Jing Wang

Shenyang Pharmaceutical University, Feng-t’ien, Liaoning, China

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Publications (156)361.17 Total impact

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    ABSTRACT: Aim: Leflunomide is an immunosuppressive agent marketed as a disease-modifying antirheumatic drug. But it causes severe side effects, including fatal hepatitis and liver failure. In this study we investigated the contributions of hepatic metabolism and transport of leflunomide and its major metabolite teriflunomide to leflunomide induced hepatotoxicity in vitro and in vivo. Methods: The metabolism and toxicity of leflunomide and teriflunomide were evaluated in primary rat hepatocytes in vitro. Hepatic cytochrome P450 reductase null (HRN) mice were used to examine the PK profiling and hepatotoxicity of leflunomide in vivo. The expression and function of sodium/bile acid cotransporter (NTCP) were assessed in rat and human hepatocytes and NTCP-transfected HEK293 cells. After Male Sprague Dawley (SD) rats were administered teriflunomide (1,6, 12 mg·kg(-1)·d(-1), ig) for 4 weeks, their blood samples were analyzed. Results: A nonspecific CYPs inhibitor aminobenzotriazole (ABT, 1 mmol/L) decreased the IC50 value of leflunomide in rat hepatocytes from 409 to 216 μmol/L, whereas another nonspecific CYPs inhibitor proadifen (SKF, 30 μmol/L) increased the cellular accumulation of leflunomide to 3.68-fold at 4 h. After oral dosing (15 mg/kg), the plasma exposure (AUC0-t) of leflunomide increased to 3-fold in HRN mice compared with wild type mice. Administration of leflunomide (25 mg·kg(-1)·d(-1)) for 7 d significantly increased serum ALT and AST levels in HRN mice; when the dose was increased to 50 mg·kg(-1)·d(-1), all HRN mice died on d 6. Teriflunomide significantly decreased the expression of NTCP in human hepatocytes, as well as the function of NTCP in rat hepatocytes and NTCP-transfected HEK293 cells. Four-week administration of teriflunomide significantly increased serum total bilirubin and direct bilirubin levels in female rats, but not in male rats. Conclusion: Hepatic CYPs play a critical role in detoxification process of leflunomide, whereas the major metabolite teriflunomide suppresses the expression and function of NTCP, leading to potential cholestasis.
    No preview · Article · Jan 2016 · Acta Pharmacologica Sinica
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    ABSTRACT: The effects of particle size of microspheres on the drug release from a microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot (m-SAIB) was investigated to develop a long-term sustained release drug delivery system with low burst release both in vitro and in vivo. A model drug, risperidone, was firstly encapsulated into PLGA microspheres with different particle size using conventional emulsification and membrane emulsification methods respectively. The m-SAIB was prepared by dispersing the risperidone-microspheres in the SAIB depot. The drug release from m-SAIB was double controlled by the drug diffusion from the microspheres into SAIB matrix and the drug diffusion from the SAIB matrix into the medium. Large microspheres (18.95±18.88 μm) prepared by the conventional homogenization method exhibited porous interior structure, which contributed to the increased drug diffusion rate from microspheres into SAIB matrix. Consequently, m-SAIB containing such microspheres showed rapid initial drug release (Cmax=110.1±54.2 ng/ml) and subsequent slow drug release (Cs(4-54d)= 2.7±0.8 ng/ml) in vivo. Small microspheres (5.91±2.24 μm) showed dense interior structure with a decreased drug diffusion rate from microspheres into SAIB matrix. The initial drug release from the corresponding m-SAIB was significantly decreased (Cmax=40.9±13.7 ng/ml), whereas the drug release rate from 4 to 54 days was increased (Cs(4-54d)=4.1±1.0 ng/ml). By further decreasing the size of microspheres to 3.38±0.70 μm, the drug diffusion surface area was increased, which subsequently increased the drug release from the m-SAIB. These results demonstrated that drug release from the m-SAIB can be tailored by varying the size of microspheres to reduce the in vivo burst release of SAIB system alone.
