Publications by authors named "Yan-Jie Chen"

24 Publications

  • Page 1 of 1

Interferon regulatory factor family influences tumor immunity and prognosis of patients with colorectal cancer.

J Transl Med 2021 09 6;19(1):379. Epub 2021 Sep 6.

Department of Medical Oncology, and Cancer Center, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Background: Since interferon regulatory factor (IRF) family functions in immune response to viral infection, its role in colorectal cancer (CRC) has not been inspected before. This study tries to investigate members of IRF family using bioinformatics approaches in aspect of differential expressions, biological function, tumor immune infiltration and clinical prognostic value for patients with CRC.

Methods: Transcriptome profiles data, somatic mutations and clinical information of CRC were obtained from COAD/READ dataset of The Cancer Genome Atlas (TCGA) as a training set. Gene expression data (GSE17536 and GSE39582) were downloaded from the Gene Expression Omnibus as a validating set. A random forest algorithm was used to score the risk for every case. Analyzing gene and function enrichment, constructing protein-protein interaction and noncoding RNA network, identifying hub-gene, characterizing tumor immune infiltration, evaluating differences in tumor mutational burden (TMB) and sensitivity to chemotherapeutics or immunotherapy were performed by a series of online tools and R packages. Immunohistochemical (IHC) examinations were carried out validation in tissue samples.

Results: Principal-component analysis (PCA) suggested that the transcript expression levels of nine members of IRF family differed between normal colorectum and CRC. The risk score constructed by IRF family not only acted as an independent factor for predicting survival in CRC patients with different biological processes, signaling pathways and TMB, but also indicated different immunotherapy response with diverse immune and stromal cells infiltration. IRF3 and IRF7 were upregulated in CRC and suggested a shorter survival time in patients with CRC. Differentially expressed members of IRF family exhibited varying degrees of immune cell infiltration. IHC analysis showed a positive association between IRF3 and IRF7 expression and tumor-infiltrating immune cells, including CD4 T cell and CD68 macrophages.

Conclusions: On account of differential expression, IRF family members can help to predict both response to immunotherapy and clinical prognosis of patients with CRC. Our bioinformatic investigation not only gives a preliminary picture of the genetic features as well as tumor microenvironment, but it may provide a clue for further experimental exploration and verification on IRF family members in CRC.
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http://dx.doi.org/10.1186/s12967-021-03054-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422700PMC
September 2021

Impact of probiotics supplement on the gut microbiota in neonates with antibiotic exposure: an open-label single-center randomized parallel controlled study.

World J Pediatr 2021 Aug 31;17(4):385-393. Epub 2021 Jul 31.

Department of Pediatrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, No. 301 Middle Yanchang Road, Shanghai, China.

Background: Antibiotics, a common strategy used for neonatal infection, show consistent effect on the gut microbiota of neonates. Supplementation with probiotics has become increasingly popular in mitigating the loss of the gut microbiota. However, no clear consensus recommending the use of probiotics in the infection of neonates currently exists. This study examined the effects of probiotics on the gut microbiota of infectious neonates when used concurrently with or during the recovery period following antibiotic therapy.

Methods: Fifty-five full-term neonates diagnosed with neonatal infections were divided into the following groups: NI (no intervention, antibiotic therapy only), PCA (probiotics used concurrently with antibiotics), and PAA (probiotics used after antibiotics). The NI group received antibiotic treatment (piperacillin-tazobactam) for 1 week and the PCA group received antibiotic treatment together with probiotics (Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis) for 1 week. The PAA group received antibiotic treatment for 1 week followed by probiotics for 1 week. Fecal samples were collected at four time nodes: newborn, 1 week, 2 weeks, and 42 days after birth. The composition of the gut microbiota was determined by the high-throughput sequencing of 16S rRNA amplicons.

Results: Antibiotic exposure was found to dramatically alter gut microbiota, with a significant decrease of Bifidobacterium and Lactobacillus. The use of probiotics did not restore the overall diversity of the gut microbiota. However, using probiotics simultaneously with the antibiotics was found to be beneficial for the gut microbiota as compared to delaying the use of probiotics to follow treatment with antibiotics, particularly in promoting the abundance of Bifidobacterium.

Conclusions: These results suggest that the early use of probiotics may have a potential ability to remodel the gut microbiota during recovery from antibiotic treatment. However, further study is required to fully understand the long-term effects including the clinical benefits.
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http://dx.doi.org/10.1007/s12519-021-00443-yDOI Listing
August 2021

Muramyl dipeptide promotes Aβ1-42 oligomer production via the NOD2/p-p38 MAPK/BACE1 signaling pathway in the SH-SY5Y cells.

J Integr Neurosci 2020 Sep;19(3):421-428

Department of Chinese Medicine, East Hospital, Tongji University, Shanghai, 310000, P. R. China.

