Publications by authors named "Ruibo Zhao"

38 Publications

Characterization, Antioxidant activity, and Biocompatibility of Selenium Nanoparticle-loaded Thermosensitive Chitosan Hydrogels.

J Biomater Sci Polym Ed 2021 Apr 16:1-14. Epub 2021 Apr 16.

Institute of Smart Biomedical Materials, School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hang zhou, China.

In this study, we recruited chitosan (CS) both for selenium nanoparticles (SeNPs) synthesis and for the development of a thermoresponsive nanocomposite hydrogel with the addition of glycerol phosphate (GP). Considering that SeNPs are toxic at high concentrations, five different ingredients of the nanocomposite hydrogel system with low concentrations of SeNPs (1.25-20 μg/mL) were prepared. The gelation conditions, structural characteristics, and mechanical properties of SeNPs-loaded thermosensitive CS/GP hydrogels were investigated. We also evaluated their antioxidizing activities and biocompatibility of the CS/GP/SeNPs hydrogels. Our study demonstrated that the incorporation of SeNPs in the hydrogel improved its mechanical properties, antioxidant activity, and degree of swelling. According to the properties of SeNPs and CS/GP thermosensitive hydrogels, the combination of these two technologies in an appropriate manner would be a promising antioxidant system for drug delivery and tissue engineering.
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http://dx.doi.org/10.1080/09205063.2021.1917813DOI Listing
April 2021

Discovery of A031 as effective proteolysis targeting chimera (PROTAC) androgen receptor (AR) degrader for the treatment of prostate cancer.

Eur J Med Chem 2021 Apr 23;216:113307. Epub 2021 Feb 23.

State Key Laboratory of Applied Organic Chemistry, Department of Chemistry, Lanzhou University, 222 S. Tianshui Rd, Lanzhou, 730000, PR China. Electronic address:

Androgen receptor (AR) is an effective therapeutic target for the treatment of prostate cancer. We report herein the design, synthesis, and biological evaluation of highly effective proteolysis targeting chimeras (PROTAC) androgen receptor (AR) degraders, such as compound A031. It could induce the degradation of AR protein in VCaP cell lines in a time-dependent manner, achieving the IC 50 value of less than 0.25 μM. The A031 is 5 times less toxic than EZLA and works with an appropriate half-life (t 1/2) or clearance rate (Cl). Also, it has a significant inhibitory effect on tumor growth in zebrafish transplanted with human prostate cancer (VCaP). Therefore, A031 provides a further idea of developing novel drugs for prostate cancer.
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http://dx.doi.org/10.1016/j.ejmech.2021.113307DOI Listing
April 2021

Enantioselective α-Functionalization of 1,3-Dithianes by Iridium-Catalyzed Allylic Substitution.

J Org Chem 2020 10 21;85(19):12456-12467. Epub 2020 Sep 21.

State Key Laboratory of Applied Organic Chemistry, Department of Chemistry, Lanzhou University, Lanzhou 730000, P. R. China.

An iridium-catalyzed asymmetric allylic substitution reaction with 2-alkoxy carbonyl-1,3-dithianes has been achieved with high regio- and enantioselectivities. The transformation provides a new method for the enantioselective α-functionalization of dithianes. The corresponding dithiane-containing products are easily converted into many other derivatives with high yields and enantioselectivities.
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http://dx.doi.org/10.1021/acs.joc.0c01683DOI Listing
October 2020

Biosilicified oncolytic adenovirus for cancer viral gene therapy.

Biomater Sci 2020 Oct 11;8(19):5317-5328. Epub 2020 Aug 11.

School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China.

Oncolytic adenoviruses (OAs) have shown great potential for cancer viral gene therapy in clinical studies. To date, clinical trials have shown that the curative efficacy of OAs is still limited by hepatic sequestration and preexisting neutralizing antibodies (nAbs), which decrease the accumulation of the OAs in tumors. Herein, with the biosilicification method, we encapsulated an OA encoding the anticancer gene Trail (OA-Trail) with silica, which significantly improved virus distribution and tumor inhibition. In vitro and in vivo results indicated that compared with the native OA, biosilicified OA-Trail (OA-Trail@SiO) showed significantly reduced viral clearance in the liver and evaded nAb degradation, inducing an efficacious anticancer effect under the premise of biocompatibility. These achievements present an alternative strategy involving biosilicification for enhanced OA-based cancer gene therapy.
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http://dx.doi.org/10.1039/d0bm00681eDOI Listing
October 2020

Multifunctional nanoparticles as photosensitizer delivery carriers for enhanced photodynamic cancer therapy.

Mater Sci Eng C Mater Biol Appl 2020 Oct 16;115:111099. Epub 2020 May 16.

Key Laboratory of Advanced Textile Materials and Manufacturing Technology of Ministry of Education, School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou, China; Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue Engineering, Zhejiang Sci-Tech University, Hangzhou, China.