    No preview · Article · Jan 2016 · Drug Development and Industrial Pharmacy
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    ABSTRACT: Aberrant hypermethylation of CpG islands of tumor suppressor is one of the mechanisms for epigenetic loss of gene function. In the present study, the methylation status of the promoter regions of protein tyrosine phosphatase (PTPN) 6, DAPK, and p16 were studied using methylation-specific polymerase chain reaction (MSP) in 26 diffuse large B cell lymphoma (DLBCL) lymphomas. In OCI-LY1 cell line, gene methylation status, expression of PTPL1 and its reactivation by DNA demethylation was determined by PCR and on the protein level by western blotting. ELISA-like reaction was used to detect global DNA methylation measurement. Induction of apoptosis by 5-azacitidine was analyzed by Annexin V/PI staining and flow cytometry. Our results show that hypermethylation of the PTPN6 gene promoter region was found in 15.4% (4/26), the DAPK gene promoter region in 30.8% (8/26), the p16 gene promoter region in 7.7% (2/26). Notably, we identified that PTPL1 was hypermethylated and transcriptionally silenced in OCI-LY1 cell line. The expression of PTPL1 was re-inducible by 5-azacytidine. 5-azacytidine also inhibits the proliferation and decreases the global methylation level of the OCI-LY1 cell line. We can conclude from our study that a higher prevalence of methylation of PTPL1, PTPN6, DAPK and p16 occur in DLBCL. Our data also highlights 5-azacytidine as a potential therapeutic candidate for DLBCL. Further studies are required to substantiate the role of methylation of PTPL1, PTPN6, DAPK and p16 as a marker in diffuse large B cell lymphoma.
    No preview · Article · Oct 2015 · Oncology Reports
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    ABSTRACT: Background/Aims: There have been many studies on the etiology of osteoarthritis (OA) with regard to the function of inflammatory cytokines, the process of cartilage degradation, the function of miR-146a, hypoxia stimulation and autophagy in OA chondrocytes, but there have been no reports on the relationship between miR-146a and autophagy in cartilage, especially under hypoxia. This study aimed to confirm the relationship of miR-146a and autophagy in cartilage under hypoxia. Methods: Chondrocytes were treated by hypoxia gradients, and the main factors including HIF-1α, HIF-2α, miR-146a and Bcl-2 and autophagy markers ULK-1, ATG-5 were detected by quantitative PCR (Q-PCR) and western blotting. The autophagy marker LC-3 was detected by immunofluorescence. The reciprocal effects between miR-146a and Bcl-2 were confirmed by several combinations of shRNAs and adenovirus-gene systems followed by Q-PCR and western blot detection. Results: Hypoxia maintained the chondrocytes phenotype and promoted autophagy and miR-146a expression via HIF-1α, but not HIF-2α, while miR-146a did not reversely affect HIF-1α. The autophagy induced by hypoxia through HIF-1α, miR-146a and Bcl-2. Simply, hypoxia induced HIF-1α, and HIF-1α increased miR-146a, but miR-146a suppressed Bcl-2, an autophagy inhibitor. While Bcl-2 affected neither HIF-1α nor miR-146a. The absence of both HIF-1α and miR-146a or Bcl-2 over-expression inhibited hypoxia-induced autophagy. Conclusion: HIF-1α, miR-146a and Bcl-2 play crucial roles during hypoxia-induced autophagy, Hypoxia, HIF-1α and miR-146a promote chondrocytes autophagy via depressing Bcl-2. We conclude that miR-146a may serve as a novel therapeutic target for protecting cartilage from degeneration in OA.
