Orthopaedics, Zhejiang Provincial People's Hospital, Hangzhou 310014, Zhejiang, China;

Objective: To conclude of the technical notes of percutaneous transforaminal endoscope-assisted lumbar interbody fusion (PT-Endo-LIF), and to investigate its safety and efficacy for treatment of degenerative lumbar disease.

Methods: Twenty-four patients were treated by PT-Endo-LIF combined with posterior percutaneous pedicle screws fixation from October 2017 to April 2018. There were 16 males and 8 females, ranging in age from 39 to 72 years old, with a mean of (59.6±9.5) years old. There were 15 cases diagnosed with lumbar intervertebral disc herniation combined with degenerative disc, the other 9 cases were diagnosed as low level lumbar spondylolistheses w/o segmental instability. Single segmental fusion was performed for 22 cases(one for L₂,₃, 3 for L₃,₄ and 18 for L₄,₅) and 2 segmental fusion was performed for the other 2 cases (both for L₃,₄ and L₄,₅). PT-Endo-LIF was performed under local anesthesia with conscious sedation, followed by decompression through endoscopic technics. After that, end-plate preparation and autogenous bone and expandable cage implantation were performed. Finally, percutaneous screws and rod instrumentation were used. The visual analogue scale (VAS) and Oswestry Disability Index (ODI) were used to evaluate the clinical efficacy. The operation time, intraoperative bleeding volume, intraoperative and postoperative complications were recorded. All patients underwent X-ray, CT plain scan, three-dimensional reconstruction and MRI examination to evaluate the stability of the implants and fusion rate before 3 days and 1, 3, 6, 12 and 18 months after operation.

Results: All patients were followed up, and the duration ranged from 12 to 18 months. The operation time of single-segment fusion was (192.3±22.7) min, and that of double-segment fusion was (272.5±24.7) min. The estimated intraoperative bleeding volume was less than 50 ml per segment, and no blood transfusion was performed in all patients. The VAS improved from preoperative 7.4±1.1 to postoperative 2.3±0.8 (=-19.65, <0.000 5). The ODI improved from preoperative (41.2±3.3)% to the final follow-up (12.3±2.5)%(=-35.76, <0.000 5). Postoperative complications occurred in 4 cases, and contralateral radicular symptoms occurred in 2 cases. After contralateral foraminoscopic decompression, the symptoms were completely alleviated. One case had neurological symptoms related to percutaneous screw placement, and the symptoms were alleviated after removal of the lateral screw rod internal fixation. The other cases had surgical incision infection and improved after debridement and suture. At the latest follow-up, no displacement or loosening of the fusion cage and screw rod system occurred in all patients, and 14 cases showed signs of fusion.

Conclusions: PT-Endo-LIF is a minimal invasive, safe and efficient surgical procedure for treatment of degenerative lumbar disease. Nevertheless, the long-term results still need to be confirmed by a multi-center and lagre sample follow-up study.
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http://dx.doi.org/10.3969/j.issn.1003-0034.2019.12.014DOI Listing
December 2019

Synthesis and Electrochemical Properties of CuC₂O₄·H₂O and CuC₂O₄·H₂O/Carbon Nanotubes (CNTs) Anodes for Lithium-Ion Batteries.

J Nanosci Nanotechnol 2020 Mar;20(3):1740-1748

Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory of Green Preparation and Application for Functional Materials, Hubei University, Wuhan 430062, P. R. China.

Pure CuC₂O₄·H₂O and CuC₂O₄·H₂O/carbon nanotubes (CNTs) composites are synthesized by a low-temperature hydrothermal process. The structure and morphology of the products are analyzed by X-ray diffraction (XRD), scanning electron microscopy (SEM), thermogravimetric analysis (TG) and Raman spectrum. The results demonstrate that the as-prepared CuC₂O₄·H₂O takes on a microsphere-like morphology, all CuC₂O₄·H₂O/CNTs nanocomposites are constructed by the intertwining of tabular CuC₂O₄·H₂O nanoparticles (NPs) and CNTs to form a tanglesome net. When evaluated as an anode materials for lithium ion batteries (LIBs), all CuC₂O₄·H₂O/CNTs electrodes possess higher reversible discharge capacities (more than 1000 mAh g) than the pure CuC₂O₄·H₂O, up to 200th cycle at a current density of 100 mA g. The results illustrate that the addition of CNTs can enhance the electrochemical performance of CuC₂O₄·H₂O. Overall, CuC₂O₄·H₂O/CNTs composite can be a promising candidate used as a promising anode for LIBs.
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http://dx.doi.org/10.1166/jnn.2020.17139DOI Listing
March 2020

Melotenuines A-E, cytotoxic monoterpenoid indole alkaloids from Melodinus tenuicaudatus.

Fitoterapia 2019 Oct 27;138:104347. Epub 2019 Aug 27.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, Yunnan, PR China. Electronic address:

Five new monoterpenoid indole alkaloids, melotenuines A-E (1-5), along with 18 known indole alkaloids, were isolated from the twigs and leaves of Melodinus tenuicaudatus. The structures of the new alkaloids were determined by a combination of MS, NMR and ECD analysis. Melotenuine A (1) represents the first example of aspidosperma-meloscandonine type bisindole alkaloids characterized by a methylene bridge between the two monomers, while melotenuine B (2) possessed a rare eburnamine-melsocandonine skeleton. All of the new indole alkaloids were evaluated for in vitro cytotoxicities against five human cancer cell lines. Among them, alkaloid 4 showed specific cytotoxicity against HL-60 cell line with IC value (5.15 ± 0.16 μM) comparable with that of positive control.
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http://dx.doi.org/10.1016/j.fitote.2019.104347DOI Listing
October 2019

miR-27a-3p regulates proliferation and apoptosis of colon cancer cells by potentially targeting BTG1.