Photodynamic therapy (PDT) is an emerging cancer treatment combining light, oxygen, and a photosensitizer (PS) to produce highly cytotoxic reactive oxygen species that cause cancer cell death. However, most PSs are hydrophobic molecules that have poor water solubility and cannot target tumor tissues, causing damage to normal tissues and cells during PDT. Thus, there is a substantial demand for the development of nanocarrier systems to achieve targeted delivery of PSs into tumor tissues and cells. This review summarizes the research progress in PS delivery systems for PDT treatment of tumors and focuses on the recent design and development of multifunctional nanoparticles as PS delivery carriers for enhanced PDT. These multifunctional nanoparticles possess unique properties, including tunable particle size, changeable shape, stimuli-responsive PS activation, controlled PS release, and hierarchical targeting capability. These properties can increase tumor accumulation, penetration, and cellular internalization of nanoparticles to achieve PS activation and/or release in cancer cells for enhanced PDT. Finally, recent developments in multifunctional nanoparticles for tumor-targeted PS delivery and their future prospects in PDT are discussed.
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http://dx.doi.org/10.1016/j.msec.2020.111099DOI Listing
October 2020

Poly(amidoamine)-modified mesoporous silica nanoparticles as a mucoadhesive drug delivery system for potential bladder cancer therapy.

Colloids Surf B Biointerfaces 2020 May 30;189:110832. Epub 2020 Jan 30.

School of Materials Science and Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China; Zhejiang-Mauritius Joint Research Center for Biomaterials and Tissue Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China. Electronic address:

Bladder cancer, with the highest recurrence rate in all malignancy, is a common urologic cancer that arises on the bladder mucosa. Currently, tumor resection followed by intravesical chemotherapy is the primary treatment of bladder cancer, which has limited effectiveness ascribe to short dwell-time of intravesical drugs in bladder. Therefore, there is a need to develop mucoadhesive and sustained drug delivery systems to increase drug residence time for intravesical chemotherapy. In this study, poly(amidoamine) (PAMAM) dendrimers were modified onto the surface of mesoporous silica nanoparticles (MSNPs) through a layer-by-layer grafting method. A series of PAMAM-modified MSNPs were prepared and compared for their mucoadhesive capabilities on pig bladder wall and controlled drug release properties. Results demonstrated an increase in the mucoadhesive capacity of PAMAM-modified MSNPs upon an increase in the number of PAMAM amino groups, and the maximum nanoparticle mucoadhesivity was observed after two-generation PAMAM were grafted on the surface of MSNPs. An antineoplastic, doxorubicin, was encapsulated in the mesopores of PAMAM-modified MSNPs, and the drug-loaded nanoparticles can provide a sustained drug release triggered by acidic pH. The present study demonstrates that the mucoadhesive and drug release properties of MSNPs can be controlled by the layer number of PAMAM dendrimers on the nanoparticle surface, holding significant potential for the development of mucoadhesive drug delivery systems for bladder cancer therapy.
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http://dx.doi.org/10.1016/j.colsurfb.2020.110832DOI Listing
May 2020

Biomineralization improves the thermostability of foot-and-mouth disease virus-like particles and the protective immune response induced.

Nanoscale 2019 Dec 10;11(47):22748-22761. Epub 2019 Oct 10.

State Key Laboratory of Veterinary Etiological Biology and Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, Gansu 730046, P.R. China.

Virus-like particles (VLPs) are an ideal substitute for traditionally inactivated or attenuated viruses in vaccine production. However, given the properties of their native proteins, the thermal stability of VLPs is poor. In this study, calcium mineralization was used to fabricate foot-and-mouth disease virus (FMDV) VLPs as immunogenic core-shell particles with improved thermal stability. The biomineralized VLPs were stably stored at 24 °C and 37 °C for 13 and 11 days, respectively. Animal experiments showed that the biomineralized VLPs induced specific protective immunogenic effects, even after storage at 37 °C for 7 days. The biomineralized VLPs also effectively activated dendritic cells (DCs) to express high levels of surface MHC-II, costimulatory molecules, and proinflammatory cytokines. The DCs activated by the mineralized VLPs rapidly localized to the secondary lymphoid tissues and promoted the activation of the native T-cell population. These results suggest that the biomineralization of VLPs is an effective approach to vaccine production insofar as the mineralized shell provides an adjuvant effect which improves the immunogenicity of the VLPs. Biomineralization can also confer superior heat resistance on VLPs, an advantage in vaccine production. The successful development of thermally stable, biomineralized VLPs will reduce our dependence on cold storage and delivery.
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http://dx.doi.org/10.1039/c9nr05549eDOI Listing
December 2019

Diagnosis and treatment of hyperextension bicondylar tibial plateau fractures.

J Orthop Surg Res 2019 Jun 25;14(1):191. Epub 2019 Jun 25.

Department of Orthopedic Trauma, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, 410008, Hunan, China.

Purpose: To report the diagnosis, injury mechanisms, and imaging characteristics of hyperextension bicondylar tibial plateau fractures and examine the indications and feasibility of the modified anterior midline incision as a treatment strategy.

Methods: We performed a retrospective analysis of 11 cases of hyperextension bicondylar tibial plateau fractures who were treated with open reduction and internal fixation, predominantly via an anterolateral and posteromedialdouble incision or a modified anterior midline incision. Radiological and functional evaluations were performed.

Results: Eleven patients were followed-up for a mean period of 11.5 months (range 3-24 months). The mean time to radiographic bony union was 12.5 weeks (range 10-26 weeks). At final follow-up, the average Rasmussen functional score was 26.8 (range 24 - 29); five patients had an excellent rating, and six a good rating. The average range of motion of the affected knees was 3.4-130° postoperatively. Fixation failure was not observed in any of the treated fractures.

