Publications by authors named "Wenwei Jiang"

11 Publications

  • Page 1 of 1

Glutathionylation-dependent proteasomal degradation of wide-spectrum mutant p53 proteins by engineered zeolitic imidazolate framework-8.

Biomaterials 2021 04 14;271:120720. Epub 2021 Feb 14.

School of Medicine and Institute for Life Sciences, South China University of Technology, Guangzhou, 510006, China; Department of Cardiology, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. Electronic address:

Point mutations within the DNA-binding domain of the TP53 gene occur in a significant percentage of human cancer, leading to cellular accumulation of highly stabilized mutant p53 proteins (mutp53) with tumor-promoting properties. Depletion of mutp53, through inducing either autophagic or proteasomal degradation, is an attractive strategy for the therapy of p53-mutated cancer, but the currently-known degradation inducers, almost exclusively small molecules, are inadequate. Here we show that pH-responsive zeolitic imidazolate framework-8 (ZIF-8) offers a novel solution to mutp53 degradation. ZIF-8 facilitated ubiquitination-mediated and glutathionylation-dependent proteasomal degradation of all of the nine mutp53 we tested, including six hot-spot mutp53, but not the wild-type p53 protein. Sustained elevation of intracellular Zn level, resulted from decomposition of the internalized ZIF-8 in the acidic endosomes, decreased the intracellular reduced glutathione (GSH): oxidized glutathione (GSSG) ratio and was essential for mutp53 glutathionylation and degradation. ZIF-8 modified with an Z1-RGD peptide, exhibiting enhanced cellular internalization and improved decomposition behavior, preferentially killed mutp53-expressing cancer cells and demonstrated remarkable therapeutic efficacy in a p53 S241F ES-2 ovarian cancer model as well as in a p53 Y220C patient-derived xenograft (PDX) breast cancer model. The ability to induce wide-spectrum mutp53 degradation gives ZIF-8 a clear advantage over other degradation-inducers, and engineered nanomaterials may be promising alternatives to small molecules for the development of mutp53-targeting drugs.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120720DOI Listing
April 2021

mTORC1-dependent TFEB nucleus translocation and pro-survival autophagy induced by zeolitic imidazolate framework-8.

Biomater Sci 2020 Jul;8(15):4358-4369

Department of Surgery, Guangzhou First People's Hospital, School of Medicine and Institutes for Life Sciences, South China University of Technology, Guangzhou 510006, China. and Key Laboratory of Biomedical Engineering of Guangdong Province, and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China and National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China.

A great variety of nanoparticles are known to induce autophagy, leading to either pro-death or pro-survival. Zeolitic imidazolate framework-8 (ZIF-8), a type of porous metal-organic framework (MOF) material and a promising drug delivery vector, has reportedly shown excellent efficacy for cancer therapy. However, less attention has been paid to the potential biological effect of ZIF-8 per se, and if so, how the effect impacts cell fate and therapy outcomes. Herein, we showed that ZIF-8 induced autophagy in HeLa cells, characterized by increased autophagosome formation without disruption of autophagic flux, in a dose- and time-dependent fashion. ZIF-8 also caused dephosphorylation of the transcription factor EB (TFEB) at serine-142 and serine-211, leading to the nucleus translocation of TFEB, an event that promoted lysosome biogenesis and is necessary for autophagy induction. We further pinpointed the inhibition of mTORC1 as the critical event upstream of ZIF-8-elicited TFEB dephosphorylation and the subsequent nucleus translocation. Furthermore, autophagy induced by ZIF-8 promoted cell survival, as inhibiting autophagy by either 3-methyladenine (3-MA) or ATG5 knockdown significantly enhanced ZIF-8-elicited HeLa cell death. Most importantly, doxorubicin-encapsulated ZIF-8 ([email protected]) also elicited strong pro-survival autophagy, and the co-delivery of an autophagic inhibitor (3-MA) dramatically enhanced the cytotoxicity of [email protected] in HeLa cells. Our results revealed the unique ability of ZIF-8, both in a free and drug-loaded form, to induce pro-survival autophagy in certain cancer cells, a finding with important implications for potential clinical studies that utilize ZIF-8 as a drug carrier.
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http://dx.doi.org/10.1039/d0bm00773kDOI Listing
July 2020

Tripartite Motif-Containing 46 Promotes Viability and Inhibits Apoptosis of Osteosarcoma Cells by Activating NF-B Signaling Through Ubiquitination of PPAR.

Oncol Res 2020 Sep 15;28(4):409-421. Epub 2020 Apr 15.

Department of Orthopedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal HospitalSuzhouP.R. China.

