Publications by authors named "Songlin Xu"

20 Publications

  • Page 1 of 1

Mechanical property characterization of partially crystalline Poly-Ether-Ether-Ketone.

J Mech Behav Biomed Mater 2021 Jun 1;121:104600. Epub 2021 Jun 1.

CAS Key Laboratory for Mechanical Behavior and Design of Materials, Department of Modern Mechanics. University of Science and Technology of China, Hefei, Anhui, 230027, China.

The present study investigates the mechanical properties of partially crystalline Poly-Ether-Ether-Ketone between the glass transition and the cold crystallization. Biaxial tension, uniaxial tension, and DMA experiments were conducted to investigate the influence of temperature-induced crystallization on mechanical properties, and three stiffening behaviors are observed. Firstly, a 'U' type mechanical property is observed for all three experiments with first softening and then significant stiffening behavior with increasing temperature. Secondly, stiffening also occurs during low strain rate tests but not in higher strain rate tests. Thirdly, the stiffening behavior of the anisotropic film shows orientation dependence. Crystallinity evolution is predicted by the Nakaruma non-isothermal crystallization kinetics with optimized parameters, with which we demonstrate and explain that the stiffening behaviors are connected to the onset of crystallization. Therefore, the conclusion provides a new tool to approach and distinguish extrinsic and intrinsic properties during characterization, promoting future implementation for constitutive modeling and corresponding simulation that could replicate the influence of temperature-induced crystallization.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104600DOI Listing
June 2021

Prognostic value of ferroptosis-related genes in patients with lung adenocarcinoma.

Thorac Cancer 2021 Jun 12;12(12):1890-1899. Epub 2021 May 12.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Background: The prevalence of lung adenocarcinomas (LUADs) has dramatically increased in recent decades. Ferroptosis is a process of iron-dependent regulatory cell death. It is still unclear whether the expression of ferroptosis-related genes (FRGs) is involved in the pathogenesis and survival of patients with LUAD.

Methods: We retrieved LUAD data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and used LASSO Cox regression analysis to select the gene signature suitable for modeling. The risk score was calculated according to the model, and the patients were divided into high- and low-risk groups according to the median risk score. Functional enrichment analysis was carried out by this group, and a model for predicting clinical prognosis was established by combining this group with clinical factors.

Results: Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) analysis showed that there were several immune-related pathways and immune infiltration differences between high- and low-risk groups. A prognostic model integrating 10 ferroptosis-related genes (FR-DEGs), and clinical factors were constructed and validated in an external cohort.

Conclusions: The FR-DEGs signature was related to immune infiltration, and a model based on FR-DEGs and clinical factors was established to predict the prognosis of patients with LUAD.
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http://dx.doi.org/10.1111/1759-7714.13998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201541PMC
June 2021

[Immune Microenvironment Comparation Study between EGFR Mutant and EGFR Wild Type Lung Adenocarcinoma Patients Based on TCGA Database].

Zhongguo Fei Ai Za Zhi 2021 Apr;24(4):236-244

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.

Background: Lung cancer is a malignant with high incidence and mortality and adenocarcinoma is among the most popular subtypes. Epidermal growth factor receptor (EGFR) mutation is one of the most important driver mutations for lung adenocarcinoma and EGFR-tyrosine kinase inhibitor (TKI) will benefit those patients with sensitive EGFR mutations. Recently, immune checkpoint inhibitor (ICI) therapy, provide a new breakthrough treatment for lung cancer patients. Whereas immunotherapy as an emerging treatment does not benefit patients with EGFR mutations, for which mechanistic studies are poorly defined and focused on the link of EGFR mutations and programmed cell death-ligand 1 (PD-L1) expression, we speculate that the different immune microenvironment associated with the two classes of patients.

Methods: Lung adenocarcinoma datasets were collected from the Cancer Genome Atlas (TCGA) database, and clinical information and gene expression profiles were downloaded. The immune related lymphocyte infiltration in TCGA database were generated through timer 2.0 GSEA was used to analyze the difference of pathway expression between EGFR mutant patients and wild type patients.

