Publications by authors named "Chensi Wu"

10 Publications

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Indole-3-carbinol ameliorates necroptosis and inflammation of intestinal epithelial cells in mice with ulcerative colitis by activating aryl hydrocarbon receptor.

Exp Cell Res 2021 Jul 17;404(2):112638. Epub 2021 May 17.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang province, China. Electronic address:

Ulcerative colitis (UC) is a disease characterized by inflammation and disruption of the intestinal epithelial barrier. Necroptosis plays a critical role in disease progression. Indole-3-carbinol (I3C), a natural dietary agonist of aryl hydrocarbon receptor (AHR), has shown alleviating effects on UC. However, its mechanisms of action have not been comprehensively elucidated. Therefore, we aimed at investigating the protective role of I3C in DSS-induced colitis mice models. I3C significantly ameliorated body weight loss, colon length shortening and colonic pathological damage in colitis mice, reduced disease activity index (DAI) and histological (HI) scores, as well as alleviated colonic necroptosis and inflammation. In vitro, I3C attenuated necroptosis and inflammation of colonoids and NCM460 cells. AHR, activated by I3C, inhibits activation of receptor-interacting protein kinase 1 (RIPK1) and the subsequent assembly of necrosome in a time-dependent manner, as well as suppressing NF-κB activation and decreasing TNF-α, IL-1β, IL-6 and IL-8 expression. Silencing of AHR aggravated necroptosis and inflammation of NCM460 cells, and did not be ameliorated by I3C. Furthermore, AHR activation induces the expression of inhibitor of apoptosis proteins (IAPs) and the ubiquitination of RIPK1. In conclusion, I3C exerts a protective effect in DSS-induced colitis mice models by alleviating the necroptosis and inflammation of IECs through activating AHR.
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http://dx.doi.org/10.1016/j.yexcr.2021.112638DOI Listing
July 2021

Optimization, and and evaluation of etomidate intravenous lipid emulsion.

Drug Deliv 2021 Dec;28(1):873-883

School of Pharmacy, North China University of Science and Technology, Tangshan, China.

The aim of this investigation was to develop an etomidate intravenous lipid emulsion (ETM-ILE) and evaluate its properties and . Etomidate (ETM) is a hydrophobic drug, and organic solvents must be added to an etomidate injectable solution (ETM-SOL) to aid dissolution, that causes various adverse reactions on injection. Lipid emulsions are a novel drug formulation that can improve drug loading and reduce adverse reactions. ETM-ILE was prepared using high-pressure homogenization. Univariate experiments were performed to select key conditions and variables. The proportion of oil, egg lecithin, and poloxamer 188 (F68) served as variables for the optimization of the ETM-ILE formulation by central composite design response surface methodology. The optimized formulation had the following characteristics: particle size, 168.0 ± 0.3 nm; polydispersity index, 0.108 ± 0.028; zeta potential, -36.4 ± 0.2 mV; drug loading, 2.00 ± 0.01 mg/mL; encapsulation efficiency, 97.65% ± 0.16%; osmotic pressure, 292 ± 2 mOsmol/kg and pH value, 7.63 ± 0.07. Transmission electron microscopy images showed that the particles were spherical or spheroidal, with a diameter of approximately 200 nm. The stability study suggested that ETM-ILE could store at 4 ± 2 °C or 25 ± 2 °C for 12 months. Safety tests showed that ETM-ILE did not cause hemolysis or serious vascular irritation. The results of the pharmacokinetic study found that ETM-ILE was bioequivalent to ETM-SOL. However, a higher concentration of ETM was attained in the liver, spleen, and lungs after administration of ETM-ILE than after administration of ETM-SOL. This study found that ETM-ILE had great potential for clinical applications.
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http://dx.doi.org/10.1080/10717544.2021.1917729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118403PMC
December 2021

Antibiotics Modulate Chemotherapy Efficacy in Patients with Esophageal Cancer.