Conclusion: Hyperextension bicondylar tibial plateau fractures show a special Tiankeng-like collapse characteristic, while the changes in posterior tibial slope angle are easy to overlook. The modified anterior midline incision is a safe and effective approach for treatment of hyperextension bicondylar tibial plateau fractures with less rear displacement. Open reduction and double plating for the treatment of hyperextension bicondylar tibial plateau fractures provides excellent results.
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http://dx.doi.org/10.1186/s13018-019-1220-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593530PMC
June 2019

miR-381 modulates human bone mesenchymal stromal cells (BMSCs) osteogenesis via suppressing Wnt signaling pathway during atrophic nonunion development.

Cell Death Dis 2019 06 17;10(7):470. Epub 2019 Jun 17.

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, China.

The osteogenic differentiation of human bone mesenchymal stromal cells (BMSCs) has been considered as a central issue in fracture healing. Wnt signaling could promote BMSC osteogenic differentiation through inhibiting PPARγ. During atrophic nonunion, Wnt signaling-related factors, WNT5A and FZD3 proteins, were significantly reduced, along with downregulation of Runx2, ALP, and Collagen I and upregulation of PPARγ. Here, we performed a microarray analysis to identify differentially expressed miRNAs in atrophic nonunion tissues that were associated with Wnt signaling through targeting related factors. Of upregulated miRNAs, miR-381 overexpression could significantly inhibit the osteogenic differentiation in primary human BMSCs while increase in PPARγ protein level. Through binding to the 3'UTR of WNT5A and FZD3, miR-381 modulated the osteogenic differentiation via regulating β-catenin nucleus translocation. Moreover, PPARγ, an essential transcription factor inhibiting osteogenic differentiation, could bind to the promoter region of miR-381 to activate its expression. Taken together, PPARγ-induced miR-381 upregulation inhibits the osteogenic differentiation in human BMSCs through miR-381 downstream targets, WNT5A and FZD3, and β-catenin nucleus translocation in Wnt signaling. The in vivo study also proved that inhibition of miR-381 promoted the fracture healing. Our finding may provide a novel direction for atrophic nonunion treatment.
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http://dx.doi.org/10.1038/s41419-019-1693-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572824PMC
June 2019

The association between CD31Emcn endothelial cells and bone mineral density in Chinese women.

J Bone Miner Metab 2019 Nov 27;37(6):987-995. Epub 2019 Mar 27.

Department of Orthopedics, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.

Osteoporosis is the most common bone disease in humans. During bone remodeling, specialized blood vessels influenced by the endothelial cells (CD31Emcn, also called type H cells) are formatted to supply nutrients. Reductions in vascular supply are associated with bone loss resulting in osteoporosis. Therefore, the objective of the present study was to explore the association between the CD31Emcn endothelial cells and bone mineral density (BMD). In this prospective study, 134 Chinese women were enrolled and examined. BMD was measured by DEXA method while the percentage of CD31Emcn endothelial cells in the intertrochanteric part was measured by flow cytometry. The percentage of CD31Emcn endothelial cells in postmenopausal subjects was significantly lower compared with premenopausal women (8.7 ± 4.0% vs 13.2 ± 5.6%, P < 0.01). Meanwhile, the CD31Emcn endothelial cell levels in osteopenia and osteoporosis were significantly lower compared with subjects with normal BMD (9.84 ± 4.2% in osteopenia and 7.11 ± 3.2% in osteoporosis vs 12.7 ± 5.6% in subjects with normal T score, P < 0.01). Multiple regression analyses showed that the CD31Emcn endothelial cells level was positively associated with femur neck and total hip BMD, but not with lumbar BMD. Our study suggests a significantly positive association between CD31Emcn endothelial cells and local BMD in Chinese women. The proportion of CD31Emcn endothelial cells is a marker of bone quality and represents a potential target for treatment of bone loss.
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http://dx.doi.org/10.1007/s00774-019-01000-4DOI Listing
November 2019

Neutrophil-Based Delivery Systems for Nanotherapeutics.

Small 2018 10 24;14(42):e1801674. Epub 2018 Aug 24.

Department of Infectious Diseases, The Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, 310009, China.

Neutrophils, the most abundant leukocytes (50-70% of the total leukocytes in circulation), are the major type of cells recruited to sites of inflammation during infection and tumorigenesis, suggesting that neutrophils could contribute to nanotherapeutics for inflammation and cancer therapy. Neutrophil-based delivery has shown great potential in circumventing nanotherapeutics limitations, such as low biocompatibility, short circulation time, and immunogenicity of nanomaterials. In this review, the current development of neutrophil-based nanotherapeutic drugs in the treatment of inflammatory diseases and cancers is summarized. These successful neutrophil-based nanotherapeutic systems indicate that introducing functional nanomaterials into neutrophils and neutrophil-based vesicles may be a promising strategy for improving the nanotherapeutics in more complex conditions. The integration between neutrophils and nanomaterials will create more opportunities for future materials and medical studies.
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http://dx.doi.org/10.1002/smll.201801674DOI Listing
October 2018

2D amphiphilic organoplatinum(ii) metallacycles: their syntheses, self-assembly in water and potential application in photodynamic therapy.

Chem Commun (Camb) 2018 Jul;54(58):8068-8071

College of Chemistry and Chemical Engineer, Nantong University, Nantong, Jiangsu 226019, P. R. China.

