Publications by authors named "Chaoyuan Huang"

21 Publications

  • Page 1 of 1

Examining the Mechanisms of Huachansu injection on Liver Cancer through Integrated Bioinformatics Analysis.

Recent Pat Anticancer Drug Discov 2022 May 11. Epub 2022 May 11.

Department of gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Objective: To explore the potential anti-liver cancer mechanism of Huachansu injection through integrated bioinformatics analysis.

Methods: Active ingredients of Huachansu injection (extraction of toad skin) were obtained, and their potential drug targets were predicted via SwissTargetPrediction database. Liver cancer disease targets were identified from the GEO (Gene Expression Omnibus) dataset and four public databases. Then protein-protein interaction(PPI) network of toad skin was constructed. GO (Gene ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis were performed subsequently. Finally, molecular docking was performed using AutoDock Vina.

Results: In the search for therapeutic targets, twenty active components of toad skin were screened for further study, five hundred and sixty-eight targets of components were identified. In the search for disease targets, three thousand two hundred and twenty-seven genes were identified after removal of duplicated genes, one hundred and fifty-nine genes were up-regulated in liver cancer samples while two hundred and seventy-eight were down-regulated in liver cancer patients. After predicting the therapeutic targets of the components, the results were cross-checked with the disease targets, thirteen up-regulated targets and ten down-regulated targets were obtained. Finally, in the results of molecular docking, seven targets (CDK1, AKR1B1, MMP12, AURKB, CHEK1, AURKA, TTK) were potential up-regulated targets, three targets (SHBG, SRD5A2, NR1I2) were potential down-regulated targets, all of which have the best binding energy and molecular interactions.

Conclusion: CDK1, AKR1B1, MMP12, AURKB, CHEK1, AURKA, TTK could be potential up-regulated target proteins of Huachansu injection for treating liver cancer. The mechanism of Huachansu injection in the treatment of liver cancer through these up-regulated targets is related to cell cycle, cellular senescence cellular senescence, viral carcinogenesis, p53 signaling pathway. SHBG, SRD5A2, and NR1I2 could be potential down-regulated target proteins of Huachansu injection in treating liver cancer.
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http://dx.doi.org/10.2174/1574892817666220511162046DOI Listing
May 2022

Ferroptosis-related lncRNA signature predicts the prognosis and immune microenvironment of hepatocellular carcinoma.

Sci Rep 2022 Apr 22;12(1):6642. Epub 2022 Apr 22.

Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510403, Guangdong, China.

This study aimed to construct a ferroptosis-related lncRNA signature to probe the prognosis and immune infiltration of HCC patients. The Cancer Genome Atlas (TCGA) database was randomly divided into two parts, with two-thirds training and one-third testing sets. Univariate, multivariate, and least absolute selection operator (LASSO) Cox regression analyses were performed to establish a ferroptosis-related lncRNA signature. The prognostic signature was constructed by 6 ferroptosis-related lncRNAs (PCAT6, MKLN1-AS, POLH-AS1, LINC00942, AL031985.3, LINC00942) shows a promising clinical prediction value in patients with HCC. Patients with high-risk score indicated a poorer prognosis than patients with low-risk score were shown in the training set (p < 0.001) and testing set (p = 0.024). Principal component analysis (PCA) and nomogram were performed to verify the value of the prognostic signature. The area under curves (AUCs) for 1-, 3-, and 5-year survival rates were 0.784, 0.726, 0.699, respectively. Moreover, TCGA revealed that immune cell subpopulations and related functions, including cytolytic activity, MHC class I, type I and type II IFN response, were significantly different between the two risk groups. Immune checkpoints such as PDCD1, CTLA4, CD44, VTCN1 were also abnormally expressed between the two risk groups. This prognostic signature based on the ferroptosis-related lncRNAs may be promising for the clinical prediction of prognosis and immunotherapeutic responses in patients with HCC.
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http://dx.doi.org/10.1038/s41598-022-10508-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9033801PMC
April 2022

Exploration of Potential Roles of m5C-Related Regulators in Colon Adenocarcinoma Prognosis.

Front Genet 2022 24;13:816173. Epub 2022 Feb 24.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