The relationship between chronic bacterial colonization in the brain and Alzheimer's disease is attracting extensive attention. Recent studies indicated that the components of bacterial biofilm drive the amyloid-β production. Muramyl dipeptide, the minimal bioactive peptidoglycan motif common to all bacteria, contributes to the development of many central inflammatory and neurodegenerative disorders. However, the involvement of Muramyl dipeptide in amyloid-β production is not completely defined. In our present study, wild type mice received an intracerebroventricular injection of normal saline or Muramyl dipeptide. Data showed that the production of Aβ1-42 oligomers was significantly increased after Muramyl dipeptide injection in the wild type mice or incubation of the SH-SY5Y cells with Muramyl dipeptide. Moreover, the action of Muramyl dipeptide was dose- and time-dependent. The above results suggested a possibility that the Muramyl dipeptide-induced Aβ1-42 oligomer production might be related to the NOD2/p-p38 MAPK/BACE1 pathway. To confirm this, the SH-SY5Y cells were transfected with siRNA NOD2. Data showed that the transfected SH-SY5Y cells exhibited decreased expression of Aβ1-42 oligomer, NOD2, p-p38 MAPK, and BACE1 after treatment with Muramyl dipeptide. Finally, SH-SY5Y cells were pretreated with SB203580, an inhibitor of the p-38-MAPK pathway. The results indicated that these pretreated SH-SY5Y cells exhibited decreased expression of Aβ1-42 oligomer, p-p38 MAPK, and BACE1 after treatment with Muramyl dipeptide. In conclusion, these results suggested that Muramyl dipeptide was the trigger factor for Aβ1-42 oligomer production, which probably acts via the NOD2/p-p38 MAPK/BACE1 signaling pathway.
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http://dx.doi.org/10.31083/j.jin.2020.03.112DOI Listing
September 2020

ISO-alpha-acids improve the hematoma resolution and prevent peri-hematoma inflammations by transforming microglia via PPARgamma-CD36 axis in ICH rats.

Int Immunopharmacol 2020 Jun 16;83:106396. Epub 2020 Mar 16.

Department of Neurosurgery, Huashan Hospital, Fudan University, 12 Wulumuqi Road (M), Shanghai 200040, PR China. Electronic address:

Objective: To elucidate the effects of ISO-α-acids (IAAs), a PPAR-γ agonist, on ICH rats and its potential mechanism.

Material And Methods: The Sprague Dawley rats ICH model was induced by stereotactic injecting of 100 μl autologous artery blood. Ninety male rats were randomly allocated to five groups: autologous blood and IAAs (IAA); received autologous blood, IAAs and PPAR-γ inhibitor (IAA + GW9662); autologous blood and normal Saline (Saline); only autologous blood (Mock); and only needle injection (Sham). Neurological functions were assessed by mNSS. Hematoma volume, brain water content, surface proteins and inflammatory factors were detected. The microglia anti-inflammatory abilities were also evaluated.

Results: IAAs were able to significantly decrease ICH rat's mNSS scores, alleviate brain water content, improve hematoma resolution than Saline, Mock (p < 0.05). More "M2" microglial/macrophage can be induced by IAAs. The expression of CD 36 was statistically higher in IAA than other groups (p < 0.05). Injection of IAAs led to a greatly increasing in CD 11b and CD 206 double-positive anti-inflammatory type microglial/macrophage, moreover, a reduction of inflammatory cytokines expression (p < 0.05). Such protective effects can be relieved by GW9662.

Conclusions: This is the first study to elucidate the relationship between IAAs and ICH. IAAs were able to accelerate hematoma absorption, alleviate brain edema, suppress peri-hematoma inflammations and finally improved the outcome of ICH rats. The phenotype was due to the IAAs induction of "M2" microglial/macrophage via activating of PPAR-γ and increasing CD 36 expression.
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http://dx.doi.org/10.1016/j.intimp.2020.106396DOI Listing
June 2020

IRF-2 Inhibits Gastric Cancer Invasion and Migration by Down-Regulating MMP-1.

Dig Dis Sci 2020 01 26;65(1):168-177. Epub 2019 Jul 26.

Department of Gastroenterology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

Purpose: The interferon regulatory factor 2 (IRF-2) acted as a tumor suppressor. We inspected IRF-2 as a predictor of prognosis in gastric cancer (GC) patients and tried to find out the potential molecular mechanism.

Methods: In this study, the association between IRF-2 expression and clinical or prognosis significance was investigated in 86 pairs of tumor and the adjacent normal gastric tissues from GC patients. After establishing the stable cell lines, the Transwell assays were deduced to evaluate the malignancy of tumor. Then, microarray assay was carried out and the GO/KEGG pathway analyses were conducted to identify IRF-2's target gene. The relationship between IRF-2 and matrix metalloproteinases 1 (MMP-1) was also investigated by the immunohistochemistry in 15 pairs of tumor and adjacent normal gastric tissues.

