Publications by authors named "Yuenan Liu"

16 Publications

  • Page 1 of 1

Development of a four-gene prognostic model for clear cell renal cell carcinoma based on transcriptome analysis.

Genomics 2021 Apr 7;113(4):1816-1827. Epub 2021 Apr 7.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan 430022, China. Electronic address:

This study aimed to develop a prognostic model for clear cell renal cell carcinoma (ccRCC) based on transcriptome analysis. We screened Gene Expression Omnibus (GEO) database and the Cancer Genome Atlas (TCGA) database for gene expression data and clinical characteristics of ccRCC. After differentially expression analysis, we identified 533 key genes of the development of ccRCC. Next, a weighted gene co-expression network analysis (WGCNA) was executed to investigate the association between differentially expressed genes and clinical characteristics. Then, based on protein-protein interaction (PPI) network, least absolute shrinkage and selection operator (LASSO) regression and Cox regression, a four-gene (COL4A5, ABCB1, NR3C2 and PLG) prognostic model has been constructed in TCGA training cohort. Finally, we examined the predictive power of this model with survival analysis and receiver operating characteristic (ROC) curve both in training cohort and in validation cohorts. And we found this model was significantly correlated with infiltrating immune cells. The four-gene prognosis model could be a potential prediction tool with high accuracy and reliability for ccRCC patients.
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http://dx.doi.org/10.1016/j.ygeno.2021.04.005DOI Listing
April 2021

A novel tumor suppressor CECR2 down regulation links glutamine metabolism contributes tumor growth in laryngeal squamous cell carcinoma.

Clin Transl Oncol 2021 Apr 7. Epub 2021 Apr 7.

Department of Otolaryngology-Head and Neck Surgery, Otolaryngology Institute of Shanghai JiaoTong University, Shanghai JiaoTong University Affiliated Sixth People's Hospital, 600 Yishan Road, Xuhui, 200233, Shanghai, China.

Purpose: Glutamine plays an important role in tumor metabolism and progression. This research aimed to find out how Gln exert their effects on laryngeal squamous cell carcinoma (LSCC).

Methods: Cell proliferation was measured by CCK8 and EdU assay, mitochondrial bioenergetic activity was measured by mitochondrial stress tests. Gene expression profiling was revealed by RNA sequencing and validated by RT-qPCR. In LSCC patients, protein expression in tumor and adjacent tissues was examined and scored by IHC staining. RNAi was performed by stably expressed shRNA in TU177 cells. In vivo tumor growth analysis was performed using a nude mouse tumorigenicity model.

Results: Gln deprivation suppressed TU177 cell proliferation, which was restored by αKG supplementation. By transcriptomic analysis, we identified CECR2, which encodes a histone acetyl-lysine reader, as the downstream target gene for Gln and αKG. In LSCC patients, the expression of CECR2 in tumors was lower than adjacent tissues. Furthermore, deficiency of CECR2 promoted tumor cell growth both in vitro and in vivo, suggesting it has tumor suppressor effects. Besides, cell proliferation inhibited by Gln withdrawal could be restored by CECR2 depletion, and the proliferation boosted by αKG supplementation could be magnified either, suggested that CECR2 feedback suppressed Gln and αKG's effect on tumor growth. Transcriptomic profiling revealed CECR2 regulated the expression of a series of genes involved in tumor progression.

Conclusion: We confirmed the Gln-αKG-CECR2 axis contributes to tumor growth in LSCC. This finding provided a potential therapeutic opportunity for the use of associated metabolites as a potential treatment for LSCC.
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http://dx.doi.org/10.1007/s12094-021-02603-yDOI Listing
April 2021

The Identification of Critical mA RNA Methylation Regulators as Malignant Prognosis Factors in Prostate Adenocarcinoma.

Front Genet 2020 4;11:602485. Epub 2020 Dec 4.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