Cancer Manag Res 2020 25;12:4991-4997. Epub 2020 Jun 25.

Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.

Purpose: Accumulating evidence suggests that microbiota dysbiosis induced by antibiotic administration plays a crucial role in regulating the efficacy and toxicity of cancer therapy. We explored the influence of antibiotic administration on the efficacy of chemotherapy in patients with esophageal cancer (EC).

Patients And Methods: EC patients were stratified into two groups: antibiotic-treated group and control group. The antibiotic-treated group included patients who received antibiotics within 60 days before or after chemotherapy initiation, and the control group included patients who did not receive antibiotics within 60 days before or after chemotherapy initiation. Progression-free survival (PFS) and overall survival (OS) curves were constructed using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analyses.

Results: The rate of primary progressive disease in the antibiotic-treated group was significantly higher than that in the control group (36.58% vs 10.45%, = 0.002) as calculated using the chi-square test. Further, antibiotic administration was associated with shorter PFS (6.7 vs 14.6 months, hazard ratio (HR): 2.545, 95% confidence interval (CI): 1.554-4.168, < 0.001) and reduced OS (15.0 vs 21.0 months, HR: 2.007, 95% CI: 1.213-3.319, = 0.007) in univariate analysis. Subsequent multivariate analysis indicated that antibiotic administration was a significant independent prognostic factor for PFS (HR: 2.350, 95% CI: 1.423-3.882, = 0.001) and OS (HR: 1.900, 95% CI: 1.140-3.167, = 0.014).

Conclusion: Antibiotic administration was associated with reduced chemotherapy efficacy and poor prognosis in patients with EC.
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http://dx.doi.org/10.2147/CMAR.S248130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323800PMC
June 2020

Chiral 4--acylterpineol as transdermal permeation enhancers: insights of the enhancement mechanisms of a transdermal enantioselective delivery system for flurbiprofen.

Drug Deliv 2020 Dec;27(1):723-735

School of Pharmacy, North China University of Science and Technology, Tangshan, China.

In order to devise more effective penetration enhancers, 4--acylterpineol derivatives which were expected to be hydrolyzed into nontoxic metabolites by esterase in the living epidermis, were synthesized from 4-terpineol (4-TER) enantiomers and straight chain fatty acids. Their promoting activities on the -flurbiprofen and its enantiomers were tested across full-thickness rabbit skin, as well as to correlate under and conditions. The permeation studies indicated that both -4--acylterpineol and -4--acylterpineol had significant enhancing effects, interestingly, -4--aclyterpineol had higher enhancing effects than -4--aclyterpineol with the exception of -4-methyl-1-(1-methylethyl)-3-cyclohexen-1-yl octadec-9-enoate (-4-T-dC18). The mechanism of 4--acylterpineol facilitating the drug penetration across the skin was confirmed by Attenuated total reflection-Fourier transformed infrared spectroscopy (ATR-FTIR) and molecular simulation. The mechanism of penetration enhancers promoting drug release was explored by the release experiment. Finally, a relative safety skin irritation of enhancers was also investigated by histological evaluation. The present research suggested that -4--aclyterpineol and -4--aclyterpineol could significantly promote the penetration of -flurbiprofen and its enantiomers both and , with the superiorities of high flux and low dermal toxicity.
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http://dx.doi.org/10.1080/10717544.2020.1760403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269032PMC
December 2020

LncRNA SNHG3 Promotes Hepatocellular Tumorigenesis by Targeting miR-326.

Tohoku J Exp Med 2019 09;249(1):43-56

Department of Hepatology, Qilu Hospital of Shandong University.