Oncol Lett 2019 Sep 18;18(3):2825-2834. Epub 2019 Jul 18.

Department of Surgery, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, P.R. China.

microRNA (miR/miRNA)-27a-3p has been reported to be abnormally expressed in various types of cancer, including colorectal cancer (CRC). B-cell translocation gene 1 (BTG1) has also been implicated with CRC. However, the association between miR-27a-3p and BTG1 in CRC, to the best of our knowledge, has not been investigated. In order to assess whether miR-27a-3p is associated with CRC, reverse transcription-quantitative PCR was performed on 20 paired CRC and paracancerous tissues for miRNA analysis. For the screening and validation of miR-27a-3p expression in colon cancer, several colon cancer cell lines (HCT-116, HCT8, SW480, HT29, LOVO and Caco2) and the normal colorectal epithelial cell line NCM460 were examined. The highest expression levels of miR-27a-3p were detected in the HCT-116, which was selected for further experimentation. The HCT-116 cells were divided into control, miR-27a-3p mimic and inhibitor groups, and cell proliferation was tested using an MTT assay. Additionally, miR-27a-3p inhibitor/mimic or BTG1 plasmid were transfected into the HCT-116 cells, and flow cytometry was performed to analyze cell cycle distributions. TUNEL analysis was performed to detect apoptosis. Protein levels of factors in the downstream signaling pathway mediated by miR-27a-3p [ERK/mitogen-activated extracellular signal-regulated kinase (MEK)] were detected. miR-27a-3p was revealed to be overexpressed in human CRC tissues and colon cancer cell lines. Knockdown of miR-27a-3p suppressed proliferation of HCT-116 cells and apoptosis was increased. It further markedly upregulated expression levels of BTG1 and inhibited activation of proteins of the ERK/MEK signaling pathway. In addition, overexpression of BTG1 in HCT-116 cells triggered G/S phase cell cycle arrest and increased apoptosis via the ERK/MEK signaling pathway. In conclusion, the present study demonstrated that the effects of miR-27a-3p on colon cancer cell proliferation and apoptosis were similar to those of the tumor suppressor gene BTG1. The miR-27a-3p/BTG1 axis may have potential implications for diagnostic and therapeutic approaches in CRC.
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http://dx.doi.org/10.3892/ol.2019.10629DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676402PMC
September 2019

Effect of microwave chlorine depleted pyrolyzate on the combustion characteristics of refuse derived fuel derived from package waste.

Waste Manag 2018 Dec 13;82:1-8. Epub 2018 Oct 13.

School of Architecture and Urban Planning, Hunan University of Technology, Zhuzhou 412007, China.

Thermogravimetric-Fourier Transform Infrared Spectroscopy was conducted to evaluate the combustion characteristics of refuse derived fuel (RDF) adding of microwave chlorine depleted pyrolyzate in the mass proportion of 5-15%. It studied the catalyze effect of chlorine depleted pyrolyzate on RDF combustion performance. The combustion process of RDF could be divided into four stages. The temperature range of the most significant combustion stage of 10-RDF was much more extensive than another three ones. According to the FTIR analysis, the addition of chlorine depleted pyrolyzate might promote the combustion of CH and carbonyls to CO and HO earlier. Based on the distributed activation energy model (DAEM), the E value of RDF with chlorine depleted pyrolyzate added was much lower than that with no chlorine depleted pyrolyzate added. The chlorine depleted pyrolyzate enhanced the combustion performance of RDF with the lower ignition, lower burnout temperature, better combustion ability, better flammability and more outstanding combustion performance. The best combustion characteristic was obtained when the dosage of chlorine depleted pyrolyzate was 10%.
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http://dx.doi.org/10.1016/j.wasman.2018.09.053DOI Listing
December 2018

GM1 Ameliorates Lead-Induced Cognitive Deficits and Brain Damage Through Activating the SIRT1/CREB/BDNF Pathway in the Developing Male Rat Hippocampus.

Biol Trace Elem Res 2019 Aug 9;190(2):425-436. Epub 2018 Nov 9.

MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People's Republic of China.

Developmental lead (Pb) exposure involves various serious consequences, especially leading to neurotoxicity. In this study, we examined the possible role of monosialoganglioside (GM1) in lead-induced nervous impairment in the developing rat. Newborn male Sprague-Dawley rat pups were exposed to lead from birth for 30 days and then subjected to GM1 administration (0.4, 2, or 10 mg/kg; i.p.) or 0.9% saline. The results showed that developmental lead exposure significantly impaired spatial learning and memory in the Morris water maze test, reduced GM1 content, induced oxidative stress, and weakened the antioxidative systems in the hippocampus. However, co-treatment with GM1 reversed these effects. Moreover, GM1 counteracted lead-induced apoptosis by decreasing the expression of Bax, cleaved caspase-3, and by increasing the level of Bcl-2 in a dose-dependent manner. Furthermore, we found that GM1 upregulated the expression of SIRT1, CREB phosphorylation, and BDNF, which underlie learning and memory in the lead-treated developing rat hippocampus. In conclusion, our study demonstrated that GM1 exerts a protective effect on lead-induced cognitive deficits via antioxidant activity, preventing apoptosis, and activating SIRT1/CREB/BDNF in the developing rat hippocampus, implying a novel potential assistant therapy for lead poisoning.
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http://dx.doi.org/10.1007/s12011-018-1569-6DOI Listing
August 2019

Feiji Recipe inhibits the growth of lung cancer by modulating T-cell immunity through indoleamine-2,3-dioxygenase pathway in an orthotopic implantation model.

J Integr Med 2018 07 22;16(4):283-289. Epub 2018 Apr 22.

Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Oncology Institute of Traditional Chinese Medicine, Institute of TCM Oncology, Shanghai 200032, China. Electronic address:

Objective: Escape from the body's immune response is a basic characteristic of lung cancer, and indoleamine-2,3-dioxygenase (IDO) plays a key role in mediating immune escape of non-small-cell lung cancer, which leads to recurrence and metastasis. Feiji Recipe, a compound Chinese herbal medicine, has the effect of stabilizing lesions and prolonging survival in patients with lung cancer. The purpose of this study was to investigate the mechanisms underlying the anticancer properties of Feiji Recipe.

Methods: An orthotopic transplant model of mouse Lewis lung cancer, with stable expression of IDO gene, was established in C57BL/6 mice. Optical imaging was used to observe the effects of Feiji Recipe in the treatment of lung cancer in vivo. The effects of Feiji Recipe on the proliferation of mouse Lewis lung cancer cell line 2LL, 2LL-enhanced green fluorescent protein (2LL-EGFP) and 2LL-EGFP-IDO were investigated, and the apoptosis of T-cells was examined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide using flow cytometry. Chemical composition of Feiji Recipe was validated by high-performance liquid chromatography.

Results: Compared to the control group, the survival of animals treated with Feiji Recipe was significantly prolonged (P = 0.0074), and the IDO protein level decreased (P = 0.0072); moreover, the percentages of CD4CD25 T-cells and Foxp3 T-cells were significantly decreased (P < 0.05). The molecular mechanism of Feiji Recipe against lung cancer may relate to the regulation of immune cells, such as T-cells and regulatory T-cells.

Conclusion: The molecular mechanism of Feiji Recipe in treatment of lung cancer is to restore the function of T-cells in the cancer microenvironment through interfering with the IDO pathway.
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http://dx.doi.org/10.1016/j.joim.2018.04.008DOI Listing
July 2018

Menstruation recovery in scar pregnancy patients undergoing UAE and curettage and its influencing factors.

Medicine (Baltimore) 2018 Mar;97(11):e9584

Department of Interventional Therapy, Henan Provincival People's Hospital/The People's Hospital of Zhengzhou University, Zhengzhou, China.

This study aims to investigate the menstrual recovery outcome of scar pregnancy patients who received uterine artery embolization combined with curettage, and its influencing factors.The data of 119 patients with scar pregnancy, who received uterine artery embolization combined with curettage between December 2012 and December 2016 in Henan Provincival People's Hospital, were collected. The menstruation recovery of these patients was followed up, and factors that have influence on menstrual blood volume were analyzed using SPSS V.17.0.Follow-up data were available in 101/119 (84.9%) women. The median follow-up time was 22.7 months (range: 1.6-50.6 months); 58 (57.4%) patients had reduced menstrual blood volume, and 2 patients (2%) had amenorrhea. The proportion of patients with reduced menstrual blood volume, who were embolized with polyvinyl alcohol (PVA), PVA combined with gelatin sponge, and gelatin sponge between < and ≥33 years old was 41.7% versus 66.7%, 40% versus 57.1% and 60.6% versus 68.0%. The average age of patients with reduced menstrual blood volume (34.3 years) was greater than patients with normal menstrual blood volume (31.4 years), but the difference was not statistically significant (P = .07).Reduced menstrual blood volume can occur in scar pregnancy patients who received uterine artery embolization combined with curettage. The influence of the embolic agent PVA on menstrual blood volume depends on age, but the difference was not statistically significant.
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http://dx.doi.org/10.1097/MD.0000000000009584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882401PMC
March 2018

Virtual identification of novel PPARα/γ dual agonists by scaffold hopping of saroglitazar.

J Biomol Struct Dyn 2018 Oct 28;36(13):3496-3512. Epub 2017 Oct 28.

a Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy , Tianjin Medical University , Tianjin , China.

The thiazolidinedione class PPARγ agonists as antidiabetic agents are restricted in clinical use because of the side effects such as edema, weight gain, and heart failure. The single and selective agonism of PPARγ is the main cause of side effects. The multi-target cooperative PPARα/γ dual agonist development is a hot topic in the antidiabetic medicinal chemistry field. Saroglitazar is the first approved PPARα/γ dual agonist, available in India for the treatment of diabetic dyslipidemia. It got rid of these side effects. With the aim of finding more protent PPARα/γ dual agonists, the scaffold hopping was used to replace α-o phenylpropionic acid skeleton of saroglitazar with L-tyrosine skeleton. Then, the structural modification was carried out designing 72 compounds. Considering the importance of chirality, opposite configuration of 72 compounds was also studied. 12 compounds with better -cdocker energy were screened by molecular docking. Subsequently, the pharmacokinetic properties and toxicity evaluated by ADMET prediction, 11 of them showed better properties. Comp#L-17-1 and comp#L-3-1 were regarded as representatives to study the binding stability by molecular dynamics (MD) simulations. The MD simulation results of comp#L-17-1-PPARs (α, γ) and comp#L-3-1-PPARs (α, γ) provided structure reference for the research and development of novel PPARα/γ dual agonists.
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http://dx.doi.org/10.1080/07391102.2017.1392363DOI Listing
October 2018

Identification of novel PPARα/γ dual agonists by virtual screening, ADMET prediction and molecular dynamics simulations.

J Biomol Struct Dyn 2018 Aug 5;36(11):2988-3002. Epub 2017 Oct 5.

a Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy , Tianjin Medical University , Tianjin 300070 , China.