Results: EGFR mutation was more frequently among women and never smokers. Immunoinfiltration analysis showed that patients with EGFR mutation tends to have more tumor associated fibroblasts, common myeloid progenitor cells, hematopoietic stem cells, effector CD4⁺ T cells and natural killer T cells infiltration, and less memory B cells, naïve B cells, plasma B cells, plasmacytoid dendritic cells, memory CD4⁺ T cells, CD4⁺ helper T cells 2, naive CD8⁺ T cells, CD8⁺ T cells and central memory CD8⁺ T cells infiltration. Moreover, patients with more infiltration of CD8⁺ T cells, natural killer T cells, memory B cells and hematopoietic stem cells, tends have better prognosis (Log-rank test, P=0.017, 0.0093, 0.018, 0.016). However, the patients with more CD4⁺ T th2 infiltration in the tumor tends to have worse prognosis (Log-rank test, P=0.016). Furthermore, the results of gene set enrichment analysis showed that compared with the lung adenocarcinoma patients with EGFR wild type, the three pathways positive regulation of natural killer (NK) cell-mediated immune response to tumor cells, NK cell activation involved in immune response, and NK cell-mediated immune response to tumor cells related to natural killer cells in patients with EGFR mutation were down regulated, while the pathway the positive regulation of cytokine secretion involved in immune response was up-regulated in EGFR mutation patients.

Conclusions: The tumour microenvironment of patients with EGFR mutations lacks potent tumour killing effector cells and appears dysfunctional with effector cells. This may be a potential reason for the poor efficacy of immunotherapy in patients with EGFR mutations.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.102.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105612PMC
April 2021

Identification of small proline-rich protein 1B (SPRR1B) as a prognostically predictive biomarker for lung adenocarcinoma by integrative bioinformatic analysis.

Thorac Cancer 2021 03 26;12(6):796-806. Epub 2021 Jan 26.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Background: With the ongoing development of targeted therapy and immunotherapy in recent years, the overall five-year survival rate of NSCLC patients has not improved, and the search for novel diagnostic and prognostic markers for lung adenocarcinoma continues.

Methods: Lung adenocarcinoma (LUAD) gene expression data and relevant clinical information were obtained from the TCGA. Hub genes were identified with weighted gene co-expression network analysis (WGCNA) and protein-protein interaction network (PPI). Survival analyses were also performed using GEPIA. The 536 LUAD patients were divided into two groups according to the SPRR1B expression level and analyzed by gene set enrichment analysis (GSEA) and verified by immunoblotting. The effects of SPRR1B on cell proliferation and cell metastasis and apoptosis were evaluated by 5-ethynyl-2'-deoxyuridine (EdU) staining, colony formation assay, transwell migration and invasion assay, and flow cytometry, respectively.

Results: A total of 2269 DEGs were analyzed by WGCNA and five hub genes (CCK, FETUB, PCSK9, SPRR1B, and SPRR2D) were identified. Among them, SPRR1B was selected as one of the most significant prognostic genes in LUAD. SPRR1B was found to be highly expressed in lung adenocarcinoma cells compared with that in normal bronchial epithelial cells. In addition, silencing of SPRR1B could inhibit the cell proliferation, invasion, and migration of lung adenocarcinoma cells, but induced cell apoptosis and G2/M phase arrest in vitro. The result of GSEA and immunoblotting revealed that SPRR1B activated the MAPK signaling pathway involved in the proliferation and metastasis of lung cancer.

Conclusions: Our findings demonstrate that SPRR1B may function as a prognosis predictor in lung adenocarcinoma.
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http://dx.doi.org/10.1111/1759-7714.13836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952803PMC
March 2021

[Apatinib Combined with CCI-779 Inhibits the Proliferation and Migration of Small Cell Lung Cancer NCI-H446 Cells In Vitro].

