Publications by authors named "Yonglian Guo"

10 Publications

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Theaflavin ameliorates renal ischemia/reperfusion injury by activating the Nrf2 signalling pathway in vivo and in vitro.

Biomed Pharmacother 2021 Feb 16;134:111097. Epub 2020 Dec 16.

Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address:

Studies have demonstrated that oxidaive stress-induced apoptosis may be the main pathogenic mechanism of renal ischemia/reperfusion (I/R) injury. Theaflavin, a polyphenolic compound extracted from black tea, has been proven to exert strong antioxidant biological function. The objective of the present study was to investigate the potential role of theaflavin on renal I/R injury and its potential molecular mechanism both in vitro and in vivo. C57/BL6 J mice were used to create a model of I/R injury wherein mice were ligated with bilateral renal pedicles for 45 min, and then reperfused for 24 h. A hypoxia/reoxygenation (H/R) model of TCMK-1 cells was used to simulate I/R in vitro. Theaflavin were administered to the treatment group first and then established the model. Kidney Injury Molecule-1 (KIM-1), serum creatinine, urea nitrogen, and 24-h urinary protein levels were evaluated and changes in mitochondrial membrane potential and the ultrastructure of mitochondria were observed. Cell viability, oxidative stress damage, and apoptosis were assessed. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes HO-1 and NQO1 were evaluated. Our results revealed that pretreatment with theaflavin significantly inhibited I/R- and H/R-induced renal injury and cell apoptosis. Theaflavin improved mitochondrial dysfunction by attenuating mitochondrial damage and promoting mitochondrial membrane potential. Theaflavin pretreatment significantly reduced malondialdehyde content, while enhancing superoxide dismutase activity in vivo and in vitro. It also reduced oxidative stress and apoptosis mainly by upregulating Nrf2 and its downstream targets in TCMK-1 cells. Thus, theaflavin exerted a protective effect against renal I/R injury by inhibiting oxidative stress and apoptosis via activation of the Nrf2-NQO1/HO-1 pathway as well as correcting mitochondrial dysfunction, thereby presenting its potential as a clinical therapeutic in cases of acute kidney injury.
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http://dx.doi.org/10.1016/j.biopha.2020.111097DOI Listing
February 2021

Low DAPK1 expression correlates with poor prognosis and sunitinib resistance in clear cell renal cell carcinoma.

Aging (Albany NY) 2020 11 16;13(2):1842-1858. Epub 2020 Nov 16.

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

We investigated the prognostic significance of Death-Associated Protein Kinase 1 (DAPK1) and its role in sunitinib resistance in clear cell renal cell carcinoma (ccRCC). DAPK1 mRNA levels were significantly lower in tumor tissues than normal kidney tissues in TCGA-KIRC dataset (n=428). Both overall survival and disease-free survival were significantly shorter in ccRCC patients with low DAPK1 expression than those with high DAPK1 expression. Receiver operating characteristic curve analysis showed that low DAPK1 expression correlated with poor prognosis in ccRCC patients. Multivariate analysis confirmed that DAPK1 expression was an independent prognostic indicator in ccRCC. Gene set enrichment analysis showed that low DAPK1 expression correlates with upregulation of pathways related to metastasis, drug resistance, hypoxia and invasiveness in ccRCC patients. Sunitinib-resistant ccRCC cells show significantly lower DAPK1 mRNA and protein levels than sunitinib-sensitive ccRCC cells. DAPK1 overexpression enhances apoptosis in sunitinib-resistant ccRCC cells via the ATF6-dependent ER stress pathway. Xenograft tumors derived from DAPK1-overxpressing ccRCC cells were significantly smaller than the controls in nude mice. Our finding demonstrates that low DAPK1 expression is an independent prognostic indicator that correlates with ccRCC progression and sunitinib resistance.
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http://dx.doi.org/10.18632/aging.103638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880360PMC
November 2020

A-kinase interacting protein 1, a potential biomarker associated with advanced tumor features and CXCL1/2 in prostate cancer.

Int J Biol Markers 2020 Jun 27;35(2):74-81. Epub 2020 Apr 27.

Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China.

Objective: This study aimed to investigate the correlation of A-kinase interacting protein 1 (AKIP1) with chemokine (C-X-C motif) ligand 1 (CXCL1) and CXCL2, as well as their associations with clinical characteristics and prognosis in prostate cancer patients.