RNA methylation accounts for over 60% of all RNA modifications, and N-methyladenosine (mA) is the most common modification on mRNA and lncRNA of human beings. It has been found that mA modification occurs in microRNA, circRNA, rRNA, and tRNA, etc. The mA modification plays an important role in regulating gene expression, and the abnormality of its regulatory mechanism refers to many human diseases, including cancers. Pitifully, as it stands there is a serious lack of knowledge of the extent to which the expression and function of mA RNA methylation can influence prostate cancer (PC). Herein, we systematically analyzed the expression levels of 35 mA RNA methylation regulators mentioned in literatures among prostate adenocarcinoma patients in the Cancer Genome Atlas (TCGA), finding that most of them expressed differently between cancer tissues and normal tissues with the significance of < 0.05. Utilizing consensus clustering, we divided PC patients into two subgroups based on the differentially expressed mA RNA methylation regulators with significantly different clinical outcomes. To appraise the discrepancy in total transcriptome between subgroups, the functional enrichment analysis was conducted for differential signaling pathways and cellular processes. Next, we selected five critical genes by the criteria that the regulators had a significant impact on prognosis of PC patients from TCGA through the last absolute shrinkage and selection operator (LASSO) Cox regression and obtained a risk score by weighted summation for prognosis prediction. The survival analysis curve and receiver operating characteristic (ROC) curve showed that this signature could excellently predict the prognosis of PC patients. The univariate and multivariate Cox regression analyses proved the independent prognostic value of the signature. In summary, our effort revealed the significance of mA RNA methylation regulators in prostate cancer and determined a mA gene expression classifier that well predicted the prognosis of prostate cancer.
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http://dx.doi.org/10.3389/fgene.2020.602485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746824PMC
December 2020

LINC00160 mediates sunitinib resistance in renal cell carcinoma via SAA1 that is implicated in STAT3 activation and compound transportation.

Aging (Albany NY) 2020 Sep 13;12(17):17459-17479. Epub 2020 Sep 13.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Patients with advanced renal cell carcinoma who are resistant to sunitinib currently have limited clinical options for treatment. Therefore, it is necessary to explore the biological basis of sunitinib resistance and to uncover new targets for the intervention of sunitinib resistance. In this study, we identified that LINC00160 was associated with sunitinib resistance in renal cell carcinoma. Resistant tumor cells highly expressed LINC00160 to recruit transcriptional factor TFAP2A, which bound to SAA1 promoter regions and activated its expression. On one hand, SAA1 linked to ABCB1 protein, which facilitated sunitinib cellular efflux and diminished drug accumulation. On the other hand, SAA1 stimulated JAK-STAT signaling pathways, which countered cellular survival inhibition from drug. All these regulatory networks were well organized and collaborated, thus promoting sunitinib resistance in renal cell carcinoma. LINC00160 mediates sunitinib resistance in renal cell carcinoma via SAA1 that is implicated in STAT3 activation and compound transportation, which offers an opportunity for targeted intervention and molecular therapies in the future.
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http://dx.doi.org/10.18632/aging.103755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521490PMC
September 2020

Long noncoding RNA SNHG12 promotes tumour progression and sunitinib resistance by upregulating CDCA3 in renal cell carcinoma.

Cell Death Dis 2020 07 8;11(7):515. Epub 2020 Jul 8.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, 430022, Wuhan, China.

Renal cell carcinoma (RCC) is one of the most frequently observed malignant tumours in the urinary system and targeted drug resistance is quite common in RCC. Long noncoding RNA SNHG12 (lncRNA SNHG12) has emerged as a key molecule in numerous human cancers, but its functions in renal cell carcinoma (RCC) sunitinib resistance remain unclear. In this study, we found SNHG12 was highly expressed in RCC tissues and in sunitinib-resistant RCC cells and was associated with a poor clinical prognosis. SNHG12 promoted RCC proliferation, migration, invasion and sunitinib resistance via CDCA3 in vitro. Mechanically, SNHG12 bound to SP1 and prevented the ubiquitylation-dependent proteolysis of SP1. Stabilised SP1 bound to a specific region in the promoter of CDCA3 and increased CDCA3 expression. Furthermore, in vivo experiments showed that SNHG12 increased tumour growth and that knocking down SNHG12 could reverse RCC sunitinib resistance. Our study revealed that the lncRNA SNHG12/SP1/CDCA3 axis promoted RCC progression and sunitinib resistance, which could provide a new therapeutic target for sunitinib-resistant RCC.
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http://dx.doi.org/10.1038/s41419-020-2713-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343829PMC
July 2020

TMSB10 acts as a biomarker and promotes progression of clear cell renal cell carcinoma.

Int J Oncol 2020 May 19;56(5):1101-1114. Epub 2020 Feb 19.