Two 2D amphiphilic organoplatinum(ii) metallacycles with a porphyrin unit as the core and hydrophilic glycol units as the tail were designed and fabricated successfully through a new method called "coordination-driven self-assembly". They can self-assemble into micelles in water and have potential applications in photodynamic therapy.
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http://dx.doi.org/10.1039/c8cc04423fDOI Listing
July 2018

CXCR4-mediated osteosarcoma growth and pulmonary metastasis is suppressed by MicroRNA-613.

Cancer Sci 2018 Aug 26;109(8):2412-2422. Epub 2018 Jun 26.

Department of Orthopedic Surgery, Xiangya Hospital, Central South University, Changsha, China.

Osteosarcoma is the most common primary bone malignancy. Recently, studies showed chemokine receptor 4 (CXCR4) played a critical role in osteosarcoma. However, the regulation of CXCR4 is not fully understood. microRNAs are short, non-coding RNAs that play an important roles in post-transcriptional regulation of gene expression in a variety of diseases including osteosarcoma. miR-613 is a newly discovered miRNA and has been reported to function as a tumor suppressor in many cancers. In this study, we confirmed that both Stromal Cell-Derived Factor (SDF-1) and CXCR4 could be prognostic markers for osteosarcoma. Meanwhile this study found that SDF-1/CXCR4 pathway regulated osteosarcoma cells proliferation, migration and reduced apoptosis. Besides, we demonstrated that miR-613 was significantly downregulated in osteosarcoma patients. Elevated expression of miR-613 directly suppressed CXCR4 expression and then decreased the proliferation, migration and induced apoptosis of osteosarcoma cells. Moreover, our study found that CXCR4 promoted the development of lung metastases and inhibition of CXCR4 by miR-613 reduced lung metastases. These data indicated that CXCR4 mediated osteosarcoma cell growth and lung metastases and this effect can be suppressed by miR-613 through directly downregulating CXCR4.
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http://dx.doi.org/10.1111/cas.13653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113448PMC
August 2018

Nanomaterial-Based Organelles Protect Normal Cells against Chemotherapy-Induced Cytotoxicity.

Adv Mater 2018 Jul 15;30(27):e1801304. Epub 2018 May 15.

Center for Biomaterials and Biopathways, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang, 310027, P. R. China.

Chemotherapy-induced cytotoxicity in normal cells and organs triggers undesired lesions. Although targeted delivery is used extensively, more than half of the chemotherapy dose still concentrates in normal tissues, especially in the liver. Enabling normal cells or organs to defend against cytotoxicity represents an alternative method for improving chemotherapy. Herein, rationally designed nanomaterials are used as artificial organelles to remove unexpected cytotoxicity in normal cells. Nanocomposites of gold-oligonucleotides (Au-ODN) can capture intracytoplasmic doxorubicin (DOX), a standard chemotherapy drug, blocking the drug's access into the cell nucleus. Cells with implanted Au-ODN are more robust since their viability is maintained during DOX treatment. In vivo experiments confirm that the Au-ODN nanomaterials selectively concentrate in hepatocytes and eliminate DOX-induced hepatotoxicity, increasing the cell's capacity to resist the threatening chemotherapeutic milieu. The finding suggests that introducing functional materials as biological devices into living systems may be a new strategy for improving the regulation of cell fate in more complex conditions and for manufacturing super cells.
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http://dx.doi.org/10.1002/adma.201801304DOI Listing
July 2018

MiR-204/14-3-3ζ axis regulates osteosarcoma cell proliferation through SATA3 pathway.

Pharmazie 2017 Oct;72(10):593-598

Hyperproliferation of cells is a major problem is osteosarcoma (OS). So, further elucidation of the molecular mechanisms underlying hyperproliferation of OS is needed. Western blots results showed that 14-3-3ζ protein was upregulated in OS cell lines; 14-3-3ζ knockdown significantly suppressed OS cell proliferation, as well as the protein levels of p-STAT3, c-Myc and Cyclin D1. MicroRNA-204 (miR-204) has been regarded as an essential regulator in cancer carcinogenesis, including OS. Here, we revealed that miR-204 directly targets the 3'UTR of 14-3-3ζ to inhibit its expression, thus to suppress 14-3-3ζ -induced OS cell hyperproliferation. Further, we demonstrated that the STAT3 pathway was involved in miR-204/14-3-3ζ regulation of OS cell proliferation. Our findings provide information about the underlying mechanisms of miR-204/14-3-3ζ in OS cell proliferation through the STAT3 pathway, and suggest miR-204 and 14-3-3ζ as potential therapeutic targets in OS.
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http://dx.doi.org/10.1692/ph.2017.7574DOI Listing
October 2017

Citrate Improves Collagen Mineralization via Interface Wetting: A Physicochemical Understanding of Biomineralization Control.

Adv Mater 2018 Feb 8;30(8). Epub 2018 Jan 8.

Center for Biomaterials and Biopathways, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang, 310027, P. R. China.

Biological hard tissues such as bones always contain extremely high levels of citrate, which is believed to play an important role in bone formation as well as in osteoporosis treatments. However, its mechanism on biomineralization is not elucidated. Here, it is found that the adsorbed citrate molecules on collagen fibrils can significantly reduce the interfacial energy between the biological matrix and the amorphous calcium phosphate precursor to enhance their wetting effect at the early biomineralization stage, sequentially facilitating the intrafibrillar formation of hydroxyapatite to produce an inorganic-organic composite. It is demonstrated experimentally that only collagen fibrils containing ≈8.2 wt% of bound citrate (close to the level in biological bone) can reach the full mineralization as those in natural bones. The effect of citrate on the promotion of the collagen mineralization degree is also confirmed by in vitro dentin repair. This finding demonstrates the importance of interfacial controls in biomineralization and more generally, provides a physicochemical view about the regulation effect of small biomolecules on the biomineralization front.
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http://dx.doi.org/10.1002/adma.201704876DOI Listing
February 2018

miR-139-5p Represses BMSC Osteogenesis via Targeting Wnt/β-Catenin Signaling Pathway.

