Publications by authors named "Zhenguo Zeng"

22 Publications

  • Page 1 of 1

Isoalantolactone inhibits pancreatic cancer proliferation by regulation of PI3K and Wnt signal pathway.

PLoS One 2021 4;16(3):e0247752. Epub 2021 Mar 4.

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.

Background/aims: Isoalantolactone (IATL) is one of multiple isomeric sesquiterpene lactones and is isolated from inula helenium. IATL has multiple functions such as antibacterial, antihelminthic and antiproliferative activities. IATL also inhibits pancreatic cancer proliferation and induces apoptosis by increasing ROS production. However, the detailed mechanism of IATL-mediated pancreatic cancer apoptosis remains largely unknown.

Methods: In current study, pancreatic carcinoma cell lines (PANC-1, AsPC-1, BxPC-3) and a mouse xenograft model were used to determine the mechanism of IATL-mediated toxic effects.

Results: IATL (20μM) inhibited pancreatic adenocarcinoma cell lines proliferation in a time-dependent way; while scratch assay showed that IATL significantly inhibited PANC-1 scratch closure (P<0.05); Invasion assays indicated that IATL significantly attenuated pancreatic adenocarcinoma cell lines invasion on matrigel. Signal analysis showed that IATL inhibited pancreatic adenocarcinoma cell proliferation by blocking EGF-PI3K-Skp2-Akt signal axis. Moreover, IATL induced pancreatic adenocarcinoma cell apoptosis by increasing cytosolic Caspase3 and Box expression. This apoptosis was mediated by inhibition of canonical wnt signal pathway. Finally, xenograft studies showed that IATL also significantly inhibited pancreatic adenocarcinoma cell proliferation and induced pancreatic adenocarcinoma cell apoptosis in vivo.

Conclusions: IATL inhibits pancreatic cancer proliferation and induces apoptosis on cellular and in vivo models. Signal pathway studies reveal that EGF-PI3K-Skp2-Akt signal axis and canonical wnt pathway are involved in IATL-mediated cellular proliferation inhibition and apoptosis. These studies indicate that IATL may provide a future potential therapy for pancreatic cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247752PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932101PMC
March 2021

Systematic construction and validation of an epithelial-mesenchymal transition risk model to predict prognosis of lung adenocarcinoma.

Aging (Albany NY) 2020 12 3;13(1):794-812. Epub 2020 Dec 3.

Department of Critical Care Medicine, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.

Epithelial-mesenchymal transition (EMT) has been shown to be linked to a poor prognosis, particularly in patients with non-small-cell lung cancer. Nevertheless, little is known regarding the existence of EMT-related gene signatures and their prognostic values in lung adenocarcinoma (LUAD). In the current study, we systematically profiled the mRNA expression data of patients with LUAD in The Cancer Genome Atlas and Gene Expression Omnibus databases using a total of 1,184 EMT-related genes. The prognostic values of the EMT-related genes used to develop risk score models for overall survival were determined using LASSO and Cox regression analyses. A prognostic signature that consisted of nine unique EMT-related genes was generated using a training set. A nomogram, incorporating this EMT-related gene signature and clinical features of patients with LUAD, was constructed for potential clinical use. Calibration plots, decision-making curves, and receiver operating characteristic curve analysis showed that this model had a good ability to predict the survival of patients with LUAD. The EMT-associated gene signature and prognostic nomogram established in this study were reliable in predicting the survival of patients with LUAD. Thus, we first identified a novel EMT-related gene signature and developed a nomogram for predicting the prognosis of patients with LUAD.
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http://dx.doi.org/10.18632/aging.202186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835007PMC
December 2020

Autophagy alleviates mitochondrial DAMP-induced acute lung injury by inhibiting NLRP3 inflammasome.

Life Sci 2021 Jan 1;265:118833. Epub 2020 Dec 1.

Department of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. Electronic address:

Aim: Acute lung injury (ALI) is characterized by alveolar macrophage overactivation and uncontrolled pulmonary inflammation. Mitochondrial damage-associated molecular patterns (MTDs), one type of damage-associated molecular patterns (DAMPs) released from ruptured mitochondrial, can induce inflammation which participates in the pathogenesis of ALI. Despite the critical role of autophagy in inflammatory response, little is known about its function in MTDs-induced ALI. Herein we have studied how autophagy attenuates MTDs-induced ALI in vitro and in vivo.

Main Methods: Exogenous MTDs were injected into mice through tail vein injection or directly treated with cultured alveolar macrophage cell lines to construct MTDs-induced ALI models. Rapamycin and 3-MA were used to regulate autophagy in vivo and in vitro. The expressions of Caspase-1, IL-1β, and their precursor were measured. Inhibition the activation of NLRP3 inflammasome to discover the candidate targets and potential molecular pathways involved in autophagy mitigating the MTDs-induced ALI.

Key Findings: After treatment with MTDs the expression levels of inflammatory cytokines and NLRP3 inflammasome-associated proteins were gradually increased in vitro and in vivo. Most importantly, with autophagy enhanced by rapamycin, all the secretion of inflammation cytokine, the level of lung injury, and the expression level of NLRP3 inflammasome-associated proteins were greatly decreased in MTDs-induced mouse model. MTDs-induced inflammation and lung injury were alleviated by autophagy enhancement. Autophagy can function as an effective way to alleviate inflammation in MTDs-induced ALI by inhibiting NLRP3 inflammasome and may represent a therapeutic target in modulating MTDs-induced inflammatory response.
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http://dx.doi.org/10.1016/j.lfs.2020.118833DOI Listing
January 2021

Development and validation of a nomogram with an epigenetic signature for predicting survival in patients with lung adenocarcinoma.