Zhongguo Fei Ai Za Zhi 2020 Apr 26;23(4):216-222. Epub 2020 Mar 26.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.

Background: Lung cancer is the most common malignancy world-wide. Small cell lung cancer is the deadliest subtype of lung cancer, which features such as rapid growth, early metastasis, and high vascularization. Apatinib is a vascular endothelial growth factor receptor 2 inhibitor independently developed in China, which has a significant inhibition in a variety of solid tumors. The purpose of this study is to investigate the effects of Apatinib alone or Apatinib combined with mammalian target of rapamycin (mTOR) inhibitor, CCI-779, on small cell lung cancer cell line NCI-H446 in vitro.

Methods: The small cell lung cancer cell line NCI-H446 was grew in vitro. The effects of Apatinib alone or Apatinib combined with CCI-779 on proliferation, apoptosis, cell cycle and migration of NCI-H446 small cell lung cancer cells were detected by CCK8; FACS and transwell assays were also carried out; Western blot assays were used to detect vascular endothelial growth factor and cell cycle related protein expression.

Results: CCK8 assays showed that high concentration of Apatinib could inhibit the proliferation of NCI-H446 cells. Apoptosis assays showed that high concentration of Apatinib could induce NCI-H446 cell apoptosis. Transwell assays showed that high concentration of Apatinib could inhibit NCI-H446 cell migration. After combined with mTOR inhibitor CCI-779, low concentration of Apatinib could inhibit the proliferation and migration of NCI-H446 small cell lung cancer cells and induce apoptosis.

Conclusions: Apatinib has a concentration-dependent effect on the small cell lung cancer cell line NCI-H446. High concentration of Apatinib can inhibit the proliferation and migration of NCI-H446 small cell lung cancer cells, induce apoptosis. Apatinib combined with the mTOR inhibitor CCI-779 can sensitize the NCI-H446 cells to Apatinib.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2020.104.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210093PMC
April 2020

Modification of the contact surfaces for improving the puncture resistance of laminar structures.

Sci Rep 2017 07 26;7(1):6615. Epub 2017 Jul 26.

CAS Key Laboratory of Mechanical Behavior and Design of Materials, Department of Modern Mechanics, University of Science and Technology of China, Hefei, 230027, China.

Uncovering energy absorption and surface effects of various penetrating velocities on laminar structures is essential for designing protective structures. In this study, both quasi-static and dynamic penetration tests were systematical conducted on the front surfaces of metal sheets coated with a graphene oxide (GO) solution and other media. The addition of a GO fluid film to the front impact surface aided in increasing the penetration strength, improving the failure extension and dissipating additional energy under a wide-range of indentation velocity, from 3.33 × 10 m/s to 4.42 m/s. The coated -surfaces improved the specific energy dissipation by approximately 15~40% relative to the dry-contact configuration for both single-layer and double-layer configurations, and specific energy dissipations of double-layer configurations were 20~30% higher than those of the single-layer configurations. This treatment provides a facile strategy in changing the contact state for improving the failure load and dissipate additional energy.
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http://dx.doi.org/10.1038/s41598-017-06007-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529432PMC
July 2017

Evaluation of a Non-aqueous Ibuprofen-Phospholipid Complex Formulation in Rats.

In Vivo 2016 Jul-Aug;30(4):479-83

Zhejiang Haichang Biopharm Co. Ltd., Hangzhou, P.R. China Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.

Aim: In the present study, a non-aqueous ibuprofen-phospholipid complex was developed to reduce the gastrointestinal (GI) toxicity of ibuprofen.

Materials And Methods: A non-aqueous ibuprofen-phospholipid complex (IBU-PC) was prepared by mixing phosal-35SB and ibuprofen. In vitro release behavior was studied using a dissolution apparatus. Irritation to gastrointestinal (GI) tract and pharmacokinetics of IBU-PC were studied in rats.