    No preview · Article · Oct 2015 · Cellular Physiology and Biochemistry
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    ABSTRACT: Biocompatible polymer scaffolds are promising as potential carriers for the delivery of retinal progenitor cells (RPCs) in cell replacement therapy for the repair of damaged or diseased retinas. The primary goal of the present study was to investigate the effects of blended electrospun nanofibrous membranes of silk fibroin (SF) and poly(L-lactic acid-co-ε-caprolactone) (PLCL), a novel scaffold, on the biological behaviour of RPCs in vitro. To assess the cell-scaffold interaction, RPCs were cultured on SF/PLCL scaffolds for indicated durations. Our data revealed that all the SF/PLCL scaffolds were thoroughly cytocompatible, and the SF:PLCL (1:1) scaffolds yielded the best RPC growth. The in vitro proliferation assays showed that RPCs proliferated more quickly on the SF:PLCL (1:1) than on the other scaffolds and the control. Quantitative polymerase chain reaction (qPCR) and immunocytochemistry analyses demonstrated that RPCs grown on the SF:PLCL (1:1) scaffolds preferentially differentiated toward retinal neurons, including, most interestingly, photoreceptors. In summary, we demonstrated that the SF:PLCL (1:1) scaffolds can not only markedly promote RPC proliferation with cytocompatibility for RPC growth but also robustly enhance RPCs' differentiation toward specific retinal neurons of interest in vitro, suggesting that SF:PLCL (1:1) scaffolds may have potential applications in retinal cell replacement therapy in the future.
    Preview · Article · Sep 2015 · Scientific Reports
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    ABSTRACT: p38 mitogen-activated protein kinase (MAPK) activity has been reported to either promote or suppress cell death, which depends on cell type and stimulus. Our previous report indicates that p38 exerts a protective role in tumor necrosis factor (TNF)-α-induced cell death in L929 fibroblastoma cells. However, key molecules regulating p38 activation remain unclear. Here, we show that ectopic expression of scaffold protein receptor for activated C kinase 1 (RACK1) suppressed TNF-α-induced cell death in L929 cells, which was associated with enhanced p38 activation. Knockdown of endogenous RACK1 expression exhibited opposite effects. The protective role of RACK1 in TNF-α-induced cell death diminished upon blockade of p38 activation. Therefore, RACK1 antagonizes TNF-α-induced cell death through, at least partially, augmenting p38 activation. Further exploration revealed that RACK1 directly bound to MKK3/6 and enhanced the kinase activity of MKK3/6 without affecting MKK3/6 phosphorylation. Similar effects of RACK1 were also observed in primary murine hepatocytes, another cell type sensitive to TNF-α-induced cell death. Taken together, our data suggest that RACK1 is a key factor involved in p38 activation as well as TNF-α-induced cell death.
    Preview · Article · Sep 2015 · Scientific Reports
  • Fei Dong · Yifan Pang · Jing Wang · Xiaoyan Ke
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    ABSTRACT: To analyze the efficacy of cyclophosphamideplus, epirubicin, vincristine, prednisone plus etoposide and/or bleomycin, with or without rituximab (R±BEACOP) regimen in patient with poor-prognosis lymphoma. A total of 89 patients, who had poor-prognosis lymphoma and received at least 1 cycle of R±BEACOP regimen during 2002 to 2012, were enrolled and analyzed by a retrospective study. The rate of complete response was 62.9% (56 patients). The efficacy of Hodgkin lymphoma (HL) and T/NK NHL was better than that of other types of lymphoma. There was no significant difference in efficacy among the patients with different age, stage or international prognosis index (IPI) (all P>0.05). R±BEACOP regimen is effective in some patients with poor prognosis, especially in HL patients. Thus, multicenter prospective study regarding the R±BEACOP regimen needs to be done to further test its efficacy.
