Publications by authors named "Zhiyang Wu"

10 Publications

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Protectin D1 decreases pancreatitis severity in mice by inhibiting neutrophil extracellular trap formation.

Int Immunopharmacol 2021 Feb 24;94:107486. Epub 2021 Feb 24.

Department of Critical Care Medicine, PLA Key Laboratory of Emergency and Critical Care Research, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China. Electronic address:

Background: Docosahexaenoic acid-derived protectin D1 (PD1) was identified critical in the resolution of inflammation in vivo, where it modulates the innate immune response and stimulates resolution. Acute pancreatitis (AP) is characterized by local pancreatic inflammation with mild forms whereas systemic inflammation with severe forms. Herein we investigate the impact of PD1 in murine models of pancreatitis.

Methods: Three independent AP models, which induced in male mice via intraperitoneal injection of caerulein, L-arginine or pancreatic duct ligation, were used to confirm the protective effect of PD1. Infiltrationsof neutrophils and macrophages in pancreas were detected by flow cytometry and immunohistochemistry. In vitro and in vivo neutrophil extracellular traps formation was detected by immunofluorescence staining. Expression of peptidylarginine deiminase 4 (PAD4) in activated neutrophils was evaluated by western blotting.

Results: Systemic treatment with PD1 reduced serum activities of amylase and lipase, blunted the concentrations of tumor necrosis factor-α and interleukin-6 in serum and protected against pancreas histologic damage in three AP models. PD1 also prolonged the survival in the pancreatic duct ligation model. Moreover, pancreatic infiltrationofneutrophils and neutrophil CitH3 expression were reduced after PD1 administration. In vitro studies revealed PD1 decreased supernatant cell-free DNA and CitH3 levels and downregulated PAD4 expression in mouse bone-marrow derived neutrophils. However, in the caerulein mice pretreated with GSK484 hydrochloride, an inhibitor of PAD4, PD1 treatment showed no more protective effect.

Conclusions: PD1 ameliorates AP by decreasing early infiltration of neutrophils into the pancreas and neutrophil extracellular traps formation through PAD4. These results supply the foundation to consider PD1 as a therapy for AP.
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http://dx.doi.org/10.1016/j.intimp.2021.107486DOI Listing
February 2021

Vagus Nerve Stimulation Decreases Pancreatitis Severity in Mice.

Front Immunol 2020 14;11:595957. Epub 2021 Jan 14.

Department of Critical Care Medicine, Research Institute of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Background: Vagus nerve stimulation (VNS) is effective in reducing inflammation in various diseases, such as rheumatoid arthritis, colitis and acute kidney injury. The anti-inflammatory effect of vagus nerve in these diseases necessitates the interactions of neural activation and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. In this study, we aimed to investigate the effect of VNS on severity in experimental acute pancreatitis (AP).

Methods: Two independent AP models were used, which induced in ICR mice with caerulein or pancreatic duct ligation (PDL). Thirty minutes after modeling, the left cervical carotid sheath containing the vagus nerve was electrically stimulated for 2 min. Plasma lipase and amylase activities, TNF-α levels and pancreas histologic damage were evaluated. In caerulein mice, the percentages of α7nAChR macrophage in pancreas and spleen were assessed by flow cytometry. Furthermore, splenectomy and adoptive transfer of VNS-conditioned α7nAChR splenocytes were performed in caerulein mice to evaluate the role of spleen in the protective effect of VNS.

Results: VNS reduced plasma lipase and amylase activities, blunted the concentrations of TNF-α and protected against pancreas histologic damage in two AP models. Survival rates were improved in the PDL model after VNS. In caerulein AP mice, VNS increased the percentages of α7nAChR macrophages in pancreas and spleen. Adoptive transfer of VNS-treated α7nAChR splenocytes provided protection against pancreatitis in recipient mice. However, splenectomy did not abolish the protective effect of VNS.

Conclusions: VNS reduces disease severity and attenuates inflammation in AP mice. This effect is independent of spleen and is probably related to α7nAChR on macrophage.
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http://dx.doi.org/10.3389/fimmu.2020.595957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840568PMC
January 2021

Discovery of Prognostic Markers for Early-Stage High-Grade Serous Ovarian Cancer by Maldi-Imaging.