Results: Rapid release of drug occurred with approximately 85% of ibuprofen released from the composition within the first 30 min. The GI injury in IBU-PC-treated rats was minimal compared to those of Advil Liqui-gels-treated group. There was no significant difference between IBU-PC and Motrin-treated groups. The area under the concentration-time curve (AUC0~24) of IBU-PC and Motrin were 366±115 and 391±105 μg/h/ml, respectively. The relative bioavailability of IBU-PC was 94.2%.

Conclusion: IBU-PC can decrease GI adverse reaction induced by ibuprofen.
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July 2017

CD33-Targeted Lipid Nanoparticles (aCD33LNs) for Therapeutic Delivery of GTI-2040 to Acute Myelogenous Leukemia.

Mol Pharm 2015 Jun 28;12(6):2010-8. Epub 2015 Apr 28.

†Division of Pharmaceutics, College of Pharmacy, ‡Division of Hematology-Oncology, §Molecular, Cellular and Developmental Biology Program, and ∥Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio 43210, United States.

CD33-targeted lipid nanoparticles (aCD33LNs) were synthesized for delivery of GTI-2040, an antisense oligonucleotide (ASO) against the R2 subunit of ribonucleotide reductase, to acute myelogenous leukemia (AML). These LNs incorporated a deoxycholate-polyethylenimine (DOC-PEI) conjugate, which has shown significant activity to facilitate oligonucleotide delivery. Anti-CD33 scFv (aCD33) was added as a targeting ligand. The delivery efficiency of this system was investigated both in vitro and in vivo. When cells were treated with aCD33LN/GTI-2040, significant uptake was observed in CD33 positive Kasumi-1 cells. aCD33LNs loaded with GTI-2040 induced significant down-regulation of R2 mRNA and protein levels in AML cells. Moreover, aCD33LN/GTI-2040 showed a 15-fold reduction in the IC50 of antileukemic drug Ara-C in Kasumi-1 cells. In Kasumi-1 xenograft model, aCD33LN/GTI-2040 showed significant R2 downregulation compared to LN/GTI-2040. Furthermore, aCD33LN/GTI-2040 coadministered with Ara-C was shown to be highly effective in tumor growth inhibition and to greatly increase survival time of mice bearing Kasumi-1 xenograft tumors. The conjugate DOC-PEI has shown an ability to include calcein release from lipid nanoparticles, suggesting a potential mechanism contributing to efficient endosome release by DOC-PEI2K. These results indicate that aCD33LNs are a highly effective vehicle for the therapeutic delivery of antisense agents to AML.
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http://dx.doi.org/10.1021/mp5008212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4962870PMC
June 2015

A microfluidic method to synthesize transferrin-lipid nanoparticles loaded with siRNA LOR-1284 for therapy of acute myeloid leukemia.

Nanoscale 2014 Aug 8;6(16):9742-51. Epub 2014 Jul 8.

College of Pharmacy, The Ohio State University, 500 W 12th Ave, 43210, Columbus, Ohio, USA.

The siRNA LOR-1284 targets the R2 subunit of ribonucleotide reductase (RRM2) and has shown promise in cancer therapy. In this study, transferrin (Tf) conjugated lipid nanoparticles (Tf-NP-LOR-1284) were synthesized by microfluidic hydrodynamic focusing (MHF) and evaluated for the targeted delivery of LOR-1284 siRNA into acute myeloid leukemia (AML) cells. The in vitro study showed that Tf-NP-LOR-1284 can protect LOR-1284 from serum nuclease degradation. Selective uptake of Tf-NP-LOR-1284 was observed in MV4-11 cells. In addition, qRT-PCR and Western blot results revealed that Tf-NP-LOR-1284 was more effective than the free LOR-1284 in reducing the R2 mRNA and protein levels. The Tf-NP-LOR-1284 showed prolonged circulation time and increased AUC after i.v. administration relative to the free LOR-1284. Furthermore, Tf-NP-LOR-1284 facilitated increased accumulation at the tumor site along with the decreased R2 mRNA and protein expression in a murine xenograft model. These results suggest that Tf-conjugated NPs prepared by MHF provide a suitable platform for efficient and specific therapeutic delivery of LOR-1284 into AML cells.
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http://dx.doi.org/10.1039/c4nr01510jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312591PMC
August 2014

DABCO-based ionic liquids: recyclable catalysts for aza-Michael addition of α,β-unsaturated amides under solvent-free conditions.