Methods: A total of 248 eligible prostate cancer patients who underwent surgery were consecutively recruited, and tumor tissues were collected during the surgery. AKIP1, CXCL1, and CXCL2 expression in tumor tissues were assessed by immunohistochemistry. Disease-free survival and overall survival were recorded, and the median follow-up time was 27 months.

Results: The proportion of patients with AKIP1, CXCL1, and CXCL2 high expression was 56.5%, 63.7%, and 56.9%, respectively. Additionally, AKIP1 expression positively correlated with CXCL1 expression (<0.001) and CXCL2 expression (<0.001), and CXCL1 expression was positively associated with CXCL2 expression (<0.001). Furthermore, AKIP1 expression positively correlated with pathological T stage (<0.001) and pathological N stage (=0.003). CXCL1 expression was positively associated with pathological T stage (<0.001) and pathological N stage (<0.001) as well. However, the CXCL2 expression only positively correlated with pathological T stage (=0.002). Also, AKIP1 high expression correlated with worse disease-free survival (=0.049) and OS (=0.013), and CXCL1 high expression was associated with unfavorable disease-free survival (=0.023) but not overall survival (=0.052). CXCL2 expression was not correlated with disease-free survival (=0.083) or overall survival (=0.065). Multivariate Cox's regression disclosed that AKIP1 high expression independently predicted worse overall survival (=0.009).

Conclusion: AKIP1 positively associates with CXCL1/2 and is a potential biomarker for disease monitoring as well as prognosis in prostate cancer.
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http://dx.doi.org/10.1177/1724600820914944DOI Listing
June 2020

Limonene terpenoid obstructs human bladder cancer cell (T24 cell line) growth by inducing cellular apoptosis, caspase activation, G2/M phase cell cycle arrest and stops cancer metastasis.

J BUON 2020 Jan-Feb;25(1):280-285

Department of Urology, Affiliated Dongguan People's Hospital, Southern Medical University, Dongguan 523059, Guangdong, P.R. China.

Purpose: The primary purpose of the current study was to investigate the antitumor activity of limonene which is a plant monoterpene along with evaluating its effects on cell apoptosis, cell cycle phase distribution, cell migration and invasion.

Methods: The cell proliferation of T24 bladder cancer cells was examined by WTS-1 assay. The apoptotic effects induced by limonene were investigated by a combination of fluorescence microscopy and flow cytometry and then confirmed by western blot assay. The effects of limonene on cell cycle in T24 bladder cancer cells were studied by flow cytometry. The effects on cell migration and invasion were examined by wound healing assay and transwell assay using Matrigel.

Results: The results showed that limonene induced cytotoxic effects and reduced cell viability of T24 human bladder cancer cells showing an IC50 value of 9 μM. Limonene also induced significant apoptosis in bladder cancer cells since it induced significant nuclear fragmentation, chromatin condensation, and splitting of the nucleus, representative of the apoptotic cascade. The apoptotic cell percentage was 1.95, 5.35, 15.61 and 34.71% at limonene concentrations of 0, 9, 18 and 36 µM. Further, the apoptotic effects of limonene were also confirmed by Western blot analysis and the results showed increase in the expression of Bax and caspase-3 and decrease of Bcl-2 expression. Limonene also caused G2/M phase cell cycle arrest as well as suppression of cell migration and invasion.

Conclusions: These results indicate that limonene might be used as a potent anticancer agent against human bladder cancer for which further in depth studies are needed, especially over its toxicological studies.
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January 2021

A 17-Gene Signature Predicted Prognosis in Renal Cell Carcinoma.

Dis Markers 2020 26;2020:8352809. Epub 2020 Feb 26.

Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China.

