Publications by authors named "Ai Zhuang"

18 Publications

  • Page 1 of 1

A Novel Forkhead Box L2 Missense Mutation, c.1068G>C, in a Chinese Family With Blepharophimosis/Ptosis/Epicanthus Inversus Syndrome.

J Craniofac Surg 2021 Aug 9. Epub 2021 Aug 9.

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.

Abstract: The aim of the study was to report a novel forkhead box L2 (FOXL2) missense mutation in a Chinese blepharophimosis/ptosis/epicanthus inversus syndrome family. Three generations of the Chinese family with blepharophimosis/ptosis/epicanthus inversus syndrome were enrolled in this study. Blood samples from patients of this family were collected and then analyzed by whole-exome sequencing. Confocal microscopy was performed to detect the subcellular location of FOXL2. Transactivation studies were performed and verified with real time polymerase chain reaction. A novel mutation (c.1068G>C) located in the downstream of deoxyribonucleic acid-binding forkhead domain was identified. Confocal photos showed the novel mutation did not disturb FOXL2 function, and the mutant protein could still transactivate steroidogenic acute regulatory protein, a key regulator of primary ovarian failure (POF). Our study revealed a novel missense mutation (c.1068G>C) and expanded the spectrum of FOXL2 gene mutations.
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http://dx.doi.org/10.1097/SCS.0000000000008042DOI Listing
August 2021

A Novel Stimuli-Responsive Injectable Antibacterial Hydrogel to Achieve Synergetic Photothermal/Gene-Targeted Therapy towards Uveal Melanoma.

Adv Sci (Weinh) 2021 Sep 31;8(18):e2004721. Epub 2021 Jul 31.

Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, P. R. China.

Uveal melanoma (UM) is the most prevalent primary intraocular malignant tumor with a high lethal rate. Patients who undergo conventional enucleation treatments consistently suffer permanent blindness, facial defects, and mental disorders, therefore, novel therapeutic modalities are urgently required. Herein, an injectable and stimuli-responsive drug delivery antibacterial hydrogel ([email protected]@DC_AC50) is constructed via a facile grinding method that is inspired by the preparation process of traditional Chinese medicine. The incorporation of gold nanorods can enhance the mechanical strength of the hydrogel and realize photothermal therapy (PTT) and thermosensitive gel-sol transformation to release the gene-targeted drug DC_AC50 on demand in response to low-density near-infrared (NIR) light. The orthotopic model of UM is built successfully and indicates the excellent efficiency of [email protected]@DC_AC50 in killing tumors without damage to normal tissue because of its synergistic mild temperature PTT and gene-targeted therapy. Moreover, the eyeball infection model reveals the remarkable antibacterial properties of the hydrogel which can prevent endophthalmitis in the eyeball. There is negligible difference between the [email protected]@DC_AC50+NIR group and normal group. This NIR light-triggered gene-targeted therapy/PTT/antibacterial treatment pattern provides a promising strategy for building multifunctional therapeutic platform against intraocular tumors and exhibits great potential for the clinical treatment of UM.
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http://dx.doi.org/10.1002/advs.202004721DOI Listing
September 2021

Cathelicidin LL37 Promotes Osteogenic Differentiation and Bone Regeneration .

Front Bioeng Biotechnol 2021 3;9:638494. Epub 2021 May 3.