PPARα and PPARγ have been the most widely studied Peroxisome proliferator-activated receptor (PPAR) subtypes due to their important roles in regulating glucose, lipids, and cholesterol metabolism. By combining the lowering serum triglyceride levels benefit of PPARα agonists (such as fibrates) with the glycemic advantages of the PPARγ agonists (such as TZD), the dual PPAR agonists approach can both improve the metabolic effects and minimize the side effects caused by either agent alone, and hence, has become a promising strategy for designing effective drugs against type-2 diabetes. In this study, by means of virtual screening, ADMET prediction and molecular dynamics (MD) simulations techniques, one compound-ASN15761007 with high binding score, low toxicity were gained. It was observed by MD simulations that ASN15761007 not only possessed the same function as AZ242 did in activating PPARα and BRL did in activating PPARγ, but also had more favorable conformation for binding to the two receptors. Our results provided an approach to rapidly produce novel PPARα/γ dual agonists which might be a potential lead compound to develop against insulin resistance and hyperlipidemia.
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http://dx.doi.org/10.1080/07391102.2017.1373706DOI Listing
August 2018

Effects of low-temperature pretreatment on enhancing properties of refuse-derived fuel via microwave irradiation.

Waste Manag Res 2017 Jul 6;35(7):757-765. Epub 2017 Jun 6.

1 Chang Zhu Tan Institute of Two-oriented Social, Hunan University of Technology, China.

The present study focuses on pretreatment of enhancing the properties of refuse-derived fuel (RDF) via low-temperature microwave irradiation. These improved properties include lower chlorine content, a more porous surface structure and better combustion characteristics. In this study, low-temperature microwave irradiation was carried out in a modified microwave apparatus and the range of temperature was set to be 220-300℃. We found that the microwave absorbability of RDF was enhanced after being partly carbonized. Moreover, with the increasing of the final temperature, the organochlorine removal ratio was greatly increased to 80% and the content of chlorine was dramatically decreased to an extremely low level. It was also interesting to find that the chlorine of RDF was mainly released as HCl rather than organic chloride volatiles. The finding is just the same as the polyvinyl chloride pyrolysis process. In addition, pores and channels emerged during the modifying operation and the modified RDF has better combustibility and combustion stability than traditional RDF. This work revealed that low-temperature modification of RDF via microwave irradiation is significant for enhancing the quality of RDF and avoiding HCl erosion of equipment substantially.
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http://dx.doi.org/10.1177/0734242X17705724DOI Listing
July 2017

Dechlorination of organochloride waste mixture by microwave irradiation before forming solid recovered fuel.

Waste Manag 2017 Apr 22;62:118-124. Epub 2016 Nov 22.

Chang Zhu Tan Institute of Two-oriented Social, Hunan University of Technology, Zhuzhou 412007, China.

In order to form a modified solid recovered fuel (SRF) with low chlorine content, high calorific value and well combustion performance, low temperature microwave irradiation was applied to remove the chlorine of the organochloride waste mixture before they were mixed to form SRF. The optimizing conditions of final temperature, microwave absorbents and heating rate were also detected to obtain high dechlorination ratio and high ratio of hydrogen chloride (HCl) to volatiles. In the temperature range of 220-300°C, 280°C would be chose as the optimal low microwave modified temperature concerning at which the dechlorination ratio was high and ratio of HCl to volatiles was relatively high as well; The use of microwave absorbents of graphite and silicon carbide (SiC) had a pronounced effect on the dechlorination of organochloride waste mixture, and the dechlorination ratio was increased significantly which could be reached to 87%, almost 20% higher than absorbent absent sample; The heating rate should set be not too fast nor too slow, and there was no big difference between the heating rate of 13°C/min and 15°C/min; The content of Cl of modified SRF is dramatically decreased and reaches to a low level 0.328%. Hence, the modified SRF can be ascended from the third class to the second class according to the Finland chlorine Classes I-III. Moreover, the combustibility of modified SRF was substantial improved compared to the traditional SRF. The low heating value was almost 20.56MJ/kg which is close to the LHV of lignite coal and bituminous coal in China, and it increased by 60% over that of traditional SRF. Removing chlorine of organochloride waste mixture before they are mixed with other kinds of combustible waste to form a modified SRF which is expected to be an alternative fuel for combustion in the future.
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http://dx.doi.org/10.1016/j.wasman.2016.11.022DOI Listing
April 2017

p38 mitogen-activated protein kinase inhibition modulates nucleus pulposus cell apoptosis in spontaneous resorption of herniated intervertebral discs: An experimental study in rats.

Mol Med Rep 2016 May 22;13(5):4001-6. Epub 2016 Mar 22.

Department of Orthopaedic Surgery, Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu 215009, P.R. China.

The present study was performed to investigate the role of p38 mitogen‑activated protein kinase (MAPK) in the resorption of herniated intervertebral discs in 30 rats. In the non‑contained and p38 MAPK inhibition (p38i) groups, two coccygeal intervertebral discs (IVDs) were removed and wounded prior to relocation into the subcutaneous space of the skin of the back. In the contained group, the cartilage endplates maintained their integrity. Furthermore, SB203580 was injected intraperitoneally into the p38i group, whereas saline was injected into the other two groups. In the non‑contained group, the weight of the relocated IVDs decreased to a greater extent over time when compared with the contained and p38i groups. Phosphorylated p38, tumor necrosis factor‑α, and interleukin‑1β were observed to exhibit higher expression levels in the non‑contained group compared with the contained and p38i groups, at weeks 1 and 4 post‑surgery. The expression level of caspase‑3 and the densities of apoptotic disc cells were significantly higher in the non‑contained group compared with the contained and p38i groups at 4 weeks post‑surgery. In conclusion, p38 MAPK induces apoptosis in IVDs, while also accelerating the resorption of the relocated IVDs. Thus, p38 MAPK may be important in spontaneous resorption of IVDs.
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http://dx.doi.org/10.3892/mmr.2016.5039DOI Listing
May 2016

An investigation of antitumor efficiency of novel sustained and targeted 5-fluorouracil nanoparticles.