Results: We found that IRF-2 expression level in GC was significantly correlated with the prognosis of the patients. Transwell assays suggested an impaired ability of invasion and migration in IRF-2-overexpressed GC cells and a progressive malignant phenotype in IRF-2-knockdown GC cells. Ninety differentially expressed genes were found between IRF-2-overexpressed GC cells and its normal control sets by microarray. We demonstrated that MMP-1 was canonical in the network of differentially expressed genes by GO and KEGG pathway analysis and its expression level was markedly decreased in IRF-2-overexpressed cells of MKN-45 and increased in IRF-2-knockdown cells of SGC-7901. The expression of MMP-1 was inversely correlated with IRF-2 in GAC TMA specimens.

Conclusion: IRF-2 may inhibit GC progression by down-regulating MMP-1 level.
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http://dx.doi.org/10.1007/s10620-019-05739-8DOI Listing
January 2020

Inhibition of JAK2/STAT3 Signaling Pathway Suppresses Proliferation of Burkitt's Lymphoma Raji Cells via Cell Cycle Progression, Apoptosis, and Oxidative Stress by Modulating HSP70.

Med Sci Monit 2018 Sep 8;24:6255-6263. Epub 2018 Sep 8.

Department of Hematology, Central Hospital of Lishui City, Lishui, Zhejiang, China (mainland).

BACKGROUND The aim of this study was to investigate the effect of the JAK2/STAT3 pathway on the proliferation, cell cycle distribution, apoptosis, and oxidative stress of Raji cells via regulating HSP70 expression. MATERIAL AND METHODS Raji cells were divided into Blank, HSP70 siRNA, NC siRNA, AG490 (a JAK2/STAT3 signaling pathway inhibitor), and HSP70 siRNA + rh JAK2 (recombinant human JAK2) groups. HSP70 expression was detected by quantitative real-time reverse transcription-PCR (qRT-PCR); the expression levels of HSP70 and JAK2/STAT3 pathway-related proteins were evaluated by Western blotting; cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays; cell cycle distribution was observed by flow cytometry; cell apoptosis was tested by Annexin V-FITC/PI and Hoechst 33342/PI staining; reactive oxygen species (ROS) production was measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) assays; and MDA content and SOD and GSH-Px activities were determined using detection kits. RESULTS AG490 obviously down-regulated HSP70 expression, inhibited proliferation, induced cell cycle arrest at the G0/G1 phase, and promoted apoptosis in Raji cells; these effects were similar to the effects of HSP70 siRNA. Furthermore, ROS production and MDA content were increased in Raji cells treated with HSP70 siRNA or AG490, while SOD and GSH-Px activities were reduced. Raji cells in the HSP70 siRNA + rh JAK2 group did not significantly differ from those in the Blank group in regards to proliferation, cell cycle, apoptosis, and oxidative stress. CONCLUSIONS Blocking the JAK2/STAT3 signaling pathway may inhibit proliferation, induce cell cycle arrest, and promote oxidative stress and apoptosis in Raji cells via the down-regulation of HSP70.
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http://dx.doi.org/10.12659/MSM.910170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140376PMC
September 2018

Diagnostic and Prognostic Value of Circulating MicroRNAs for Esophageal Squamous Cell Carcinoma: a Systematic Review and Meta-analysis.

J Cancer 2018 30;9(16):2876-2884. Epub 2018 Jul 30.

Department of Gastroenterology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China.

MicroRNAs, dysregulated in the circulation of esophageal squamous cell carcinoma (ESCC) patient, have been assumed to be with great potential in the diagnosis and prognosis of esophageal cancer. We aimed to review previous articles on ESCC. A search of electronic databases was performed before Nov 12, 2017. We summarized the identification of microRNA imbalance in the blood of ESCC compared with the healthy controls, with the objective to evaluate the efficiency of microRNAs in diagnosing and forecasting ESCC. A total of 35 studies investigating plasma or serum microRNAs were included in the meta-analysis. Based on the consequences of the quality assessment of each study, the articles involved were appropriate for quantitative synthesis. For diagnostic meta-analysis. The overall pooled sensitivity, specificity, and area under the curve of circulating microRNA is 0.794 (95% CI: 0.765 - 0.820), 0.779 (95%CI: 0.746 - 0.808), 0.86 (95%CI: 0.82 - 0.88). The diagnostic value of each microRNA was calculated respectively. For prognostic meta-analysis, the overall pooled hazard ratios of higher microRNA expression in circulation was 1.34 (95% CI: 1.14-1.58), which could significantly predict poorer survival in ESCC. Circulating microRNAs distinguish patients with ESCC from healthy controls with high sensitivity and specificity, compared to other invasive currently used screening methods. Simultaneously, there was prognostic value for the prognosis of ESCC.
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http://dx.doi.org/10.7150/jca.25351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6096380PMC
July 2018

Parasutterella, in association with irritable bowel syndrome and intestinal chronic inflammation.