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Different types of biomaterials have been used to repair the defect of bony orbit. However, exposure and infections are still critical risks in clinical application. Biomaterials with characteristics of osteogenesis and antibiosis are needed for bone regeneration. In this study, we aimed to characterize the antimicrobial effects of cathelicidin-LL37 and to assess any impacts on osteogenic activity. Furthermore, we attempted to demonstrate the feasibility of LL37 as a potential strategy in the reconstruction of clinical bone defects. Human adipose-derived mesenchyme stem cells (hADSCs) were cultured with different concentrations of LL37 and the optimum concentration for osteogenesis was selected for further studies. We then evaluated the antibiotic properties of LL37 at the optimum osteogenic concentration. Finally, we estimated the efficiency of a PSeD/hADSCs/LL37 combined scaffold on reconstructing bone defects in the rat calvarial defect model. The osteogenic ability on hADSCs was shown to be dependent on the concentration of LL37 and reached a peak at 4 μg/ml. The optimum concentration of LL37 showed good antimicrobial properties against and . The combination scaffold of PSeD/hADSCs/LL37 showed superior osteogenic properties compared to the PSeD/hADSCs, PSeD, and control groups scaffolds, indicating a strong bone reconstruction effect in the rat calvarial bone defect model. In Conclusion, LL37 was shown to promote osteogenic differentiation as well as antibacterial properties. The combination of PSeD/hADSCs/LL37 was advantageous in the rat calvarial defect reconstruction model, showing high potential in clinical bone regeneration.
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http://dx.doi.org/10.3389/fbioe.2021.638494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126666PMC
May 2021

mA RNA hypermethylation-induced BACE2 boosts intracellular calcium release and accelerates tumorigenesis of ocular melanoma.

Mol Ther 2021 06 15;29(6):2121-2133. Epub 2021 Feb 15.

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai 200001, China. Electronic address:

Ocular melanoma, including uveal melanoma (UM) and conjunctival melanoma (CM), is the most common and deadly eye cancer in adults. Both UM and CM originate from melanocytes and exhibit an aggressive growth pattern with high rates of metastasis and mortality. The integral membrane glycoprotein beta-secretase 2 (BACE2), an enzyme that cleaves amyloid precursor protein into amyloid beta peptide, has been reported to play a vital role in vertebrate pigmentation and metastatic melanoma. However, the role of BACE2 in ocular melanoma remains unclear. In this study, we showed that BACE2 was significantly upregulated in ocular melanoma, and inhibition of BACE2 significantly impaired tumor progression both in vitro and in vivo. Notably, we identified that transmembrane protein 38B (TMEM38B), whose expression was highly dependent on BACE2, modulated calcium release from endoplasmic reticulum (ER). Inhibition of the BACE2/TMEM38B axis could trigger exhaustion of intracellular calcium release and inhibit tumor progression. We further demonstrated that BACE2 presented an increased level of N-methyladenosine (mA) RNA methylation, which led to the upregulation of BACE2 mRNA. To our knowledge, this study provides a novel pattern of BACE2-mediated intracellular calcium release in ocular melanoma progression, and our findings suggest that mA/BACE2/TMEM38b could be a potential therapeutic axis for ocular melanoma.
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http://dx.doi.org/10.1016/j.ymthe.2021.02.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178445PMC
June 2021

Clinical characteristics and germline mutation spectrum of RB1 in Chinese patients with retinoblastoma: A dual-center study of 145 patients.

Exp Eye Res 2021 04 23;205:108456. Epub 2021 Jan 23.

Department of Ophthalmology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China. Electronic address:

Retinoblastoma (Rb) is the most common primary intraocular childhood malignancy and one of the main causes of blindness in children. In China, most tumors are diagnosed at an advanced stage and have relatively poor outcomes compared to developed countries. Here, we aimed to update the clinical manifestations and RB transcriptional corepressor 1 (RB1) mutation spectrum in Chinese Rb patients. Medical charts of 184 eyes in 145 Chinese Rb patients belonging to unrelated families were reviewed. Genomic DNA was isolated from peripheral blood of the patients and their parents. Mutation analysis of whole coding regions, promoter regions and flanking splice sites in the RB1 gene was performed. In addition, multiplex ligation-dependent probe amplification (MLPA) was done to detect gross aberrations. Germline RB1 mutations were observed in 37.2% (54/145) of Rb patients. RB1-mutated patients presented with earlier age of diagnosis (p = 0.019), with a significantly larger proportion of bilateral cases (p = <0.001) and secondary malignancies (p = 0.027) relative to those without RB1 mutations. For ocular clinical presentations, RB1-mutated retinoblastomas presented with a larger proportion of ectropion uveae (p = 0.017) and iris neovascularization (p = 0.001). These RB1 mutations comprised of 13 (24.1%) nonsense mutation, 13 (24.1%) splicing mutations, 11 (20.4%) frameshift deletions, 11 (20.4%) gross mutations, 3 (5.6%) missense mutations, 2 (3.7%) promoter mutations and 1 (1.9%) non-frameshift deletion. In addition, 8 novel RB1 mutations were identified. These germline RB1 mutations were not related to age at diagnosis or laterality. Here, we provide a comprehensive spectrum of RB1 germline mutations in Chinese Rb patients and describe correlations between RB1 mutations and clinical presentations. Our study also provides new evidence that will inform management and genetic counselling of Rb patients and families.
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http://dx.doi.org/10.1016/j.exer.2021.108456DOI Listing
April 2021