Aging (Albany NY) 2020 11 18;12(22):23200-23216. Epub 2020 Nov 18.

Department of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.

Epigenetic factors play crucial roles in carcinogenesis by modifying chromatin architecture. Here, we established an epigenetic biosignature-based model for examining survival in patients with lung adenocarcinoma (LUAD). We retrieved gene-expression profiles and clinical data from The Cancer Genome Atlas and Gene Expression Omnibus and clustered the data into training ( = 490) and Validation ( = 226) datasets, respectively. To establish an epigenetic model, we identified prognostic epigenetic regulation-related genes by LASSO and Cox regression analyses, and established a novel 11-gene signature, including and , for predicting LUAD overall survival (OS). The biosignature performed optimally in both the training and validation sets according to receiver operating characteristic and calibration plots. Moreover, the biosignature classified patients into high- and low-risk clusters with distinct survival times, with Cox regression analysis revealing the biosignature as an independent LUAD prognostic index. Furthermore, the generated nomogram integrating the prognostic gene biosignature and clinical indices predicted LUAD OS with high efficiency and outperformed tumor-node-metastasis staging in LUAD survival prediction. These results demonstrated the efficacy of the epigenetic signature prognostic nomogram for reliably predicting LUAD OS and its potential application for informing clinical decision making and individualized treatment.
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http://dx.doi.org/10.18632/aging.104090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746339PMC
November 2020

Cigarette Smoke and Nicotine-Containing Electronic-Cigarette Vapor Downregulate Lung WWOX Expression, Which Is Associated with Increased Severity of Murine Acute Respiratory Distress Syndrome.

Am J Respir Cell Mol Biol 2021 01;64(1):89-99

Division of Pulmonary, Critical Care, Sleep and Allergy Medicine, University of Illinois, Chicago, Illinois.

A history of chronic cigarette smoking is known to increase risk for acute respiratory distress syndrome (ARDS), but the corresponding risks associated with chronic e-cigarette use are largely unknown. The chromosomal fragile site gene, WWOX, is highly susceptible to genotoxic stress from environmental exposures and thus an interesting candidate gene for the study of exposure-related lung disease. Lungs harvested from current versus former/never-smokers exhibited a 47% decrease in WWOX mRNA levels. Exposure to nicotine-containing e-cigarette vapor resulted in an average 57% decrease in WWOX mRNA levels relative to vehicle-treated controls. In separate studies, endothelial (EC)-specific WWOX knockout (KO) versus WWOX flox control mice were examined under ARDS-producing conditions. EC WWOX KO mice exhibited significantly greater levels of vascular leak and histologic lung injury. ECs were isolated from digested lungs of untreated EC WWOX KO mice using sorting by flow cytometry for CD31 CD45cells. These were grown in culture, confirmed to be WWOX deficient by RT-PCR and Western blotting, and analyzed by electric cell impedance sensing as well as an FITC dextran transwell assay for their barrier properties during methicillin-resistant or LPS exposure. WWOX KO ECs demonstrated significantly greater declines in barrier function relative to cells from WWOX flox controls during either methicillin-resistant or LPS treatment as measured by both electric cell impedance sensing and the transwell assay. The increased risk for ARDS observed in chronic smokers may be mechanistically linked, at least in part, to lung WWOX downregulation, and this phenomenon may also manifest in the near future in chronic users of e-cigarettes.
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http://dx.doi.org/10.1165/rcmb.2020-0145OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780991PMC
January 2021

A novel risk score based on a combined signature of 10 immune system genes to predict bladder cancer prognosis.

Int Immunopharmacol 2020 Oct 5;87:106851. Epub 2020 Aug 5.

Department of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China. Electronic address:

Bladder cancer (BC) is a common internal malignant tumor with a poor prognosis worldwide. There is an urgent need to better understand the pathogenesis and progression of BC and to find useful biomarkers for diagnosis and prognosis. This study was aimed at developing a potential immunogenomic prognostic signature for BC patients. To identify possible immune-system-related genes (IRGs) whose parameters predict the survival of BC patients, we chose 371 BC patients and analyzed differentially expressed IRGs from The Cancer Genome Atlas (TCGA) datasets. We then derived a 10-IRG formula, including MMP9, RBP7, PDGFRA, AHNAK, OAS1, OLR1, RAC3, SLIT2, IGF1, and AGTR1, to estimate BC prognosis. To validate the mRNA levels of these IRGs, we performed quantitative PCR and found that the expression of these genes almost matched the corresponding mRNA expression levels in TCGA. Furthermore, we validated the prognostic value of the new risk model using two external datasets from Gene Expression Omnibus: GSE13507 (n = 165) and GSE32894 (n = 224). Our data pointed to a significant correlation between the risk model and patients' prognosis. Bioinformatic analysis revealed that products of the IRGs have possible effects on tumor immune processes such as an inflammatory response and cytokine-cytokine receptor interaction. Finally, assessment of the clinical value of the immune-system-based risk signature showed that several of these IRGs were differentially expressed between patients with different clinical characteristics: a high risk score positively correlated with female sex, advanced tumor stage, more advanced T stage, and lymph node metastasis. This immunogenomic signature may represents a reliable prognostic tool for BC and can help to design an individualized immunotherapy.
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http://dx.doi.org/10.1016/j.intimp.2020.106851DOI Listing
October 2020

Gene expression and prognosis of sirtuin family members in ovarian cancer.