The purpose of this study was to investigate the role of 13 mC-related regulators in colon adenocarcinoma (COAD) and determine their prognostic value. Gene expression and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) datasets. The expression of mC-related regulators was analyzed with clinicopathological characteristics and alterations within mC-related regulators. Subsequently, different subtypes of patients with COAD were identified. Then, the prognostic value of mC-related regulators in COAD was confirmed univariate Cox regression and least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The prognostic value of risk scores was evaluated using the Kaplan-Meier method, receiver operating characteristic (ROC) curve. The correlation between the two mC-related regulators, risk score, and clinicopathological characteristics were explored. Additionally, Gene Set Enrichment Analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and Gene Ontology (GO) analysis were performed for biological functional analysis. Finally, the expression level of two mC-related regulators in clinical samples and cell lines was detected by quantitative reverse transcription-polymerase chain reaction and through the Human Protein Atlas database. mC-related regulators were found to be differentially expressed in COAD with different clinicopathological features. We observed a high alteration frequency in these genes, which were significantly correlated with their mRNA expression levels. Two clusters with different prognostic features were identified. Based on two independent prognostic mC-related regulators (NSUN6 and ALYREF), a risk signature with good predictive significance was constructed. Univariate and multivariate Cox regression analyses suggested that the risk score was an independent prognostic factor. Furthermore, this risk signature could serve as a prognostic indicator for overall survival in subgroups of patients with different clinical characteristics. Biological processes and pathways associated with cancer, immune response, and RNA processing were identified. We revealed the genetic signatures and prognostic values of mC-related regulators in COAD. Together, this has improved our understanding of mC RNA modification and provided novel insights to identify predictive biomarkers and develop molecular targeted therapy for COAD.
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http://dx.doi.org/10.3389/fgene.2022.816173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8908034PMC
February 2022

Restrains Hepatic Pro-Inflammatory Macrophages to Ameliorate Non-Alcoholic Fatty Liver Disease.

Front Pharmacol 2021 18;12:816032. Epub 2022 Jan 18.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Non-alcoholic fatty liver disease (NAFLD) has become a progressive metabolic disease that is emerging as a global epidemic. Considering that the complex pathogenesis has not been fully elucidated, barely specific pharmacological therapy is recommended in current guidelines. (GS) is a commonly used herb in Tibetan medicine, which has received much attention in recent years due to its diverse pharmacological properties, including anti-inflammation, anti-oxidation, and anti-fibrosis. However, the therapeutic mechanisms are still unclear. Our investigation demonstrated a regulatory effect of GS on pro-inflammatory macrophages, which was extensively investigated in NAFLD that revealed intimate participation in the disease evolution, and the non-canonical IKK family member TANK-binding kinase 1 (TBK1) was involved in this process. Plasmid vectors for shTBK1 and amlexanox (AML), an inhibitor of TBK1, were used in this study to verify the mechanisms of TBK1 both and , while a co-culture system for hepatocytes and BMDMs was constructed to confirm the critical role of macrophages for inflammatory cascade. The results revealed that metabolic burden up-regulated the phosphorylation of TBK1, resulting in activation of NF-κB signaling pathway, and consequently caused an elevated expression of MCP1 to induce the macrophage recruitment and accelerate the inflammatory cascade. In contrast, GS could inhibit the TBK1 phosphorylation and the MCP1 expression to restrain the recruitment of pro-inflammatory macrophages, so as to provide curative effects on metabolic dysfunction and inflammation. Considering that GS is non-toxic and can be used as a kind of tea for long-term drinking, we propose it may be an effective option for the prevention and treatment of NAFLD, which deserves further exploration and application, and may provide new insights to improve the current standardized intervention strategy.
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http://dx.doi.org/10.3389/fphar.2021.816032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803634PMC
January 2022

Correction to: Inhibition of PAD4 enhances radiosensitivity and inhibits aggressive phenotypes of nasopharyngeal carcinoma cells.

Cell Mol Biol Lett 2021 Dec 30;26(1):55. Epub 2021 Dec 30.

Department of Endoscopy, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China.

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http://dx.doi.org/10.1186/s11658-021-00303-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903591PMC
December 2021

Identification of N6-Methylandenosine-Related lncRNAs for Subtype Identification and Risk Stratification in Gastric Adenocarcinoma.

Front Oncol 2021 27;11:725181. Epub 2021 Sep 27.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Objectives: The purpose of this study was to investigate the role of mA-related lncRNAs in gastric adenocarcinoma (STAD) and to determine their prognostic value.

Methods: Gene expression and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) database. Correlation analysis and univariate Cox regression analysis were conducted to identify mA-related prognostic lncRNAs. Subsequently, different clusters of patients with STAD were identified consensus clustering analysis, and a prognostic signature was established by least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The clinicopathological characteristics, tumor microenvironment (TME), immune checkpoint genes (ICGs) expression, and the response to immune checkpoint inhibitors (ICIs) in different clusters and subgroups were explored. The prognostic value of the prognostic signature was evaluated using the Kaplan-Meier method, receiver operating characteristic curves, and univariate and multivariate regression analyses. Additionally, Gene Set Enrichment Analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Ontology (GO) analysis were performed for biological functional analysis.

Results: Two clusters based on 19 mA-related lncRNAs were identified, and a prognostic signature comprising 14 mA-related lncRNAs was constructed, which had significant value in predicting the OS of patients with STAD, clinicopathological characteristics, TME, ICGs expression, and the response to ICIs. Biological processes and pathways associated with cancer and immune response were identified.