Biomimetic nanofibrous hybrid hydrogel membranes with sustained growth factor release for guided bone regeneration.

Biomater Sci 2021 Feb;9(4):1256-1271

Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. and Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.

Bone regeneration, a complex physiological process, remains a challenge due to the susceptibility to the environment and absence of osteogenic growth factors around the defect region. Although autologous bone grafting is regarded as the gold standard for bone defect treatment, guided bone regeneration membranes in combination with multiple functional growth factors show a striking regeneration effect. Here, a biomimetic nanofibrous hybrid hydrogel composed of bacterial cellulose membranes and alginate/CaCl2 for sustained growth factor delivery was developed. The antibacterial peptide beta-defensin 2 served as an antibacterial, osteogenic, and angiogenic growth factor and was loaded into the aforementioned hydrogel. The mechanical and physical properties of the biomimetic nanofibrous hybrid hydrogel were investigated. Then, the in vitro osteogenic and angiogenic differentiation was confirmed by alkaline phosphatase (ALP) activity, Alizarin Red S staining, qPCR, western blot analysis and tube formation assays. After implantation into a rat calvarial defect model for 12 weeks, nanofibrous hybrid hydrogel membranes could adhere to the defect surface and promote new bone and vessel regeneration.
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http://dx.doi.org/10.1039/d0bm01821jDOI Listing
February 2021

Fluorinated-functionalized hyaluronic acid nanoparticles for enhanced photodynamic therapy of ocular choroidal melanoma by ameliorating hypoxia.

Carbohydr Polym 2020 Jun 4;237:116119. Epub 2020 Mar 4.

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200011, China. Electronic address:

Photodynamic therapy (PDT) is a method for killing cancer cells by employing reactive singlet oxygen (O). However, the inherent hypoxia and oxygen consumption in tumors during PDT lead to a deficient oxygen supply, which in turn hinder the photodynamic efficacy. To overcome this issue, fluorinated-functionalized polysaccharide-based nanocomplexes were prepared by anchoring perfluorocarbons (PFCs) and pyropheophorbide a (Ppa) onto the polymer chains of hyaluronic acid (HA) to deliver O in hypoxia area. These amphiphilic conjugates can self-assemble into micelles and its application in PDT is evaluated. Due to the high oxygen affinity of perfluorocarbon segments, and the tumor-targeting nature of HA, the photodynamic effect of the oxygen self-carrying micelles is remarkably enhanced, which is confirmed by increased generation of O and elevated phototoxicity in vitro and in vivo. These results emphasize the promising potential of polysaccharide-based nanocomplexes for enhanced PDT of Ocular Choroidal Melanoma.
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http://dx.doi.org/10.1016/j.carbpol.2020.116119DOI Listing
June 2020

Effect of Bifunctional β Defensin 2-Modified Scaffold on Bone Defect Reconstruction.

ACS Omega 2020 Mar 18;5(8):4302-4312. Epub 2020 Feb 18.

Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Road, Shanghai 200011, P. R. China.

