Publications by authors named "Qifang Lei"

7 Publications

  • Page 1 of 1

Nitazoxanide impairs mitophagy flux through ROS-mediated mitophagy initiation and lysosomal dysfunction in bladder cancer.

Biochem Pharmacol 2021 May 4;190:114588. Epub 2021 May 4.

Institute of Urology, The Third Affiliated Hospital of Shenzhen University (Luohu Hospital Group), Shenzhen 518000, China; Shenzhen Following Precision Medical Research Institute, Luohu Hospital Group, Shenzhen 518000, China; Teaching Center of Shenzhen Luohu Hospital, Shantou University Medical College, Shenzhen 518000, China; Department of Urology and Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China. Electronic address:

Bladder cancer is one of the most common malignancy in the urinary tract with high recurrence and drug resistance in clinics. Alternative treatments from existing drugs might be a promising strategy. Nitazoxanide (NTZ), an FDA-approved antiprotozoal drug, has got increasingly noticed because of its favorable safety profile and antitumor potential, yet the effects in bladder cancer and underlying mechanisms remain poorly understood. Herein, we find that NTZ induces mitochondrial damage and mitophagy initiation through PINK1-generated phospho-ubiquitin(pS65-Ub) and autophagy receptor-mediated pathway even in the absence of Atg5/Beclin1. Meanwhile, NTZ inhibits lysosomal degradation activity, leading to mitophagy flux impairment at late stage. Mitochondrial reactive oxygen species (ROS) production is critical in this process, as eliminating ROS with N-acetylcysteine (NAC) efficiently inhibits PINK1 signaling-mediated mitophagy initiation and alleviates lysosomal dysfunction. Co-treatment with NTZ and autophagy inhibitor Chloroquine (CQ) to aggravate mitophagy flux impairment promotes NTZ-induced apoptosis, while alleviation of mitophagy flux impairment with ROS scavenger reduces cell death. Moreover, we also discover a similar signaling response in the 3D bladder tumor spheroid after NTZ exposure. In vivo study reveals a significant inhibition of orthotopic bladder tumors with no obvious systemic toxicity. Together, our results uncover the anti-tumor activities of NTZ with the involvement of ROS-mediated mitophagy modulation at different stages and demonstrate it as a potential drug candidate for fighting against bladder tumors.
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http://dx.doi.org/10.1016/j.bcp.2021.114588DOI Listing
May 2021

Fluorinated Chitosan To Enhance Transmucosal Delivery of Sonosensitizer-Conjugated Catalase for Sonodynamic Bladder Cancer Treatment Post-intravesical Instillation.

ACS Nano 2020 02 7;14(2):1586-1599. Epub 2020 Feb 7.

Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices , Soochow University , Suzhou 215123 , China.

Sonodynamic therapy (SDT) is a noninvasive ultrasound-triggered therapeutic strategy for site-specific treatment of tumors with great depth penetration. The design of nano-sonosensitizers suitable for SDT treatment of bladder cancer (BCa) post-intravesical instillation has not yet been reported. Herein, a transmucosal oxygen-self-production SDT nanoplatform is developed to achieve highly efficient SDT against BCa. In this system, fluorinated chitosan (FCS) is synthesized as a highly effective nontoxic transmucosal delivery carrier to assemble with -tetra(4-carboxyphenyl)porphine-conjugated catalase (CAT-TCPP). The formed CAT-TCPP/FCS nanoparticles after intravesical instillation into the bladder cavity exhibit excellent transmucosal and intratumoral penetration capacities and could efficiently relieve hypoxia in tumor tissues by the catalase-catalyzed O generation from tumor endogenous HO to further improve the therapeutic efficacy of SDT to ablate orthotopic bladder tumors under ultrasound. Our work presents a nano-sonosensitizer formulation with FCS to enhance transmucosal delivery and intratumoral diffusion and CAT to improve tumor oxygenation, promising for instillation-based SDT to treat bladder tumors without the concern of systemic toxicity.
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http://dx.doi.org/10.1021/acsnano.9b06689DOI Listing
February 2020

Rapid and quantitative detection of urinary Cyfra21-1 using fluorescent nanosphere-based immunochromatographic test strip for diagnosis and prognostic monitoring of bladder cancer.