Eur J Med Chem 2015 Mar 24;92:882-9. Epub 2014 Dec 24.

Department of Molecular & Cellular Pharmacology, Biomedical Nanotechnology Center, State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address:

Traditional chemotherapeutic drugs remain the major treatment for advanced colorectal cancer. However, due to the lack of tumor specificity these drug also destroy healthy tissue and organs, which has been the main reason for treatment failure and mortality. Folate-based drug delivery systems for improving nanoparticle endocytosis have been used to address these problems. Here, folic acid (FA) conjugated mPEG-b-P(CABCL-co-ACL) diblock copolymers were synthesized and characterized by TEM and NMR. Drug loaded nanoparticles were prepared using dialysis method and was obtained with a mean diameter of 45.2 nm with sustained in vitro release profile. In vitro cytotoxicity assay indicated that the cytotoxicity of folate modified nanoparticles were significantly increased compared to free drug and non-folate nanoparticles. In addition, results of hemolytic and histopathologic study suggested that the non-loaded nanoparticle (NL/NP) was non-toxic and biocompatible at the testing concentration. Moreover, in vivo results showed that FA/5-FU/NP effectively inhibited growth of HCT-8 cell-based xenograft tumors in BALB/c mice and revealed stronger antitumor efficacy than other treated groups. Thus, both in vitro and in vivo results exhibited that the folate conjugated mPEG-b-P(CABCL-co-ACL) copolymers have great potential to be used as sustainable and specific colon cancer targeting delivery system for anticancer agents.
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http://dx.doi.org/10.1016/j.ejmech.2014.12.043DOI Listing
March 2015

A collagen-based multicellular tumor spheroid model for evaluation of the efficiency of nanoparticle drug delivery.

Artif Cells Nanomed Biotechnol 2016 15;44(2):540-4. Epub 2014 Oct 15.

a Department of Molecular & Cellular Pharmacology , Biomedical Nanotechnology Center, State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology , Shanghai , P.R. China.

Targeted drug delivery systems, especially those that use nanoparticles, have been the focus of research into cancer therapy during the last decade, to improve the bioavailability and delivery of anticancer drugs to specific tumor sites, thereby reducing the toxicity and side effects to normal tissues. However, the positive antitumor effects of these nanocarriers observed in conventional monolayer cultures frequently fail in vivo, due to the lack of physical and biological barriers resembling those seen in the actual body. Therefore, the collagen-based 3-D multicellular culture system, to screen new nanocarriers for drug delivery and to obtain more adequate and better prediction of therapeutic outcomes in preclinical experiments, was developed. This 3-D culture model was successfully established using optimized density of cells. Our result showed that 3-D cell colonies were successfully developed from 95-D, U87 and HCT116 cell lines respectively, after a seven-day culture in the collagen matrix. The coumarin-conjugated nanoparticles were able to penetrate the matrix gel to reach the tumor cells. The model is supposedly more accurate in reflecting/predicting the dynamics and therapeutic outcomes of candidates for drug transport in vivo, and/or investigation of tumor biology, thus speeding up the pace of discovery of novel drug delivery systems for cancer therapy.
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http://dx.doi.org/10.3109/21691401.2014.968820DOI Listing
November 2016

The effects of PTBP3 silencing on the proliferation and differentiation of MKN45 human gastric cancer cells.

Life Sci 2014 Sep 10;114(1):29-35. Epub 2014 Aug 10.

State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of Chemical Biology, East China University of Science and Technology, Shanghai 200237, PR China; Department of Molecular and Cellular Pharmacology, East China University of Science and Technology, Shanghai 200237, PR China.

Aims: PTBP3 overexpression inhibits the differentiation of leukemia cells; however, its effects on the differentiation and proliferation of solid cancer cells remain unclear. Thus, the impact of PTBP3 on the differentiation and proliferation of gastric cancer cells was investigated.

Main Methods: PTBP3 expression was analyzed in normal and tumor tissues using immunohistochemistry. A xenograft model was established in nude mice by subcutaneous injection of untransfected human gastric cancer MKN45 cells or those expressing a control vector or PTBP3 siRNA. We analyzed the tumor inhibition rate, the expression of PTBP3, the PCNA-positive rate and the serum levels of CEA, CA199, CA125, LDH, ALP and γ-GT in different groups.

Key Findings: The tumor weights in the PTBP3 siRNA group were significantly lower than that of the MKN45 cell control group (P<0.001). Immunohistochemistry analysis of PCNA expression revealed that it was markedly reduced after PTBP3 silencing. ELISAs showed that the serum levels of CEA and CA199 tumor markers as well as LDH and ALP were reduced after PTBP3 silencing. Transmission electron microscopy revealed that MKN45 cells expressing PTBP3 siRNA had reduced nuclear-to-cytoplasmic ratio and regular nuclei, suggesting differentiation.

Significance: PTBP3 may promote proliferation and inhibit the differentiation of human gastric cancer MKN45 cells.
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http://dx.doi.org/10.1016/j.lfs.2014.07.038DOI Listing
September 2014

Overcoming multidrug resistance in 2D and 3D culture models by controlled drug chitosan-graft poly(caprolactone)-based nanoparticles.

J Pharm Sci 2014 Apr 12;103(4):1064-74. Epub 2014 Feb 12.

Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.