Bone tissue engineering has emerged as an effective alternative treatment to the problem of bone defect. To repair a bone defect, antibiosis and osteogenesis are two essential aspects of the repair process. By searching the literature and performing exploratory experiments, we found that β defensin 2 (BD2), with bifunctional properties of antibiosis and osteogenesis, was a feasible alternative for traditional growth factors. The antimicrobial ability of BD2 against and was studied by the spread plate and live/dead staining methods (low effective concentration of 20 ng/mL). BD2 was also demonstrated to enhance osteogenesis, with higher messenger RNA (mRNA) and protein expression of the osteogenic markers collagen I (Col1), runt-related transcription factor 2 (Runx2), osteopontin (Opn), and osteocalcin (Ocn) in vitro (1.5-2.5-fold increase compared with the control group in the most effective concentration group), which was consistent with the alkaline phosphatase (ALP) and alizarin red S (ARS) staining results. We implanted poly(sebacoyl diglyceride) (PSeD) combined with BD2 and rat bone tissue-derived mesenchymal stem cells (rBMSCs) under the back skin of rats and found that the inflammatory response was significantly lower with this combination than with the PSeD/rBMSCs scaffold without BD2 and the pure PSeD group and was similar to the control group. Importantly, when assessed in a critical-sized in vivo rat 8 m diameter calvaria defect model, a scaffold we developed combining bifunctional BD2 with porous organic polymer displayed an osteogenic effect that was 160-200% greater than the control group. The in vivo study results revealed a significant osteogenic response and antimicrobial effect and were consistent with the in vitro results. In summary, BD2 displayed a great potential of simultaneously promoting bone regeneration and preventing infection and could provide a viable alternative to traditional growth factors applied in bone defect repair.
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http://dx.doi.org/10.1021/acsomega.9b04249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057706PMC
March 2020

Treatment of upper and lower lacrimal punctal occlusion using retrograde canaliculotomy and punctoplasty.

Int J Ophthalmol 2019 18;12(9):1498-1502. Epub 2019 Sep 18.

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.

This is a retrospective, noncomparative analysis of a case series to explore the safety and effectiveness of retrograde canaliculotomy and punctoplasty for treating epiphora due to upper and lower lacrimal punctal occlusion. During the procedure, the horizontal portion of the normal lower canaliculus was identified; the corresponding punctum was reconstructed retrograde canaliculotomy and punctoplasty. Intubation was performed to prevent postoperative reocclusion. Patients were followed up for 12 to 24mo. A total of 16 patients with unilateral upper and lower lacrimal punctal occlusion were included. Satisfactory outcomes were achieved: all 16 patients exhibited improvement of epiphora; 31 rebuilt punctal openings and canaliculi achieved recanalization. Only one upper punctal opening could not be reconstructed because the corresponding canaliculus exhibited severe injury. No significant complications occurred as a result of the treatments. Retrograde canaliculotomy and punctoplasty appears to effective, safe, and minimally invasive for treatment of upper and lower punctal occlusion.
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http://dx.doi.org/10.18240/ijo.2019.09.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739566PMC
September 2019

Bovine Acellular Dermal Matrix for Levator Lengthening in Thyroid-Related Upper-Eyelid Retraction.

Med Sci Monit 2018 May 2;24:2728-2734. Epub 2018 May 2.

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland).

BACKGROUND Eyelid retraction is the most common and often the first sign of thyroid eye disease (TED). Upper-eyelid retraction causes both functional and cosmetic problems. In order to correct the position of the upper eyelid, surgery is required. Many procedures have demonstrated good outcomes in mild and moderate cases; however, unpredictable results have been obtained in severe cases. Dryden introduced an upper-eyelid-lengthening procedure, which used scleral grafts, but outcomes were unsatisfactory. A new technique is introduced in this study as a reasonable alternative for TED-related severe upper-eyelid retraction correction. MATERIAL AND METHODS An innovative technique for levator lengthening using bovine acellular dermal matrix as a spacer graft is introduced for severe upper-eyelid retraction secondary to TED. Additionally, 2 modifications were introduced: the fibrous cords scattered on the surface of the levator aponeurosis were excised and the orbital fat pad anterior to the aponeurosis was dissected and sutured into the skin closure in a "skin-tarsus-fat-skin" fashion. RESULTS The modified levator-lengthening surgery was performed on 32 eyelids in 26 patients consisting of 21 women and 5 men (mean age, 37.8 years; age range, 19-67 years). After corrective surgery, the average upper margin reflex distance was lowered from 7.7±0.85 mm to 3.3±0.43 mm. Eighteen cases (69%) had perfect results, while 6 cases (23%) had acceptable results. CONCLUSIONS A modified levator-lengthening procedure using bovine acellular dermal matrix as a spacer graft ameliorated both the symptoms and signs of severe upper-eyelid retraction secondary to TED. This procedure is a reasonable alternative for correction of TED-related severe upper-eyelid retraction.
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http://dx.doi.org/10.12659/MSM.909306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952806PMC
May 2018