Medicine (Baltimore) 2020 Jun;99(24):e20685

Department of Endocrinology and Metabolism.

Sirtuins (SIRTs), a class of nicotinamide-adenine dinucleotide (NAD)+-dependent deacetylases, involve in modulating carcinogenesis and progression of various malignancies through their regulation of the cancer metabolism. However, the expression profiles and prognostic roles of SIRTs in ovarian cancer (OC) remain unclear. We underscore the transcriptional expression and prognostic significance of SIRTs in OC patients using online databases. Gene Expression Profiling Interactive analysis (GEPIA) was applied to analyze mRNA expression, and Kaplan-Meier plotter was used to evaluate prognostic value. In patients with OC, SIRT1/2/3 were significantly down-regulated, while rest of SIRTs were not significantly changed. High SIRT2/5/6/7 expression was correlated with favorable overall survival (OS), while high SIRT1/4 expression was correlated with poor OS. Additionally, aberrant SIRTs mRNA levels were related to the prognosis of OC patients with different clinicopathological characteristics. This is the first study to integrate bioinformatics approaches intended to identify the expression profiles and prognostic value of SIRTs in OC. These results suggest that SIRTs is related to the prognosis of OC and may be the potential therapeutic interventions in OC.
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http://dx.doi.org/10.1097/MD.0000000000020685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302638PMC
June 2020

DNA Methylation-based Diagnostic and Prognostic Biomarkers for Glioblastoma.

Cell Transplant 2020 Jan-Dec;29:963689720933241

Department of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Jiangxi, China.

Glioblastomas are the most common primary central nervous system malignancy tumor in adults. Glioblastoma patients have poor prognosis, with an average survival period of approximately 14 mo after diagnosis. To date, there are a limited number of effective treatment methods for glioblastoma, and its molecular mechanisms remain elusive. In this article, we analyzed the key biomarkers and pathways in glioblastoma patients based on gene expression and DNA methylation datasets. The 60 hypomethylated/upregulated genes and 110 hypermethylated/downregulated genes were identified in GSE50923, GSE50161, and GSE116520 microarrays. Functional enrichment analyses indicated that these methylated-differentially expressed genes were primarily involved in collagen fibril organization, chemical synaptic transmission, extracellular matrix-receptor interaction, and GABAergic synapse. The hub genes were screened from a protein-protein interaction network; in selected genes, increased NMB mRNA level was associated with favorable overall survival, while elevated CHI3L1, POSTN, S100A4, LOX, S100A11, IGFBP2, SLC12A5, VSNL1, and RGS4 mRNA levels were associated with poor overall survival in glioblastoma patients. Additionally, CHI3L1, S100A4, LOX, and S100A11 expressions were negatively correlated with their corresponding methylation status. Furthermore, the receiver-operator characteristic curve analysis indicated that CHI3L1, S100A4, LOX, and S100A11 can also serve as highly specific and sensitive diagnostic biomarkers for glioblastoma patients. Collectively, our study revealed the possible methylated-differentially expressed genes and associated pathways in glioblastoma and identified four DNA methylation-based biomarkers of glioblastoma. These results may provide insight on diagnostic and prognostic biomarkers, and therapeutic targets in glioblastoma.
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http://dx.doi.org/10.1177/0963689720933241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563836PMC
June 2021

Combined signature of nine immune-related genes: a novel risk score for predicting prognosis in hepatocellular carcinoma.

Am J Transl Res 2020 15;12(4):1184-1202. Epub 2020 Apr 15.

Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanchang University Nanchang, Jiangxi, People's Republic of China.

Hepatocellular carcinoma (HCC) is one of the most common internal malignancies worldwide and is associated with a poor prognosis. There is an urgent need to identify diagnostic and prognostic biomarkers of HCC pathogenesis and progression. Accordingly, in this study, we analyzed differentially expressed immune-related genes (IRGs) from 329 patients with HCC from The Cancer Genome Atlas datasets. Functional analysis revealed that the IRGs had potential effects on tumor immune processes, such as inflammatory responses and growth factor activity. In the training group, we constructed a nine-IRG formula to predict prognosis in patients with HCC. To validate the protein and mRNA levels of these IRGs, we used the Human Protein Atlas database and quantitative PCR analysis and found that most protein expression levels matched the corresponding mRNA expression levels. Furthermore, we also validated the prognostic value of the new risk model in another independent cohort (n = 277) from a Gene Expression Omnibus dataset (GSE14520). Our data suggested that there was a significant association between our risk model and patient prognosis. Stratification analysis showed that the nine-IRG signature was significantly associated with overall survival in men. Finally, the signature was found to be correlated with various clinicopathological features. Intriguingly, the prognostic index based on the IRGs reflected infiltration by several types of immune cells. In summary, our data provided evidence that the nine-IRG signature could serve as an independent biomarker to predict prognosis in patients with HCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191166PMC
April 2020

Distinct expression and prognostic value of members of SMAD family in non-small cell lung cancer.

Medicine (Baltimore) 2020 03;99(10):e19451

Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.