The principal limitations of chemotherapy are dose-limiting systemic toxicity and the development of multidrug-resistant phenotypes. The aim of this study was to investigate the efficiency of a new sustained drug delivery system based on chitosan and ε-caprolactone to overcome multidrug resistance in monolayer and drug resistance associated with the three-dimensional (3D) tumor microenvironment in our established 3D models. The 5-fluorouracil (5-FU)-loaded nanoparticles (NPs) were characterized by transmission electron microscope and dynamic light scattering, and its released property was determined at different pH values. 5-FU/NPs exhibited well-sustained release properties and markedly enhanced the cytotoxicity of 5-FU against HCT116/L-OHP or HCT8/VCR MDR cells in two-dimensional (2D) and its parental cells in 3D collagen gel culture with twofold to threefold decrease in the IC50 values, as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Hoechst/propidium iodide staining and flow cytometry analysis. Furthermore, the possible mechanism was explored by high-performance liquid chromatography and rhodamine 123 accumulation experiment. Overall, the results demonstrated that 5-FU/NPs increase intracellular concentration of 5-FU and enhance its anticancer efficiency by inducing apoptosis. It was suggested that this novel NPs are a promising carrier to decrease toxic of 5-FU and has the potential to reverse the forms of both intrinsic and acquired drug resistance in 2D and 3D cultures.
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http://dx.doi.org/10.1002/jps.23860DOI Listing
April 2014

Large amplitude motion in cold monohydrated dihydrogen phosphate anions H2PO4(-)(H2O): infrared photodissociation spectroscopy combined with ab initio molecular dynamics simulations.

Phys Chem Chem Phys 2014 Jan;16(4):1314-8

Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 4-6, D-14195 Berlin, Germany.

The vibrational spectroscopy of monohydrated dihydrogen phosphate anions, H2PO4(-)(H2O), is studied in the O-H stretching (2700-3900 cm(-1)) and the fingerprint regions (600-1800 cm(-1)). Assignment of the experimental infrared multiple photon photodissociation spectra based on the predicted harmonic spectra of energetically low-lying 0 K structures is not conclusive. Ab initio molecular dynamics simulations reveal that the water molecule undergoes large amplitude motion, even at low internal temperatures, and that the dipole time correlation function qualitatively captures the anharmonic effects of the low-barrier isomerization reaction on the infrared intensities.
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http://dx.doi.org/10.1039/c3cp54250eDOI Listing
January 2014

Thermal methane activation by a binary V-Nb transition-metal oxide cluster cation: a further example for the crucial role of oxygen-centered radicals.

Chemistry 2013 Aug 9;19(35):11496-501. Epub 2013 Aug 9.

Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 135, 10623 Berlin, Germany.

The heteronuclear transition-metal oxide cluster activates methane: VNbO5(+) reacts with CH4 under ambient conditions via hydrogen-atom transfer (HAT), thus providing an interesting prototype example of room-temperature methane activation by a binary transition-metal oxide cluster.
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http://dx.doi.org/10.1002/chem.201302133DOI Listing
August 2013

Synthesis and biological evaluation of noscapine analogues as microtubule-interfering agents.

Yao Xue Xue Bao 2012 Oct;47(10):1347-57

School of Pharmacy, East China University of Science and Technology, Shanghai, China.

A series of noscapine analogues have been synthesized via 13-step reaction starting from 2-hydroxy-3-methoxybenzaldehyde. Anti-tumor activities of these compounds were evaluated against HL-60 cell lines in vitro by the standard MTT assay. It was found that most of these derivatives showed appreciable inhibitory activity against HL-60 and tubulin polymerization. The results also indicated that the potency of compound 31 is about three times more than that ofnoscapine against HL-60 cell line and tubulin polymerization. Moreover, it induced a massive accumulation of cells in G2/M phase. These results showed noscapine and its derivatives were worth to be intensively studied further.
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October 2012

[Surgical treatment of ossification of ligamentum flavum in thoracic spine and its therapeutic effect analysis].

Zhongguo Gu Shang 2012 Jun;25(6):482-6

Department of Orthopaedics, People's Hospital of Zhejiang, Hangzhou 310014, Zhejiang, China.

Objective: To explore the correlation between CT classification and operative method and to discuss its therapeutic effect.

Methods: From January of 2001 to June of 2010, 30 patients with thoracic ossification of ligamentum flavum were reviewed retrospectively, including 22 males and 8 females with an average age of 52.8 years old (ranged from 37 to 68 years old). The course of duration ranged from 2 months to 6 years. Single segment lesion was in 11 cases and multiple segments were in 19 cases. Two patients were accompanied by cervical ossification of ligamentum flavum and 1 was accompanied by ossification of posterior longitudinal ligament. The ossified lesions were located at T1,2 to T4,5 in 5 cases,T5,6 to T8,9 in 7 cases, T9,10 to T11,12 in 12 cases, at the upper and middle thoracic levels in 2 cases, at the middle and lower thoracic levels in 4 cases. They were divided into 2 types according to the morphologic features of the CT scan:simple type, 18 segments with lateral, slice or unfused type; complex type, 42 segments with thickened, fused or nodular type. The clinical manifestation was paralysis of upper motor neuron in 21 cases, and of upper and lower motor neuron in other 9 cases. Sphincter dysfunction was found in 26 cases. Preoperative JOA sphincter function score was 1.97 +/- 0.56. Preoperative modified JOA motor function score of lower limb was 1.20 +/- 0.76. Different surgical procedure was applied to one of the 2 types. For the simple type, an en bloc laminectomy was performed. However,for the complex type, a laminar shelling decompression was done. Laminectomy combined with internal fixation and lateral fusion was performed in patients whose decompressive areas were wider.

Results: The mean decompression length was 3.1 lamina (2 to 6 lamina). Cerebrospinal fluid leakage was found in 3 cases and hematoma in incision was found in 1 case. The mean follow-up duration was 26 months (12 to 96 months). Twenty-two patients with the feel of constriction of trunk or lower limbs were completely recovered; 18 cases with sensation disturbance, numbness and pain of the lower limb were totally recovered, and relived in 10 cases. Postoperative JOA sphincter function score was 2.73 +/- 0.45, comparing with the preoperative score, and the difference was significant (P < 0.01). Postoperative JOA motor function score was 3.57 +/- 0.77, comparing with the preoperative score, and the difference was significant (P < 0.01 ). The lower limb function relief rate was 86.1%, 24 patients got an excellent results, 3 good, 2 poor and 1 bad.