Department of Urology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

Clear cell renal cell carcinoma (ccRCC) is one of the most common urological malignancies. Identifying novel biomarkers and investigating the underlying mechanism of ccRCC development will be crucial to the management and treatment of ccRCC in patients. Thymosin b10 (TMSB10), a member of the thymosin family, is involved in various physiological processes, including tissue regeneration and inflammatory regulation. Moreover, it has been found to be upregulated in many types of carcinoma. However, its roles in ccRCC remain to be elucidated. The present study aimed to explore the expression of TMSB10 in ccRCC through mining The Cancer Genome Atlas (TCGA) and Oncomine databases, and to investigate the association between TMSB10 expression and clinicopathological factors. Furthermore, immunohistochemistry assays and western blotting were conducted to verify TMSB10 expression levels in human ccRCC tissues and cell lines. Functional analyses were also performed to identify the roles of TMSB10 in vitro. The results revealed that TMSB10 was significantly upregulated in RCC tissues and cell lines. The expression of TMSB10 was closely associated with various clinicopathological parameters. In addition, high expression of TMSB10 predicted poor clinical outcome. The receiver operating characteristic curve revealed that TMSB10 could sufficiently distinguish the tumor from normal kidney (area under the curve = 0.9543, P<0.0001). Furthermore, knockdown of TMSB10 impaired the proliferation of ccRCC cells, and attenuated cell and invasion in vitro. In addition, TMSB10 knockdown downregulated reduced the phosphorylation of PI3K and the expression of vascular endothelial growth factor. In conclusion, the present study demonstrated that high expression of TMSB10 could serve as a useful diagnostic and prognostic biomarker and a potential therapeutic target for ccRCC.
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http://dx.doi.org/10.3892/ijo.2020.4991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115359PMC
May 2020

ISG20 serves as a potential biomarker and drives tumor progression in clear cell renal cell carcinoma.

Aging (Albany NY) 2020 01 30;12(2):1808-1827. Epub 2020 Jan 30.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignancies and lacks reliable biomarkers for diagnosis and prognosis, which results in high incidence and mortality rates of ccRCC. In this study, ISG20, HJURP, and FOXM1 were identified as hub genes via weighted gene co-expression network analysis (WGCNA) and Cox regression analysis. Samples validation showed that only ISG20 was up-regulated in ccRCC. Therefore, ISG20 was selected for further study. High ISG20 expression was associated with poor overall survival and disease-free survival. Furthermore, the expression of ISG20 could effectively differentiate ccRCC from normal tissues and was positively correlated to clinical stages. Functional experiments proved that knockdown of ISG20 expression could obviously inhibit cell growth, migration, and invasion in ccRCC cells. To find the potential mechanisms of ISG20, gene set enrichment analysis (GSEA) was performed and revealed that high expression of ISG20 was significantly involved in metastasis and cell cycle pathways. In addition, we found that ISG20 could regulate the expression of MMP9 and CCND1. In conclusion, these findings suggested that ISG20 promoted cell proliferation and metastasis via regulating MMP9/CCND1 expression and might serve as a potential biomarker and therapeutic target in ccRCC.
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http://dx.doi.org/10.18632/aging.102714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053611PMC
January 2020

Association between Upper-airway Surgery and Ameliorative Risk Markers of Endothelial Function in Obstructive Sleep Apnea.

Sci Rep 2019 12 27;9(1):20157. Epub 2019 Dec 27.

Department of Otolaryngology Head and Neck Surgery & Center of Sleep Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Yishan Road 600, Shanghai, 200233, China.

The objective of our study was to evaluate the effects of upper-airway surgery on improvement of endothelial function-related markers in patients with obstructive sleep apnea (OSA). Subjects with moderate to severe OSA who underwent upper-airway surgery, with a follow-up duration of at least 6 months, were included. Pre- and postoperative polysomnographic variables and endothelial function-related markers were compared. Subgroup and correlation analyses were conducted to find possible indicators for better endothelial function-related markers after upper-airway surgery. In total, 44 patients with OSA were included. The mean follow-up duration was 1.72 ± 0.92 years. Serum VEGFA [-20.29 (CI: -35.27, -5.31), p < 0.05], Ang2 [-0.06 (CI: -0.16, 0.03), p < 0.05], E-selectin [-7.21 (CI: -11.01, -3.41), p < 0.001], VWF [-58.83 (CI: -103.93, -13.73), p < 0.05], VWFCP [-33.52 (CI: -66.34, -0.70), p < 0.05], and TM [-0.06 (CI: -0.09, -0.03), p < 0.05] were significantly lower after upper-airway surgery. However, other risk markers of endothelial function, such as Ang1, ICAM1, VEGFR1, and VCAM, did not change significantly. Correlations between improved endothelial function-related markers and ameliorated oxyhemoglobin saturation and glucolipid metabolism were established. Upper-airway surgery might be associated with an improvement in endothelial function in patients with OSA. These changes may be associated with improved oxygen saturation after upper-airway surgery.
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http://dx.doi.org/10.1038/s41598-019-56601-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934655PMC
December 2019

RAC2 acts as a prognostic biomarker and promotes the progression of clear cell renal cell carcinoma.