Non-small cell lung cancer (NSCLC) is the major cause of cancer mortality worldwide. Though multidisciplinary therapies have been widely used for NSCLC, its overall prognosis remains very poor, presumably owing to lack of effective prognostic biomarkers. SMAD, a well-known transcription factor, plays an essential role in carcinogenesis. Aberrant expression of SMAD have been found in various cancers, and may be regarded as prognostic indicator for some malignancies. However, the expression and prognostic role of SMAD family member, especially at the mRNA level, remain elusive in NSCLC. In the present study, we report the distinct expression and prognostic value of individual SMAD in patients with NSCLC by analyzing several online databases including ONCOMINE, Gene Expression Profiling Interactive Analysis, Human Protein Atlas database, Kaplan-Meier plotter, cBioPortal, and Database for Annotation, Visualization and Integrated Discovery. The mRNA levels of SMAD6/7/9 in NSCLC were significantly down-regulated in NSCLC, and aberrant SMAD2/3/4/5/6/7/9 mRNA levels were all correlated with the prognosis of NSCLC. Collectively, SMAD2/3/4/5/6/7/9 may server as prognostic biomarkers and potential targets for NSCLC, and thus facilitate the customized treatment strategies for NSCLC patients.
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http://dx.doi.org/10.1097/MD.0000000000019451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220383PMC
March 2020

High-Flow Oxygen Therapy to Speed Weaning From Mechanical Ventilation: A Prospective Randomized Study.

Am J Crit Care 2019 09;28(5):370-376

Fen Liu, Zhenguo Zeng, Chengzhi Ding, and Ning Zhao are physicians, Rong Jiang is matron, and Kejian Qian is director, Department of Critical Care Medicine, First Affiliated Hospital of Nanchang University, Nanchang, China. Yang Liu is docimaster in the Department of Bacteriology, Yong Li is a physician in the Department of Oncology, and Qin Liu is a physician in the Department of Respirology, First Affiliated Hospital of Nanchang University. Qiang Shao is a doctoral candidate at Nanchang University and a physician in the Department of Critical Care Medicine at First Affiliated Hospital of Nanchang University. Zhiyong Peng is director, Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.

Background: High-flow oxygen therapy has been widely adopted, but its use for weaning patients from mechanical ventilation has not been reported.

Objective: To evaluate whether high-flow oxygen therapy improves the efficiency of weaning patients from mechanical ventilation.

Methods: In a single-center, prospective study, patients receiving mechanical ventilation were randomly assigned to 1 of 3 groups (T-tube, pressure support ventilation, or high-flow oxygen) during 2-hour spontaneous breathing trials in a 14-day study. Participants were followed up until hospital discharge or death.

Results: Of 268 patients included, 90 were assigned to the T-tube group, 96 to the pressure support ventilation group, and 82 to the high-flow oxygen group. The first-day 2-hour spontaneous breathing trial passing rates were higher in the pressure support ventilation and high-flow oxygen groups than in the T-tube group ( < .05). The time needed to pass the spontaneous breathing trial was less in the pressure support ventilation and high-flow oxygen groups than in the T-tube group ( < .05). The reintubation rate was lower and the successful weaning rate on the first day was higher in the high-flow oxygen group than in the T-tube and pressure support ventilation groups ( < .05). During the 14-day study period, the weaning time was less in the high-flow oxygen group than in the T-tube and pressure support ventilation groups ( < .05).

Conclusion: High-flow oxygen therapy can reduce the time needed to wean patients from mechanical ventilation by shortening the time needed to pass a spontaneous breathing trial and by decreasing the reintubation rate.
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http://dx.doi.org/10.4037/ajcc2019130DOI Listing
September 2019

Epigenetic regulation of histone H3 in the process of hepatocellular tumorigenesis.

Authors:
Dan Li Zhenguo Zeng

Biosci Rep 2019 08 2;39(8). Epub 2019 Aug 2.

Department of Critical Care Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China

Better understanding of epigenetic regulation of hepatocellular carcinoma (HCC) will help us to cure this most common malignant liver cancer worldwide. The underlying mechanisms of HCC tumorigenesis are genomic aberrations regulated by genetic and epigenetic modifications. Histone H3 lysine modifications regulate histone structure and modulate transcriptional factor binding with target gene promoters. Targetting genes include VASH2, fatty acids synthase, RIZ1, FBP1, MPP1/3, YAP, which affect tumorigenesis, metabolisms, angiogenesis, and metastasis. Signal pathway studies demonstrate that the HGF-MET-MLL axis, phosphatase and tensin homolog (PTEN)-PI3K-Akt axis; WNT-β-catenin signal pathway is involved in histone H3 modification. A variety of factors such as virus infection, reactive oxygen species, food-borne toxins, irradiation, or non-coding RNA cause hepatocellular DNA damage or modification. Dysfunctional DNA repair mechanisms, including those at the epigenetic level are also major causes of HCC tumorigenesis. The development of therapies based on epigenetic regulatory mechanisms has great potential to advance the care of HCC patients in the future.
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http://dx.doi.org/10.1042/BSR20191815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680372PMC
August 2019

Mitochondrial DNA plays an important role in lung injury induced by sepsis.

J Cell Biochem 2018 Dec 5. Epub 2018 Dec 5.