Renal cell carcinoma (RCC), which was one of the most common malignant tumors in urinary system, had gradually increased incidence and mortality in recent years. Although significant advances had been made in molecular and biology research on the pathogenesis of RCC, effective treatments and prognostic indicators were still lacking. In order to predict the prognosis of RCC better, we identified 17 genes that were associated with the overall survival (OS) of RCC patients from The Cancer Genome Atlas (TCGA) dataset and a 17-gene signature was developed. Through SurvExpress, we analyzed the expression differences of the 17 genes and their correlation with the survival of RCC patients in five datasets (ZHAO, TCGA, KIPAN, KIRC, and KIRP), and then evaluated the survival prognostic significance of the 17-gene signature for RCC. Our results showed that the 17-gene signature had a predictive prognostic value not only in single pathologic RCC, but also in multiple pathologic types of RCC. In conclusion, the 17-gene signature model was related to the survival of RCC patients and could help predict the prognosis with significant clinical implications.
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http://dx.doi.org/10.1155/2020/8352809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063218PMC
October 2020

Efficacy of bladder perfusion of alternating hydroxycamptothecin and gemcitabine combined with low-dose tuberculin in the treatment of non-muscle invasive bladder cancer after TURBT.

J BUON 2019 Jul-Aug;24(4):1652-1658

Department of Urology, Central Hospital of Wuhan, Tonji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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April 2020

Inhibition of miR-9-5p suppresses prostate cancer progress by targeting StarD13.

Cell Mol Biol Lett 2019 8;24:20. Epub 2019 Mar 8.

Department of Urology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No. 26 Shengli Street, Jiang'an District, Wuhan, 430014 China.

Background: This study aims to investigate the effects of inhibiting microRNA-9-5p (miR-9-5p) on the expression of StAR-related lipid transfer domain containing 13 (StarD13) and the progress of prostate cancer.

Methods: The mRNA expression levels of miR-9-5p and StarD13 were determined in several prostate cancer cell lines. We chose DU145 and PC-3 cells for further research. The CCK8 assay was used to measure the cell viability. The cell invasion and wound-healing assays were respectively applied to evaluate invasion and migration. The expression of E-cadherin (E-cad), N-cadherin (N-cad) and vimentin were measured via western blot. DU145 and PC-3 cells overexpressing StarD13 were generated to investigate the variation in proliferation, invasion and migration. A luciferase reporter assay was used to identify the target of miR-9-5p.

Results: Our results show that miR-9-5p was highly expressed and StarD13 was suppressed in prostate cancer cells. MiR-9-5p inhibition repressed the cells' viability, invasion and migration. It also increased the expression of E-cad and decreased that of N-cad and vimentin. StarD13 overexpression gave the same results as silencing of miR-9-5p: suppression of cell proliferation, invasion and migration. The bioinformatics analysis predicted StarD13 as a target gene of miR-9-5p. Quantitative RT-PCR, western blot analysis and the dual-luciferase reporter assay were employed to confirm the prediction.

Conclusion: Our results show that miR-9-5p plays a powerful role in the growth, invasion, migration and epithelial-mesenchymal transition (EMT) of prostate cancer cells by regulating StarD13. A therapeutic agent inhibiting miR-9-5p could act as a tumor suppressor for prostate cancer.
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http://dx.doi.org/10.1186/s11658-019-0145-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408831PMC
April 2019

1-Pyrroline-5-carboxylate released by prostate Cancer cell inhibit T cell proliferation and function by targeting SHP1/cytochrome c oxidoreductase/ROS Axis.

J Immunother Cancer 2018 12 13;6(1):148. Epub 2018 Dec 13.

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

Background: Tumor cell mediated immune-suppression remains a question of interest in tumor biology. In this study, we focused on the metabolites that are released by prostate cancer cells (PCC), which could potentially attenuate T cell immunity.

Methods: Prostate cancer cells (PCC) media (PCM) was used to treat T cells, and its impact on T cell signaling was evaluated. The molecular mechanism was further verified in vivo using mouse models. The clinical significance was determined using IHC in human clinical specimens. Liquid chromatography mass spectroscopy (LC/MS-MS) was used to identify the metabolites that are released by PCC, which trigger T cells inactivation.

Results: PCM inhibits T cells proliferation and impairs their ability to produce inflammatory cytokines. PCM decreases ATP production and increases ROS production in T cells by inhibiting complex III of the electron transport chain. We further show that SHP1 as the key molecule that is upregulated in T cells in response to PCM, inhibition of which reverses the phenotype induced by PCM. Using metabolomics analysis, we identified 1-pyrroline-5-carboxylate (P5C) as a vital molecule that is released by PCC. P5C is responsible for suppressing T cells signaling by increasing ROS and SHP1, and decreasing cytokines and ATP production. We confirmed these findings in vivo, which revealed changed proline dehydrogenase (PRODH) expression in tumor tissues, which in turn influences tumor growth and T cell infiltration.