Conclusions: We revealed the role and prognostic value of mA-related lncRNAs in STAD. Together, our finding refreshed the understanding of mA-related lncRNAs and provided novel insights to identify predictive biomarkers and immunotherapy targets for STAD.
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http://dx.doi.org/10.3389/fonc.2021.725181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504261PMC
September 2021

Regulation of decorin by ursolic acid protects against non-alcoholic steatohepatitis.

Biomed Pharmacother 2021 Nov 21;143:112166. Epub 2021 Sep 21.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; Baiyun Hospital of The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address:

Non-alcoholic steatohepatitis (NASH) has become a global health issue, which poses additional financial burden to public health care. However, no specific pharmacological therapy is recommended in current guidelines. Ursolic acid (UA) has been proven to perform multiple biological activities, thereby having a broad application prospect in healthcare field. Thus, this current research was conducted to investigate the protective mechanisms of UA on NASH. Integrative genomic analyses were performed to identify characteristic genes for NASH, and human proteomics chip was applied to seek out differentially binding proteins for UA. The combining bioinformatic analyses revealed 529 and 502 differentially expressed genes for NASH and UA, respectively. And further enrichment analyses indicated that IGF-IR signaling pathway was intimately involved in the therapeutic effects of UA on NASH. Experimental studies displayed that UA up-regulated the decorin expression to activate IGF-IR signaling as well as to inhibit HIF-1 signaling, resulting in alleviation on metabolic dysfunction, liver steatosis, inflammation and hypoxia in high-fat-fed mice. And additionally, these results were confirmed by lipotoxic and decorin-interference cell model. Taken together, we found that UA could regulate IGF-IR and HIF-1 signaling pathways via decorin to provide dual protective functions on metabolic dysfunction and liver hypoxia, and therefore turned to be an effective option for the treatment of NASH.
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http://dx.doi.org/10.1016/j.biopha.2021.112166DOI Listing
November 2021

AURKB, CHEK1 and NEK2 as the Potential Target Proteins of on Hepatocellular Carcinoma: An Integrated Bioinformatics Analysis.

Int J Gen Med 2021 12;14:3295-3312. Epub 2021 Jul 12.

Department of gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People's Republic of China.

Objective: We aim to explore the potential anti-HCC mechanism of through integrated bioinformatics analysis.

Methods: We searched active ingredients and related targets of via TCMSP database, PubChem and SwissTargetPrediction database. Then, we identified HCC disease targets from GEO dataset by WGCNA. Next, the intersected targets of disease targets and drug targets were input into STRING database to construct PPI networking in order to obtain potential therapeutic targets of . Cytoscape software was used to carry out network topology analysis of potential targets. We used the R package for GO analysis and KEGG analysis. Finally, we used AutoDock vina and PyMOL software for molecular docking.

Results: Sixteen active components from were lastly selected for further investigation. A total of 442 component targets were identified from 16 active ingredients of after the removal of duplicate targets. GSE45436 was selected for construction of WGCNA and screening of differentially expressed genes. A total of 354 genes were up-regulated in HCC samples and 100 were down-regulated in HCC patients. Twenty-one common genes were obtained by intersection and 10 critical targets were filtered for further investigation. The enrichment analysis showed that cell cycle, DNA replication, p53 signaling pathway were mainly involved. The molecular docking results showed that 4 potential combinations were with the best binding energy and molecular interactions.

Conclusion: AURKB, CHEK1 and NEK2 could be the potential target proteins of in treating HCC. Cell cycle, DNA replication, p53 signaling pathway consist of the fundamental regulation cores in this mechanism.
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http://dx.doi.org/10.2147/IJGM.S318077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285231PMC
July 2021

Ethacrynic Acid Enhances the Antitumor Effects of Afatinib in EGFR/T790M-Mutated NSCLC by Inhibiting WNT/Beta-Catenin Pathway Activation.

Dis Markers 2021 27;2021:5530673. Epub 2021 Apr 27.

Research Department, GuangXi Medical University Cancer Hospital, Nanning, Guangxi, China.