Int J Oncol 2019 Sep 26;55(3):645-656. Epub 2019 Jul 26.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

As one of the most commonly reported malignancies of the urinary system, clear cell renal cell carcinoma (ccRCC) is an advanced metastatic tumor with high mortality rates. The Rac family small GTPase 2 (RAC2) is a member of the Rho GTPases. Although Rho GTPases play an important role in numerous different types of tumor, whether they have functions in ccRCC remains uncertain. The present study utilized bioinformatics analyses in order to compare the expression levels of RAC2 in ccRCC tumors vs. adjacent tissues, and assessed the association between RAC2 expression and clinicopathological parameters. Furthermore, reverse transcription‑quantitative PCR, western blotting and immunohistochemistry assays were performed to validate RAC2 expression levels in human ccRCC tissues and cell lines. Functional experiments were also conducted in order to identify the roles of RAC2 in vitro. The results revealed that RAC2 was upregulated in ccRCC tissues and cell lines. In addition, elevated expression levels of RAC2 were significantly associated with a poor overall survival (P=0.0061), higher Tumor‑Node‑Metastasis stage and worse G grade. Receiver operating characteristic analysis indicated that high expression levels of RAC2 could be a diagnostic index for ccRCC (area under the curve, 0.9095; P<0.0001). Furthermore, knockdown of RAC2 in vitro attenuated the proliferation, migration and invasion of renal carcinoma cells. In conclusion, the results of the present study demonstrated that RAC2 may act as a promising prognostic and diagnostic biomarker of ccRCC, and could be considered as a potential therapeutic target for treating ccRCC.
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http://dx.doi.org/10.3892/ijo.2019.4849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685597PMC
September 2019

Long noncoding RNA SNHG12 indicates the prognosis of prostate cancer and accelerates tumorigenesis via sponging miR-133b.

J Cell Physiol 2020 02 2;235(2):1235-1246. Epub 2019 Jul 2.

Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Prostate cancer (PCa) is the second leading cause of death among American men. Increasing evidence has shown that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis of PCa. In this study, we explored the biological functions of small nucleolar RNA host gene 12 (SNHG12) and investigated the interaction between miR-133b and SNHG12 in the progression of PCa. Data was downloaded from The Cancer Genome Atlas and Human Cancer Metastasis Database, and clinicopathological characteristics were analyzed with relapse-free survival rate. We detected SNHG12 expression level in PCa cells and tissues, and then analyzed its clinical significance, which revealed that SNHG12 has the potent to predict prognosis of PCa. Bioinformatic analysis revealed that SNHG12 was closely related to the progression of PCa and could target candidate microRNA (miR-133b). After transfecting SNHG12 silencing plasmid and miR-133b mimic/sponge, biological function assays were conducted and results illustrated that SNHG12 associated with miR-133b exerted biological effects on cancer cell growth, migration, and invasion. Direct interactions between miR-133b and SNHG12 have been found and SNHG12 acts as an oncogene to promote tumorigenesis of PCa by sponging tumor suppressor gene miR-133b.
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http://dx.doi.org/10.1002/jcp.29039DOI Listing
February 2020

Association of TNF-α-308(G/A) and -238(G/A) polymorphisms with non-traumatic osteonecrosis of the femoral head risks: a meta-analysis.

Int Orthop 2018 07 7;42(7):1711-1721. Epub 2018 Mar 7.

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, Hubei, 430022, China.

Purpose: The association between TNF-α-308(G/A) and -238(G/A) polymorphisms and the susceptibility of non-traumatic osteonecrosis of the femoral head (NONFH) was investigated in many studies with conflicting results. We aimed to conduct a meta-analysis to evaluate the relationship between them comprehensively.

Methods: Relevant literatures published in PubMed, Web of Science, Embase, Cochrane library databases, China National Knowledge Infrastructure (CNKI), WANFANG Data, and China Science and Technology Journal Database (CSTJ) updated to January 30, 2018, were reviewed by two investigators independently. Odds ratios (ORs) and its 95% confidence intervals (95% CIs) were calculated by a fixed-effect model based on the indistinctive heterogeneity.