J Org Chem 2014 Jul 27;79(14):6510-6. Epub 2014 Jun 27.

School of Pharmaceutical and Chemical Engineering, Taizhou University , Taizhou 318000, People's Republic of China.

An array of novel 1,4-diazobicyclo[2.2.2]octane (DABCO) based ionic liquids were developed and used as recyclable catalysts for the aza-Michael addition at room temperature without any organic solvent. [DABCO-PDO][OAc] was found to be the most efficient catalyst, and the amount of catalyst was only 10 mol %. Various amines reacted with a wide range of α,β-unsaturated amides, smoothly affording target products in good to excellent yields within hours. Moreover, the catalyst could be reused up to eight times, still maintaining a high catalytic activity. Finally, a plausible mechanism was proposed. FTIR and computational chemistry were used to verify the catalytic mechanism.
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http://dx.doi.org/10.1021/jo500937aDOI Listing
July 2014

Development and validation of a rapid LC-MS/MS method for the determination of JCC76, a novel antitumor agent for breast cancer, in rat plasma and its application to a pharmacokinetics study.

Biomed Chromatogr 2012 Sep 27;26(9):1118-24. Epub 2011 Dec 27.

Department of Chemistry, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, USA.

JCC76 is a novel nimesulide analog that selectively inhibits the human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cell proliferation and tumor progression. To support further pharmacological and toxicological studies of JCC76, a novel and rapid method using liquid chromatography and electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) has been developed and validated for the quantification of the compound in rat plasma. A C₁₈ column was used for chromatographic separation, and the mobile phase was aqueous ammonium formate (pH 3.7; 5 mm)-methanol (1:9, v/v) with an isocratic elution. With a simple liquid-liquid extraction procedure using the mixture of methyl tert-butyl ether-hexane (1:2, v/v), the mean extraction efficiency of JCC76 in rat plasma was determined as 89.5-97.3% and no obvious matrix effect was observed. This method demonstrated a linear calibration range from 0.3 to 100 ng/mL for JCC76 in rat plasma and a small volume of sample consumption. The intra- and inter-assay accuracy and precision were within ±10%. The pharmacokinetics of JCC76 was also profiled using this validated method in rats. In conclusion, this rapid and sensitive method has been proven to effectively quantify JCC76 for pharmacokinetics study.
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http://dx.doi.org/10.1002/bmc.1757DOI Listing
September 2012

Synthesis and evaluation of a novel lipophilic folate receptor targeting ligand.

Anticancer Res 2011 May;31(5):1521-5

Department of Pharmacy, Wuhan University, China.

Background: Folate receptor (FR)-targeted liposomes have been investigated as delivery vehicles for anticancer drugs. A novel lipophilic FR ligand, folate-glutathione-polyethyleneglycol-distearoyl phosphatidylethanolamine (F-GSH-PEG-DSPE), was synthesized, incorporated into liposomes and evaluated for FR targeting efficiency. These liposomes were then evaluated as carriers of the chemotherapy agent vincristine (VIN).

Materials And Methods: F-GSH-PEG-DSPE was synthesized and FR-targeted liposomes loaded with either calcein (F-L-Calcein) or VIN (F-L-VIN) were prepared by thin film hydration followed by polycarbonate membrane extrusion and, in the case of VIN, by remote loading. To assess liposome stability, the uptake of F-L-VIN in KB (FR+) cancer cells was measured after storage under 4°C for 3 months. Comparative pharmacokinetic studies were carried out with F-L-VIN and L-VIN (non-targeted control liposomes).