Conclusion: Different surgical procedures will be safely and effectively applied to treat thoracic ossification of ligamentum flavum according to CT classification.
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June 2012

A new method of spermatic cord mobilization in herniorrhaphy.

Clin Anat 2012 Nov 3;25(8):1074-9. Epub 2012 Feb 3.

Third Department of General Surgery, The Affiliated Nanhai Hospital of Southern Medical University, Foshan, People's Republic of China.

Spermatic cord mobilization is a routine part of inguinal hernia repair, but the method of cord mobilization varies among surgeons. This study establishes an anatomic plane for spermatic cord mobilization. We studied the anatomy of the superficial cremasteric fascia in 105 male patients during herniorrhaphy for primary inguinal hernias. The mean patient age was 44.8 (18-71) years and mean body mass index was 24.1 kg/m(2) (21.5-27.1 kg/m(2)). The two layers of the superficial cremasteric fascia between the spermatic cord and the inguinal falx were incised to mobilize the cord. We found that spermatic cord mobilization during herniorrhaphy can be easily approached through an anatomic plane between the spermatic cord and the conjoined tendon with subsequent division of the superficial cremasteric fascia. None of the patients experienced any hemorrhage or nerve injury during cord mobilization. We found this method to be both safe and easy to learn.
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http://dx.doi.org/10.1002/ca.22037DOI Listing
November 2012

A novel human derived cell-penetrating peptide in drug delivery.

Mol Biol Rep 2011 Apr 16;38(4):2649-56. Epub 2010 Nov 16.

State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Mailbox 365, 130 Meilong Road, Shanghai, 200237, People's Republic of China.

Cell-penetrating peptides can carry a variety of biologically active molecules into cells. Here we have identified a novel CPP derived from the C-terminus of human extracellular superoxide dismutase (hC-SOD3) which was shown to be located throughout in the cytoplasm and nucleus by fluorescence microscopy investigation. Furthermore, when apoptin fused to hC-SOD3, it was translocated efficiently into HeLa cells resulting in antitumor activities. This study shows that hC-SOD3 has the potential to penetrate and translocate cargo molecules into cells and has no cytotoxicity at effective concentration.
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http://dx.doi.org/10.1007/s11033-010-0406-6DOI Listing
April 2011

[Effects of serum containing Fructus Cnidii and Psoralea corylifolia on highly metastatic human breast cancer cell line MDA-MB-231BO and bone marrow stromal cell line ST-2].

Zhong Xi Yi Jie He Xue Bao 2010 Sep;8(9):877-82

Department of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.

Objective: To explore the effects of different proportions of Fructus Cnidii (Shechuangzi) and Psoralea corylifolia (Buguzhi) on highly metastatic human breast cancer cell line MDA-MB-231BO and bone marrow stromal cell line ST-2 in vitro.

Methods: Thirty-six female SD rats were randomly divided into 6 groups to prepare the drug-medicated sera by administering with different proportions of Fructus Cnidii and Psoralea corylifolia, including 4:0 group, 3:1 group, 1:1 group, 1:3 group, 0:4 group and control group. MDA-MB-231BO cells and ST-2 cells were cultured in Dulbecco's modified Eagle's medium containing drug-medicated serum. Inhibition rates of MDA-MB-231BO cells and ST-2 cells were measured by methyl thiazolyl tetrazolium (MTT) method; migration ability of MDA-MB-231BO cells was tested by a cell migration experiment; alkaline phosphatase activity (ALP) of ST-2 cells was measured by using 4-nitrophenyl phosphate disodium salt, and mineralized nodule formation of ST-2 cells was measured by alizarin red staining.

Results: Sera contaning different proportions of Fructus Cnidii and Psoralea corylifolia inhibited the migration activity of MDA-MB-231BO cells as compared with the blank serum, and serum contaning Fructus Cnidii and Psoralea Corylifolia at proportion of 1:1 had the best function (P<0.01). Fructus Cnidii and Psoralea corylifolia at ratio of 1:1 also enhanced the ALP activity of ST2 cells (P<0.05) and increased the number of mineralized nodules of ST2 cells (P<0.01).

Conclusion: Kidney-warming recipe of Fructus Cnidii and Psoralea corylifolia can inhibit proliferation and migration of MDA-MB-231BO cells and increase the activity of ST-2 cells.
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http://dx.doi.org/10.3736/jcim20100912DOI Listing
September 2010

[Identification of the active material of anti-hepatic fibrosis from Amydae Carapax].

Zhonghua Gan Zang Bing Za Zhi 2010 May;18(5):346-52

Department of Infectious Diseases, Zhejiang Quhua Hospital ,Quzhou Zhejiang Province 324004, China.

Objective: To identify the active material of anti-hepatic fibrosis from Amydae Carapax.

Methods: Membrane separation technology was adopted to screen active fraction in Amydae Carapax, and the active components were isolated from the active fraction using gel chromatography and high performance liquid chromatography. The purified active components in Amydae Carapax were further analyzed using 4700 series time-of-flight mass spectrometer.

Results: Proteins and peptides of Amydae Carapax with molecular weight less than 6000 were proved to have biological activity. 8 components (Bj1-Bj8) were isolated from the active fraction. Bj4, Bj6 and Bj7 were screened as active components. Bj7 was further purified, resulting in 7 components (Bj701-Bj707). Bj704 and Bj707 showed significant biological activity. Mass spectrometry showed three molecular ion peaks with highest abundance, i.e. m/e 526, 542 and 572, i.e. m/e 526, 542 and 572, in Bj707 -A The amino acid sequences of above three peptide compounds were NDDY (Asn-Asp-Asp-Tyr), NPNPT (Asn-Pro-Asn-Pro-Thr), and HGRFG (His-Gly-Arg-Phe-Gly), respectively. And M572 was the most abandunt components.