Artif Cells Nanomed Biotechnol 2019 Dec;47(1):4266-4272

Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.

Bladder cancer is a common malignant tumour with high recurrence rate. Cytokeratin 19 fragments (Cyfra21-1) in urine has been regarded as a promising biomarker for the prognosis and diagnosis of bladder cancer due to the relevance of its high urinary level to the bladder cancer patients. However, currently detection methods of Cyfra21-1 have their limits, such as complicated steps, limited sensitivity or unsatisfying specificity. In this study, we developed a novel time-resolved fluoroimmuno test strip by using europium chelate microparticle (Eu-CM). Detection was performed in simple steps by carrying drops of sample into the well of the test strip, waiting for 15 min and inserting the strip into a fluorescence strip reader for quantitation. The standard curve equation of the test strip was  = 0.0177 + 0.01 ( = .9993). In the analysis of human urine samples ( = 115), it demonstrated a good performance (accuracy: CV < 10%, AUC: 0.989). With the cut-off value of 81 ng/mL, the sensitivity and specificity for bladder cancer were 92.86 and 100%, respectively. In comparison to ELISA and electrochemiluminescence methods, the Eu-CM based time-resolved fluoroimmuno test strip provided a rapid, sensitive and reliable method for monitoring bladder cancer. It may be applied as a non-invasive approach for in point-of-care for bladder cancer detection.
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http://dx.doi.org/10.1080/21691401.2019.1687491DOI Listing
December 2019

Fluorinated Polymer Mediated Transmucosal Peptide Delivery for Intravesical Instillation Therapy of Bladder Cancer.

Small 2019 06 10;15(25):e1900936. Epub 2019 May 10.

Department of Urology, The Affiliated Luohu Hospital of Shenzhen University, Shenzhen University, Shenzhen, 518000, China.

Surgical intervention combined with intravesical instillation of chemotherapeutics to clear residual cancer cells after operation is the current standard treatment method for bladder cancer. However, the poor bioavailability of active pharmaceutical ingredients for bladder cancer cells on account of the biological barriers of bladder mucosa, together with significant side effects of currently used intravesical medicine, have limited the clinical outcomes of localized adjuvant therapy for bladder cancer. Aiming at improved intravesical instillation therapy of bladder cancer, a fluorinated polyethylenimine (F-PEI) is employed here for the transmucosal delivery of an active venom peptide, polybia-mastoparan I (MPI), which shows selective antiproliferative effect against various bladder cancer cell lines. Upon simple mixing, MPI and F-PET would coassemble to form stable nanoparticles, which show greatly improved cross-membrane and transmucosal penetration capacities compared with MPI alone or nonfluorinated MPI/PEI nanoparticles. MPI/F-PEI shows higher in vivo tumor growth inhibition efficacy for local treatment of a subcutaneous tumor model. More excitingly, as further demonstrated in an orthotopic bladder cancer model, MPI/F-PEI offers remarkably improved therapeutic effects compared to those achieved by free MPI or the first-line bladder cancer drug mitomycin C. This work presents a new transmucosal delivery carrier particularly promising for intravesical instillation therapy of bladder cancer.
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http://dx.doi.org/10.1002/smll.201900936DOI Listing
June 2019

In silico target fishing and pharmacological profiling for the isoquinoline alkaloids of Macleaya cordata (Bo Luo Hui).

Chin Med 2015 17;10:37. Epub 2015 Dec 17.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing, 100193 China.

Background: Some isoquinoline alkaloids from Macleaya cordata (Willd). R. Br. (Bo Luo Hui) exhibited antibacterial, antiparasitic, antitumor, and analgesic effects. The targets of these isoquinoline alkaloids are undefined. This study aims to investigate the compound-target interaction network and potential pharmacological actions of isoquinoline alkaloids of M. cordata by reverse pharmacophore database screening.