    No preview · Article · Aug 2015 · Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences
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    ABSTRACT: Previous studies have examined the association between breastfeeding and rheumatoid arthritis (RA), but their results were inconsistent. The aim of this study was to perform a metaanalysis to clarify the effect of breastfeeding on RA risk. The PubMed, EMBASE, Chinese National Knowledge Infrastructure, and Wanfang databases were searched for relevant studies published up to September 10, 2014. Data were extracted, and multivariable-adjusted OR with 95% CI were pooled in the random-effects model. A total of 6 studies were included in the metaanalysis (RA cases: 1672, sample size: 143,670). Overall, an inverse association between breastfeeding and RA was observed (OR 0.675, 95% CI 0.493-0.924, p = 0.014). In the subgroup analysis, decreased RA risk was also found in both breastfeeding 1-12 months (OR 0.783, 95% CI 0.641-0.957, p = 0.015) and breastfeeding > 12 months (OR 0.579, 95% CI 0.462-0.726, p < 0.0005). Sensitivity analysis and cumulative analysis further strengthened the validity of the results. No publication bias was found in this metaanalysis. This metaanalysis suggests that breastfeeding is associated with a lower risk of RA, no matter if breastfeeding time is longer or shorter than 12 months.
    No preview · Article · Jul 2015 · The Journal of Rheumatology
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    ABSTRACT: Non-Hodgkin lymphoma (NHL) consists of various lymphoid malignancies with a diverse clinical pathology and biological characteristics. Methylation of cytosine residues by DNA methyltransferases at CpG dinucleotides in the promoter region of the genes is a major epigenetic modification in mammalian genomes that can have profound effects on gene expression. The PTPL1 methylation pattern was screened by methylation‑specific polymerase chain reaction (MSP) in 7 lymphoma‑derived cell lines and in 47 samples of diffuse large B cell lymphoma (DLBCL). The PTPL1 gene was hypermethylated in the CA46, Raji, Jurkat and DB cell lines; however, it was unmethylated in the Hut78, Maver and Z138 cell lines. The expression of PTPL1 mRNA was re‑inducible by 5‑azacytidine (5‑Aza), an agent of DNA demethylation. The methylations were detected in 59.6% of DLBCL versus 6.3% in reactive lymph node proliferation. Therefore, the present data showed that PTPL1 was epigenetically regulated in NHL suggesting an involvement of the PTPL1 tumor‑suppressor genes in NHL, and highlights 5-Aza as a potential therapeutic candidate for NHL.
    Preview · Article · Jul 2015 · International Journal of Molecular Medicine
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    ABSTRACT: The role of B7-H3 in acute monocytic leukemia U937 cells has not been thoroughly investigated. B7-H3 knockdown in the U937 cell line was performed using small hairpin (sh)RNA lentivirus transduction. The effects on cell proliferation, cycle, migration, and invasion were investigated by Cell Counting Kit-8 assay, methyl cellulose colony-forming assay, propidium iodide staining, and Transwell assays in vitro. Changes in cell growth inhibition and apoptosis, when combined with chemotherapy drugs, were determined using the Cell Counting Kit-8 and Annexin V-FITC/PI assays. U937 xenograft models were used to assess the effects of B7-H3 on tumorigenicity and the therapeutic effect of B7-H3 knockdown in combination with chemotherapy drugs in vivo. Downregulation of B7-H3 significantly decreased U937 cell growth and colony-forming ability. The mean inhibition rate of tumor growth with B7-H3 knockdown was 59.4%, and the expression of both Ki-67 and PCNA in xenografts was significantly reduced. After B7-H3 silencing, the U937 cell cycle was arrested at the G0/G1 phase. The cell migration rate of B7-H3 knockdown cells was reduced more than fivefold, and invasion capacity decreased by 86.7%. B7-H3 RNAi profoundly increased the antitumor effect of chemotherapy in vitro and in vivo. On day 19, inhibition rates of tumor growth in B7-H3 shRNA combined with idarubicin, cytarabine, and idarubicin plus cytarabine were 70.5%, 80.0%, and 90.0%, respectively (P=0.006, P=0.004, and P=0.016, respectively). B7-H3 may promote U937 cell progression, and shRNA targeting B7-H3 significantly enhances sensitivity to chemotherapeutic drugs. These results may provide new insight into the function of B7-H3 and a promising therapeutic approach targeting B7-H3 in acute monocytic leukemia.