Department of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

The effects and mechanisms of mitochondrial DNA (mtDNA) in the development of sepsis-induced lung injury is not well understood. In our present study, we studied the mtDNA effects in sepsis-induced lung injury model, in vitro and in vivo. Compared with the Normal group, the lung histopathological score, the number of positive apoptosis cell, wet/dry (W/D) ratio and TNF-α, IL-1β, and IL-6 concentrations of lipopolysaccharides (LPSs) and mtDNA groups were significantly increased (P < 0.001, respectively). Meanwhile, the lung histopathological score, positive W/D ratio, number of apoptosis cell and tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 concentrations of LPS + mtDNA and small interfering RNA (siRNA)-NC + LPS + mtDNA groups were significantly upregulated compared with those of LPS group (P < 0.05, respectively). However, the lung histopathological score, the number of positive apoptosis cell, W/D ratio and TNF-α, IL-1β, and IL-6 concentrations were significantly improved within the toll-like receptor (TLR9)siRNA + LPS + mtDNA group compared with the LPS group (P < 0.01, respectively). The TLR9, MyD88, and NF-κB proteins or gene expressions of the LPS group and mtDNA group were significantly upregulated compared with those of Normal group by Western blot analysis or immunohistochemistry assay (P < 0.01, respectively), and the TLR9, MyD88, and NF-κB proteins or gene expressions of LPS + mtDNA and siRNA-NC + LPS + mtDNA groups were significantly enhanced compared with those of LPS group (P < 0.05, respectively). However, the TLR9, MyD88, and NF-κB proteins or gene expressions of TLR9siRNA + LPS + mtDNA group were significantly suppressed compared with those of the LPS group (P < 0.01, respectively). In conclusion, mtDNA could provoke lung injury induced by sepsis via regulation of TLR9/MyD88/NF-κB pathway in vitro and in vivo.
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http://dx.doi.org/10.1002/jcb.28142DOI Listing
December 2018

MiR-155 Alleviates Septic Lung Injury by Inducing Autophagy Via Inhibition of Transforming Growth Factor-β-Activated Binding Protein 2.

Shock 2017 07;48(1):61-68

*Department of Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China †Department of Bacteriology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China ‡Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China §Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China ||Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.

Background: The anti-inflammatory effect of miR-155 was closely linked to transforming growth factor-β-activated kinase-1-binding protein 2 (TAB2) and autophagy. This study investigated the role of miR-155 in attenuation of septic lung injury through TAB2 and autophagy in mouse model and in vitro.

Methods: Patients who underwent fiberoptic bronchoscope examination with or without septic lung injury were recruited for the collection of bronchoalveolar lavage fluid (BALF) samples. Mouse model of septic lung injury was established by cecal ligation puncture, while alveolar macrophage cell line was treated with lipopolysaccharide (LPS). Agomir miR-155 transfection into the mouse airways was performed to induce miR-155 expression, while miR-155 mimic, miR-155 inhibitor, or TAB2-siRNA was transfected into NR8383 macrophages. Mouse BALF and cell cytokine levels, lung tissue pathology and wet/dry ratio, numbers of autophagy bodies, miR-155, gene and protein expressions were also examined accordingly.

Results: Expression of miR-155 was increased in the BALF of septic lung injury patients, in mouse model and NR8383 macrophages after LPS treatment. Increased numbers of autophagy bodies were also observed in mouse and macrophage models. MiR-155-transfected mice showed alleviation of inflammation, lower water content in lung tissues, increased number of autophagy bodies, increased expression of microtubule-associated protein 1 light chain 3 (LC3 II/I), reduced expressions of cysteinyl aspartate-specific protease-1 (Caspase-1), and TAB2, and decreased cytokines levels. Similar results were obtained in macrophages after LPS treatment. Cells transfected with miR-155 inhibitor showed increased expression of TAB2 and Caspase-1, fewer autophagy bodies, lower LC3 II/I expression, and higher cytokine levels.

Conclusion: The current study observed a higher level of miR-155 in the BALF from sepsis patients with acute respiratory distress syndrome and demonstrated that miR-155 alleviated inflammation in septic lung injury in mouse and cell models by inducing autophagy via inhibition of TAB2.
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http://dx.doi.org/10.1097/SHK.0000000000000839DOI Listing
July 2017

[Anti-inflammatory effect of acetylcholine on lipopolysaccharide induced inflammatory response of alveolar macrophages].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2015 Oct;27(10):811-5

Objective: To observe the effect of acetylcholine (ACh) on lipopolysaccharide (LPS) induced inflammatory model of rat alveolar macrophages, and to observe the effect of the acetylcholinesterase inhibitor physostigmine (Phy) on the anti-inflammatory effect of ACh.

Methods: The rat alveolar macrophages NR8383 were cultured in vitro, which were divided into five groups: blank control group, LPS group (stimulated with 1 mg/L LPS for 12 hours), LPS + ACh group (0.01, 0.1, 1, 10, 100 μmol/L of ACh were added for 5 minutes before LPS stimulation), LPS + Phy group (1 mmol/L Phy was added for 5 minutes before LPS stimulation), and LPS + ACh + Phy group (1 mmol/L Phy and 10 μmol/L ACh were added for 5 minutes before LPS stimulation). The supernatants were collected in each group, the enzyme-linked immunosorbent assay (ELISA) was used to assay the contents of tumor necrosis factor-α (TNF-α), interleukins (IL-1β, and IL-6). The activity of acetylcholine esterase (AChE ) in the supernatant was also determined.