Results: For TNF-α-308(G/A) polymorphism, we recruited five studies including 432 NONFH patients and 760 controls and a statistically significant association was identified in Asians in four modes consisting of alleles mode (OR = 0.648, 95% CI 0.475-0.885), homozygote mode (OR = 0.330, 95% CI 0.136-0.802), dominant mode (OR = 0.344, 95% CI 0.143-0.827), and recessive mode (OR = 0.674, 95% CI 0.468-0.971), but no significant association was observed in Caucasians. For TNF-α-238(G/A) polymorphism, three eligible studies including 275 cases and 610 controls were evaluated and there was a significant association in alleles mode (OR = 0.270, 95% CI 0.4148-0.490) as well as recessive mode (OR = 0.254, 95% CI 0.138-0.468).

Conclusion: This meta-analysis shows that TNF-α-308(G/A) and -238(G/A) polymorphisms are associated with the susceptibility of NONFH, while the significant association for 308(G/A) is mainly observed in Asians.
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http://dx.doi.org/10.1007/s00264-018-3859-1DOI Listing
July 2018

A potential therapeutic peptide-based neutralizer that potently inhibits Shiga toxin 2 in vitro and in vivo.

Sci Rep 2016 Feb 23;6:21837. Epub 2016 Feb 23.

State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Fengtai District, Beijing, PR China.

Shiga toxin 2 (Stx2) is a major virulence factor in infections with Stx-producing Escherichia coli (STEC), which can cause serious clinical complications in humans, such as hemolytic uremic syndrome (HUS). Recently, we screened and identified two peptide-based Stx2 neutralizers, TF-1 and WA-8, which specifically and directly bind to Stx2. Computer simulations suggested that the majority of TF-1 or WA-8 binds tightly at the receptor-binding site 3 of Stx2. The two peptides also effectively inhibited the cytotoxic activity of Stx2 by blocking the binding of Stx2 to target cells. TF-1 exhibits remarkable therapeutic potency in both mice and rat toxicity models. In mice toxicity models, TF-1 provided full protection when mice were injected with 5 LD50 of Stx2. In rat toxicity models, TF-1 reduced fatal tissue damage and completely protected rats from the lethal challenges of Stx2. In these rats, TF-1 significantly decreased the concentration of Stx2 in blood and diminished tissue distribution levels of Stx2. Furthermore, TF-1 effectively protected rats from the pathological effects caused by Stx2, especially in the kidney, thymus, adrenal gland, and lung. Taken together, these results indicate that TF-1 is a promising therapeutic agent against the pathogenicity of Stx2.
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http://dx.doi.org/10.1038/srep21837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763182PMC
February 2016

Novel fusion antigen displayed-bacterial ghosts vaccine candidate against infection of Escherichia coli O157:H7.

Sci Rep 2015 Dec 2;5:17479. Epub 2015 Dec 2.

Department of Microbiology, Anhui Medical University, Hefei, 230032, PR China.

Infection with Escherichia coli O157:H7 may develop into hemorrhagic colitis, or hemolytic uremic syndrome (HUS), which usually causes kidney failure or even death. The adhesion and toxins are the important virulent factors. In this study, a novel vaccine candidate rSOBGs was constructed based on the bacterial ghost (BG). rSOBGs maintained the integrity of cellular morphology and displayed the linear Stx2Am-Stx1B antigen on the surface of outer membrane. rSOBGs induced Stxs-specific IgA/IgG antibodies and stronger intimin-specific IgA/IgG antibodies effectively in sera in this study. In vivo, the rSOBGs provided the higher protection rate (52%) than native bacterial ghost-OBGs (12%) when challenged intragastricly with high dose (500 LD50) viable E. coli O157:H7. Meanwhile, the rSOBGs provided higher protection rate (73.33%) than OBGs when challenged with 2 LD50 even to 5 LD50 lysed E. coli O157:H7. In vitro, the rSOBGs-immunized sera possessed neutralizing activity to lysed pathogenic bacteria. Furthermore, the results of histopathology also displayed that the administration of rSOBGs have the ability to reduce or inhibit the adhesion lesions and toxins damages of organs. The novel vaccine candidate rSOBGs induced both anti-toxin and anti-adhesion immune protection, suggesting the possibility to prevent the infectious diseases caused by Escherichia coli O157:H7.
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http://dx.doi.org/10.1038/srep17479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667225PMC
December 2015

Novel fusion protein protects against adherence and toxicity of enterohemorrhagic Escherichia coli O157:H7 in mice.