    Preview · Article · Jul 2015 · OncoTargets and Therapy
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    ABSTRACT: Studies have reported limited evidence of the benefits and harms of various regimens, such as liver resection and medical therapy, for the treatment of pancreatic neuroendocrine tumors (pNETs) with liver metastases. This meta-analysis aimed to evaluate the efficacy of liver resection versus nonsurgical treatments in patients with pNET. Relevant studies published in English were retrieved from the computerized databases Medline, Embase, and Cochrane. A meta-analysis was performed to investigate the differences in the efficacy of liver resection and nonsurgical treatments based on the evaluation of 30-day mortality, symptom relief rate, median survival time, and 2-, 3-, or 5-year survival using a random-effects model. Studies were independently reviewed by two investigators. Data from eligible studies were extracted, and the meta-analysis was performed using the comprehensive meta-analysis program version 2. A total of seven studies were included in the analysis. The results demonstrated that liver resection was significantly associated with a higher rate of symptom relief, longer median survival time, higher 2- or 3-year survival rates, as well as a higher 5-year survival rate. There was no significant difference in 30-day mortality among patients with pNETs who were treated by liver resection and nonsurgical therapy or survival between functional and nonfunctional pNETs. No publication bias was detected. Liver resection has a favorable prognostic outcome in terms of higher postoperative symptom relief rates and longer survival rates. Further randomized, controlled trials with longer follow-up periods are required to confirm the advantages of liver resection for pNETs.
    No preview · Article · Jun 2015 · Annals of Surgical Oncology
  • Fei Dong · Bei Yao · Jing Wang · H M Jing · X Y Ke
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    ABSTRACT: To analyze the characteristics of hospital infection of hematological disease, so as to provide reference for clinical therapy. Bacterial strains and antimicrobial resistance of patients with hospital infection in Department of Hematology, Peking University Third Hospital from Jan. 2011 to Dec. 2013 were identified and analyzed retrospectively. The specimens were from their blood, urine, sputum, throat swabs and etc. Among the total of 168 isolates of bacteria,the majority of the bacteria strains were from sputum (42.9%);114(67.9%) bacteria strains were gram negative and 54(32. 1%) bacteria strains were gram positive; the pathogen testing showed that 20.8% were Pseudomonas aeruginosa,18.5% Escherichia coli,17.9% Staphylococcus aureus, 9.5% Klebsiellar pneumonia, 5.9% Staphylococcus epidermis and 27.4% other bacteria ; The gram negative bacilli to cefepime, amikacin and carbapenems showed the lowest antimicrobial resistance rates, and S. aureus showed the lowest antimicrobial resistance rates to vancomycin and linezolid. Patients with hemopathy are the main population of hospital infections, the gram negative bacteria are the most common pathogens.It is very important to promptly know the change in distribution of the pathogens in order to rationally select antibiotics and reduce the incidence of bacterial infections.
    No preview · Article · Jun 2015 · Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences
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    ABSTRACT: In China, a nationwide emergency system takes charge of pre-hospital emergency services, and it adopts a proximity principle to send trauma patients to the nearest hospitals. However, many severely injured patients have been sent to low level hospitals with no capability to treat severe trauma. Thus those patients with high probability of in-hospital death or intensive care unit (ICU) admission need to be identified in the emergency department (ED) for optimal utilisation of hospital resources and better patient outcomes. The purpose of the study was to develop a computerised tool to aid ED physicians’ prediction of in-hospital death and ICU admission for trauma patients after arrival to hospital.