DNA Cell Biol 2017 Aug 16;36(8):715-724. Epub 2017 Jun 16.

Department of Orthopedics, Xiangya Hospital of Central South University , Changsha, Hunan, People's Republic of China .

Osteogenesis of mesenchymal stem cells (MSCs) has played a necessary role in the repair of bone. According to some reports, microRNAs participate in different physiological activity of the cells, including cell differentiation. This study investigated the function that miR-139-5p plays in the osteogenic differentiation of human bone marrow MSCs (hBMSCs). In addition to miR-139-5p, the effects of alkaline phosphatase (ALP), a membrane-bound metalloenzyme that is considered an early osteogenic differentiation marker, have also been investigated. Calcium-rich deposit (mineralization) is also a typical osteogenic differentiation marker that could be visualized by alizarin red S (ARS) staining. Inhibiting miR-139-5p notably promotes the hBMSC osteoblast differentiation, which, however, will be reduced by overexpressed miR-139-5p. This result has been made based on the alternations of ALP activity, ARS staining, as well as expression of osteogenic genes, including runt-related gene-2 (Runx2), collagen I (Col-1), and osteocalcin (OCN). miR-139-5p exerts its role in BMSC osteogenesis most probably through the Wnt/β-catenin pathway, by direct targeting CTNNB1 and frizzled 4 (FZD4), essential factors of Wnt/β-catenin pathway. In conclusion, according to the present study, inhibiting miR-139-5p could be a promising strategy in hBMSC osteogenesis.
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http://dx.doi.org/10.1089/dna.2017.3657DOI Listing
August 2017

microRNA-497 overexpression decreases proliferation, migration and invasion of human retinoblastoma cells via targeting vascular endothelial growth factor A.

Oncol Lett 2017 Jun 24;13(6):5021-5027. Epub 2017 Apr 24.

Refractive Surgery Center, Xi'an Aier Ancient City Eye Hospital, Xi'an, Shaanxi 710061, P.R. China.

The expression level and roles of microRNA-497 (miR-497) have been frequently reported in previous studies on cancer. However, its expression, function and associated molecular mechanisms in retinoblastoma remain unknown. In the present study, miR-497 expression levels in human retinoblastoma tissues, normal retinal tissues and retinoblastoma cell lines were determined using reverse transcription-quantitative polymerase chain reaction. In addition, a Cell Counting Kit-8 assay, cell migration assay, cell invasion assay, western blot analysis and Dual-Luciferase reporter assay were used to explore the expression, functions and molecular mechanisms of miR-497 in human retinoblastoma. It was demonstrated that miR-497 was significantly downregulated in retinoblastoma tissues and cell lines compared with normal retinal tissues. Ectopic expression of miR-497 decreased the proliferation, migration and invasion of retinoblastoma cells. Furthermore, VEGFA was verified as a potential direct target of miR-497 . Taken together, the results indicate that miR-497 functions as a tumor suppressor in the carcinogenesis and progression of retinoblastoma via targeting VEGFA. miR-497 should be investigated as a potential therapeutic target for the treatment of retinoblastoma.
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http://dx.doi.org/10.3892/ol.2017.6083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452910PMC
June 2017

The biomechanical and histological effects of posterior cruciate ligament rupture on the medial tibial plateau.

J Orthop Surg Res 2017 Mar 23;12(1):48. Epub 2017 Mar 23.

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan Province, China.

Background: The objective of this study was to investigate the biomechanical and histological effects of the posterior cruciate ligament (PCL) on the medial tibial plateau.

Methods: A total of 12 cadaveric human knee specimens were collected and grouped as follows: the PCL intact group (n = 12), the anterolateral bundle rupture group (n = 6), the postmedial bundle rupture group (n = 6), and the PCL rupture group (n = 12). The strain on the anterior, middle, and posterior parts of the medial tibial plateau with an axial loading force at different flexion angles was measured and analyzed, respectively. Forty-eight rabbits were chosen for animal study: surgery was performed on the one side of each rabbit randomly (experimental group), while the other side was taken as control (control group). Every 12 rabbits were culled at each of the four selected time points to collect the medial tibial plateau for morphological and histological observation.

Results: The PCL rupture, either partial or complete, may generate an abnormal load on all the parts of the medial tibial plateau with axial loading at all positions. Noticeable time-dependent degenerative histological changes of the medial tibial plateau were observed in the rabbit models of PCL rupture. Compared with the control group, all the PCL rupture groups exhibited a higher expression of the matrix metalloproteinase-7 (MMP-7) and the tissue inhibitors of metalloproteinase-1 (TIMP-1) at all the time points.

Conclusions: Either partial or complete PCL rupture may generate an abnormal load on all the parts of the medial tibial plateau with axial loading at all the positions and may cause cartilage degeneration on the medial tibial plateau.
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http://dx.doi.org/10.1186/s13018-017-0551-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5364568PMC
March 2017

Biomineralization: From Material Tactics to Biological Strategy.