Conclusion: Three active peptide compounds of anti-hepatic fibrosis of Amydae Carapax were identified.
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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2010.05.009DOI Listing
May 2010

[Comparison of fat clearance and fat lucidification in examining rectal cancer specimen].

Zhonghua Wei Chang Wai Ke Za Zhi 2010 Apr;13(4):276-8

Department of Gastrointestinal Surgery, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.

Objective: To compare fat clearance and fat lucidification in the examination of rectal cancer specimen, and to study the distribution pattern of lymph nodes in rectal cancer specimen.

Method: Between January 2007 and December 2007, sixty-four cases undergone total mesorectal excision were divided into two groups. The fat clearance technique was used to examine the specimens in one group, while fat lucidification was used in the other. The total number and the number of metastatic lymph nodes between two groups were compared, as well as the time for processing specimens and that for dissecting the lymph nodes.

Results: An average of 37.4 lymph nodes were detected with fat clearance, in which 3.3 lymph nodes were metastatic; while an average of 36.2 nodes were detected with fat lucidification, in which 3.2 were metastatic. There were no significant differences in either the total number or the number of metastatic lymph nodes. The time for processing specimens in the fat lucidification group was 28 hours, while in the fat clearance group was 72 hours. The time for specimen processing was significantly shorter in the fat lucidification group (P<0.05). The mean time for dissecting lymph nodes in the fat clearance group was 2.1 hours, while in the fat lucidification group was 2.0 hours, the difference was not statistically significant.

Conclusion: When processing rectal cancer specimens with the fat lucidification technique can result in the similar number of lymph nodes compared to the fat clearance technique, with significantly shorter specimen processing time. The spatial position of the lymph nodes is better preserved using the fat lucidification technique, which may help study the distribution pattern of the normal and metastatic lymph nodes.
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April 2010

Ganoderic acid T inhibits tumor invasion in vitro and in vivo through inhibition of MMP expression.

Pharmacol Rep 2010 Jan-Feb;62(1):150-63

Key Laboratory of Microbial Metabolism, Ministry of Education, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dong-Chuan Road, Minhang, Shanghai 200240, China.

The traditional Chinese medicinal mushroom, Ganoderma lucidum, has been used in Asia for several thousand years for the prevention and treatment of a variety of diseases, including cancer. In previous work, we purified ganoderic acid T (GA-T) from G. lucidum [28]. In the present study, we investigate the functions of GA-T in terms of its effects on invasion in vitro and metastasis in vivo. A trypan blue dye exclusion assay indicates that GA-T inhibits proliferation of HCT-116 cells, a human colon carcinoma cell line. Cell aggregation and adhesion assays show that GA-T promotes homotypic aggregation and simultaneously inhibits the adhesion of HCT-116 cells to the extracellular matrix (ECM) in a dose-dependent manner.Wound healing assays indicate that GA-T also inhibits the migration of HCT-116 cells in a dose-dependent manner, and it suppresses the migration of 95-D cells, a highly metastatic human lung tumor cell line, in a dose- and time-dependent manner. In addition, GA-T inhibits the nuclear translocation of nuclear factor-kappaB (NF-kappaB) and the degradation of inhibitor of kappaB-alpha (IkappaBalpha), which leads to down-regulated expression of matrix metalloproteinase-9 (MMP-9), inducible nitric oxide synthase (iNOS), and urokinase-type plasminogen activator (uPA). Animal and Lewis Lung Carcinoma (LLC) model experiments demonstrate that GA-T suppresses tumor growth and LLC metastasis and down-regulates MMP-2 and MMP-9 mRNA expression in vivo. Taken together, these results demonstrate that GA-T effectively inhibits cancer cell invasion in vitro and metastasis in vivo, and thus it may act as a potential drug for treating cancer.
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http://dx.doi.org/10.1016/s1734-1140(10)70252-8DOI Listing
July 2010

Hesperidin upregulates heme oxygenase-1 to attenuate hydrogen peroxide-induced cell damage in hepatic L02 cells.

J Agric Food Chem 2010 Mar;58(6):3330-5

State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, China.

Hesperidin, a naturally occurring flavonoid presents in fruits and vegetables, has been reported to exert a wide range of pharmacological effects that include antioxidant, anti-inflammatory, antihypercholesterolemic, and anticarcinogenic actions. However, the cytoprotection and mechanism of hesperidin to neutralize oxidative stress in human hepatic L02 cells remain unclear. In this work, we assessed the capability of hesperidin to attenuate hydrogen peroxide (H(2)O(2))-induced cell damage by augmenting the cellular antioxidant defense. Real-time quantitative polymerase chain reaction, Western blot, and enzyme activity assay demonstrated that hesperidin upregulated heme oxygenase-1 (HO-1) expression to protect hepatocytes against oxidative stress. In addition, hesperidin also promoted nuclear translocation of nuclear factor erythroid 2-related factor (Nrf2). What's more, hesperidin exhibited activation of extracellular signal-regulated protein kinase 1/2 (ERK1/2). Besides, ERK1/2 inhibitor significantly inhibited hesperidin-mediated HO-1 upregulation and Nrf2 nuclear translocation. Taken together, the above findings suggested that hesperidin augmented cellular antioxidant defense capacity through the induction of HO-1 via ERK/Nrf2 signaling. Therefore, hesperidin has potential as a therapeutic agent in the treatment of oxidative stress-related hepatocyte injury and liver dysfunctions.
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http://dx.doi.org/10.1021/jf904549sDOI Listing
March 2010