. Despite afatinib as a new first-line treatment for EGFR L858R and exon 19 deletion or other rare EGFR-mutation patients, the acquired resistance or toxic effects associated with it limited its use clinically. The controlling of acquired resistance or optimization of the afatinib dosage in EGFR/T790M mutation-positive non-small-cell lung cancer (NSCLC) is still an important fundamental problem. Ethacrynic acid (EA) has been proved as a dual inhibitor of GST and WNT, and the , -unsaturated-keto structure of it is similar to that of irreversible tyrosine kinase inhibitors (TKIs). However, these beneficial effects of EA combined with afatinib have never been reported in NSCLC. Therefore, the antitumor effects of afatinib combined with EA in EGFR L858R/T790M-mutated NSCLC cells and related mechanisms were analyzed. Our and results showed that EA has strong synergistic antitumor effects with afatinib in EGFR L858R/T790M-mutated NSCLC cells, but has no cytotoxic effects in NSCLC cells when used it alone, i.e., the cytotoxic effects of afatinib (IC30) plus EA (IC30) were stronger than the effects of afatinib (IC50) alone. Our functional studies found that the antitumor mechanisms of afatinib when combined with EA mainly occurred by inhibiting WNT/-catenin pathway activation and suppression of the secretion of anti-inflammatory factors. These results revealed that combination of afatinib with EA derivatives not only provided a new therapeutic approach for EGFR/T790M-mutated NSCLC patients but also offered a new idea for developing new drugs or optimizing the dose of afatinib in clinical use in future antitumor therapy.
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http://dx.doi.org/10.1155/2021/5530673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168479PMC
December 2021

Identifying Dendritic Cell-Related Genes Through a Co-Expression Network to Construct a 12-Gene Risk-Scoring Model for Predicting Hepatocellular Carcinoma Prognosis.

Front Mol Biosci 2021 24;8:636991. Epub 2021 May 24.

Department of Gastroenterology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

The prognostic prediction of hepatocellular carcinoma (HCC) is still challenging. Immune cells play a crucial role in tumor initiation, progression, and drug resistance. However, prognostic value of immune-related genes in HCC remains to be further clarified. In this study, the mRNA expression profiles and corresponding clinical information of HCC patients were downloaded from public databases. Then, we estimated the abundance of immune cells and identified the differentially infiltrated and prognostic immune cells. The weighted gene co-expression network analysis (WGCNA) was performed to identify immune-related genes in TCGA cohort and GEO cohort. The least absolute shrinkage and selection operator (LASSO) Cox regression model was applied to establish a risk-scoring model in the TCGA cohort. HCC patients from the GSE14520 datasets were utilized for risk model validation. Our results found that high level of dendritic cell (DC) infiltration was associated with poor prognosis. Over half of the DC-related genes (58.2%) were robustly differentially expressed between HCC and normal specimens in the TCGA cohort. 17 differentially expressed genes (DEGs) were found to be significantly associated with overall survival (OS) by univariate Cox regression analysis. A 12-gene risk-scoring model was established to evaluate the prognosis of HCC. The high-risk group exhibits significantly lower OS rate of HCC patients than the low-risk group. The risk-scoring model shows benign predictive capacity in both GEO dataset and TCGA dataset. The 12-gene risk-scoring model may independently perform prognostic value for HCC patients. Receiver operating characteristic (ROC) curve analysis of the risk-scoring model in GEO cohort and TCGA cohort performed well in predicting OS. Taken together, the 12-gene risk-scoring model could provide prognostic and potentially predictive information for HCC. SDC3, NCF2, BTN3A3, and WARS were noticed as a novel prognostic factor for HCC.
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http://dx.doi.org/10.3389/fmolb.2021.636991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181399PMC
May 2021

Inhibition of PAD4 enhances radiosensitivity and inhibits aggressive phenotypes of nasopharyngeal carcinoma cells.

Cell Mol Biol Lett 2021 Mar 16;26(1). Epub 2021 Mar 16.

Department of Oncology, The Second Nanning People's Hospital, No.13 Dancun Road, Jiangnan District, Nanning, 530031, Guangxi, China.

Background: Nasopharyngeal carcinoma (NPC) is a tumor deriving from nasopharyngeal epithelium. Peptidyl-arginine deiminase 4 (PAD4) is a vital mediator of histone citrullination and plays an essential role in regulating disease process. Radiotherapy is an essential method to treat NPC. In this research, we explored the effect of PAD4 on NPC radiosensitivity.

Methods: We enrolled 50 NPC patients, established mice xenograft model, and purchased cell lines for this study. Statistical analysis and a series of experiments including RT-qPCR, clonogenic survival, EdU, Transwell, and wound healing assays were done.

Results: Our data manifested that PAD4 (mRNA and protein) presented a high expression in NPC tissues and cells. GSK484, an inhibitor of PAD4, could inhibit activity of PAD4 in NPC cell lines. PAD4 overexpression promoted the radioresistance, survival, migration, and invasion of NPC cells, whereas treatment of GSK484 exerted inhibitory effects on radioresistance and aggressive phenotype of NPC cells. Additionally, GSK484 could attenuate the effect of PAD4 of NPC cell progression. More importantly, we found that GSK484 significantly inhibited tumor size, tumor weight and tumor volume in mice following irradiation.

Conclusions: PAD4 inhibitor GSK484 attenuated the radioresistance and cellular progression in NPC.
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http://dx.doi.org/10.1186/s11658-021-00251-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962337PMC
March 2021

Identification of key genes and immune profile in limited cutaneous systemic sclerosis-associated pulmonary arterial hypertension by bioinformatics analysis.