Conclusions: Our study uncovered a key immunosuppressive axis, which is triggered by PRODH upregulation in PCa tissues, P5C secretion in media and subsequent SHP1-mediated impairment of T cell signaling and infiltration in PCa.
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http://dx.doi.org/10.1186/s40425-018-0466-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291986PMC
December 2018

Huachansu suppresses human bladder cancer cell growth through the Fas/Fasl and TNF- alpha/TNFR1 pathway in vitro and in vivo.

J Exp Clin Cancer Res 2015 Feb 25;34:21. Epub 2015 Feb 25.

Department and Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Background: Huachansu (HCS), a class of toxic steroids extracted from toad venom, which has been shown to be a valuable anticancer drug in many kinds of cancers. However, the effect of HCS on bladder cancer has not been elucidated. In this study, we focused on the antitumor activities and related mechanisms of HCS on bladder cancer in vitro and in vivo.

Methods: Cell viability of T24, EJ, RT-4, SV-HUC-1 cells after HCS treatment was measured by MTS, whereas the changes of cell morphology were observed by transmission electron microscopy. The early apoptosis induced by HCS was evaluated by flow cytometry, and the expression level of apoptosis-related molecules (Bax, Bcl-2, XIAP, PARP, cleaved-Caspases 3, 8, 9) was detected using Western blot. We then evaluated the impact of HCS on the expression of Fas/Fasl, TNF- alpha/TNFR1, and the activation of NF-Kappa B pathway, and furthermore the effect of these pathways in HCS induced-apoptosis were also detected. At last, xenograft tumor in nude mice was used to further investigate the antitumor effect of HCS in vivo.

Results: Our results showed that HCS could efficiently inhibit proliferation and induce apoptosis in human bladder cancer cell lines. The expression of Fas, Fasl, TNF- alpha were all elevated at both mRNA and protein level after HCS treatment. Furthermore, down regulation of TNF- alpha, TNFR1, Fas or inhibition of Fas/Fasl interaction decreased the relative number of death cells induced by HCS. In vivo, HCS treatment significantly suppressed tumor growth and induced apoptosis in xenografts tumor in nude mice.

Conclusions: HCS could efficiently inhibit proliferation and induce apoptosis in human bladder cancer cells in vitro and in vivo, which is largely mediated by Fas/Fasl and TNF- alpha/TNFR1 pathway.
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http://dx.doi.org/10.1186/s13046-015-0134-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354737PMC
February 2015

Restoration of LRIG1 suppresses bladder cancer cell growth by directly targeting EGFR activity.

J Exp Clin Cancer Res 2013 Dec 8;32:101. Epub 2013 Dec 8.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Background: Recently, leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1), a negative regulator of EGFR, was discovered is a novel agent for suppressing bladder cancer. The aim of this study was to investigate the impact of LRIG1 on the biological features of aggressive bladder cancer cells and the possible mechanisms of enhanced apoptosis induced by upregulation of LRIG1.

Methods: In this study, we examined the mRNA and protein expression of LRIG1 and EGFR in bladder cancers and normal bladder. Meanwhile, we overexpressed LRIG1 with adenovirus vector in T24/5637 bladder cancer cell lines, and we used real time-PCR, western blot, and co-immunoprecipitation analysis in order to examine the effects of LRIG1 gene on EGFR. Furthermore, we evaluate the impact of LRIG1 gene on the function of human bladder cancer cells and EGFR signaling.

Results: The expression of LRIG1 was decreased, while the expression of EGFR was increased in the majority of bladder cancer, and the ratio of EGFR/LRIG1 was increased in tumors versus normal tissue. We found that upregulation of LRIG1 induced cell apoptosis and cell growth inhibition, and further reversed invasion in bladder cancer cell lines in vitro by inhibiting phosphorylation of downstream MAPK and AKT signaling pathway.

Conclusion: Taken together, our findings provide us with an insight into LRIG1 function, and we conclude that LRIG1 evolved in bladder cancer as a rare feedback negative attenuator of EGFR, thus could offer a novel therapeutic target to treat patients with bladder cancer.
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http://dx.doi.org/10.1186/1756-9966-32-101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880093PMC
December 2013