Publications by authors named "Yansong Chen"

12 Publications

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Glucose-triggered in situ forming keratin hydrogel for the treatment of diabetic wounds.

Acta Biomater 2021 Apr 1;125:208-218. Epub 2021 Mar 1.

Key Laboratory of Science & Technology of Eco-Textile, Donghua University, Ministry of Education, Shanghai 201620, China; Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China. Electronic address:

The development of protein-based in situ forming hydrogel remains a big challenge due to the limited chemical groups in proteins. Keratins are a group of cysteine-rich structural protein found abundant in skin and skin appendant. Recently, our lab has established a disulfide shuffling strategy to prepare keratin hydrogels via oxygen (O) oxidation. However, such hydrogel still needed to be molded in advance. In this work, inspired by the fact that glucose commonly exists in body fluids, a glucose-triggered in situ forming keratin hydrogel was developed based on the disulfide shuffling strategy via a higher oxidation force of hydrogen peroxide (HO). The hydrogel precursor solution consisted of keratin, cysteine and glucose oxidase (GOD), which could generate HO in an indirect and mild way via GOD-catalyzed oxidation of glucose in body fluids. Our findings demonstrated that the GOD-catalyzed oxidation method not only shortened the gelation time but improved the mechanical strength of the hydrogel by comparison with O oxidation and direct addition of HO solution methods, and realized in situ gelation within 3 min on a full-thickness wound bed in normal mice. Moreover, the in situ forming keratin hydrogel was applied as a drug depot for wound repair, and the deferoxamine-loaded one accelerated healing in the full-thickness wounds of streptozotocin-induced diabetic rats, notably by promoting angiogenesis and neovascularization in wounds. STATEMENT OF SIGNIFICANCE: Studies show that keratin hydrogels possess tissue regeneration capacity, especially in skin wound repair. However, most of the reported keratin hydrogels needed to be molded in advance and cannot fit irregular wound shape. This work describes a glucose-triggered in situ forming keratin hydrogel via a disulfide shuffling strategy under the oxidation of hydrogen peroxide. Of note, the hydrogen peroxide was supplied indirectly by glucose oxidase-catalyzed oxidation of glucose in wound fluids, and this method needed no additional crosslinking agents or chemical modifications on keratins. Our findings showed that this hydrogel realized in situ gelation within 3 min on a full-thickness wound bed and enabled an injectable mode with good filling ability toward irregular wounds. Moreover, this hydrogel could be applied as a drug depot for the treatment of diabetic wounds.
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http://dx.doi.org/10.1016/j.actbio.2021.02.035DOI Listing
April 2021

The knockdown of the sepiapterin reductase gene suppresses the proliferation of breast cancer by inducing ROS-mediated apoptosis.

Int J Clin Exp Pathol 2020 1;13(9):2228-2239. Epub 2020 Sep 1.

Department of Surgical Oncology, The First Affiliated Hospital of Bengbu Medical College Bengbu, Anhui, China.

Background: Sepiapterin reductase (SPR) is an important regulator of the biosynthesis of tetrahydrobiopterin (BH), which has been shown to be a promoter of different kinds of tumors. This study aims to investigate the role of SPR in breast cancer and to explore its molecular mechanism.

Methods: SPR expressions in breast cancer tissues with different pathological stages were compared with the corresponding pericarcinomatous tissues and were analyzed using immunohistochemical staining and western blot. SPR knockdown was performed in MDA-MB-231 and MDA-MB-468 triple-negative breast cancer cells using specific siRNAs. Quantitative real-time PCR and western blot were used to determine the efficiency of the SPR knockdown. The intracellular BH levels were measured using HPLC, and the intracellular ROS levels were measured using an ROS detection kit. Clone formation and cell proliferation assays were used to study the effect of the SPR knockdown on cell proliferation. Annexin V/PI double staining, cell mitochondria isolation, and western blot were performed to study the effect of the SPR knockdown on cell apoptosis. ROS scavenger NAC was used to inhibit increased ROS caused by the SPR knockdown.