Life Sci 2021 Apr 1;271:119151. Epub 2021 Feb 1.

The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address:

Aims: Limited cutaneous systemic sclerosis-associated pulmonary arterial hypertension (lcSSc-PAH) is a complex multi-system disease with high morbidity and mortality. The purpose of this study is to identify the hub genes and immune characteristics of limited cutaneous systemic sclerosis (lcSSc) and lcSSc-PAH through bioinformatics.

Main Methods: LcSSc-PAH raw data were obtained from the GEO database (GSE19617). Weighted gene Co-expression Network analysis (WGCNA) was used to evaluate key modules. Then, we performed Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis with R software and verified the diagnostic value of the hub genes. Finally, Immune Cell Abundance Identifier (ImmuCellAI) was used to analyze the immune characteristics of the normal subjects, lcSSc and lcSSc-PAH patients, the results were displayed graphically.

Key Findings: Enrichment of two important modules by GO and KEGG identified key biological processes and pathways related to pathogen infection and immune function. Three hub genes (BID, IFNGR1, ZAP70) related to immune function were identified. The analysis of immune characteristics showed that the correlation and abundance of immune cells such as inducible regulatory T (iTreg) cells, B cells, macrophages, natural killer (NK) cells, CD8T cells, mucosal-associated invariant T(MAIT) cells and dendritic cells(DCs) were significantly different in the normal subjects, lcSSc and lcSSc-PAH patients.

Significance: Pathogen infection, changes in the number and function of immune cells, and interactions among immune cells may preliminarily reveal the pathological mechanism of lcSSc-PAH. The hub genes, pathways and immune characteristics identified in this research remains to be further studied.
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http://dx.doi.org/10.1016/j.lfs.2021.119151DOI Listing
April 2021

Effect of Fufang Biejia Ruangan Tablet on lowering biochemical and virological parameters of hepatic fibrosis in patients with chronic hepatitis B: Protocol for a systematic review and meta-analysis of randomized controlled trials and cohort studies.

Medicine (Baltimore) 2019 Apr;98(17):e15297

School of Basic Medical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: Liver cirrhosis is one of the end-stage chronic liver diseases. Individuals with chronic hepatitis B (CHB) are at an increased risk of developing liver cirrhosis. Practice guidelines underline that Nucleos(t)ide analogs (NAs) should be the first-line treatment for hepatitis B virus (HBV)-related cirrhosis. However, prolonged use of NAs may lead to drug resistance and kidney impair and does not reverse the fibrosis of liver. Fufang Biejia Ruangan Tablet (RGT), as a traditional Chinese medicine (TCM), has been proved to be effective in the treatment of liver fibrosis. Hence, we will perform meta-analysis in order to evaluate the efficacy and safety of RGT in the treatment of hepatic fibrosis in patients with CHB.

Methods: To search for relative literatures up to February 2019 by computer from the following databases: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodicals Database, Chinese BioMedical Database and Wanfang Data. Included criteria are randomized controlled trials and cohort studies of hepatic fibrosis in patients with CHB treated by RGT. The primary outcome measures include biochemical and virological parameters. We will use Stata 13.0 software for data synthesis, sensitivity analysis, meta regression, subgroup analysis, and risk of bias assessment. The reporting bias will be assessed by a funnel plot and the funnel plot symmetries will be evaluated by Begg and Egger tests. We will use the Grading of Recommendations Assessment, Development and Evaluation system to assess the quality of evidence.

Results: This systematic review will provide a synthesis of RGT for hepatic fibrosis in patients with CHB from various evaluation aspects including biochemical and virological parameters, HBV DNA levels HBeAg status and seroconversion, adverse events incidence.

Conclusion: The systematic review will provide evidence to assess the efficacy and safety of RGT in the treatment of hepatic fibrosis in patients with CHB.

Prospero Registration Number: ROSPERO CRD 42018095122.
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http://dx.doi.org/10.1097/MD.0000000000015297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831400PMC
April 2019

Modulating the 3' end-DNA and the fermentation process for enhanced production and biological activity of porcine interferon-gamma.

PLoS One 2019 26;14(3):e0214319. Epub 2019 Mar 26.

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou, Guangdong, China.