    Full-text · Article · Jun 2015 · Injury
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    ABSTRACT: In the scientific community, a scientist's productivity is usually measured by his scientific output. The productivity of a group, an institution or, on a larger scale, a country can be assessed in similar manner. This study aims to show the contribution of Chinese authors to orthopedics research, from three major regions, namely Mainland China, Taiwan, and Hong Kong. Articles published in 63 orthopedics journals originating from Mainland China, Taiwan, and Hong Kong from 2003 to 2012 were retrieved from the PubMed database and Journal Citation Report. Quantitative and qualitative analyses were conducted for the total number of articles, clinical trials, randomized controlled trails, case reports, impact factors (IF), citations, and articles published in high-impact journals. There were totally 3473 articles from Mainland China (1859), Taiwan (1111), and Hong Kong (503) from 2003 to 2012, showing gradual increase from 2003 to 2012. From 2006 onward, the number of published articles from Mainland China exceeded that from Hong Kong and exceeded that from Taiwan in 2008. The accumulated IF of articles from Mainland China (3746.21) was higher than that from Taiwan (2466.74) and that from Hong Kong (1089.35). However, Taiwan witnessed the highest mean IF (2.22), followed by Hong Kong (2.17), and Mainland China (2.02). Hong Kong displayed the highest mean citations of each article (9.35), followed by Taiwan (9.12), and Mainland China (5.71). By contract, Spine was the most popular journal to choose in these three regions. The total number of orthopedics articles in China increased markedly from 2003 to 2012. Of the three regions, Mainland China published the most articles, clinical trials, randomized controlled trails, and case reports. In general, Spine was the most popular journal to choose in the three regions.
    No preview · Article · Jun 2015 · European Spine Journal
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    ABSTRACT: Malignant giant cell tumor (MGCT) in the spine is extremely rare and there is little published information regarding this subject in the literature. We attempted to correlate different treatment options and outcomes over time. A retrospective study of patients with spinal MGCT who were surgically treated in our center between 2006 and 2012 was performed. Overall, three surgical management strategies, including subtotal resection, piecemeal total resection, and total en bloc spondylectomy were applied. Postoperative radiotherapy was carried out in 4 cases. Clinical data and efficacy of surgical treatment strategy were analyzed via chart review. A total of 14 patients with spinal MGCT were included in the study. Three cases were diagnosed as primary MGCT (PMGCT), while the other 11 patients were secondary MGCT (SMGCT). The mean follow-up period was 41 (range 3-75) months. Recurrence was found in 7 patients after surgery in our center, while distant metastasis and death occurred in 4 and 6 cases, respectively. MGCT of bone is always a high-grade sarcoma with a poor prognosis and complete excision, while also preserving neural function, is recommended. In our study, patients who underwent total en bloc spondylectomy had significantly lower local recurrence rate for MGCT in the spine.
    No preview · Article · Jun 2015 · Journal of Neuro-Oncology
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    ABSTRACT: Giant cell tumor (GCT) of bone consists of three major cell types: giant cells, monocytic cells, and stromal cells. From microarray analysis, we found that miR-106b was down-regulated in GCT clinical samples and further determined by fluorescence in situ hybridization. In addition, the expression of novel potential target of miR-106b, RANKL, was elevated in GCT along with previously determined targets in other tumors such as IL-8, MMP2 and TWIST. In a RANKL 3'UTR luciferase reporter assays, agomiR-106b repressed the luciferase activity and the effect was eliminated when the targeting site in the reporter was mutated, suggesting a direct regulation of miR-106b on RANKL mRNA. Moreover, overexpression of miR-106b in GCTSCs through TALEN-mediated site-specific knockin clearly inhibited osteoclastogenesis and osteolysis. By grafting the GCT onto the chick CAM, we confirmed the inhibitory effect of miR-106b on RANKL expression and giant cell formation. Furthermore, in an OVX mouse model, silencing of miR-106b increased RANKL protein expression and promoted bone resorption, while up-regulation of miR-106b inhibited bone resorption. These results suggest that miR-106b is a novel suppressor of osteolysis by targeting RANKL and some other cytokines, which indicates that miR-106b may be a potential therapeutic target for the treatment of GCT.