Results: SPR is highly expressed in breast cancer tissues compared with the pericarcinomatous tissues and positively correlated with the pathological stages. The knockdown of SPR causes decreased intracellular BH and increased intracellular ROS and inhibits the proliferation of MDA-MB-231 and MDA-MB-468 cells. The knockdown of SPR also induces mitochondrial pathway-mediated apoptosis. NAC suppresses the SPR knockdown-caused cell apoptosis and cell death.

Conclusions: SPR promotes the proliferation of breast cancer cells. The knockdown of SPR suppresses the proliferation of breast cancer cells by inducing ROS-mediated apoptosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539867PMC
September 2020

Interactions between heavy metals and other mineral elements from soil to medicinal plant Fengdan (Paeonia ostii) in a copper mining area, China.

Environ Sci Pollut Res Int 2020 Sep 13;27(27):33743-33752. Epub 2020 Jun 13.

School of Life Science, Hefei Normal University, Lianhua Road 1688, Hefei, 230601, China.

In order to analyze the interaction relationship between heavy metals and other mineral elements during the processes of absorption and translocation by plant grown on heavy metal-contaminated area, the concentrations of Cu, Zn, Mn, Cd, Pb, Ca, Mg, Fe, and K in the medicinal plant Paeonia ostii T. Hong et J. X. Zhang and its rhizospheric soil were determined, which grow around an abandoned copper tailings reservoir in Tongling City, China. Geo-accumulation index (I) calculation indicated that Cu and Pb are the main pollution elements in the rhizospheric soil. Moreover, the Cu and Pb concentrations in the cortex moutan of P. ostii exceeded the maximum permissible limits for food product safety. The bioaccumulation factor values of the tested metals in plant roots were found < 0.50, with the exception of Ca (maximum 5.99). The translocation factor values of detected heavy metals Cd and Pb were more than 1.00, which indicated that P. ostii could be considered a potential accumulator plant for Cd and Pb. Significant positive correlations including Cu-Cd, Cu-Zn, Cu-Pb, Cd-Zn, Cd-Fe, Cd-Fe, Zn-Pb, Pb-Fe, Mn-Fe, and Ca-Mg in the cortex moutan and Cu-Zn, Cu-Fe, Zn-Mg, Zn-Fe, and Mn-K in the leaves were observed (P < 0.05). Significant positive correlation between Cu, Zn, Mg, and Fe was also confirmed in the processes of absorption and translocation from the soil to plant (P < 0.05), which evidenced that synergistic element interactions of the essential elements Cu, Zn, Mg, and Fe are a result of the similarity in their ionic radii and octahedral coordination geometry.
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http://dx.doi.org/10.1007/s11356-020-09358-zDOI Listing
September 2020

Effects of oral maintenance chemotherapy and predictive value of circulating EBV DNA in metastatic nasopharyngeal carcinoma.

Cancer Med 2020 04 23;9(8):2732-2741. Epub 2020 Feb 23.

Department of Radiation Oncology, Fujian Cancer Hospital &, Fujian Medical University Cancer Hospital, Fuzhou, China.

Background/objectives: Oral maintenance chemotherapy can effectively prolong overall survival (OS) in many types of metastatic cancer, but its role in metastatic nasopharyngeal carcinoma (mNPC) is unclear. In this study, the efficacy of oral maintenance chemotherapy in mNPC and the effectiveness of circulating tumor EBV-DNA for screening patients were evaluated.

Methods: Between June 2016 and December 2017, 141 patients with mNPC who received platinum-based systemic chemotherapy were included (median follow-up time, 21 months). Patients were classified into two groups according to the administration of oral maintenance chemotherapy. Plasma samples were collected before, during, and after treatment for the measurement of circulating EBV DNA.