Porcine gamma interferon is a cytokine produced by activated T cells and NK cells with broad-spectrum antiviral activity and immunomodulatory function. However, pIFN-γ is a secretory protein that has a short half-life in organisms and is easily inactivated, making it difficult to apply widely in clinics. Therefore, we tried to optimize the expression of pIFN-γ in Pichia pastoris to obtain a large amount of highly active, easily purified pIFN-γ protein in vitro. Through C-terminal sequence analysis, we found a signal sequence (EKREAEAE) that was easily enzymolysed by a signal peptide enzyme, resulting in degradation and inactivation of the pIFN-γ protein. In this study, we optimized the pIFN-γ gene recombination sequence and mutated the 3' end of the pIFN-γ gene, resulting in a higher expression level and stronger biological activity, as well as a significant upregulation in the expression of the interferon-stimulated genes Mx1 and OAS1 in IPEC-J2 jejunal epithelial cells. Our data also showed that the fermentation process could significantly improve productivity. A recombinant Pichia pastoris strain with the optimized pIFN-γ gene could obtain a high yield of pIFN-γ protein, up to 9536 mg/L, after staged incubation for 0-24 h at 28°C, pH 6.0, and 50% dissolved oxygen (DO), followed by incubation for 24-72 h at 25°C, pH 6.0 and 30% DO. These data demonstrated, for the first time, that the expression level of pIFN-γ in Pichia pastoris was improved significantly by gene optimization with 3' end mutation and a fermentation process that maintained good biological activity, which is beneficial to the application of pIFN-γ in animal husbandry.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214319PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435167PMC
December 2019

MicroRNA-144-3p suppresses tumor growth and angiogenesis by targeting SGK3 in hepatocellular carcinoma.

Oncol Rep 2017 Oct 11;38(4):2173-2181. Epub 2017 Aug 11.

Research Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.

In our previous studies, the Illumine Soledad massively parallel signature sequencing of miRNomes in non‑tumor and hepatocellular carcinoma (HCC) tissues revealed that microRNA (miR)-144-3p was significantly downregulated in HCC, but its role in HCC development, especially angiogenesis, remains unclear. In this investigation, we found recovering miR‑144‑3p expression can significantly suppress the growth, migration and induced angiogenic capacity of HCC cells through both in vivo and in vitro experiments. Moreover, clinical correlation analysis showed that low expression of miR‑144‑3p was positively correlated to poor disease-free survival (DFS) of HCC patients. Mechanistically, serum and glucocorticoid kinase 3 (SGK3), the putative targets of miR‑144‑3p, was predicted by Target Scan database and identified to be suppressed by miR‑144‑3p so that inhibiting the activation of mTOR-VEGF downstream signals was activated by the phosphoinositide 3-kinase (PI3K)-independent pathway. Hence, we concluded that miR‑144‑3p, which is frequently downregulated in HCC, can inhibit proliferation, migration and repress angiogenesis by regulating SGK3 activation with PI3K independent signal pathway, and acts as a prognostic factor for HCC patients.
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http://dx.doi.org/10.3892/or.2017.5900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652965PMC
October 2017

Adalimumab for Moderately to Severely Active Ulcerative Colitis: A Systematic Review and Meta-Analysis.

BioDrugs 2016 Jun;30(3):207-17

The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China.

Background: Evidence-based studies are increasingly being focused on evaluating the efficacy and safety of adalimumab (ADA) for moderately to severely active ulcerative colitis (UC). However, the dosage pattern of ADA for UC management is still not clear.

Objective: A meta-analysis was conducted to evaluate the efficacy and safety of different ADA dosage regimens for moderately to severely active UC.

Methods: The Medline, EMBASE, ISI Web of Knowledge, and Cochrane databases were searched from their inception to January 2015. Randomized controlled trials (RCTs) comparing ADA with placebo were eligible for initial inclusion. The efficacy and side effects were evaluated for ADA 160/80 (ADA 160/80 mg at weeks 0/2 and then 40 mg at weeks 4 and 6), and ADA 80/40 (ADA 80/40 mg at weeks 0/2 and then 40 mg at weeks 4 and 6) induction therapy, with ADA 40 mg every other week (EOW) for maintenance therapy of 52 weeks. The pooled risk ratio (RR) and its 95 % confidence interval (CI) were calculated.

Results: Three RCTs were included. All of the studies were considered to have a low risk of bias. ADA 160/80 was more effective than placebo for induction of clinical remission (RR 1.62, 95 % CI 1.15-2.29), clinical response (RR 1.37, 95 % CI 1.19-1.59), mucosal healing (RR 1.27, 95 % CI 1.08-1.50), and inflammatory bowel disease questionnaire (IBDQ) response (RR 1.22, 95 % CI 1.05-1.43) and did not increase adverse events (RR 1.10, 95 % CI 0.95-1.27). Compared with placebo, ADA 80/40 did not show significant differences for induction of clinical remission and clinical response and did not increase adverse events. ADA 40 mg EOW was superior to placebo in maintaining clinical remission (RR 2.38, 95 % CI 1.57-3.59), clinical response (RR 1.69, 95 % CI 1.29-2.21), mucosal healing (RR 1.69, 95 % CI 1.26-2.28), and IBDQ response (RR 1.73, 95 % CI 1.28-2.34). Compared with placebo, ADA 40 mg EOW increased adverse events (RR 1.28, 95 % CI 1.06-1.54).