Small nucleolar RNA host gene 3 (SNHG3), a long noncoding RNA (lncRNA), acts as an oncogene in hepatocellular carcinoma (HCC), whereas microRNA (miR)-326 plays an inhibitory role in some types of human cancers, including melanoma, osteosarcoma, and gastric cancer. In the present study, by analyzing 47 tissue specimens of human HCC, we found that the relative expression levels of SNHG3 were significantly higher in HCC tissues than those in the adjacent noncancerous tissues, whereas the relative expression levels of miR-326 were significantly lower in HCC tissues. Furthermore, the relative mRNA levels of Sma and Mad Related Family 3 (SMAD3) and zinc finger E-box binding homeobox 1 (ZEB1) were significantly higher in HCC tissues compared with the adjacent noncancerous tissues. In human HCC cell lines, SNHG3 overexpression promoted the proliferation, migration, and epithelial-mesenchymal transition and inhibited apoptosis, whereas knockdown of SNHG3 expression exerted the opposite effects. Importantly, miR-326 or miR-326 inhibitor restored the aforementioned effects of SNHG3 overexpression or SNHG3 knockdown. We thus found that the miR-326-response element is present in SNHG3 and the 3'-untranslated region of SMAD3 mRNA. In fact, SNHG3 overexpression increased the expression levels of SMAD3 and ZEB1, while miR-326 decreased the expression levels of SMAD3. These results suggest that SNHG3 may function as a competing endogenous RNA (ceRNA) for miR-326, which in turn enhances SMAD3 and ZEB1 expression. In conclusion, we propose that SNHG3 promotes HCC progression via the miR-326/SMAD3/ZEB1 signaling pathway. The findings may provide novel targets for the diagnosis and treatment of HCC.
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http://dx.doi.org/10.1620/tjem.249.43DOI Listing
September 2019

Mutations in hepatitis B virus small genes predict postoperative survival in hepatocellular carcinoma.

Onco Targets Ther 2016 2;9:7367-7372. Epub 2016 Dec 2.

Department of Gastroenterology and Hepatology.

Hepatitis B virus (HBV) DNA is prone to mutations due to proofreading deficiencies of HBV polymerase. We have previously identified hepatocellular carcinoma (HCC) survival-associated HBV mutations in the X, precore, and core regions. In the present study, we extended our research to assess HCC survival-associated HBV mutations in the small gene of HBV genome in 115 HCC patients including 60 patients with HBV B genotype, 52 patients with HBV C genotype, and 3 patients with other genotypes. The overfrequencies of mutations at nucleotides 529 and 735 are 8.5% and 91.5%, respectively, but the distribution frequencies of these mutations are not different between HBV genotypes B and C. Mutational sites 529 (relative risk: 3.611, 95% confidence interval [CI]: 1.414-9.221, =0.007) and 735 (relative risk: 1.905, 95% CI: 1.101-3.297, =0.021) were identified as statistically significant independent predictors for HCC survival by multivariate survival analysis using a Cox proportional hazards model. Moreover, the mutated 529A and 735T were associated with both short survival time and high HBV DNA load score in HCC patients. The analysis of DNA mutations in the HBV gene may help identify HCC subgroups with poor prognosis and may provide reference for therapeutic decisions.
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http://dx.doi.org/10.2147/OTT.S121785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5144890PMC
December 2016

[Case report of aspergillus infection in a patient with drug-induced liver injury].

Zhonghua Gan Zang Bing Za Zhi 2015 Dec;23(12):958-9

Department of Gastroenterology and Hepatology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.

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http://dx.doi.org/10.3760/cma.j.issn.1007-3418.2015.12.010DOI Listing
December 2015

A polymorphism at the miR-502 binding site in the 3' untranslated region of the SET8 gene is associated with the risk of epithelial ovarian cancer.

Cancer Genet 2012 Jul-Aug;205(7-8):373-6

Department of Gynaecology Ultrasound, The Fourth Hospital of Hebei Medical University, Shijiazhuang, P.R. China.