Cancers (Basel) 2020 Jul 22;12(8). Epub 2020 Jul 22.

Tumorbank Ovarian Cancer Network, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.

With regard to relapse and survival, early-stage high-grade serous ovarian (HGSOC) patients comprise a heterogeneous group and there is no clear consensus on first-line treatment. Currently, no prognostic markers are available for risk assessment by standard targeted immunohistochemistry and novel approaches are urgently required. Here, we applied MALDI-imaging mass spectrometry (MALDI-IMS), a new method to identify distinct mass profiles including protein signatures on paraffin-embedded tissue sections. In search of prognostic biomarker candidates, we compared proteomic profiles of primary tumor sections from early-stage HGSOC patients with either recurrent (RD) or non-recurrent disease (N = 4; each group) as a proof of concept study. In total, MALDI-IMS analysis resulted in 7537 spectra from the malignant tumor areas. Using receiver operating characteristic (ROC) analysis, 151 peptides were able to discriminate between patients with RD and non-RD (AUC > 0.6 or < 0.4; < 0.01), and 13 of them could be annotated to proteins. Strongest expression levels of specific peptides linked to Keratin type1 and Collagen alpha-2(I) were observed and associated with poor prognosis (AUC > 0.7). These results confirm that in using IMS, we could identify new candidates to predict clinical outcome and treatment extent for patients with early-stage HGSOC.
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http://dx.doi.org/10.3390/cancers12082000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463791PMC
July 2020

Genome-Wide Identification, Evolutionary Patterns, and Expression Analysis of Gene Family in Olive ( L.).

Genes (Basel) 2020 05 5;11(5). Epub 2020 May 5.

Department of Bioresource Chemistry, College of Science, Sichuan Agricultural University, Ya'an 625000, China.

Olive (.L) is an economically important oleaginous crop and its fruit cold-pressed oil is used for edible oil all over the world. The basic region-leucine zipper () family is one of the largest transcription factors families among eukaryotic organisms; its members play vital roles in environmental signaling, stress response, plant growth, seed maturation, and fruit development. However, a comprehensive report on the gene family in olive is lacking. In this study, 103 genes from the olive genome were identified and divided into 12 subfamilies according to their genetic relationship with 78 bZIPs of . Most genes are clustered in the subgroup that has a similar gene structure and conserved motif distribution. According to the characteristics of the leucine zipper region, the dimerization characteristics of 103 OebZIP proteins were predicted. Gene duplication analyses revealed that 22 genes were involved in the expansion of the family. To evaluate the expression patterns of genes, RNA-seq data available in public databases were analyzed. The highly expressed genes and several lipid synthesis genes () in fruits of two varieties with different oil contents during the fast oil accumulation stage were examined via qRT-PCR. By comparing the dynamic changes of oil accumulation, , , , and were shown to have a close relationship with fruit development and lipid synthesis. Additionally, some had a significant positive correlation with various genes. This study gives insights into the structural features, evolutionary patterns, and expression analysis, laying a foundation to further reveal the function of the 103 genes in olive.
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http://dx.doi.org/10.3390/genes11050510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288668PMC
May 2020

MALDI-Imaging for Classification of Epithelial Ovarian Cancer Histotypes from a Tissue Microarray Using Machine Learning Methods.

Proteomics Clin Appl 2019 01 14;13(1):e1700181. Epub 2018 Dec 14.

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.

Purpose: Precise histological classification of epithelial ovarian cancer (EOC) has immanent diagnostic and therapeutic consequences, but remains challenging in histological routine. The aim of this pilot study is to examine the potential of matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry in combination with machine learning methods to classify EOC histological subtypes from tissue microarray.

Experimental Design: Formalin-fixed-paraffin-embedded tissue of 20 patients with ovarian clear-cell, 14 low-grade serous, 19 high-grade serous ovarian carcinomas, and 14 serous borderline tumors are analyzed using MALDI-Imaging. Classifications are computed by linear discriminant analysis (LDA), support vector machines with linear (SVM-lin) and radial basis function kernels (SVM-rbf), a neural network (NN), and a convolutional neural network (CNN).

Results: MALDI-Imaging and machine learning methods result in classification of EOC histotypes with mean accuracy of 80% for LDA, 80% SVM-lin, 74% SVM-rbf, 83% NN, and 85% CNN. Based on sensitivity (69-100%) and specificity (90-99%), CCN and NN are most suited to EOC classification.