Adv Mater 2017 Apr 23;29(14). Epub 2017 Feb 23.

Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang, 310027, China.

Biomineralization is an important tactic by which biological organisms produce hierarchically structured minerals with marvellous functions. Biomineralization studies typically focus on the mediation function of organic matrices on inorganic minerals, which helps scientists to design and synthesize bioinspired functional materials. However, the presence of inorganic minerals may also alter the native behaviours of organic matrices and even biological organisms. This progress report discusses the latest achievements relating to biomineralization mechanisms, the manufacturing of biomimetic materials and relevant applications in biological and biomedical fields. In particular, biomineralized vaccines and algae with improved thermostability and photosynthesis, respectively, demonstrate that biomineralization is a strategy for organism evolution via the rational design of organism-material complexes. The successful modification of biological systems using materials is based on the regulatory effect of inorganic materials on organic organisms, which is another aspect of biomineralization control. Unlike previous studies, this study integrates materials and biological science to achieve a more comprehensive view of the mechanisms and applications of biomineralization.
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http://dx.doi.org/10.1002/adma.201605903DOI Listing
April 2017

Towards understanding the distribution and tumor targeting of sericin regulated spherical calcium phosphate nanoparticles.

Microsc Res Tech 2017 Mar 17;80(3):321-330. Epub 2016 Nov 17.

Institute of Biomaterials and Marine Biological Resources, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, 310018, China.

The study of calcium phosphate (CaP) nanoparticles in vivo is still incomplete, which has limited their applications for biomedical delivery. Herein, we synthesized amorphous spherical calcium phosphate (S-CaP) nanoparticles with an average size of 80 nm via a co-precipitation method in the presence of silk sericin as the regulation template. S-CaP was labeled by the near-infrared dye reagent DiR, and then, the labeled nanoparticles (S-CaP@DiR) were used to investigate the distribution and degradation in healthy mice by IVIS and TEM. The results showed that the S-CaP nanoparticles were mainly distributed in the liver, and ∼90% of them (500 μg) could be degraded by the liver within 2 weeks. Tumor-bearing mice were then prepared, and the S-CaP was injected intravenously. Strikingly, the nanoparticles can effectively target solid tumors in cancer cell-bearing mice, indicating that the solid tumor was a foundation for the enrichment of the nanoparticles by the EPR effect, which showed the important potential of biodegradable inorganic nanoparticles in clinical drugs for tumor therapy.
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http://dx.doi.org/10.1002/jemt.22800DOI Listing
March 2017

Percutaneous compression plate versus dynamic hip screw for treatment of intertrochanteric hip fractures: A overview of systematic reviews and update meta-analysis of randomized controlled trials.

Int J Surg 2016 Sep 26;33 Pt A:1-7. Epub 2016 Jul 26.

Department of Orthopedics, Xiangya Hospital, Central South University, China. Electronic address:

Purpose: Intertrochanteric hip fractures lead to high morbidity and mortality rates. As a minimally invasive technique, many studies reported the efficacy of PCCP for the treatment of intertrochanteric fractures, but the controversy still existed in some outcomes. The purpose of this study was to evaluate the efficacy of PCCP and DHS by a overview of systematic reviews and well-designed, comprehensive update meta-analysis.

Methods: PUBMED, SCOPUS, CCRCT, WANFANG and CNKI database were searched in all languages published up to April 2016. Systematic reviews and randomized controlled trials reporting outcomes of PCCP and DHS for intertrochanteric fractures were included. Meta-analyses comparing the two techniques were performed according to the Cochrane Handbook.

Results: Five original trials and four systematic reviews met the inclusion criteria. Meta-analyses showed that the blood loss [SMD = -2.35, 95%CI(-4.26--0.44)], transfusion volume [SMD = -0.26, 95%CI(-0.47--0.06)] and complications [RR = 0.33, 95%CI(0.14-0.77)] was statistically less in PCCP group than DHS group while there was no significant difference between two groups in mortality rate, transfusion rate and length of hospital day.

Conclusions: PCCP is recommended to treat intertrochanteric hip fractures as an alternative minimally invasive method. More high-quality, randomized controlled trials that are adequately powered are needed to further evaluate the efficacy of PCCP and DHS.
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http://dx.doi.org/10.1016/j.ijsu.2016.07.005DOI Listing
September 2016

miR-199b-5p modulates BMSC osteogenesis via suppressing GSK-3β/β-catenin signaling pathway.

Biochem Biophys Res Commun 2016 09 27;477(4):749-754. Epub 2016 Jun 27.

Department of Orthopedics, Xiangya Hospital Central South University, PR China. Electronic address:

miR-199b-5p is up-regulated significantly during the osteogenesis process in human bone marrow stromal cells (BMSCs). Inhibiting miR-199b-5p notably reduces while over-expressing miR-199b-5p promotes the BMSCs osteoblast differentiation, suggested by the alternations of osteogenic genes expression, ALP activity and the ARS-stained mineral nodules. miR-199b-5p exerts its role in BMSC osteogenesis most probably through the GSK-3β/β-catenin signaling pathway. In conclusion, the present study revealed for the first time that miR-199b-5p plays a positive role in osteoblast differentiation.
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http://dx.doi.org/10.1016/j.bbrc.2016.06.130DOI Listing
September 2016

Multifunctional Gd,Ce,Tb co-doped β-tricalcium phosphate porous nanospheres for sustained drug release and bioimaging.