Results: The 2-year OS was higher for patients who received maintenance chemotherapy than for patients without maintenance chemotherapy (78.9% vs 62.7%, P = .016). Patients with undetectable posttreatment EBV-DNA after 4-6 cycles of systemic chemotherapy (n = 73) had a higher 2-year OS than that of patients with detectable EBV-DNA (n = 68) (82.16% vs 51.45%, P = .001). For patients with undetectable posttreatment EBV-DNA, OS was better for those with maintenance chemotherapy than for those without (86.7% vs 73%, P = .027). For patients with detectable posttreatment EBV-DNA, maintenance chemotherapy did not improve outcomes (49.5% vs 55.4%, P = .824). The most common acute events were hematological toxicity, and all were tolerable and curable.

Conclusions: Oral maintenance chemotherapy with S1 or capecitabine can improve OS in mNPC. Posttreatment EBV-DNA was not only an independent prognosis factor for mNPC but also can screen out beneficiaries of maintenance chemotherapy.
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http://dx.doi.org/10.1002/cam4.2926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163084PMC
April 2020

Diagnostic and prognostic value of the cancer-testis antigen lactate dehydrogenase C4 in breast cancer.

Clin Chim Acta 2020 Apr 30;503:203-209. Epub 2019 Nov 30.

Laboratory of Biochemistry and Molecular Biology Research, Fujian Provincial Key Laboratory of Tumor Biotherapy, Department of Clinical Laboratory, Fujian Medical University Cancer Hospital, Fuzhou, Fujian, PR China. Electronic address:

Background: Lactate dehydrogenase C4 (LDH-C4) as a cancer/testis antigen (CTA) is abnormally expressed in some malignant tumors. However, the expression and clinical significance of LDH-C4 in breast cancer (BC) has not been characterized.

Methods: We determined LDHC mRNA expression in serum and serum-derived exosomes of BC patients by quantitative RT-PCR. We also evaluated the protein expression of LDH-C4 in BC tissues using high-throughput tissue microarray analysis and immunohistochemistry.

Results: Our results showed high mRNA expression level of LDHC in serum and serum-derived exosomes of BC patients. The LDHC level in serum and exosomes could distinguish BC cases from healthy individuals based on their AUCs of 0.9587 and 0.9464, respectively. Besides, the LDHC level in exosomes of BC patients associated with tumor size, and positively correlated with HER2 and Ki-67 expressions (all with P < 0.05). Serum and exosomal level of LDHC negatively correlated with medical treatment and positively with the recurrence of BC. Survival analysis showed that LDH-C4 expression negatively correlated with BC prognosis.

Conclusion: Serum and exosomal LDHC may be an effective indicator for the diagnosis, efficacy evaluation, and monitoring the recurrence of BC. LDH-C4 may act as a biomarker that predicts BC prognosis.
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http://dx.doi.org/10.1016/j.cca.2019.11.032DOI Listing
April 2020

3‑Bromopyruvate sensitizes human breast cancer cells to TRAIL‑induced apoptosis via the phosphorylated AMPK‑mediated upregulation of DR5.

Oncol Rep 2018 Nov 14;40(5):2435-2444. Epub 2018 Aug 14.

Faculty of Pharmacy, Bengbu Medical College, Bengbu, Anhui 233000, P.R. China.