Conclusion And Clinical Relevance: The pilot study demonstrates the potential of MALDI-Imaging derived proteomic classifiers in combination with machine learning algorithms to discriminate EOC histotypes. Applications may support the development of new prognostic parameters in the assessment of EOC.
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http://dx.doi.org/10.1002/prca.201700181DOI Listing
January 2019

Position-deviation-compensation demodulation method for multi-channel polarized low-coherence interferometry.

Opt Express 2018 Jun;26(13):17407-17417

A position-deviation-compensation demodulation method is proposed to improve the channel adaptability of Fabry-Perot (F-P) sensor in a multi-channel optical fiber F-P sensing system. By combining the envelope peak position (EPP) retrieval process and the position compensation process, the proposed method enables the accurate demodulation of F-P sensors in all channels. Thereinto, the EPP retrieval process uses the phase information to recover the EPP with high precision; the position compensation process compensates the position deviation by an optical-path-based model, which is established to illustrate the principle of the position deviation between different channels. We carried out the pressure experiment to verify the effectiveness of the proposed method. The experiment results showed that the demodulation errors of all channels are no more than 0.13 kPa, which demonstrated that our approach is reliable for improving the channel adaptability of F-P sensors.
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http://dx.doi.org/10.1364/OE.26.017407DOI Listing
June 2018

The regulatory effects of metformin on the [SNAIL/miR-34]:[ZEB/miR-200] system in the epithelial-mesenchymal transition(EMT) for colorectal cancer(CRC).

Eur J Pharmacol 2018 Sep 11;834:45-53. Epub 2018 Jul 11.

Cancer Center, Shandong University Qilu Hospital, West Wenhua Road 107, Jinan 250012, Shandong Province, PR China. Electronic address:

The epithelial-mesenchymal transition (EMT) plays a critical role in cancer progression, metastasis and drug resistance. The transcription factor(TF) and microRNA (miR) chimeric [SNAIL/miR-34]:[ZEB/miR-200] unit is the core regulatory system for the EMT process. Here, we proposed to assess the anti-EMT abilities and explore the inherent pharmacological mechanisms of the classic hypoglycaemic agent metformin for colorectal cancer(CRC). For the EMT model, the TGF-β-induced CRC cell lines SW480 and HCT116 were treated with metformin. The viability, migration and invasion abilities of the cells were evaluated with the Cell Counting Kit-8, wound-healing and trans-well assay. The alterations of the [SNAIL/miR-34]:[ZEB/miR-200] system and the EMT markers E-cadherin and vimentin were detected by western blot, qPCR and immunofluorescent staining. Metformin exhibited inhibitory effects on the proliferation, migration and invasion of the CRC SW480 cells. The up-regulation of E-cadherin and the down-regulation of vimentin for both SW480 and HCT116 cells revealed the anti-EMT abilities of metformin. For the [SNAIL/miR-34]:[ZEB/miR-200] system, metformin increased miR-200a, miR-200c and miR-429 levels and decreased miR-34a, SNAIL1 and ZEB1 levels in the TGF-β-induced EMT. From immunofluorescence, we observed increased E-cadherin and ZEB1 co-expression in metformin-treated cells. Metformin may perform bidirectional regulations of the [SNAIL/miR-34]:[ZEB/miR-200] system in the EMT process for colorectal cancer. Such regulation is expressed as the inhibition of EMT in general as well as an increased higher proportion of E/M hybrid cells in the total population.
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http://dx.doi.org/10.1016/j.ejphar.2018.07.006DOI Listing
September 2018

Diversity of antibiotic resistance genes and encoding ribosomal protection proteins gene in livestock waste polluted environment.

J Environ Sci Health B 2018 22;53(7):423-433. Epub 2018 Feb 22.

a College of Resource and Environment, Northeast Agricultural University , Harbin , Heilongjiang , PR China.