Results: (1) The contents of TNF-α (ng/L: 605.09 ± 57.13 vs. 34.07 ± 8.62), IL-1β (ng/L: 377.09 ± 28.55 vs. 32.33 ± 10.62) and IL-6 (ng/L: 558.04 ± 77.45 vs. 42.62 ± 11.21) in the LPS group were significantly higher than those in the blank control group (all P < 0.05). These results indicated that the inflammatory model of rat alveolar macrophages was constructed successfully. (2) ACh with the final concentrations of 0.01, 0.1, and 1 μmol/L had less influence on the production of TNF-α, IL-1β and IL-6 in the culture supernatants of alveolar macrophages stimulated with LPS compared with LPS group (all P > 0.05). Nevertheless, 10 μmol/L and 100 μmol/L ACh notably reduced the production of TNF-α (ng/L: 451.19 ± 30.67, 332.19 ± 32.19 vs. 604.96 ± 22.56), IL-1β (ng/L: 261.08 ± 24.78, 143.98 ± 28.39 vs. 367.06 ± 10.44) and IL-6 (ng/L: 342.75 ± 54.60, 235.48 ± 29.75 vs. 562.69 ± 63.34) in the culture supernatants compared with the LPS group (all P < 0.05). (3) The activity of AChE in the LPS group was significantly higher than that in the blank control group (kU/L: 5.21 ± 0.63 vs. 3.09 ± 0.10, P < 0.05). The activity of AChE was successfully inhibited by 1 mmol/L acetylcholinesterase inhibitor Phy pretreatment compared with that in the LPS group (1.51 ± 0.12 vs. 5.21 ± 0.63, P < 0.05). (4) The level of TNF-α (ng/L: 183.17 ± 35.44 vs. 451.19 ± 30.67), IL-1β (ng/L: 91.49 ± 12.27 vs. 261.08 ± 24.78) and IL-6 (ng/L: 108.17 ± 22.82 vs. 342.75 ± 54.60) in the culture supernatants of LPS + ACh + Phy group was significantly decreased as compared with LPS + ACh group (all P < 0.05).

Conclusions: ACh with the final concentrations of 10 μmol/L and 100 μmol/L can inhibit the LPS induced inflammatory reaction in alveolar macrophages. The acetylcholinesterase inhibitor Phy can reinforce the ACh-mediated anti-inflammatory effect on alveolar macrophages inflammatory model.
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October 2015

Reversible splenial lesion syndrome associated with encephalitis/encephalopathy presenting with great clinical heterogeneity.

BMC Neurol 2016 Apr 18;16:49. Epub 2016 Apr 18.

Department of Neurology, the First Affiliated Hospital of Nanchang University, Yong Wai Zheng Street 17#, Nanchang, 330006, P. R. China.

Background: Reversible splenial lesion syndrome (RESLES) is a disorder radiologically characterized by reversible lesion in the splenium of the corpus callosum (SCC). Most of patients with RESLES associated with encephalitis/encephalopathy were identified in Japanese population, but almost no Chinese patients were diagnosed as RESLES associated with encephalitis/encephalopathy.

Methods: Possible patients with reversible isolated SCC lesions were retrieved from January 2012 to July 2015 using keyword "restricted diffusion and isolated SCC lesion" in MRI report system from a large academic center. The clinical, laboratory and radiological data were summarized.

Results: A total of 15 encephalitis/encephalopathy patients (9 males and 6 females) were identified with a reversible isolated SCC lesion. Except for 13 patients with fever symptom, 8 patients also had cold symptoms before the onset of neurological symptoms. The neurological symptoms included headache, vertigo, seizure, disturbance of consciousness, and delirious behavior. Thirteen patients completely recovered within 1 month, but 2 patients who were subjected to mechanical ventilation had persistent neurological deficits. The initial MRI features showed isolated ovoid or extending SCC lesions with homogeneous hyperintense on diffusion weighted imaging (DWI) and decreased apparent diffusion coefficient (ADC) values. The follow-up MRI revealed that isolated SCC lesions with diffuse restriction disappeared at 10 to 32 days after the initial MRI study. Fractional anisotropy map revealed the decreased value of SCC lesion in a severe case with poor prognosis.

Conclusions: RESLES associated with encephalitis/encephalopathy is a reversible syndrome with an excellent prognosis in most patients, while a few patients required ventilator supporting at the early stage might have severe neurological sequelae. Reversible signal changes on DWI and ADC are identified in all patients, but fractional anisotropy values can be decreased in severe patient with neurological sequelae.
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http://dx.doi.org/10.1186/s12883-016-0572-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4835842PMC
April 2016

[The protective effects of transfected microRNA-146a on mice with sepsis-induced acute lung injury in vivo].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2015 Jul;27(7):591-4

Department of Critical Care Medicine, Linyi People's Hospital, Linyi 276003, Shandong, China. Corresponding author: Qian Kejian, Department of Critical Care Medicine, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China, Email:

Objective: To investigate the protective effect of transfected microRNA-146a (miR-146a) on mice with sepsis-induced acute lung injury (ALI) in vivo.

Methods: Twenty-four healthy male BALB/C mice were randomly divided into sham group, sepsis group, transfection group and transfection control group, each n=6. Mice in transfection group were given miR-146a agomir loaded by in vivo-jetPEITM via airway before reproduction of model, and mice in transfection control group were given negative control loaded by in vivo-jetPEITM only via airway. The septic model was reproduced by cecal ligation and puncture (CLP) 12 hours after transfection , and the mice in the sham group underwent laparotomy and closure only without ligation and puncture of the cecum. The mice of each group were sacrificed at 24 hours post-operation. The expression of miR-146a in lung tissue was determined by real time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR), and the quantity of tumor necrosis factor-α (TNF-α) in the bronchial alveolar lavage fluid (BALF) was determined with enzyme-linked immunosorbent assay (ELISA). The wet/dry ratio of lung (W/D) was determined. The pathohistological changes in the lung were observed and scored.