    Preview · Article · May 2015 · Oncotarget

  • No preview · Article · May 2015 · Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi
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    ABSTRACT: Cornea transplant technology has progressed markedly in recent decades, allowing surgeons to replace diseased corneal endothelium by a thin lamellar structure. A thin, transparent, biocompatible, tissue-engineered substratum with corneal endothelial cells for endothelial keratoplasty is currently of interest. Electrospinning a nanofibrous structure can simulate the extracellular matrix and have beneficial effects for cell culture. Silk fibroin (SF) has good biocompatibility but poor mechanical properties, while poly(l-lactic acid-co-ε-caprolactone) (P(LLA-CL)) has good mechanical properties but poor biocompatibility. Blending SF with P(LLA-CL) can maintain the advantages of both these materials and overcome their disadvantages. Blended electrospun nanofibrous membranes may be suitable for regeneration of the corneal endothelium. The aim of this study was to produce a tissue-engineered construct suitable for endothelial keratoplasty. Five scaffolds containing different SF:P(LLA-CL) blended ratios (100:0, 75:25, 50:50, 25:75, 0:100) were manufactured. A human corneal endothelial (B4G12) cell line was cultured on the membranes. Light transmission, speed of cell adherence, cell viability (live-dead test), cell proliferation (Ki-67, BrdU staining), and cell monolayer formation were detected on membranes with the different blended ratios, and expression of some functional genes was also detected by real-time polymerase chain reaction. Different blended ratios of scaffolds had different light transmittance properties. The 25:75 blended ratio membrane had the best transmittance among these scaffolds. All electrospun nanofibrous membranes showed improved speed of cell adherence when compared with the control group, especially when the P(LLA-CL) ratio increased. The 25:75 blended ratio membranes also had the highest cell proliferation. B4G12 cells could form a monolayer on all scaffolds, and most functional genes were also stably expressed on all scaffolds. Only two genes showed changes in expression. All blended ratios of SF:P(LLA-CL) scaffolds were evaluated and showed good biocompatibility for cell adherence and monolayer formation. Among them, the 25:75 blended ratio SF:P(LLA-CL) scaffold had the best transmittance and the highest cell proliferation. These attributes further the potential application of the SF:P(LLA-CL) scaffold for corneal endothelial transplantation.
    No preview · Article · May 2015 · International Journal of Nanomedicine
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    ABSTRACT: Although the thiol click reaction is an attractive tool for post-polymerization modification of thiolmers, thiol groups are easily oxidized, limiting the potential for covalent immobilization of bioactive molecules. In this study, a series of biodegradable polyurethane elastomers incorporating stable cyclic disulfide groups was developed and characterized. These poly(ester urethane)urea (PEUU-SS) polymers were based on polycaprolactone diol (PCL), oxidized DL-dithiothreitol (O-DTT), lysine diisocyanate (LDI) or butyl diisocyanate (BDI), with chain extension by putrescine. The ratio of O-DTT:PCL was altered to investigate different levels of potential functionalization. PEG acrylate was employed to study the mechanism and availability of both bulk and surface click modification of PEUU-SS polymers. All synthesized PEUU-SS polymers were elastic with breaking strengths of 38-45 MPa, while the PEUU-SS(LDI) polymers were more amorphous, possessing lower moduli and relatively small permanent deformations versus PEUU-SS(BDI) polymers. Variable bulk click modification of PEUU-SS(LDI) polymers was achieved by controlling the amount of reduction reagent, and rapid reaction rates occurred using a one-pot, two-step process. Likewise, surface click reaction could be carried out quickly under mild, aqueous conditions. Furthermore, a maleimide-modified affinity peptide (TPS) was successfully clicked on the surface of an electrospun PEUU-SS(BDI) fibrous sheet, which improved endothelial progenitor cell adhesion versus corresponding unmodified films. The cyclic disulfide containing biodegradable polyurethanes described provide an option for soft tissue regenerative medicine applications where a temporary, elastic scaffold with designed biofunctionality from a relatively simple click chemistry approach is desired.