J Gastroenterol Hepatol 2018 Nov 3;33(11):1844-1852. Epub 2018 Jun 3.

Department of Gastroenterology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China.

Background And Aim: Irritable bowel syndrome (IBS) is a highly prevalent chronic functional gastrointestinal disorder. Recent studies have showed increasing important role of gut microbiota in the pathophysiological changes of IBS. Our study aims to elaborate the association between intestinal flora with the genesis and the development of IBS.

Methods: Illumina high-throughput sequencing technology was applied to investigate microbial communities of IBS patients and healthy donors. Stool specimens from the IBS-D patients were equally premixed and implanted into germ free C57B/6 mice to construct IBS animal model, and the normal group was also transplanted with normal premixed feces. The post-transplant defecation and intra-epithelial lymphocyte counts were evaluated. Microbial communities were also checked by the illumina high-throughput sequencing technology.

Results: Fifteen genuses significantly different were found expressed in the gut flora of IBS patients, and six genuses showed significantly different abundances between the stool specimens of mice of IBS group and normal group. Among these differences, Parasutterella expression was remarkably different in both screening and validation experiments and also related to chronic intestinal inflammation; therefore, Parasutterella expression is considered in association with the development and progression of IBS.

Conclusion: Parasutterella may be related with the genesis and development of IBS and also associated with chronic intestinal inflammation in IBS patients.
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http://dx.doi.org/10.1111/jgh.14281DOI Listing
November 2018

Serum microRNA signatures and metabolomics have high diagnostic value in gastric cancer.

BMC Cancer 2018 04 13;18(1):415. Epub 2018 Apr 13.

Department of Gastroenterology, Zhongshan Hospital of Fudan University, Room 207, Building 3, Zhongshan Hospital, Fenglin Road 180#, Xuhui District, Shanghai, China.

Background: Many novel diagnostic biomarkers have been developed for gastric cancer (GC) recently. We chose two methods with high diagnostic value, the detection of serum microRNAs and metabolomics based on gas chromatography/mass spectrometry (GC/MS), and aimed to establish appropriate models.

Methods: We reviewed the diagnostic accuracies of all microRNAs identified by previous diagnostic tests. Then appropriate microRNAs and their combinations were validated the diagnostic value. We included 80 patients with GC and 82 healthy controls (HCs) and detected the expression of the microRNAs. GC/MS analysis was conducted, and we used three multivariate statistical analyses to establish diagnostic models. The concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected for comparison with the novel models.

Results: Sixty-seven published studies and 70 microRNAs were finally included in the systematic review. MiR-18a, miR-19a, miR-21, miR-92a, miR-199a and miR-421 were chosen to further validate their diagnostic efficiencies. Five of those microRNAs in GC patients had significantly different expression. The combination of miR-19a and miR-92a had the highest area under the curve (AUC) at 0.850 with a sensitivity of 91.3% and a specificity of 61.0%. The GC/MS analysis performed an excellent diagnostic value and the AUC reached 1.0.

Conclusion: There is a good potential for microRNAs and GC/MS analysis as new diagnostic methods in view of their high diagnostic value compared with traditional biomarkers.
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http://dx.doi.org/10.1186/s12885-018-4343-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899358PMC
April 2018

Serum microRNA signatures and metabolomics have high diagnostic value in colorectal cancer using two novel methods.

Cancer Sci 2018 Apr 26;109(4):1185-1194. Epub 2018 Feb 26.

Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.

Recently, many new diagnostic biomarkers have been developed for colorectal cancer. We chose 2 methods with high diagnostic efficiency, the detection of serum microRNA and metabolomics based on gas chromatography/mass spectrometry (GC/MS), and aimed to establish appropriate models. We reviewed the diagnostic value of all microRNA identified by previous diagnostic tests. We selected appropriate microRNA to validate their diagnostic efficiency, and determined the optimal combination. We included 85 patients with colorectal cancer (CRC) and 78 healthy controls (HC) and detected the expression of the microRNA. GC/MS analysis was conducted, and we used 3 multivariate statistical methods to establish diagnostic models. The concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected for comparison with the novel models. Ultimately, 62 published studies and 63 microRNA were included in this review. MiR-21, miR-29a, miR-92a, miR-125b and miR-223 were selected to further validate their diagnostic value. The serum levels of the 5 microRNA in CRC patients were significantly higher than those in the HC. The combination of miR-21, miR-29a, miR-92a and miR-125b had the highest area under the curve (AUC) at 0.952, with a sensitivity of 84.7% and a specificity of 98.7%. The GC/MS analysis exhibited an excellent diagnostic value and the AUC reached 1.0. With regard to traditional biomarkers, the AUC of CEA and CA19-9 were 0.808 and 0.705, respectively. The application prospects are good for microRNA and metabolomics as new diagnostic methods because of their high diagnostic value compared with traditional biomarkers.
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http://dx.doi.org/10.1111/cas.13514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891204PMC
April 2018

Serum microRNA signatures and metabolomics have high diagnostic value in hepatocellular carcinoma.