Conclusion: ADA 160/80 was a safe and effective treatment for induction management of moderately to severely active UC, but the benefits of ADA 80/40 application were limited. ADA 40 mg EOW was effective for maintenance management of UC. Additional well designed RCTs are needed to confirm these results.
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http://dx.doi.org/10.1007/s40259-016-0173-6DOI Listing
June 2016

Effect of cooperation of chaperones and gene dosage on the expression of porcine PGLYRP-1 in Pichia pastoris.

Appl Microbiol Biotechnol 2016 Jun 17;100(12):5453-65. Epub 2016 Feb 17.

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Wushan Road, Tianhe district, Guangzhou, Guangdong, 510642, China.

Mammalian peptidoglycan recognition proteins (PGLYRPs) are highly conserved pattern-recognition molecules of the innate immune system with considerable bactericidal activity, which manifest their potential values for the application to food and pharmaceutical industry. However, the effective expression of porcine PGLYRP-1 in Pichia pastoris has not been reported so far. In this study, expression in P. pastoris was explored as an efficient way to produce functional porcine PGLYRP-1. Cooperation of chaperones co-expression and gene dosage (including protein disulfide isomerase (PDI)/binding protein (BiP) and pglyrp-1) were used to enhance functional expression of antimicrobial protein in P. pastoris. Overexpression of PDI was certainly able to increase secretion level of PGLYRP-1 protein because the increase in secreted PGLYRP-1 secretion was correlated with the copy numbers of PDI in high copy pglyrp-1 clones. However, co-expression of BiP was proved to be detrimental to PGLYRP-1 secretion. In addition, we also found that excessive expression of PDI and/or BiP could decrease the mRNA expression of pglyrp-1 gene. This showed that PDI and BiP as the target genes of unfolded protein response (UPR) might regulate the transcription of the target protein. These data demonstrated for the first time that the combination of chaperones and gene dosages could improve the yield of PGLYRP-1, which could facilitate the application to food and pharmaceutical industry.
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http://dx.doi.org/10.1007/s00253-016-7372-4DOI Listing
June 2016

Lysyl Oxidase Is Predictive of Unfavorable Outcomes and Essential for Regulation of Vascular Endothelial Growth Factor in Hepatocellular Carcinoma.

Dig Dis Sci 2015 Oct 6;60(10):3019-31. Epub 2015 Jun 6.

Department of Hepatobiliary Surgery, Guangxi Tumor Hospital, Nanning, 530000, People's Republic of China.

Background: Lysyl oxidase (LOX) is frequently overexpressed in a variety of malignancies and involved in tumor invasion and metastasis. Furthermore, it has been shown that LOX is closely related to vascular endothelial growth factor (VEGF).

Aims: In this study, we aimed to investigate the exact role of LOX and the correlation between LOX and VEGF in hepatocellular carcinoma (HCC).

Methods: The expression levels of LOX in HCC tissue and adjacent noncancerous tissue were evaluated by quantitative reverse transcription polymerase chain reaction and immunohistochemical analysis. The effect of LOX knockdown on cell proliferation, migration, and invasion was investigated in vitro. The role of LOX in the regulation of VEGF was further characterized in HCC cells that had been treated with transforming growth factor beta (TGF-β).

Results: Our study showed that LOX was up-regulated in HCC cell lines and tissue. HCC patients with elevated expression of LOX had relatively shorter disease-free survival and overall survival. Knockdown of LOX reduced the proliferation, migration, and invasion of HCC cells. Additionally, the expression level of LOX positively correlated with that of VEGF. After treatment with TGF-β, the levels of LOX and VEGF were both up-regulated in a dose-dependent manner. In the cells treated with siRNA of LOX, levels of VEGF and phosphorylated p38 were significantly decreased and could not be up-regulated by TGF-β. Inhibition of p38 MAPK signaling abrogated TGF-β-mediated up-regulation of VGEF but did not affect LOX expression.

Conclusions: LOX appears to be a predictor of less favorable outcomes and may regulate the expression of VEGF via p38 MAPK signaling.
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http://dx.doi.org/10.1007/s10620-015-3734-5DOI Listing
October 2015

The association between three cyclooxygenase-2 polymorphisms and hepatocellular carcinoma risk: a meta-analysis.

PLoS One 2015 2;10(3):e0118251. Epub 2015 Mar 2.

Hepatobiliary Surgery Department, Tumor Hospital of Guangxi Medical University, Nanning, P.R.China.

Background: A quantity of case-control studies have been performed to address the association between three cyclooxygenase-2(COX-2) polymorphisms (-1195G/A, -765G/C and +8473T/C) and the risk of hepatocellular carcinoma (HCC). However, previous research results are inconsistent. We conducted this meta-analysis to clarify the correlation between these COX-2 polymorphisms and HCC risk.