MicroRNAs (miRNAs) bind to the 3' untranslated regions (UTRs) of messenger RNAs, where they interfere with the translation of genes that regulate cell differentiation, apoptosis, and tumorigenesis. SET8 reportedly methylates TP53 and regulates genomic stability. We analyzed a single nucleotide polymorphism (rs16917496) within the miR-502 mRNA seed region of the 3' UTR of SET8 in Chinese epithelial ovarian cancer (EOC) patients. The SET8 CC genotype was associated with a decreased risk of EOC in this case-control study. The analysis of genetic polymorphisms in miRNA binding sites may help identify subgroups of populations that are at high risk for EOC.
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http://dx.doi.org/10.1016/j.cancergen.2012.04.010DOI Listing
October 2012

A polymorphism at the miR-502 binding site in the 3'-untranslated region of the histone methyltransferase SET8 is associated with hepatocellular carcinoma outcome.

Int J Cancer 2012 Sep 11;131(6):1318-22. Epub 2012 Jan 11.

Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.

MicroRNAs (miRNAs) can bind to the 3'-untranslated regions (UTRs) of messenger RNAs, where they interfere with translation and thereby regulate cell differentiation, apoptosis and tumorigenesis. Genetic polymorphisms in the 3'-UTRs targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behavior of individual miRNAs. The histone methyltransferase SET8 has been reported to methylate TP53 and regulate genomic stability. We analyzed a single-nucleotide polymorphism (rs16917496) within the miR-502 miRNA seed region for the 3'-UTR of SET8 in Chinese patients with hepatocellular carcinoma (HCC). The SET8 CC genotype was independently associated with longer postoperative survival in patients with HCC by multivariate analysis (relative risk, 0.175; 95% CI = 0.053-0.577; p = 0.004). The SET8 CC genotype was associated with reduced SET8 protein levels based on the immunostaining of 51 HCC tissue samples. We also found that the low SET8 levels were associated with longer HCC survival. Our data suggest that SET8 modifies HCC outcome by altering its expression, which depends, at least in part, on its binding affinity with miR-502. The analysis of genetic polymorphisms in miRNA binding sites can help to identify patient subgroups that are at high risk for poor disease outcomes.
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http://dx.doi.org/10.1002/ijc.27352DOI Listing
September 2012

Single nucleotide polymorphisms in the mitochondrial displacement loop and outcome of esophageal squamous cell carcinoma.

J Exp Clin Cancer Res 2010 Nov 26;29:155. Epub 2010 Nov 26.

Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, PR China.

Background: Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) has been described for different types of cancers and might be associated with cancer risk and disease outcome. We used a population-based series of esophageal squamous cell carcinoma (ESCC) patients for investigating the prediction power of SNPs in mitochondrial D-loop.

Methods: The D-loop region of mtDNA was sequenced for 60 ESCC patients recorded in the Fourth Hospital of Hebei Medical University between 2003 and 2004. The 5 year survival curve were calculated with the Kaplan-Meier method and compared by the log-rank test at each SNP site, a multivariate survival analysis was also performed with the Cox proportional hazards method.

Results: The SNP sites of nucleotides 16274G/A, 16278C/T and 16399A/G were identified for prediction of post-operational survival by the log-rank test. In an overall multivariate analysis, the 16278 and 16399 alleles were identified as independent predictors of ESCC outcome. The length of survival of patients with the minor allele 16278T genotype was significantly shorter than that of patients with 16278C at the 16278 site (relative risk, 3.001; 95% CI, 1.029 - 8.756; p = 0.044). The length of survival of patients with the minor allele 16399G genotype was significantly shorter than that of patients with the more frequent allele 16399A at the 16399 site in ESCC patients (relative risk, 3.483; 95% CI, 1.068 - 11.359; p = 0.039).

Conclusion: Genetic polymorphisms in the D-loop are independent prognostic markers for patients with ESCC. Accordingly, the analysis of genetic polymorphisms in the mitochondrial D-loop can help identify patient subgroups at high risk of a poor disease outcome.
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http://dx.doi.org/10.1186/1756-9966-29-155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000395PMC
November 2010