Oncotarget 2017 Dec 1;8(65):108810-108824. Epub 2017 Nov 1.

Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai 200032, China.

Background: Many new diagnostic biomarkers have been developed for hepatocellular carcinoma (HCC). We selected two methods with high diagnostic value, the detection of serum microRNAs and metabolomics based on gas chromatography/mass spectrometry (GC/MS), and attempted to establish appropriate models.

Methods: We reviewed the diagnostic efficiencies of all microRNAs identified by previous diagnostic tests. Then we chose appropriate microRNAs to validate the diagnostic efficiencies, and determined the optimal combination. We included 66 patients with HCC and 82 healthy controls (HCs) and detected the expression of the microRNAs. GC/MS analysis was performed, and we used three multivariate statistical methods to establish diagnostic models. The concentration of alpha feto-protein (AFP) was determined for comparison with the novel models.

Results: 82 published studies and 92 microRNAs were ultimately included in this systematic review. Seven microRNAs were selected for further validation of their diagnostic efficiencies. Among which, miR-21, miR-106b, miR-125b, miR-182 and miR-224 had a significantly different expression in HCC patients. The combination of miR-21, miR-106b and miR-224 had the highest area under the curve (AUC) at 0.950 with a sensitivity of 80.3% and a specificity of 92.7%. The GC/MS analysis exhibited an excellent diagnostic value and the AUC reached 1.0. In comparison, the AUC of the traditional biomarker, AFP, was 0.755.

Conclusion: MicroRNAs and metabolomics shows promising potential as new diagnostic methods due to their high diagnostic value compared with traditional biomarkers.
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http://dx.doi.org/10.18632/oncotarget.22224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752483PMC
December 2017

Interferon regulatory factors: A key to tumour immunity.

Int Immunopharmacol 2017 Aug 19;49:1-5. Epub 2017 May 19.

Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai 200032, China; Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China. Electronic address:

Interferon regulatory factors (IRFs), which have 10 members, belong to the transcription factor family and were named because of the regulation of interferon expression. They play important roles in the immune regulation, cell differentiation, cell apoptosis, and cell cycle regulation. This article will review the functional characteristics and immune activity of the family members, especially in the role of cell differentiation and autoimmune diseases. Intensive studies will help uncover the pathogenesis of the disease in a more comprehensive view, and provide novel targets for disease treatment. But the most important problems yet to solve is IRFs function in the development processes of tumour, and whether IRFs can be an important regulator in tumour immune treatment.
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http://dx.doi.org/10.1016/j.intimp.2017.05.010DOI Listing
August 2017

Altered molecular signature of intestinal microbiota in irritable bowel syndrome patients compared with healthy controls: A systematic review and meta-analysis.

Dig Liver Dis 2017 Apr 21;49(4):331-337. Epub 2017 Jan 21.

Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China. Electronic address:

Background: Many studies have reported significant changes in intestinal microbiota in irritable bowel syndrome (IBS) patients based on quantitative real-time PCR analysis.

Aims: We aimed to review the alterations in intestinal microbiota.

Methods: An online search up to June 9, 2016, was conducted. This systematic review and meta-analysis included differential expression of intestinal microbiota in patients with IBS versus healthy controls (HCs) and subgroup analysis. We assessed the quality of the included studies using an original assessment tool.

Results: A total of 13 articles involving 360 IBS patients and 268 healthy controls were included. The quality assessment scores for these articles ranged from 5 to 8. Significant differences in expression in IBS patients were observed for Lactobacillus (SMD=-0.85, P<0.001, I=28%), Bifidobacterium (SMD=-1.17, P<0.001, I=79.3%), and Faecalibacterium prausnitzii (SMD=-1.05, P<0.001, I=0.0%) but not Bacteroides-Prevotella group, Escherichia coli or other genera or species. Subgroup analysis showed that diarrhea-predominant IBS patients had significantly different expression of Lactobacillus (SMD=-1.81, P<0.001) and Bifidobacterium (SMD=-1.45, P<0.001).

Conclusion: Down-regulation of bacterial colonization including Lactobacillus, Bifidobacterium and F. prausnitzii was observed in IBS patients, particularly in diarrhea-predominant IBS (IBS-D). Microbiota changes participate in the pathogenesis of IBS and may underlie the efficacy of probiotic supplements.
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http://dx.doi.org/10.1016/j.dld.2017.01.142DOI Listing
April 2017

Prp19 facilitates invasion of hepatocellular carcinoma via p38 mitogen-activated protein kinase/twist1 pathway.

Oncotarget 2016 Apr;7(16):21939-51

Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.