Methods: The targets of 26 isoquinoline alkaloids identified from M. cordata were predicted by a pharmacophore-based target fishing approach. Discovery Studio 3.5 and two pharmacophore databases (PharmaDB and HypoDB) were employed for the target profiling. A compound-target interaction network of M. cordata was constructed and analyzed by Cytoscape 3.0.

Results: Thirteen of the 65 predicted targets identified by PharmaDB were confirmed as targets by HypoDB screening. The targets in the interaction network of M. cordata were involved in cancer (31 targets), microorganisms (12 targets), neurodegeneration (10 targets), inflammation and autoimmunity (8 targets), parasitosis (5 targets), injury (4 targets), and pain (3 targets). Dihydrochelerythrine (C6) was found to hit 23 fitting targets. Macrophage migration inhibitory factor (MIF) hits 15 alkaloids (C1-2, C11-16, C19-25) was the most promising target related to cancer.

Conclusion: Through in silico target fishing, the anticancer, anti-inflammatory, and analgesic effects of M. cordata were the most significant among many possible activities. The possible anticancer effects were mainly contributed by the isoquinoline alkaloids as active components.
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http://dx.doi.org/10.1186/s13020-015-0067-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4683977PMC
December 2015

A new cyclohexylacetic acid derivative from the aerial parts of Emilia sonchifolia.

Nat Prod Res 2013 Aug 19;27(15):1330-4. Epub 2012 Nov 19.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100193, P.R. China.

A new cyclohexylacetic acid derivative, named 2-{4-hydroxy-7-oxabicyclo [2.2.1] heptanyl}-acetic acid (1), was isolated from Emilia sonchifolia, together with a known analogue, 2-(1,4-dihydroxy cyclohexanyl)-acetic acid (2). Their structures were determined on the basis of spectroscopic techniques including IR, NMR, HR-ESI-MS and X-ray diffraction.
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http://dx.doi.org/10.1080/14786419.2012.738205DOI Listing
August 2013

Quantitative analysis of five kudinosides in the large-leaved Kudingcha and related species from the genus Ilex by UPLC-ELSD.

Phytochem Anal 2012 Nov-Dec;23(6):677-83. Epub 2012 May 17.

Beijing Key Laboratory of Plant Resources Research and Development, Beijing Technology and Business University, Beijing, 100048, China.

Introduction: The large-leaved Kudingcha from the genus Ilex, which is used as a traditional Chinese tea, contains several characteristic triterpenoid saponins that can be subjected to quality control evaluation.

Objective: To develop and validate a rapid method incorporating reverse-phase ultra-performance liquid chromatography coupled with evaporative light scattering detection (UPLC-ELSD) for the simultaneous determination of the five triterpenoid saponins kudinoside L (1), kudinoside C (2), kudinoside A(3), kudinoside F(4) and kudinoside D(5) in several species of the large-leaved Kudingcha from the genus Ilex and 'Yerba Mate' (Ilex paraguariensis).

Methodology: The five compounds were separated using a water-acetonitrile mobile phase with a Waters Acquity BEH C(18)-column (100 × 2.1 mm, 1.7 µm).

Results: Separation took 13 min with detection and quantification limits ranging from 12.5 to 29.8 ng and 41.3 to 98.2 ng, respectively. The method was validated according to the regulatory guidelines with respect to precision, stability, repeatability and recovery. The triterpenoid saponins showed a good regression relationship (r(2) > 0.999) within the test ranges, and the recovery of the method was in the 95-105% range.

Conclusion: The present method can be used successfully for the quality control of the large-leaved Kudingcha. The different Ilex species showed differences in distribution of the five triterpenoids. Ilex kudingcha, which makes up the major species of the large-leaved Kudingcha, contains the maximum amount of triterpenoid saponins.
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http://dx.doi.org/10.1002/pca.2372DOI Listing
April 2013