J Mater Chem B 2016 Jun 13;4(22):3903-3910. Epub 2016 May 13.

Centre for Biomaterials and Biopathways and Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China.

Multifunctional Gd,Ce,Tb co-doped β-tricalcium phosphate (TCP) porous nanospheres are prepared by a facile solvothermal strategy with trimethyl phosphate as the phosphorus source. The as-prepared nanomaterial (average diameter of 100 nm) has a multiple level pore size distribution with the specific surface area of 124.33 m g, which benefits drug loading. Its photoluminescent and magnetic multifunctions are realized by the co-doping of Gd, Ce and Tb ions, which make the nanomaterial promising for both fluorescence and magnetic resonance imaging techniques. Furthermore, the nanomaterial exhibits excellent cytocompatibility and a relatively high doxorubicin loading capacity as well as sustained pH-sensitive drug release behaviour. It is suggested that the Gd,Ce,Tb co-doped β-TCP porous nanospheres are promising for applications in the biomedical fields such as multifunctional drug delivery systems and tissue engineering scaffolds with bioimaging guidance.
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http://dx.doi.org/10.1039/c5tb02767eDOI Listing
June 2016

Improved in vivo tumor therapy via host-guest complexation.

J Mater Chem B 2016 Apr 4;4(15):2691-2696. Epub 2016 Apr 4.

State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance & Novel Materials, Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China.

In order to improve the effectiveness of cancer therapy and reduce the adverse effects of conventional chemotherapy, the development of less toxic, biocompatible, decomposable and pH-responsive nano-containers is of great importance. In this work a novel nano-container is designed and synthesized by doping a water-soluble pillar[5]arene WP5 onto hollow mesoporous silica nanoparticles (HMNPs) via host-guest complexation. This nano-container decomposes into small water-soluble fragments to achieve a highly efficient release of the loaded anticancer drug doxorubicin. Importantly, the complexation of WP5 molecules with HMNPs significantly improves the inhibition of tumor growth in vivo with minimal side effects, which can be attributed to the pH-responsiveness of the host-guest interactions. Under the extracelluar conditions, the host-guest complexation between WP5 and HMNPs enhances the loading of doxorubicin molecules. However, this host-guest complexation is prohibited under the low pH conditions in intracellular lysosomes, so that doxorubicin is released readily from the vector. The present novel drug delivery system demonstrates the great potential of host-guest complexation for cancer therapy improvement.
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http://dx.doi.org/10.1039/c5tb02611cDOI Listing
April 2016

A Drug-Free Tumor Therapy Strategy: Cancer-Cell-Targeting Calcification.

Angew Chem Int Ed Engl 2016 Apr 17;55(17):5225-9. Epub 2016 Mar 17.

Center for Biomaterials and Biopathways, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang, 310027, China.

Herein, we propose a drug-free approach to cancer therapy that involves cancer cell targeting calcification (CCTC). Several types of cancer cells, such as HeLa cells, characterized by folate receptor (FR) overexpression, can selectively adsorb folate (FA) molecules and then concentrate Ca(2+) locally to induce specific cell calcification. The resultant calcium mineral encapsulates the cancer cells, inducing their death, and in vivo assessments confirm that CCTC treatment can efficiently inhibit tumor growth and metastasis without damaging normal cells compared with conventional chemotherapy. Accordingly, CCTC remarkably improve the survival rate of tumor mice. Notably, both FA and calcium ions are essential ingredients in human metabolism, which means that CCTC is a successful drug-free method for tumor therapy. This achievement may further represent an alternative cancer therapy characterized by selective calcification-based substitution of sclerosis for tumor disease.
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http://dx.doi.org/10.1002/anie.201601364DOI Listing
April 2016

In vivo dual-targeted chemotherapy of drug resistant cancer by rationally designed nanocarrier.

Biomaterials 2016 Jan 9;75:71-81. Epub 2015 Oct 9.

Centre for Biomaterials and Biopathways, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang, 310027, PR China; Qiushi Academy for Advanced Studies, Zhejiang University, Hanghzou, Zhejiang 310027, China. Electronic address:

Multidrug resistance is one of major obstacles to the effective cancer chemotherapy. To address this issue, we developed the effective circumvention of multidrug resistance in cancer cells by a yolk-shell Fe3O4@MgSiO3 nanoplatform with the polymerpoly(ethylene glycol) and folic acid modifications can achieve active targeted delivery of anti-cancer drug by using combined magnetic and ligand targeting. The direct intracellular drug delivery of doxorubicin by nanocarrier was much more effectively than free DOX for multidrug resistant Hep-G2/MDR cancer cells. Besides the excellent biocompatibility, high drug loading efficiency, dual-targeting delivery, and controlled releasing behavior, in vivo experiments demonstrate that this nanocarrier can specifically deliver and concentrate doxorubicin hydrochloride in tumor sites to overcome drug resistance. It follows an alternative strategy for effective chemotherapy against drug resistant cancers by using rationally designed nanomaterial.
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http://dx.doi.org/10.1016/j.biomaterials.2015.09.030DOI Listing
January 2016

Rapid stabilisation of atherosclerotic plaque with 5-aminolevulinic acid-mediated sonodynamic therapy.

Thromb Haemost 2015 Oct 16;114(4):793-803. Epub 2015 Jul 16.