    No preview · Article · Apr 2015 · Biomacromolecules
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    ABSTRACT: Perfluorooctane sulfate (PFOS), a persistent organic pollutant, has recently been closely linked with an increased risk of tumorigenesis. However, PFOS has yielded negative results in various tests of genotoxicity. The present study aimed to investigate the mutagenic response to PFOS in the gpt delta transgenic mouse mutation system and to illustrate the contribution of hydrogen peroxide (H2O2) to PFOS genotoxicity. Mutations at the redBA/gam loci were determined by Spi- assay both in vitro and in vivo. DNA damage was measured by phosphorylated histone H2AX (γ-H2AX) and mouse bone marrow micronucleus (MN) testing. Our data showed that PFOS induced concentration-dependent increases in γ-H2AX foci and in mutation frequencies at redBA/gam loci in transgenic mouse embryonic fibroblast cells, which were confirmed by the formation of MNs in the bone marrow and the observations of mutation induction in the livers of gpt delta transgenic mice. Concurrent treatment with catalase, an efficient H2O2 scavenger, significantly decreased the formation of γ-H2AX foci and the mutation yields induced by PFOS. In addition, the generation of H2O2 was found to be closely related to the abnormal peroxisomal β-oxidation caused by PFOS. These finding might provide new mechanistical information about genotoxic effects of PFOS.
    No preview · Article · Apr 2015 · Environmental Science & Technology

Publication Stats

988 Citations
361.17 Total Impact Points

Institutions

  • 2008-2016
    • Shenyang Pharmaceutical University
      • • College of Pharmacy
      • • School of Pharmaceutics
      • • Department of Pharmacy
      Feng-t’ien, Liaoning, China
    • Medical University of Graz
      • Institute of Cell Biology, Histology and Embryology
      Gratz, Styria, Austria
    • Henan University
      • Institute of Immunology
      K’ai-feng-shih, Henan Sheng, China
  • 2015
    • Donghua University
      • State Key Laboratory for Modification of Chemical Fibers and Polymer Materials
      Shanghai, Shanghai Shi, China
    • Xuzhou Medical College
      Suchow, Jiangsu, China
  • 2014-2015
    • Second Military Medical University, Shanghai
      • Department of Orthopaedics
      Shanghai, Shanghai Shi, China
    • Logistical College of Chinese People's Armed Police Force
      T’ien-ching-shih, Tianjin Shi, China
    • University of Science and Technology, Beijing
      Peping, Beijing, China
    • Heilongjiang University
      • School of Mathematical Sciences
      Charbin, Heilongjiang Sheng, China
    • Beijing Tiantan Hospital
      Peping, Beijing, China
  • 2009-2015
    • Shanghai Jiao Tong University
      • • Department of Ophthalmology
      • • Department of Laboratory Medicine
      Shanghai, Shanghai Shi, China
  • 2007-2015
    • Peking University Third Hospital
      Peping, Beijing, China
    • 307 Hospital of the Chinese People's Liberation Army
      Peping, Beijing, China
  • 2005-2015
    • Peking University People's Hospital
      Peping, Beijing, China
  • 2002-2015
    • Peking University
      • • Institute of Hematology
      • • School of Public Health
      Peping, Beijing, China
  • 2002-2014
    • The Third People's Hospital
      Shen-ch’üan-shih, Zhejiang Sheng, China
  • 2013
    • Shanghai University
      • Department of Anesthesiology
      Shanghai, Shanghai Shi, China
    • Chinese Academy of Medical Sciences
      Peping, Beijing, China
  • 2012-2013
    • The University of Sheffield
      • Department of Materials Science and Engineering
      Sheffield, England, United Kingdom
  • 2010-2013
    • Beijing FivePlus Molecular Medicine Institute
      Peping, Beijing, China
    • Beijing University of Technology
      Peping, Beijing, China
  • 2011-2012
    • Chinese PLA General Hospital (301 Hospital)
      Peping, Beijing, China
    • Nevada cancer institute
      Las Vegas, Nevada, United States
  • 2010-2012
    • Chinese Academy of Forestry
      Peping, Beijing, China
  • 2010-2011
    • Chinese Academy of Sciences
      • • Institute of Psychology
      • • Institute of Biochemistry and Cell Biology
      Peping, Beijing, China