Osteosarcoma (OS), the most common bone cancer, causes high morbidity in children and young adults. TRIM46 is a member of the family of tripartite motif (TRIM)-containing proteins that serve as important regulators of tumorigenesis. Here we investigate the possible role of TRIM46 in OS and the underlying molecular mechanism. We report an increase in the expression of TRIM46 in OS and its association with tumor size, Ennekings stage, and patient prognosis. TRIM46 knockdown inhibits OS cell viability and cell cycle progression and induces apoptosis, while TRIM46 overexpression exerts inverse effects, which are inhibited by peroxisome proliferator-activated receptor alpha (PPAR) overexpression and the nuclear factor kappa B (NF-B) inhibitor, pyrrolidine dithiocarbamate (PDTC). Furthermore, TRIM46 negatively regulates PPAR expression via ubiquitination-mediated protein degradation and modification. PPAR overexpression also inactivates NF-B signaling and NF-B promoter activity in OS cells overexpressing TRIM46. Moreover, TRIM46 knockdown inhibits tumor growth and induces apoptosis of OS cells in vivo. TRIM46 acts as an oncogene in OS by interacting with and ubiquitinating PPAR, resulting in the activation of NF-B signaling pathway. Thus, TRIM46 may be a potential biomarker of carcinogenesis.
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http://dx.doi.org/10.3727/096504020X15868639303417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851538PMC
September 2020

Preoperative low scores of Life Satisfaction Rating predicts poor outcomes after total knee arthroplasty: a prospective observational study.

J Orthop Surg Res 2020 Apr 15;15(1):145. Epub 2020 Apr 15.

Department of Orthopedic Surgery, Shanghai Tenth People's Hospital affiliated to Tongji University, 301 Yanchang Rd, Jingan District, Shanghai, 200072, People's Republic of China.

Background: Despite the continued improvement in the surgical techniques during primary total knee arthroplasty (TKA), literatures indicate that up to 10 to 20% patients are not satisfied with their outcomes. Psychological factors in this dissatisfaction are yet to be clearly identified. The aim of this study is to develop a method to assess whether the patient's current mental state is suitable enough to accept a TKA surgery.

Methods: Preoperative demographic and clinical data of 532 patients who underwent TKA were prospectively obtained from January 2012 until December 2016. We recorded the scores evaluated by SF-36 questionnaire and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) preoperatively and 1 year postoperatively. Preoperative Life Satisfaction Rating (LSR) is emphatically evaluated.

Results: Poor preoperative score of LSR was a significant predictor of dissatisfaction after TKA. Patients with low LSR reported significant pain and stiffness, although there was no remarkable effect on functionality of the replaced joint. The results also showed that age and BMI were not strong predictors of satisfaction in TKA.

Conclusion: Our outcomes can help clinicians evaluate whether a patient's current mental status is favorable for TKA. If patients have extreme low scores of LSR (less than 10), a psychological intervention should be recommended for better satisfaction following a TKA surgery. This would also allow surgeons to individually assess the risks and benefits of surgery.
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http://dx.doi.org/10.1186/s13018-020-01668-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160936PMC
April 2020

LncRNA RP11-361F15.2 promotes osteosarcoma tumorigenesis by inhibiting M2-Like polarization of tumor-associated macrophages of CPEB4.

Cancer Lett 2020 03 2;473:33-49. Epub 2020 Jan 2.

The Institute of Intervention Vessel, Shanghai Tenth People's Hospital, Shanghai, PR China. Electronic address:

Long non-coding RNAs (lncRNAs) regulates the initiation and progression of osteosarcoma (OS), specifically lncRNA RP11-361F15.2 has been shown to play prominent roles in tumorigenesis. Previously, M2-Like polarization of tumor-associated macrophages (TAMs) has been identified to play a key role in cancer migration/invasion. Hence, it is essential to understand the role of RP11-361F15.2 in tumorigenesis and its association with M2-Like polarization of TAMs. The results indicate that RP11-361F15.2 is significantly increased in OS tissues, and its expression is positively correlated with cytoplasmic polyadenylation element binding protein 4 (CPEB4) expression and negatively associated with miR-30c-5p expression. Further, overexpression of RP11-361F15.2 increased OS cell migration/invasion and M2-Like polarization of TAMs in vitro, as well as promoted xenograft tumor growth in vivo. Mechanistically, luciferase reporter assays indicated that RP11-361F15.2 upregulated CPEB4 expression by competitively binding to miR-30c-5p. Further, we have identified that RP11-361F15.2 promotes CPEB4-mediated tumorigenesis and M2-Like polarization of TAMs through miR-30c-5p in OS. We also identified that RP11-361F15.2 acts as competitive endogenous RNA (ceRNA) against miR-30c-5p thereby binding and activating CPEB4. This RP11-361F15.2/miR-30c-5p/CPEB4 loop could be used as a potential therapeutic strategy for the treatment of OS.
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http://dx.doi.org/10.1016/j.canlet.2019.12.041DOI Listing
March 2020

Grafted copolymerization of N-phenylmaleimide and styrene in porous polyvinyl chloride particles suspended in aqueous solution.