Results: F-L-Calcein showed significantly higher cellular uptake in KB cells compared to non-targeted liposomes. In addition, F-L-VIN showed enhanced cytotoxicity in KB cells in vitro compared to control liposomes. Pharmacokinetic parameters indicated that both F-L-VIN and control liposomes had higher area under the curve (AUC), mean residence time (MRT), elimination half life (t1/2-β) and lower total body clearance (CL) than those of free VIN, while there were no significant differences between these liposomal formulations.

Conclusion: F-GSH-PEG-DSPE is effective as a novel ligand for the synthesis of FR-targeted liposomes.
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May 2011

Synthesis of transferrin (Tf) conjugated liposomes via Staudinger ligation.

Int J Pharm 2011 Feb 5;404(1-2):205-10. Epub 2010 Nov 5.

Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.

Staudinger ligation was evaluated as a strategy for synthesizing receptor targeted liposomes. First, an activated lipid derivative was synthesized by reacting dioleoyl phosphatidylethanolamine (DOPE) and 2-(diphenylphosphino) terephthalic acid 1-methyl 4-penta-fluorophenyldiester. Second, transferrin (Tf) was activated with p-azidophenyl isothiocyanate. Third, liposomes containing the activated lipid were prepared and then coupled to the activated Tf via the Staudinger reaction. These liposomes were evaluated in KB cells for cellular uptake and cytotoxicity, and in mice for pharmacokinetic properties. Tf-derivatized liposomes encapsulating calcein prepared by this conjugation method effectively targeted Tf receptor expressing KB cells. In addition, the Tf-targeted liposomes entrapping doxorubicin showed greatly enhanced in vitro cytotoxicity relative to non-targeted control liposomes. Pharmacokinetic parameters indicated that these liposomes retained long circulating properties relative to the free drug. In summary, Staudinger ligation is an effective method for the synthesis of receptor targeted liposomes.
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http://dx.doi.org/10.1016/j.ijpharm.2010.10.053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010482PMC
February 2011

Ultrasound-enhanced microfluidic synthesis of liposomes.

Anticancer Res 2010 Feb;30(2):463-6

Division of Pharmaceutics, College of Pharmacy, Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH 43210, USA.

Background: Liposomes have been successfully used as delivery vehicles for anticancer drugs. Both sonication and microfluidic technologies have been used to produce liposomes. The combination of the two methods was evaluated in this study.

Materials And Methods: The microfluidic devices, mainly comprising micro-dispensers and a sonicator, were used to produce liposomal nanoparticles. Sonication was used to enhance the reduction of liposome size.

Results: Sonication significantly reduced the size of the liposomes. The particle size also decreased as the buffer to solvent flow rate ratio increased. The smallest particle sizes were achieved with a volumetric flow rate of lipids at 0.374 ml/min.

Conclusion: The microfluidic devices in combination with ultrasound are simple and may be used to produce liposomal nanoparticles with narrow size distribution.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789511PMC
February 2010

Transferrin-conjugated lipid-coated PLGA nanoparticles for targeted delivery of aromatase inhibitor 7alpha-APTADD to breast cancer cells.

Int J Pharm 2010 May 13;390(2):234-41. Epub 2010 Feb 13.

Division of Pharmaceutics, College of Pharmacy, Ohio State University, Columbus, OH 43210, USA.