The rapid development and increase of antibiotic resistance are global phenomena resulting from the extensive use of antibiotics in human clinics and animal feeding operations. Antibiotics can promote the occurrence of antibiotic resistance genes (ARGs), which can be transferred horizontally to humans and animals through water and the food chain. In this study, the presence and abundance of ARGs in livestock waste was monitored by quantitative PCR. A diverse set of bacteria and tetracycline resistance genes encoding ribosomal protection proteins (RPPs) from three livestock farms and a river were analyzed through denaturing gradient gel electrophoresis (DGGE). The abundance of sul(I) was 10 to 10 orders of magnitude higher than that of sul(II). Among 11 tet-ARGs, the most abundant was tet(O). The results regarding bacterial diversity indicated that the presence of antibiotics might have an evident impact on bacterial diversity at every site, particularly at the investigated swine producer. The effect of livestock waste on the bacterial diversity of soil was stronger than that of water. Furthermore, a sequencing analysis showed that tet(M) exhibited two genotypes, while the other RPPs-encoding genes exhibited at least three genotypes. This study showed that various ARGs and RPPs-encoding genes are particularly widespread among livestock.
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http://dx.doi.org/10.1080/03601234.2018.1438836DOI Listing
November 2018

Epithelial-Mesenchymal Transition Phenotype, Metformin, and Survival for Colorectal Cancer Patients with Diabetes Mellitus II.

Gastroenterol Res Pract 2017 28;2017:2520581. Epub 2017 Jun 28.

Cancer Center, Shandong University Qilu Hospital, West Wenhua Road 107, Jinan, Shandong Province 250012, China.

Objectives: We aimed to explore the association between metformin treatment and epithelial-mesenchymal transition (EMT) phenotype and further appraise the prognostic values of metformin and EMT markers E-cadherin and vimentin for colorectal cancer (CRC) in clinical practice.

Methods: We collected specimens and evaluated clinicopathological parameters of 102 stage I to III CRC patients with prediagnosed type 2 diabetes mellitus (DM II). Expression of E-cadherin and vimentin in tumors was detected by immunohistochemistry (IHC), and statistical analysis was performed using SPSS 19.0.

Results: In correlation tests, we found a lower tumor cell EMT degree (more E-cadherin ( = 0.014) and less vimentin ( = 0.011) expression in patients who used metformin, and the expression of E-cadherin and vimentin was associated with serum CA19-9 ( = 0.048, = 0.009), tumor invasive depth (T) ( < 0.001, = 0.045), and lymph invasion (N) ( = 0.013, = 0.001). In Cox multivariate regression analysis, E-cadherin was identified as a prognostic factor for disease-free survival (DFS) ( = 0.038) and metformin use ( = 0.015 = 0.044) and lymph invasion ( = 0.016 = 0.023) were considered as the prognostic factors for both DFS and overall survival (OS).

Conclusion: Our study suggested that metformin may impede the EMT process and improve survival for stage I-III CRC patients with DM II.
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http://dx.doi.org/10.1155/2017/2520581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5506476PMC
June 2017

Properties of an LNA-modified ricin RNA aptamer.

Biochem Biophys Res Commun 2012 Mar 3;419(1):60-5. Epub 2012 Feb 3.

Institut für Chemie und Biochemie, Freie Universität Berlin, Thielallee 63, 14195 Berlin, Germany.

'Locked nucleic acids' (LNAs) are sugar modified nucleic acids containing the 2'-O-4'C-methylene-β-D-ribofuranoses. The substitution of RNAs with LNAs leads to an enhanced thermostability. Aptamers are nucleic acids, which are selected for specific target binding from a large library pool by the 'SELEX' method. Introduction of modified nucleic acids into aptamers can improve their stability. The stem region of a ricin A chain RNA aptamer was substituted by locked nucleic acids. Different constructs of the LNA-substituted aptamers were examined for their thermostability, binding activity, folding and RNase sensitivity as compared to the natural RNA counterpart. The LNA-modified aptamers were active in target binding, while the loop regions and the adjacent stem nucleotides remained unsubstituted. The thermostability and RNase resistance of LNA substituted aptamers were enhanced as compared to the native RNA aptamer. This study supports the approach to substitute the aptamer stem region by LNAs and to leave the loop region unmodified, which is responsible for ligand binding. Thus, LNAs possess an encouraging potential for the development of new stabilized nucleic acids and will promote future diagnostic and therapeutic applications.
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http://dx.doi.org/10.1016/j.bbrc.2012.01.127DOI Listing
March 2012