Previous studies have indicated that the sensitivity of breast cancer cells to tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL)‑induced apoptosis is associated with the expression of death receptors on the cell membrane. However, drug resistance limits the use of TRAIL in cancer therapy. Numerous studies have indicated that death receptors, which induce apoptosis, are upregulated by the endoplasmic reticulum (ER) stress response. 3‑Bromopyruvate (3‑BP), an anticancer agent, inhibits cell growth and induces apoptosis through interfering with glycolysis. In the present study, it was demonstrated that 3‑BP synergistically sensitized breast cancer cells to TRAIL‑induced apoptosis via the upregulation of death receptor 5 (DR5). Furthermore, we found that the protein levels of glucose‑related protein 78 (GRP78) and CCAAT‑enhancer‑binding protein homologous protein (CHOP) increased following treatment with 3‑BP. The expression of Bax (in MCF‑7 cells) and caspase‑3 (in MDA‑MB‑231 cells) increased following co‑treatment with 3‑BP and TRAIL, whereas the expression of the anti‑apoptotic protein Bcl‑2 decreased. In order to investigate the molecular mechanism regulating this effect, the expression of adenosine monophosphate‑activated protein kinase (AMPK), activated by 3‑BP, was determined. It was demonstrated that phosphorylated‑AMPK was upregulated following treatment with 3‑BP. Notably, Compound C, an AMPK inhibitor, reversed the effects of 3‑BP. Finally, a synergistic antitumor effect of 3‑BP and TRAIL was observed in MCF‑7 cell xenografts in nude mice. In conclusion, these results indicated that 3‑BP sensitized breast cancer cells to TRAIL via the AMPK‑mediated upregulation of DR5.
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http://dx.doi.org/10.3892/or.2018.6644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6151892PMC
November 2018

PAX1 and SOX1 methylation as an initial screening method for cervical cancer: a meta-analysis of individual studies in Asians.

Ann Transl Med 2016 Oct;4(19):365

Department of Clinical Laboratory, Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Provincial Cancer Hospital, Fujian Medical University Cancer Hospital, Fuzhou 350014, China.

Background: Epigenetic alterations of gene or DNA methylation have been highlighted as promising biomarkers for early cervical cancer screening. Herein, we evaluated the diagnostic performance of paired boxed gene 1 (PAX1) and sex determining region Y-box 1 (SOX1) methylation for cervical cancer detection.

Methods: Eligible studies were retrieved by searching the electronic databases. Study quality was assessed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) checklist. The bivariate meta-analysis model was employed to plot the summary receiver operator characteristic (SROC) curve using Stata 12.0 software.

Results: The pooled sensitivity of PAX1 methylation was estimated to be 0.73 [95% confidence interval (CI): 0.70-0.75] in differentiating patients with HSIL (high-grade squamous intraepithelial lesion) or CIN3+ (cervical intraepithelial neoplasia type III/worse) or cervical cancer from normal individuals, corresponding to a specificity of 0.87 (95% CI: 0.85-0.89) and area under the curve (AUC) of 0.91. The SOX1 methylation test yielded an AUC of 0.82, under which, the pooled sensitivity was 0.71 (95% CI: 0.67-0.74) and specificity was 0.64 (95% CI: 0.61-0.67). Notably, the stratified analysis suggested that combing parallel testing of PAX1 methylation and human papillomavirus (HPV) DNA (AUC, sensitivity, and specificity of 0.89, 0.75, and 0.81, respectively) achieved higher accuracy than single HPV DNA testing (AUC, sensitivity, and specificity of 0.77, 0.81, and 0.70, respectively).

Conclusions: PAX1 or SOX1 methylation has a prospect to be an auxiliary biomarker for cervical cancer screening, and parallel testing of PAX1 methylation and HPV DNA in cervical swabs confers an improved diagnostic accuracy than single HPV DNA testing.
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http://dx.doi.org/10.21037/atm.2016.09.30DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5075846PMC
October 2016

Diagnostic Value of Serum Epstein-Barr Virus Capsid Antigen-IgA for Nasopharyngeal Carcinoma: a Meta-Analysis Based on 21 Studies.

Clin Lab 2016 ;62(6):1155-66

Background: Epstein-Barr virus capsid antigen immunoglobulin A (EBV VCA-IgA) exerts an important role in the diagnosis of nasopharyngeal carcinoma (NPC). This meta-analysis aimed to evaluate the pooled diagnostic performance of VCA-IgA for NPC.