Transferrin (Tf)-conjugated lipid-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles carrying the aromatase inhibitor, 7alpha-(4'-amino)phenylthio-1,4-androstadiene-3,17-dione (7alpha-APTADD), were synthesized by a solvent injection method. Formulation parameters including PLGA-to-lipid, egg PC-to-TPGS, and drug-to-PLGA ratios and aqueous-to-organic phase ratio at the point of synthesis were optimized to obtain nanoparticles with desired sizes and drug loading efficiency. The optimal formulation had a drug loading efficiency of 36.3+/-3.4%, mean diameter of 170.3+/-7.6nm and zeta potential of -18.9+/-1.5mV. The aromatase inhibition activity of the nanoparticles was evaluated in SKBR-3 breast cancer cells. IC(50) value of the Tf-nanoparticles was ranging from 0.77 to 1.21nM, and IC(50) value of the nanoparticles was ranging from 1.90 to 3.41nM (n=3). The former is significantly lower than the latter (p<0.05). These results suggested that the aromatase inhibition activity of the Tf-nanoparticles was enhanced relative to that of the non-targeted nanoparticles, which was attributable to Tf receptor (TfR) mediated uptake. In conclusion, Tf-conjugated lipid-coated PLGA nanoparticles are potential vehicles for improving the efficiency and specificity of therapeutic delivery of aromatase inhibitors.
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http://dx.doi.org/10.1016/j.ijpharm.2010.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807850PMC
May 2010

The mechanical behaviors of polytetrafluorethylene/Al/W energetic composites.

J Phys Condens Matter 2009 Jul 18;21(28):285401. Epub 2009 Jun 18.

The tensile and impact properties of polytetrafluorethylene (PTFE)/Al/W reactive energetic composites were investigated using a universal materials testing machine and an improved pendulum impact tester at room temperature. Samples of four types, all containing W, of differing composition and particle size were prepared by cold pressing and sintering. With increasing W content in the PTFE/Al/W samples, the mass loss during sintering and the density of the materials obtained increased. The addition of microlevel W led to the tensile strength decreasing from 25.3 to 19.8 MPa, while the elongation changed little, but substituting nanolevel W for 5 wt% Al yields a maximal strength of 31.4 MPa. The failure behavior of PTFE/Al/W includes deformation, fracture, disorganization and reaction, in four steps. The addition of 30 wt% of coarse W particles improved the impact strength of the material, but the reactive activity increased and the perfectability of the reaction decreased.
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http://dx.doi.org/10.1088/0953-8984/21/28/285401DOI Listing
July 2009

Novel poly(ethylene imine) biscarbamate conjugate as an efficient and nontoxic gene delivery system.

J Control Release 2008 Aug 10;130(1):64-8. Epub 2008 May 10.

School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.

We report a novel poly(ethylene imine) biscarbamate conjugate (PEIC) with a low molecular weight (M(W) = 2800, M(n) = 910), and low cytotoxicity which has orders of magnitude higher luciferase gene transfection activity at its optimal conditions as compared with poly(ethylene imines) (PEIs) of M(W) 2000 or 25,000. This polycationic gene carrier was synthesized by reacting low molecular weight PEI (M(W) = 800) with 1,4-Butanediol bis(chloroformate) to give a copolymer with biodegradable carbamate linkages. When added to a DNA solution, PEIC condensed DNA at a w/w ratio above 1 to form 53-91 nm polyplexes with 20-24 mV in zeta potential (about half of that of branched 25kDa PEI). PEIC can also transfect MeWo cells with large genes such as the 125kb Varicella-Zoster viral gene (VZV) at high activity.
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http://dx.doi.org/10.1016/j.jconrel.2008.04.025DOI Listing
August 2008

Preparation of dextran glassy particles through freezing-induced phase separation.

Int J Pharm 2007 Jul 23;339(1-2):76-83. Epub 2007 Feb 23.

Shanghai Jiaotong University School of Pharmacy, 800 Dongchuan Road, Shanghai 200240, China.