Ye Tian, Division of Cardiology, First Affiliated Hospital, Cardiovascular Institute, Harbin Medical University, 23 Youzheng Street, Harbin 150001, China, Tel.: +86 451 85555943, Fax: +86 451 87530341, E-mail:

5-Aminolevulinic acid-mediated sonodynamic therapy (ALA-SDT) effectively induces the apoptosis of atherogenic macrophages, but whether it can stabilise atherosclerotic plaque in vivo is unclear. Here, we used an animal model to evaluate the effects of ALA-SDT on plaque stabilisation. Sixty rabbits were induced atherosclerotic plaques in the femoral artery with a combination of silastic tube placement with atherogenic diet, and randomly assigned into control (n = 12) and SDT (n = 48) groups. In the SDT group, after intravenous injected with ALA (60 mg/kg) animals underwent the treatment of ultrasound with intensities of 0.75, 1.00, 1.50 and 2.00 W/cm(²) (n = 12 for each intensity). Seven days after the treatment, the plaque disruption assay was performed to test plaque stability. We found that ALA-SDT with ultrasound intensity of 1.5 W/cm(²) showed the strongest efficacy to stabilise plaques. Under this condition, the frequency of plaque disruption decreased by 88% (p<0.01), positive area of macrophages reduced by 94% (p<0.001) and percentage content of lipids dropped by 60% (p < 0.001), while percentage content of collagens increased by 127% (p<0.001). We also found that the plaque stabilisation by ALA-SDT was associated with increased macrophage apoptosis and apoptotic cell clearance. Moreover, ALA-SDT decreased the contents and activities of matrix metalloproteinase-2,9 and increased the levels of tissue inhibitors of matrix metalloproteinase-1,2 in plaques. Our studies demonstrate that ALA-SDT promotes plaque stabilisation by inducing macrophage elimination and inhibiting matrix degradation. This method might be a promising regimen for atherosclerosis therapy.
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http://dx.doi.org/10.1160/TH14-12-1030DOI Listing
October 2015

Enhancing in vitro bioactivity and in vivo osteogenesis of organic-inorganic nanofibrous biocomposites with novel bioceramics.

J Mater Chem B 2014 Oct 11;2(37):6293-6305. Epub 2014 Aug 11.

The Key Laboratory of Advanced Textile Materials and Manufacturing Technology, Zhejiang Sci-Tech University, Hangzhou 310018, China.

Fabricating bioactive nanofibrous scaffolds from biodegradable polymers to mimic native tissue is an important approach in repairing bony defects. Silk fibroin (SF) may contribute to bone regeneration because of its excellent mechanical properties, slow degradability, and low osteoconductivity. A combination of bioceramic-polymer materials is generally used to provide an improved osteoconductive environment for bone healing. This study attempts developing for the first time an electrospun SF-based biocomposite system by introducing new bioceramics based on mesoporous bioactive glass/hydroxyapatite nanocomposite (MGHA). The addition of MGHA into the SF matrix could regulate the physicochemical properties and surface hydrophilicity, but induce weakened tensile properties as compared to pure SF. The excellent apatite-formation ability of a MGHA-introduced nanocomposite also improved the bioactivity of the composite. The biphasic composite increasingly degraded in PBS or enzyme solution in vitro compared with pure SF. In vivo evaluation of bone formation confirmed that SF/MGHA is more advantageous in bone reconstruction than the SF group for cranial bone defects. These results indicate the suitability of the SF/MGHA composite system in bone defects, demonstrating its potential application in bone tissue regeneration.
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http://dx.doi.org/10.1039/c4tb00889hDOI Listing
October 2014

Exploration of the effect of mmu-miR-142-5p on osteoblast and the mechanism.

Cell Biochem Biophys 2015 Jan;71(1):255-60

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, 410008, China,

The objective of this study is to explore the effect of mmu-miR-142-5p on osteoblast and the mechanism. Neonatal New Zealand rabbits were selected to collect and culture primary osteoblasts after being killed. The agonists agomiR-142-5p, agomiR-NC and inhibitors antagomiR-142-5p, antagomiR-NC were transfected to establish mmu-miR-142-5p osteoblast model. 48 h after transfection, total RNA was extracted, ELISA was used to detect ALP level, Western Blot was used to detect HSP27 level, and RT-PCR was used to detect levels of RunX2 and OC. Rabbit osteoblasts showed triangle shape and grew adhering to the wall, cytoplasm extended and protruded. As the culture time prolonged, the cell volume was increased, and the amount showed exponential growth. After transfection, the abundance was significantly increased in agonist group and significantly decreased in inhibitor group, indicating that exogenous agonist can successfully up-regulate mmu-miR-142-5p level and exogenous inhibitor can down-regulate mmu-miR-142-5p level in osteoblast. Compared with control group, ALP level was significantly increased in agonist group and decreased in inhibitor group. Transfection of exogenous agonist can up-regulate HSP27 level in osteoblast, and transfection of exogenous inhibitor can decrease HSP27 level in osteoblast; however, there was no effect on HSP27 mRNA level. RunX2 mRNA and OC mRNA were significantly increased in agonist group and decreased in inhibitor group. Transfection of exogenous nucleic acid agomiR-142-5p can up-regulate the abundance and activity of mmu-miR-142-5p, and transfection of antagomiR-142-5p can down-regulate the abundance and activity of mmu-miR-142-5p, indicating that mmu-miR-142-5p can effectively helps the mineralization of osteoblast.
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http://dx.doi.org/10.1007/s12013-014-0193-0DOI Listing
January 2015