Methods: Literature fulfilling the criteria was searched in PubMed and Embase databases. The quality of the studies was assessed in terms of the Quality Assessment of Diagnosis Accuracy Studies (QUADAS) criteria. The pooled diagnostic parameters were generated using a bivariate meta-analysis model. Statistical analysis was performed based on the platforms of Meta-Disc 1.4 and Stata 12.0 software. The trim and fill adjustment method was applied to further assess the possible effects of publication bias.

Result: Twenty one studies comprising 2986 NPC patients and 3507 controls were included in this meta-analysis. The overall pooled sensitivity and specificity of serum VCA-IgA for NPC were 0.83 (95%CI: 0.82 - 0.84) and 0.88 (95% CI: 0.87 - 0.89), respectively, accompanied by a pooled diagnostic odds ratio (DOR) of 49.87 and area under curve (AUC) of 0.9390. Moreover, our stratified analyses suggested that combinations of multiple EBV antigens (sensitivity, specificity, DOR, and AUC of 0.93, 0.95, 331.8, and 0.9850, respectively) yielded higher accuracy than single VCA-IgA test (sensitivity, specificity, DOR and AUC of 0.83, 0.88, 49.87, and 0.9393, respectively). Additionally, the immunoenzyme assay (IEA) seemed to be a better alternative for the analysis of serum VCA-IgA level, with a sensitivity of 0.92, specificity of 0.94, and AUC of 0.9644.

Conclusions: Serum VCA-IgA hallmarks promising accuracy in the management of NPC and that parallel tests of multiple EBV antigens may be more suitable for NPC serodiagnosis than single VCA-IgA assay. .151122)
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http://dx.doi.org/10.7754/clin.lab.2015.151122DOI Listing
September 2016

Long noncoding RNAs as auxiliary biomarkers for gastric cancer screening: A pooled analysis of individual studies.

Oncotarget 2016 May;7(18):25791-800

Department of Clinical Laboratory, Fujian Provincial Key Laboratory of Tumor Biotherapy, Fujian Provincial Cancer Hospital, Teaching Hospital of Fujian Medical University, Fuzhou, Fujian, China.

Background: Long non-coding RNAs (lncRNAs) are highlighted as novel cancer biomarkers with great promise. Herein, we focused on summarizing the overall diagnostic performance of lncRNAs for gastric cancer (GC).

Methods: Publications fulfilling the search criteria were selected from the online databases. Study quality was assessed according to the Quality Assessment for Studies of Diagnostic Accuracy (QUADAS) checklist. The summary receiver operator characteristic (SROC) curve was plotted using a bivariate meta-analysis model. Statistical analysis was performed based on the platforms of STATA 12.0 and Meta-Disc 1.4 software.

Results: Fifteen studies with 1252 patients and 1283 matched controls were included. The pooled sensitivity and specificity for lncRNA expression profile in differentiating GC patients from cancer-free individuals were 0.68 (95%CI: 0.61-0.74) and 0.79 (95%CI: 0.72-0.84), respectively, corresponding to an area under curve (AUC) of 0.80. Moreover, the stratified analyses demonstrated that plasma-based lncRNA profiling harbored higher accuracy than that tissue-based assay (specificity: 0.80 versus 0.75; AUC: 0.84 versus 0.77).

Conclusions: LncRNA profiling hallmarks a moderate diagnostic value in the management of GC and that lncRNA expression patterns may potentially be utilized as auxiliary biomarkers in confirming GC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041944PMC
http://dx.doi.org/10.18632/oncotarget.8268DOI Listing
May 2016

Directional Movement of Droplets in Grooves: Suspended or Immersed?

Sci Rep 2016 Jan 8;6:18836. Epub 2016 Jan 8.

State Key Laboratory of Fine Chemicals, Liaoning Provincial Key Laboratory of Clean Utilization of Chemical Resources, Institute of Chemical Engineering, Dalian University of Technology, Dalian 116024, China.