Results: The expression of miR-146a showed a significant increase in sepsis group, transfection group and transfection control group, which were (3.56±0.43), (27.64±3.46) and (3.72±0.54) folds of that in sham group, respectively (P<0.05 or P<0.01). The miR-146a expression in transfection group was significantly increased compared with sepsis group and transfection control group (both P<0.01), but no statistical difference in the expression was found between sepsis group and transfection control group (P>0.05). Compared with the sham group, higher level of TNF-α in the BALF was found in the sepsis group, transfection group and transfection control group (ng/L: 511.65±43.47, 305.74±34.76, 492.27±42.21 vs. 50.72±7.23, all P<0.01). The level of TNF-α in transfection group was significantly lower than that in sepsis group and transfection control group (both P<0.01). Compared with the sham group, the W/D ratio of lung in sepsis group, transfection group and transfection control group showed a significant increase (6.11±0.32, 5.02±0.29, 6.05±0.43 vs. 4.18±0.10, all P<0.01). The W/D ratio of lung in transfection group was significantly lower than that of sepsis group and transfection control group (both P<0.01). The lung injury score of transfection group was significantly lower than that of sepsis group and transfection control group (6.12±0.75 vs. 10.53±1.52, 9.73±1.08, both P<0.01).

Conclusions: miR-146a agomir loaded by in vivo-jetPEITM instillation into airway was able to increase the expression of miR-146a in the lung tissue of septic mice. Up-regulation of miR-146a inhibit the release of the inflammatory cytokine TNF-α stimulated by sepsis, and alleviate inflammatory reaction and lung tissue injury in mice with sepsis-induced ALI.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2015.07.010DOI Listing
July 2015

miR-132 inhibits lipopolysaccharide-induced inflammation in alveolar macrophages by the cholinergic anti-inflammatory pathway.

Exp Lung Res 2015 Jun;41(5):261-9

1Department of Critical Care Medicine, the First Affiliated Hospital of Nanchang University , Nanchang, Jiangxi , China.

Objective: Although microRNA-132 (miR-132) has been shown to be involved in the inflammatory regulation, its role in sepsis-induced lung injury is unknown. We hypothesized that miR-132 attenuated lipopolysaccharide (LPS)-induced inflammation of alveolar macrophages by targeting acetylcholinesterase (AChE) and enhancing the acetylcholine (ACh)-mediated cholinergic anti-inflammatory response.

Methods: The LPS-treated rat alveolar macrophage cell line NR8383 was used as the inflammatory model. To assess the effect of miR-132, alveolar macrophages were transfected with miR-132 mimic or inhibitor.

Results: We found that miR-132 was upregulated in LPS-stimulated alveolar macrophages. Induction of AChE mRNA showed an inverse pattern with respect to AChE protein and activity, suggesting posttranscriptional regulation of AChE. Utilizing miR-132 mimic transfection, we found that overexpression of miR-132 enhanced the ACh-mediated cholinergic anti-inflammatory reaction by targeting AChE mRNA in LPS-treated alveolar macrophages. Blockage of miR-132 using miR-132 inhibitor reversed the Ach action upon LPS-induced release of inflammatory mediators and reduction in AchE protein/activity. Moreover, in the presence of ACh, upregulation of miR-132 suppressed LPS-induced nuclear translocation of NF-κB and production of STAT3 and phosphorylated STAT3, while downregulation of miR-132 enhanced the nuclear translocation of NF-κB.

Conclusion: We propose that miR-132 functions as a negative regulator of the inflammatory response in alveolar macrophages by potentiating the cholinergic anti-inflammatory pathway, and represents a potential therapeutic leverage point in modulating inflammatory responses.
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http://dx.doi.org/10.3109/01902148.2015.1004206DOI Listing
June 2015

Clinical characteristics of human infection with a novel avian-origin influenza A(H10N8) virus.

Chin Med J (Engl) 2014 ;127(18):3238-42

Department of Respiratory and Critical Care Medicine, Peking University People's Hospital, Beijing 100044, China. Email:

Background: Novel influenza A viruses of avian-origin may be the precursors of pandemic strains. This descriptive study aims to introduce a novel avian-origin influenza A (H10N8) virus which can infect humans and cause severe diseases.

Methods: Collecting clinical data of three cases of human infection with a novel reassortment avian influenza A (H10N8) virus in Nanchang, Jiangxi Province, China.

Results: Three cases of human infection with a new reassortment avian influenza A(H10N8) virus were described, of which two were fatal cases, and one was severe case. These cases presented with severe pneumonia that progressed to acute respiratory distress syndrome (ARDS) and intractable respiratory failure.

Conclusion: This novel reassortment avian influenza A (H10N8) virus in China resulted in fatal human infections, and should be added to concerns in clinical practice.
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May 2016

[The effect of transfected microRNA-146a on expression of interleukin-1 receptor-associated kinase 1 and tumor necrosis factor receptor-associated factor 6 in alveolar macrophages].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2014 May;26(5):300-3

State Drug Clinical Trial Agency, the First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China. Corresponding author: Qian Kejian, Email:

Objective: To observe the effect of transfected microRNA-146a (miR-146a) on expression of interleukin-1 receptor-associated kinase 1 (IRAK-1) and tumor necrosis factor receptor-associated factor 6 (TRAF-6) in alveolar macrophages, and to explore the regulatory mechanism of miR-146a in the inflammatory response of alveolar macrophages.