This report demonstrates a novel method to prepare fine polysaccharide glassy particles of uniform sizes under a condition without water/oil and water/air interfacial tension and cross-linking reagents. When a co-solution of dextran and polyethylene glycol (PEG) was frozen gradually, phase separation occurred during which dextran formed the dispersed phase and PEG remained in the continuous part. Fine dextran glassy particles were harvested after lyophilizing this frozen sample, followed by re-dissolving the continuous phase (PEG) in dichloromethane or acetonitrile. Desired mean particle diameter can be achieved within the range between 200 nm and 10 microm by selecting molecular weights of PEG and dextran, concentration of the co-solution, and PEG/dextran ratio. Increase in molecular weights, concentration or PEG/dextran ratio resulted in increase in particle sizes, and the vice versa. The dextran particles prepared as above showed smooth surface under an electron microscope, a phase transition temperature on thermogram, and sank in carbon tetrachloride (density = 1.592 g/ml), indicating that the particle matrix is dense and glassy. This particulate system and its forming process may have wide applications in formulating variety of pharmaceutical dosage forms and medical devices containing delicate biotech therapeutics.
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http://dx.doi.org/10.1016/j.ijpharm.2007.02.018DOI Listing
July 2007

Simulated maximum likelihood method for estimating kinetic rates in gene expression.

Bioinformatics 2007 Jan 26;23(1):84-91. Epub 2006 Oct 26.

Advanced Computational Modelling Centre, University of Queensland Brisbane, QLD 4072, Australia.

Motivation: Kinetic rate in gene expression is a key measurement of the stability of gene products and gives important information for the reconstruction of genetic regulatory networks. Recent developments in experimental technologies have made it possible to measure the numbers of transcripts and protein molecules in single cells. Although estimation methods based on deterministic models have been proposed aimed at evaluating kinetic rates from experimental observations, these methods cannot tackle noise in gene expression that may arise from discrete processes of gene expression, small numbers of mRNA transcript, fluctuations in the activity of transcriptional factors and variability in the experimental environment.

Results: In this paper, we develop effective methods for estimating kinetic rates in genetic regulatory networks. The simulated maximum likelihood method is used to evaluate parameters in stochastic models described by either stochastic differential equations or discrete biochemical reactions. Different types of non-parametric density functions are used to measure the transitional probability of experimental observations. For stochastic models described by biochemical reactions, we propose to use the simulated frequency distribution to evaluate the transitional density based on the discrete nature of stochastic simulations. The genetic optimization algorithm is used as an efficient tool to search for optimal reaction rates. Numerical results indicate that the proposed methods can give robust estimations of kinetic rates with good accuracy.
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http://dx.doi.org/10.1093/bioinformatics/btl552DOI Listing
January 2007

Characterization and quantification of eight water-soluble constituents in tubers of Pinellia ternata and in tea granules from the Chinese multiherb remedy Xiaochaihu-tang.

J Chromatogr B Analyt Technol Biomed Life Sci 2006 Nov 19;843(2):183-93. Epub 2006 Jun 19.

Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Zhangjiang Hi-Tech Park, Shanghai 201203, China.

In traditional Chinese medicine, multiple herbs are usually used in combination to generate the joint actions of a multiherb remedy. The recent development of LC-hyphenated techniques enables efficient and rapid profiling of the chemical constituent in extracts from multiherb remedies. Xiaochaihu-tang is a seven-herb remedy that has attracted a great deal of attention for reported ability to treat liver dysfunction. Dried tubers of Pinellia ternata (banxia in Chinese) is one of the ingredients, but its chemical contribution to Xiaochaihu-tang remains poorly understood. In the study presented here, LC-UV-MS, LC-MS-MS, and LC-NMR were used in a complementary manner to determine the nature and content of eight water-soluble constituents of banxia and their presence in various tea granules from Xiaochaihu-tang. Among the eight chemicals identified in banxia, cytidine, adenosine, tryptophan, uridine, and adenine are reported for the first time, while tyrosine, guanosine, and phenylalanine were previously described. These chemicals are also present in all of the samples of Xiaochaihu-tang granules, and the amounts of the chemicals ingested due to a daily dose of the multiherb remedies range from 0.008 to 6.3mg.
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http://dx.doi.org/10.1016/j.jchromb.2006.05.028DOI Listing
November 2006