Pre-mRNA processing factor 19 (Prp19) is involved in many cellular events including pre-mRNA processing and DNA damage response. However, the pathological role of Prp19 in hepatocellular carcinoma (HCC) is still elusive. Here, we reported that Prp19 was increased in most HCC tissues and HCC cell lines, and its overexpression in HCC tissues was positively correlated with vascular invasion, tumor capsule breakthrough and poor prognosis. Prp19 potentiated migratory and invasive abilities of HCC cells in vitro and in vivo. Furthermore Prp19 facilitated Twist1-induced epithelial-mesenchymal transition. Mechanistic insights revealed that Prp19 directly binded with TGF-β-activated kinase1 (TAK1) and promoted the activation of p38 mitogen-activated protein kinase (MAPK), preventing Twist1 from degradation. Finally Prp19/p38 MAPK/Twist1 axis was attested in nude mice xenografts and HCC patient specimens. This work implies that the gain of Prp19 is a critical event during the progression of HCC, making it a promising target for malignancies with aberrant Prp19 expression.
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http://dx.doi.org/10.18632/oncotarget.7877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008335PMC
April 2016

The ubiquitin-proteasome system and its potential application in hepatocellular carcinoma therapy.

Cancer Lett 2016 09 17;379(2):245-52. Epub 2015 Jul 17.

Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai 200032, China; Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai 200032, China. Electronic address:

The ubiquitin-proteasome system (UPS) is a complicated tightly controlled system in charge of degrading 80-90% of proteins, and is central to regulating cellular function and keeping protein homeostasis. Therefore, the components of UPS attract considerable attention as potential targets for hepatocellular carcinoma (HCC) therapy. The clinical success of bortezomib in multiple myeloma and mantle cell lymphoma patients has set the precedent for therapeutically targeting this pathway. This review will provide an overview of the UPS in HCC and the current status of therapeutic strategies.
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http://dx.doi.org/10.1016/j.canlet.2015.06.023DOI Listing
September 2016

MicroRNA-18a modulates P53 expression by targeting IRF2 in gastric cancer patients.

J Gastroenterol Hepatol 2016 Jan;31(1):155-63

Department of Gastroenterology.

Background And Aim: MicroRNA-18a (miR-18a) has been reported to be upregulated in gastric cancer (GC) tissues compared with normal gastric tissues. However, little is known about its prognostic value and biological roles.

Methods: In this study, miR-18a expression in gastric adenocarcinoma (GAC) tissues and adjacent non-tumor tissues was validated by in situ hybridization, and the predictive values of miR-18a were explored. The biological roles of miR-18a and the underlying signal pathway were investigated in GC cell lines.

Results: Overexpressed intra-tumoral miR-18a was associated with poor survival rate and was an independent prognostic factor for overall survival rate (P < 0.001) in GC patients. Forced expression of miR-18a remarkably enhanced cell proliferation, migration, and invasion in GC cells, while inhibition of miR-18a caused the opposite effects. Further study showed that miR-18a suppressed the expression of interferon regulatory factor 2 (IRF2) by directly binding to its 3'-untranslated region. Moreover, miR-18a expression levels are inversely correlated with IRF2 in human GC tissues. Western blot showed that forced expression of miR-18a could not only downregulate the expression of IRF2, but also inhibit the expression of P53, suggesting that IRF2 might play as a tumor suppressor by regulating P53 signaling in GC.

Conclusion: miR-18a modulated P53 expression by directly targeting IRF2 and had a high predictive value for prognosis of GAC patients. These results may lead to identification of therapeutic candidates of GC.
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http://dx.doi.org/10.1111/jgh.13041DOI Listing
January 2016

Circulating microRNAs as a fingerprint for endometrial endometrioid adenocarcinoma.

PLoS One 2014 20;9(10):e110767. Epub 2014 Oct 20.

Department of Obstetrics and Gynecology, Shanghai Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Endometrial cancer is the most common malignancy of the female genital tract worldwide, and endometrial endometrioid adenocarcinoma (EEC) is the major histological type of endometrial cancer. There is a great need for better markers with high sensitivity and specificity to permit early diagnosis and proper management of EEC. The aim of our study is to identify a miRNA classifier within plasma as a noninvasive biomarker for EEC diagnosis.

Methods: This study was a retrospective case-control analysis which contained two independent cohorts including 93 participants. First, we screened 375 miRNAs in 29 plasma samples. 9 of the miRNAs were selected to be evaluated their expression by quantitative reverse-transcriptase polymerase chain reaction. A stepwise logistic regression model was then used to establish a new classifier in the validation cohort. Area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy. Co-expression analysis was used to verify the independence of results.

Results: miR-15b, -27a, and -223 were found to be differentially expressed in the EEC plasma between the two cohorts and had few connections with other miRNAs. The areas under the curve (AUC) were 0.768, 0.813, and 0.768 for miR-15b, -27a, and 223, respectively. miR-27a and CA125 can be combined as a potential non-invasive biomarker for detecting EEC, with the AUC of 0.894.