The behavior of droplets trapped in geometric structures is essential to droplet manipulation applications such as for droplet transport. Here we show that directional droplet movement can be realized by a V-shaped groove with the movement direction controlled by adjusting the surface wettability of the groove inner wall and the cross sectional angle of the groove. Experiments and analyses show that a droplet in a superhydrophobic groove translates from the immersed state to the suspended state as the cross sectional angle of the groove decreases and the suspended droplet departs from the groove bottom as the droplet volume increases. We also demonstrate that this simple grooved structure can be used to separate a water-oil mixture and generate droplets with the desired sizes. The structural effect actuated droplet movements provide a controllable droplet transport method which can be used in a wide range of droplet manipulation applications.
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http://dx.doi.org/10.1038/srep18836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705533PMC
January 2016

Performance qualification of a new hypromellose capsule: Part II. Disintegration and dissolution comparison between two types of hypromellose capsules.

Int J Pharm 2011 Sep 26;416(1):16-24. Epub 2011 Feb 26.

Pharmaceutical Development, Wyeth Research, Pearl River, NY 10965, USA.

This Part II paper describes the disintegration and dissolution aspects of the qualification of a new hypromellose capsule (HPMC Shell 2). This new capsule does not contain any gelling agent, and is manufactured by a thermal gelation process. Rupture time of the carrageenan-containing capsule (HPMC Shell 1) and HPMC Shell 2, as measured by an improved real-time detection method, showed only slight differences that did not manifest in vivo. The absence of a gelling agent appeared to give HPMC Shell 2 advantages in dissolution in acidic media and in buffers containing potassium ions. Slow drug release of HPMC Shell 1 in 0.1M HCl was attributed to the interaction of carrageenan with drug compounds; whereas the presence of potassium ions, a gelling promoter for carrageenan, caused delay in capsule opening and larger capsule-to-capsule variation. Disintegration and dissolution performances of both hypromellose capsules are comparable in other dissolution media tested. Based on the superior dissolution performances and quality attributes in terms of physical, mechanical and processability that were detailed in Paper I, the new hypromellose capsule was satisfactorily qualified and has since been used in nearly 20 investigational new drug (IND) compounds.
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http://dx.doi.org/10.1016/j.ijpharm.2011.02.048DOI Listing
September 2011

Serum thymidine kinase 1 correlates to clinical stages and clinical reactions and monitors the outcome of therapy of 1,247 cancer patients in routine clinical settings.

Int J Clin Oncol 2010 Aug 1;15(4):359-68. Epub 2010 Apr 1.

Laboratory of Biochemistry and Molecular Biology Research, Fujian Cancer Hospital of Fujian Medical University Teaching Hospital, Fuzhou, Fujian 350014, China.

Background: Thymidine kinase 1 in serum (STK1) has been found to be a reliable proliferation marker in clinical trials. In this study, we examined the significance of STK1 in routine clinical settings.

Methods: The concentration of STK1 was determined by a sensitive dot blot ECL assay. The STK1 value was correlated to clinical stage and reactions and used for monitoring the outcome of surgery and/or multidrug chemotherapy of 1,247 patients with five different types of carcinomas (lung, esophagus, gastric, head and neck, and thyroid) in routine clinical settings.

Results: The STK1 values correlated with the clinical stage in patients with lung, esophagus, thyroid, and gastric carcinomas. After treatment, STK1 declined in all tumor groups after treatments (P < 0.01). The STK1 was low (<2 pM) or decreasing during treatment in patients with clinical reactions of complete response (CR) or partial response (PR), but high (>2 pM) or increasing in patients with stable disease (SD) or progressive disease (PD), some of them showing metastasis. STK1 also reflected the differences in clinical reactions when surgery and chemotherapy were compared.

Conclusion: We concluded that the concentration of TK1 in serum correlates to clinical stages and clinical reactions and monitors the effect of tumor therapies, not only in controlled clinical trials, but also in routine clinical settings.
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http://dx.doi.org/10.1007/s10147-010-0067-4DOI Listing
August 2010