Methods: The authors searched in PubMed, EMBASE, Google Scholar, CNKI and WanFang database for relevant articles up to April 28, 2014. The data were extracted by two independent reviewers. Odds ratios (ORs) and 95% confidence intervals were calculated.

Results: A total of 8 studies consisting of 2182 cases and 3324 controls were included in this meta-analysis. For COX-2 polymorphism -1195G/A, an association with increased risk was observed under the heterogeneous, homozygous, dominant model. However, COX-2 polymorphisms (-765G/C and +8473T/C) were not related to HCC risk in this study. We also found a similar result in the subgroup analysis of Chinese population that -1195G/A polymorphism, instead of -765G/C or +8473T/C polymorphism, was correlated with the risk of HCC.

Conclusions: Polymorphism -1195G/A of COX-2 might be associated with susceptibility to HCC, but no similar correlations were observed between polymorphisms (-765G/C and +8473T/C) and HCC risk. Further large and well-designed studies are required to validate this association.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0118251PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346398PMC
January 2016

CpG oligodeoxynucleotide protect neonatal piglets from challenge with the enterotoxigenic E. coli.

Vet Immunol Immunopathol 2014 Sep 12;161(1-2):66-76. Epub 2014 Jul 12.

Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou, 510642, Guangdong, China. Electronic address:

CpG motifs activates mammalian lymphocytes and macrophages to produce cytokines and polyclonal Ig. These include IFN-γ, IL-12, TNF-a, which are important in the control of bacterial infection. But thus far, the innate immunostimulatory effects of CpG ODN against pathogen have been established mainly in mouse, monkey, sheep, chicken, but not in neonatal piglets. The purpose of this study is to determine the potential protection of CpG ODN against enterotoxigenic Escherichia coli (ETEC) (with which neonatal piglets were susceptible to infection in our lab) in neonatal piglets. Here, we show intranasal (IN)-mucosal and intramuscularly (IM) systemic administration of CpG ODN could enhance innate cellular (cytokine) immunity in the sera and intestine mucosa post challenge, and thereafter the development of antigen-specific antibodies in piglets. IN and IM immunizations of neonatal piglets without antigen both reduced the ETEC excretion and alleviated diarrhoea symptoms upon challenge, and IN route had better protection effects than IM route. Protection in this study was linked to induction of a Th1 response which induced by CpG ODN. Co-delivery with Emulsigen (EM), could improve protection mediated by CpG ODN. These observations indicate that IN administration of 100 μg/kg CpG ODN with 20% EM codelivery may represent a valuable strategy for induction of innate immunity against ETEC infection in neonatal piglets.
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http://dx.doi.org/10.1016/j.vetimm.2014.07.003DOI Listing
September 2014

Immunization of aged pigs with attenuated pseudorabies virus vaccine combined with CpG oligodeoxynucleotide restores defective Th1 immune responses.

PLoS One 2013 13;8(6):e65536. Epub 2013 Jun 13.

College of Life Sciences, South China Agricultural University, Guangzhou, Guangdong, China.

Background And Aims: Attempts to immunize aged subjects often result in the failure to elicit a protective immune response. Murine model studies have shown that oligonucleotides containing CpG motifs (CpG ODN) can stimulate immune system in aged mice as effectively as in young mice. Since many physiological and pathophysiological data of pigs can be transferred to humans, research in pigs is important to confirm murine data. Here we investigated whether immunization of aged pig model with attenuated pseudorabies virus vaccine (PRV vaccine) formulated with CpG ODN could promote a successful development of immune responses that were comparable to those induced in young pigs in a similar manner.

Methodology: Young and aged pigs were immunized IM with PRV vaccine alone, or in combination with CpG ODN respectively. At days 3, 7, 14 post immunization sera were assayed by ELISA for IgG titres, at day 7 for IgG1 and IgG2 subtypes titres. All blood samples collected in evacuated test tubes with K-EDTA at day 7 were analyzed for flow cytometer assay. Blood samples at day 7 collected in evacuated test tubes with heparin were analysed for antigen-specific cytokines production and peripheral blood mononuclear cells (PBMCs) proliferative responses.

Results: CpG ODN could enhance Th1 responses (PRV-specific IgG2/IgG1 ratio, proliferative responses, Th1 cytokines production) when used as an adjuvant for the vaccination of aged pigs, which were correlated with enhanced CD4+ T cells percentage, decreased CD4+CD8+CD45RO+ T cells percentage and improved PRV-specific CD4+ T cells activation.

Conclusions: Our results demonstrate a utility for CpG ODN, as a safe vaccine adjuvant for promoting effective systemic immune responses in aged pig model. This agent could have important clinical uses in overcoming some of age-associated depressions in immune function that occur in response to vaccination.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0065536PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681863PMC
January 2014
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