Orbital radiotherapy plus three-wall orbital decompression in a patient with rare ocular manifestations of thyroid eye disease: case report.

BMC Endocr Disord 2018 Feb 6;18(1). Epub 2018 Feb 6.

Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 ZhiZaoJu Road, Shanghai, 200011, China.

Background: Thyroid eye disease (TED) is a debilitating autoimmune orbital disease that is often a result of Graves' disease. Dysthyroid optic neuropathy (DON) is a rare but sight-threatening manifestation of TED with therapeutic challenges that can potentially lead to visual loss.

Case Presentation: A 74-year-old man experienced active TED with extremely severe redness and swelling of the conjunctiva, loss of visual acuity and exacerbation of disfiguring proptosis. Computed tomography revealed the involvement of extraocular muscles resulting in optic nerve compression. He was in poor general condition and was intolerant to steroids. To achieve the optimal operating conditions for orbital decompression surgery, the patient was initially treated with orbital radiotherapy. The patient responded well, with improvements in clinical activity score and visual acuity.

Conclusion: This case demonstrates a rare and severe case of DON with therapeutic challenges. To date, no cases has been reported of a patient with such severe and unusual ocular manifestations. Early awareness of the occurrence of optic nerve compression and prompt treatment are important to prevent irreversible outcomes. Orbital radiotherapy should be considered as a useful surgery-delaying alternative for DON, especially in patients who have contraindications to steroids.
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http://dx.doi.org/10.1186/s12902-018-0235-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802057PMC
February 2018

A new method for locating the proximal lacerated bicanalicular ends in Chinese preschoolers and long-term outcomes after surgical repair.

Medicine (Baltimore) 2017 Aug;96(33):e7814

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.

This report is to explore the long-term outcomes of surgical repair of bicanalicular lacerations in Chinese preschool patients. In this report, 12 patients with bicanalicular lacerations were studied between September 2010 and September 2015. The distance from the punctum to the distal canalicular lacerated end was recorded before surgery to classify different types of trauma. All patients underwent surgical repair of the lacerated canaliculi by 1 surgeon within 48 hours after the trauma occurred. After treatment, the lesions were divided into 3 types according to the distance from the punctum to the distal lacerated canalicular end as follows: lateral, medial, and the central. Based on this classification, each lacerated canaliculus was successfully repaired. Nearly half of the lesions (46%) were lateral, 42% were central, and 12% were medial. The average time for locating the proximal lacerated end of the canaliculus was 3.33 ± 1.52 minutes (range, 1.0-7.0 minutes). The follow-up time ranged from 6.0 months to 4.5 year (median, 25 months). Our study showed that 96% (23) of the canaliculi were completely patent. One lateral lesion presented with residual outdoor epiphora in cold weather secondary to left lower canalicular stenosis. All 12 patients had excellent cosmetic results. Our study displayed a surgical management based on the 3 types of lesions helped to find the proximal lacerated end of the canaliculus, and provided excellent long-term outcomes of drainage function.
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http://dx.doi.org/10.1097/MD.0000000000007814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571716PMC
August 2017

In vitro osteogenic induction of bone marrow mesenchymal stem cells with a decellularized matrix derived from human adipose stem cells and in vivo implantation for bone regeneration.

J Mater Chem B 2017 Apr 15;5(13):2468-2482. Epub 2017 Mar 15.

Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Zhizaoju Road NO. 639, Shanghai, 200011, P. R. China.