Des Monomers Polym 2019 4;22(1):66-78. Epub 2019 Mar 4.

Department of Chemical Engineering, Fine Chemical Engineering Laboratory, Chemical Engineering School of Sichuan University, Chengdu, Sichuan, China.

N-phenylmaleimide (N-PMI) and its precursor, (Z)-4-oxo-4-(phenylamino)but-2-enoic acid, were synthesized from aniline and maleic anhydride. Copolymerization between N-phenylmaleimide and styrene was initiated in micropores and outside surface of porous polyvinyl chloride (PVC) resin suspended in aqueous phase. The modified PVC was characterized with Gel Permeation Chromatography, thermal gravimetric analysis and scanning electron microscopy. The result of high performance liquid chromatography shows that the purity of N-PMI reached 97.3%. Thermal gravimetric analysis indicated that the introduction of N-PMI could clearly affect the thermal degradation behavior of PVC, and when PMI was at 6.25% of the PVC mass, the decomposition temperature T of modified polymer was increased to 314.2°C. The glass transition temperature of modified polymer was increased from 70°C to 80°C.
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http://dx.doi.org/10.1080/15685551.2019.1581490DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407575PMC
March 2019

Upregulation of long noncoding RNA Xist promotes proliferation of osteosarcoma by epigenetic silencing of P21.

Oncotarget 2017 Nov 8;8(60):101406-101417. Epub 2017 Sep 8.

Department of Orthopedics, Shanghai Tenth People's Hospital, Tong Ji University School of Medicine, Shanghai 200072, People's Republic of China.

Recent studies show that lncRNAs involve in the initiation and progression of various cancers including osteosarcoma (OS). IncRNA Xist has been verified as an oncogene in several human cancers, and its abnormal expression was closely associated with tumor initiation and progression. Nevertheless, the role of Xist in OS remains unclear. Here, we revealed the Xist expression level was up-regulated in OS tissues and discovered that Xist knockdown significantly repressed OS cell proliferation. Additionally, mechanistic analysis revealed that Xist can repress P21 expression to regulate OS cell cycle and proliferation by binding to EZH2. Taking all into account, Xist may function in promoting OS cell proliferation and may potentially serve as a novel biomarker and therapeutic target for OS.
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http://dx.doi.org/10.18632/oncotarget.20738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5731884PMC
November 2017

MiR-329 suppresses osteosarcoma development by downregulating Rab10.

FEBS Lett 2016 09 19;590(17):2973-81. Epub 2016 Aug 19.

Department of Orthopedics, Suzhou Municipal Hospital of Nanjing Medical University, China.

MiR-329 has been proved to be a tumor suppressor gene in various malignancies, however, its role in osteosarcoma remains elusive. We found that miR-329 is remarkably downregulated in osteosarcoma tissues and relates to advanced stages. MiR-329 is able to inhibit osteosarcoma cell proliferation, promote apoptosis, and induce G0/G1 cell cycle arrest. In addition, miR-329 also suppresses wound-healing and migration ability of osteosarcoma cells and inhibits tumorigenicity in vivo. Rab10 was identified as a target of miR-329 in osteosarcoma and mediates its biofunction. These findings may shed light to the understanding of tumor development in osteosarcoma.
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http://dx.doi.org/10.1002/1873-3468.12337DOI Listing
September 2016

Magnesium inhibits the calcification of the extracellular matrix in tendon-derived stem cells via the ATP-P2R and mitochondrial pathways.

Biochem Biophys Res Commun 2016 09 9;478(1):314-322. Epub 2016 Jul 9.

School of Materials Science and Engineering, Tongji University, Shanghai 201804, China. Electronic address:

Tendon calcification has been widely regarded by researchers to result from the osteogenic differentiation of Tendon-Derived Stem Cells (TDSCs) and ectopic mineralization caused by the calcification of cellular matrix. Recent studies have revealed a correlation between the Mg(2+)/Ca(2+) balance and the degeneration or calcification of tendon tissues. Furthermore, the ATP-P2X/P2Y receptor pathway has been shown to play a decisive role in the process of calcification, with calcium exportation from mitochondria and calcium oscillations potentially representing the cohesive signal produced by this pathway. Our previous study demonstrated that matrix calcification is inhibited by magnesium. In this study, we examined the effects of extracellular Mg(2+) on the deposition of calcium phosphate matrix and cellular pathways in TDSCs. The suppression of the export of calcium from mitochondria has also been detected. We found that a high concentration of extracellular Mg(2+) ([Mg(2+)]e) inhibited the mineralization of the extracellular matrix in TDSCs and that 100 μM ATP reversed this inhibitory effect in vitro. In addition, the spontaneous release of ATP was inhibited by high [Mg(2+)]e levels. A high [Mg(2+)]e suppressed the expression of P2X4, P2X5 and P2X7 and activated the expression of P2Y1, P2Y2, P2Y4 and P2Y14. The interaction between Mg(2+) and Ca(2+) is therefore contradictory, Mg(2+) inhibits mitochondrial calcium concentrations, meanwhile it reverses the opening of mPTP that is induced by Ca(2+). JC-1 staining verified the protective effect of Mg(2+) on mitochondrial membrane potential and the decrease induced by Ca(2+). Taken together, these results indicate that high [Mg(2+)]e interferes with the expression of P2 receptors, resulting in decreased extracellular mineralization. The balance between Mg(2+) and Ca(2+) influences mitochondrial calcium exportation and provides another explanation for the mechanism underlying matrix calcification in TDSCs.
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http://dx.doi.org/10.1016/j.bbrc.2016.06.108DOI Listing
September 2016

A new method to diagnose discoid lateral menisci on radiographs.

Knee Surg Sports Traumatol Arthrosc 2016 May 25;24(5):1519-24. Epub 2016 Jan 25.

Department of Orthopedics, Tenth People's Hospital, Shanghai Tong Ji University School of Medicine, 301 Middle Yanchang Road, Shanghai, 200072, People's Republic of China.

Purpose: The aim of this study was to prove that it is feasible to diagnose discoid lateral meniscus in radiographs. Plain radiographic findings of discoid lateral menisci with matched controls were analysed and compared in a quantitative method.

Methods: Sixty consecutive patients (60 knees) who were diagnosed with discoid lateral meniscus (discoid group) by magnetic resonance imaging (MRI) were included. Another 60 age- and sex-matched controls with normal medial and lateral menisci on the basis of MRI findings were included as the control group. Each plain radiograph was evaluated from the anteroposterior view for the following variables: height of the fibular head (HFH), lateral joint space distance (LJSD), height of the lateral tibial spine (HLTS), obliquity of the lateral tibial plateau, obliquity of the lateral femoral condyle, distance from the lateral tibial spine to the lateral femoral condyle, height of the medial tibial spine, chordal distance of the femoral condyle (CDLF, CDMF), the HFH/LJSD, LJSD/HLTS and the CDLF/CDMF.

Results: A significant difference was found in the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS between the two groups. The cut-off values of the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS were 12.9 mm, 6.6 mm, 7.8 mm, 3.0 mm, 2.7 mm, 2.0 and 0.9, respectively. Among the cut-off values in diagnosing discoid lateral meniscus, the sensitivity, specificity and ROC curve area of LJSD/HLTS were as high as 73.6 %, 83.0 % and 0.8, respectively. The corresponding values of the HFH/LJSD were as high as 66.0 %, 86.8 % and 0.8. For the first two indicators, the results of the HFH/LJSD and LJSD/HLTS were higher than that of most other parameters. At the same time, the ROC curve area of the HFH/LJSD and LJSD/HLTS ranked highest among all the results.

Conclusion: There were significant differences in the HFH, LJSD, HLTS, DLC, CDLF, HFH/LJSD and LJSD/HLTS, especially the HFH/LJSD and the LJSD/HLTS, between plain radiographic findings of discoid lateral meniscus patients and normal controls. The results of the HFH/LJSD and the LJSD/HLTS showed a positive impact on the diagnosis of discoid lateral meniscus in this research. These findings enable radiographs to screen for discoid lateral meniscus.

Level Of Evidence: II.
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http://dx.doi.org/10.1007/s00167-016-3999-zDOI Listing
May 2016

[Application of chlorophyll fluorescence analysis in forest tree cultivation].

Ying Yong Sheng Tai Xue Bao 2006 Oct;17(10):1973-7

School of Forestry and Biotechnology, Zhejiang Forestry College, Lin'an, China.

In recent years, chlorophyll fluorescence analysis has been developed into a kind of new, fast, simple, and accurate technique in photosynthesis research, and widely applied in agriculture and horticulture but few in forest tree cultivation. This paper introduced the relevant parameters of chlorophyll fluorescence analysis and their biological meanings, and summarized its application in forest tree cultivation and in the research of forest tree stress physiology. Some perspectives and suggestions were put forward.
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October 2006
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