Conclusion: Our study demonstrated three miRNAs, including miR-15b, -27a, and -233 have a good clinical value in EEC diagnosis. The classifier, including miR-27a and CA125, demonstrated a high accuracy in the diagnosis of EEC and might serve as a novel non-invasive biomarker in the future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0110767PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203829PMC
June 2015

High expression of UCH37 is significantly associated with poor prognosis in human epithelial ovarian cancer.

Tumour Biol 2014 Nov 15;35(11):11427-33. Epub 2014 Aug 15.

Department of Obstetrics and Gynecology, Shanghai Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Ubiquitin carboxyl-terminal hydrolase 37 (UCH37) is a member of deubiquitinating enzymes. It can suppress protein degradation through disassembling polyubiquitin from the distal subunit of the chain. The aim of this study was to assess the value of UCH37 in predicting tumor recurrence after curative resection in epithelial ovarian cancer (EOC) patients. In this study, the expression level of UCH37 in 5 paired EOC and normal tissue was tested by Western blot. And the association of UCH37 expression and prognostic value was analyzed in 100 tumor specimens from EOC patients, who underwent curative resection between 2003 and 2011. We found that UCH37 was up-regulated in most of the tumor tissue and high expression of UCH37 was an independent significant predictor associated with the poor outcome and recurrence of EOC (p=0.0037 and p=0.0042 in overall and disease-free survival, respectively), especially in the advanced stage of EOC (p=0.0106 and p=0.0115 in overall and disease-free survival, respectively), and may become a novel predictor for prognosis of EOC patients after curative resection. Our data suggest for the first time that UCH37 overexpression is associated with advanced tumor progression and poor clinical outcome of EOC patients and may help physicians make informed decisions regarding adjuvant treatment following curative resection.
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http://dx.doi.org/10.1007/s13277-014-2446-3DOI Listing
November 2014

Expression and clinical significance of BIRC6 in human epithelial ovarian cancer.

Tumour Biol 2014 May 23;35(5):4891-6. Epub 2014 Jan 23.

Department of Obstetrics and Gynecology, Shanghai Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Baculoviral IAP repeat containing 6 (BIRC6), an unusually large member of the IAP family, may play an important role in oncogenesis. The aim of this study was to assess the value of BIRC6 in predicting tumor recurrence after curative resection in epithelial ovarian cancer (EOC) patients. In this study, the differences of BIRC6 expression in four paired EOC and normal tissue were performed by Western blot, and expression of BIRC6 protein was analyzed in 100 clinicopathologically characterized EOC cases from those who underwent curative resection between 2003 and 2011 by immunohistochemistry. Kaplan-Meier survival estimates and log-rank tests were used to assess the prognostic significance. It was found that BIRC6 expression was higher in the carcinoma tissue than in normal control tissue at protein level by Western blot. There was a significant difference of BIRC6 expression in patients categorized according to tumor differentiation (p = 0.016). Univariate analyses and multivariate analyses revealed that BIRC6 was an independent significant predictor for overall survival and disease-free survival. A prognostic significance of BIRC6 was also found by Kaplan-Meier method. The expression of BIRC6 in the cytoplasm is associated with EOC differentiation and may be a novel predictor for poor prognosis of EOC patients after curative resection.
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http://dx.doi.org/10.1007/s13277-014-1641-6DOI Listing
May 2014

[Anti-hepatic fibrosis effects research on serum containing extracts of Periplaneta americana in vitro].

Zhong Yao Cai 2013 May;36(5):707-11

Department of Pharmacology, College of Pharmacy and Chemistry, Dali University, Dali 671000, China.

Objective: To study the anti-hepatic fibrosis effect of serum containing extracts of Periplaneta americana.

Methods: The serum contained extracts of Periplaneta americana was prepared with serologic pharmacological method. MTT method was used to observe the effect of serum containing extracts from periplaneta americana on hepatic stellate cells (HSC), and Elisa method was used to detect the contents of TGF-beta1 and collagen I in supernatant.

Results: Serum containing extracts I and II (15%) of Periplaneta americana had inhibitory effect on HCS (P < 0.05) after HSC were cultured with serum containing extracts of different concentration of Periolaneta americana for 24, 48 and 72 h. At 24 and 48 h, serum containing extracts I and II of Periplaneta americana decreased the content of collagen I in supernatant without significant difference (P < 0.05). Serum containing extracts I (15%, 9%, 5.4%) of Periplaneta americana could reduce generation of TGF-beta1 in supernatant for 24 h (P < 0.05). As for 48 h, only high concentration serum containing extracts I (15%) deceased the content of TGF-beta1 in supernatant. For 24 and 48 h,serum containing extracts II couldn't reduce the content of TGF-beta1 in supernatant (P < 0.05).