Methods: Alveolar macrophages NR8383 were cultured and divided into two groups: transfected miR-146a mimic group was transfected 50 nmol/L Pre-miR miR-146a precursors and the negative control group was transfected Cy3-labeled Pre-miR negative control. Cells were collected at 24 hours after transfection. The miR-146a and the mRNA expression of IRAK-1 and TRAF-6 were detected by real-time fluorescent quantitation reverse transcription-polymerase chain reaction (RT-qPCR), and the protein expression of IRAK-1 and TRAF-6 was assayed by Western Blot.

Results: Compared with negative control group, the expression of miR-146a was upregulated by (24.55±6.14) fold compared with miR-146a mimic group (t=-9.353, P=0.001). The mRNA expressions of IRAK-1 and TRAF-6 in miR-146a mimic group were upregulated by (1.16±0.10) fold (t=2.701, P=0.054) and (1.19±0.16) fold (t=2.032, P=0.112) , respectively, compared with that of negative control group, but the protein levels of IRAK-1 and TRAF-6 were decreased by 73.0% (t=-9.353, P=0.001) and 64.1% (t=-6.839, P=0.002), respectively .

Conclusions: miR-146a mimic was successfully transfected into the alveolar macrophage NR8383. The overexpression of miR-146a in alveolar macrophages can down-regulate the expression of IRAK-1 and TRAF-6 in protein translation levels, and its mechanism may be related with inhibition of protein translation.
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http://dx.doi.org/10.3760/cma.j.issn.2095-4352.2014.05.003DOI Listing
May 2014

[The expression changes in microRNA-132 in the lipopolysaccharide-induced inflammation of rat alveolar macrophages].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2014 Feb;26(2):80-3

Objectives: To observe the kinetic changes in microRNA-132 (miR-132) expression in rat alveolar macrophages after lipopolysaccharide (LPS)-induced inflammation, and to investigate initially on the role of miR-132 in alveolar macrophages inflammatory response.

Methods: The rat alveolar macrophages NR8383 cultured without pyrogen in vitro were divided into blank control group and LPS (1 mg/L) stimulated 3, 6, 12, 24 hours groups. Culture supernatants and cell pellets were collected at each time point respectively. Enzyme-linked immunosorbent assay (ELISA) was used to assay the production changes in tumor necrosis factor-α (TNF-α), interleukins (IL-1β and IL-6) in the supernatant. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression of miR-132 in the cells.

Results: After stimulating rat alveolar macrophages with LPS, the production of TNF-α (ng/L: 364.83 ± 46.29 vs. 34.07 ± 8.62, P<0.01), IL-1β (ng/L: 153.83 ± 43.67 vs. 32.33 ± 10.62, P<0.05) and IL-6 (ng/L: 183.85 ± 43.52 vs. 42.62 ± 11.21, P<0.05) were all increased significantly at 3 hours post LPS stimulation compared with blank control group, reached the peak at 12 hours (TNF-α: 605.09 ± 57.13, IL-1β: 377.09 ± 28.55, IL-6: 558.04 ± 77.45, all P<0.01), and descended at 24 hours (TNF-α: 281.95 ± 41.61, IL-1β: 263.17 ± 51.36, IL-6: 438.74 ± 79.94) but the levels remained significantly higher than blank control group (all P<0.01). The expression of miR-132 started to rise at 3 hours after LPS stimulation compared with blank control group [(1.12 ± 0.11) folds, P=0.995], and presented a gradual increasing trend at 6, 12, 24 hours [(5.98 ± 0.65), (7.64 ± 0.53), (8.92 ± 0.83) folds, all P<0.01].

Conclusion: The expression of miR-132 increased gradually over time after LPS-induced inflammation of rat alveolar macrophages, suggesting that miR-132 may be involved in regulation of rat alveolar macrophages inflammatory response.
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February 2014

Upregulation of miR-146a contributes to the suppression of inflammatory responses in LPS-induced acute lung injury.

Exp Lung Res 2013 Sep 12;39(7):275-82. Epub 2013 Jul 12.

Critical Care Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Despite the critical role of microRNA in inflammatory response, little is known about its function in inflammation-induced Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS). To investigate the potential role of microRNA146a (miR-146a) in ALI, we used lipopolysaccharide (LPS)-induced ALI rat model. Our data revealed that LPS-induced lung injury in rats resulted in significant upregulation of proinflammatory cytokine tumor necrosis factor-alpha (TNF-α), IL-6, IL-1β, and miR-146a expression. LPS treatment also leads to higher expression of miR-146a as well as increase in secretion of TNF-α, IL-6, and IL-1β in alveolar macrophage (AM) NR8383 cells in a time-dependent manner. Manipulation with miR146a mimic significantly suppressed LPS-mediated TNF-α, IL-6, and IL-1β induction in NR8383 cells by repressing expression of IRAK-1 and TRAF-6. These data clearly indicate that the upregulation of miR146a suppresses inflammatory mediators in LPS induced-ALI model. Therefore, miR-146a may be therapeutically targeted as a mean to repress inflammatory response following ALI.
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http://dx.doi.org/10.3109/01902148.2013.808285DOI Listing
September 2013