Vaccine 2011 Sep 8;29(38):6656-63. Epub 2011 Jul 8.

State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, No. 20 Dongdajie, Fengtai District, Beijing 100071, PR China.

Infection with Escherichia coli (E. coli) O157:H7 may develop into bloody diarrhea, or hemorrhagic uremic syndrome (HUS), which usually causes kidney failure or even death. Considered as the pathogenesis mechanism of E. coli O157:H7 infection, attachment or adhesion that is directly mediated by intimin is the first step of E. coli O157:H7 interaction with its host, and all these serious sequelae are mainly due to Shiga toxins (Stxs) released by E. coli O157:H7. In this study, a novel SSI fusion protein that contains the critical toxin-antigens Stx2B and Stx1B, and the critical adhesion-antigen fragment Int281 was constructed. The protein induced complete immune protection, with both anti-toxin and anti-adhesion effects. The dominant increase in IgG1 and the high level of Th2-typical cytokine (IL-4 and IL-10) expression showed that SSI significantly induced Th2-mediated humoral immune response. In the mouse model, the SSI fusion protein not only elicited neutralizing antibodies against both Stx1 and Stx2 toxins, but also induced a high level of anti-adhesion antibodies. The SSI-immunized mice did not show any pathologic changes. SSI provides evident protection with two-time immunization against a highly lethal dose of E. coli O157:H7.
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http://dx.doi.org/10.1016/j.vaccine.2011.06.106DOI Listing
September 2011

Enhanced immunogenicity of a novel Stx2Am-Stx1B fusion protein in a mice model of enterohemorrhagic Escherichia coli O157:H7 infection.

Vaccine 2011 Jan 4;29(5):946-52. Epub 2010 Dec 4.

State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, No. 20 Dongdajie, Fengtai District, Beijing 100071, PR China.

Shiga toxins (Stxs) which include Stx1 and Stx2 produced by EHEC O157:H7 are responsible for severe diseases, including hemolytic uremic syndrome (HUS) in humans. In our previous study, a fusion protein Stx2B-Stx1B (2S for short) was prepared and displayed immunogenicity against low lethal dose challenge of E. coli O157:H7. To enhance the immunogenicity against both toxins above, we constructed a novel fusion protein carrying the Stx1B subunit and enzyme-inactive Stx2A subunit, designated Stx2Am-Stx1B (SAmB for short). The fusion protein SAmB elicited high level humoral IgG and IgG1 in mice and induced Th2-typical cytokines IL-4/IL-10 but not Th1-typical cytokine INF-γ, indicating a partial to humoral immunoresponse mediated by Th2-type cells that contributed to this humoral reactivity. Higher level neutralizing antibodies against Stx2 were elicited by SAmB than 2S. An enhanced effect of protection (93.3%) against high lethal dose challenge of lysed E. coli O157:H7 was observed, and the SAmB also provided cross protection against purified Stx1 and Stx2.
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http://dx.doi.org/10.1016/j.vaccine.2010.11.035DOI Listing
January 2011

Intragastric immunization of mice with enterohemorrhagic Escherichia coli O157:H7 bacterial ghosts reduces mortality and shedding and induces a Th2-type dominated mixed immune response.

Can J Microbiol 2010 May;56(5):389-98

State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, No. 20 Dongdajie, Fengtai District, Beijing 100071, P.R. China.

A bacterial ghost (BG)-based vaccine was developed against enterohemorrhagic Escherichia coli O157:H7 infection. The aim of this study was to evaluate the protective effect of E. coli O157:H7 BGs in a mouse model and to reveal the mechanism of the immune response. Booster immunization provided a higher protection rate (84%) than single-dose immunization (56%). Intragastric immunization of E. coli O157:H7 BGs induced both humoral and cellular immune responses. The proliferative response of CD4+ T cells was mediated by the antigen-presenting cells. The humoral immune response dominated the immune response, while the cellular immune response developed later. Inflammatory reaction was balanced by the mixed Th1/Th2 immune response. The immune sera anti-adhesion effect was confirmed by the inhibition effect, which could inhibit >90% of the adhesion of E. coli O157:H7 to Hep-2 target cells in vitro. Antibody titer specific for intimin, a molecule important for adhesion of E. coli O157:H7 to target cells, correlated with specific immunoglobulin A or G antibody titer. Therefore, it might be feasible to clinically test BG vaccines in the future.
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http://dx.doi.org/10.1139/w10-025DOI Listing
May 2010