Conclusion: It has definite effect on anti-hepatic fibrosis with serum containing extracts of Periplaneta americana in vitro. The mechanism may be related to inhibiting HSC propagation and reducing the production of TGF-beta1.
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May 2013

Circulating microRNAs as a Fingerprint for Liver Cirrhosis.

PLoS One 2013 21;8(6):e66577. Epub 2013 Jun 21.

Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.

Background: Sensitive and specific detection of liver cirrhosis is an urgent need for optimal individualized management of disease activity. Substantial studies have identified circulation miRNAs as biomarkers for diverse diseases including chronic liver diseases. In this study, we investigated the plasma miRNA signature to serve as a potential diagnostic biomarker for silent liver cirrhosis.

Methods: A genome-wide miRNA microarray was first performed in 80 plasma specimens. Six candidate miRNAs were selected and then trained in CHB-related cirrhosis and controls by qPCR. A classifier, miR-106b and miR-181b, was validated finally in two independent cohorts including CHB-related silent cirrhosis and controls, as well as non-CHB-related cirrhosis and controls as validation sets, respectively.

Results: A profile of 2 miRNAs (miR-106b and miR-181b) was identified as liver cirrhosis biomarkers irrespective of etiology. The classifier constructed by the two miRNAs provided a high diagnostic accuracy for cirrhosis (AUC = 0.882 for CHB-related cirrhosis in the training set, 0.774 for CHB-related silent cirrhosis in one validation set, and 0.915 for non-CHB-related cirrhosis in another validation set).

Conclusion: Our study demonstrated that the combined detection of miR-106b and miR-181b has a considerable clinical value to diagnose patients with liver cirrhosis, especially those at early stage.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0066577PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689750PMC
October 2017

Power and promise of ubiquitin carboxyl-terminal hydrolase 37 as a target of cancer therapy.

Asian Pac J Cancer Prev 2013 ;14(4):2173-9

Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China.

Ubiquitin carboxyl-terminal hydrolase 37 (UCH37, also called UCHL5), a member of the deubiquitinating enzymes, can suppress protein degradation through disassembling polyubiquitin from the distal subunit of the chain. It has been proved that UCH37 can be activated by proteasome ubiqutin chain receptor Rpn13 and incorporation into the 19S complex. UCH37, which has been reported to assist in the mental development of mice, may play an important role in oncogenesis, tumor invasion and migration. Further studies will allow a better understanding of roles in cell physiology and pathology, embryonic development and tumor formation, hopefully providing support for the idea that UCH37 may constitute a new interesting target for the development of anticancer drugs.
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http://dx.doi.org/10.7314/apjcp.2013.14.4.2173DOI Listing
October 2013

Solid lipid nanoparticles as delivery systems for Gambogenic acid.

Colloids Surf B Biointerfaces 2013 Feb 7;102:391-7. Epub 2012 Sep 7.

Department of Clinical Pharmacy, Anhui University of Traditional Chinese Medicine, Hefei 230038, China.

In this study, Gambogenic acid loaded by solid lipid nanoparticles (GNA-SLNs) was explored to reduce toxicity and improve therapeutic efficacy. GNA-SLNs were prepared by emulsification and low temperature solidification methods, and the freeze-dried powders were then developed to improve the stability. The physical-chemical properties of the products in terms of particle size, zeta potential, morphology and entrapment efficiency were well evaluated. The results revealed that the mean diameter, polydispersivity index (PI), zeta potential, and the entrapment efficiency of the nanoparticles were 163.3 nm, 0.203, -16.9 mV and 61.2%, respectively. In comparion with GNA-SLNs, the freeze-dried solid lipid nanoparticles (SLNs) showed a slight augmentation in the mean particle size (from 163.3 to 173 nm) and PI (from 0.203 to 0.253), and no significant modification in the zeta potential, entrapment efficiency and drug loading. In vitro release kinetics based on a dialysis method demonstrated that Gambogenic acid (GNA) was released in a prolonged fashion for 96 h and followed Higuchi equation unitarily. The release profile did not show any significant modification after the freeze-drying process. The Pharmacokinetic study was carried out, the i.p. administration of GNA formulations to rats at doses of 2.5mg/kg. AUC((0-t)) was increased (up to 3.1-fold) and clearance was decreased (up to 3.03-fold) when GNA entrapped in SLNs. In conclusions, the freeze-dried powders form could enhance the long-term stability of SLN, and solid lipid nanoparticles encapsulation could effectively strategy to change the poor aqueous solubility and prolong the half-life of GNA.
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http://dx.doi.org/10.1016/j.colsurfb.2012.08.058DOI Listing
February 2013

[A case of Budd-Chiari syndrome with convulsion].

Zhonghua Er Ke Za Zhi 2004 Nov;42(11):816

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November 2004
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