Tissue engineering technology that adopts mesenchymal stem cells combined with scaffolds presents a promising strategy for tissue regeneration. Human adipose-derived stem cells (hADSCs) have attracted considerable attention in bone engineering for their osteogenic potential. The extracellular matrix (ECM) is critical for the stem cell niche as a physical support and is known to be able to maintain stem cell properties. In this study, the ECM derived from ADSCs was produced and termed the ADM. The ADM was demonstrated to markedly promote proliferation of bone marrow derived stem cells (BMSCs) and exhibited strongly osteogenic simulative effects in vitro. The results showed that alkaline phosphatase (ALP) activity, Alizarin red S (ARS) staining, osteogenic gene markers and proteins were significantly up-regulated. Next, we developed a poly(sebacoyl diglyceride) (PSeD) mesh scaffold coated with the ADM and evaluated its capacity to create an osteogenic microenvironment. BMSCs were cultured on the composite scaffolds and subjected to osteogenic differentiation in vitro. The results showed that the composite scaffolds facilitated the osteogenesis more than a simple PSeD scaffold. Then the PSeD/ADM scaffold seeded with BMSCs was used to repair critical-sized calvarial defects in rats, which significantly enhanced the reparative effects as confirmed via micro-CT, sequential fluorescent labeling and histological observation. In conclusion, we demonstrated that the ADM could promote both proliferation and osteogenesis of BMSCs, and the combination of ADM and PSeD synergistically stimulated bone formation, which may provide a novel scheme for bone regeneration.
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http://dx.doi.org/10.1039/c6tb03150aDOI Listing
April 2017

Effects of miR-146a on the osteogenesis of adipose-derived mesenchymal stem cells and bone regeneration.

Sci Rep 2017 02 16;7:42840. Epub 2017 Feb 16.

Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Increasing evidence has indicated that bone morphogenetic protein 2 (BMP2) coordinates with microRNAs (miRNAs) to form intracellular networks regulating mesenchymal stem cells (MSCs) osteogenesis. This study aimed to identify specific miRNAs in rat adipose-derived mesenchymal stem cells (ADSCs) during BMP2-induced osteogenesis, we selected the most significantly down-regulated miRNA, miR-146a, to systematically investigate its role in regulating osteogenesis and bone regeneration. Overexpressing miR-146a notably repressed ADSC osteogenesis, whereas knocking down miR-146a greatly promoted this process. Drosophila mothers against decapentaplegic protein 4 (SMAD4), an important co-activator in the BMP signaling pathway, was miR-146a's direct target and miR-146a exerted its repressive effect on SMAD4 through interacting with 3'-untranslated region (3'-UTR) of SMAD4 mRNA. Furthermore, knocking down SMAD4 attenuated the ability of miR-146a inhibitor to promote ADSC osteogenesis. Next, transduced ADSCs were incorporated with poly(sebacoyl diglyceride) (PSeD) porous scaffolds for repairing critical-sized cranial defect, the treatment of miR-146a inhibitor greatly enhanced ADSC-mediated bone regeneration with higher expression levels of SMAD4, Runt-related transcription factor 2 (Runx2) and Osterix in newly formed bone. In summary, our study showed that miR-146a negatively regulates the osteogenesis and bone regeneration from ADSCs both in vitro and in vivo.
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http://dx.doi.org/10.1038/srep42840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311870PMC
February 2017

A review of the three-dimensional cell culture technique: Approaches, advantages and applications.

Curr Stem Cell Res Ther 2016 ;11(4):370-80

Department of Ophthalmology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai , China.

Cell culture is a core and basic technique in biotechnology and is widely applied in biology, medicine, drug research and development. Traditional two-dimensional cell culture methods have undergone great developments. However, with in-depth basic research, higher requirements are needed to better mimic the in vivo environment to accurately observe cell behavior and explore its mechanisms. To comply with this situation, the three-dimensional cell culture technique emerged and has made profound advances in sustaining inherent cell properties. Here, we briefly review the development of this technique, including the main approaches to form three-dimensional microtissues, and its application and potential for future clinical therapies.
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http://dx.doi.org/10.2174/1574888x11666160217154007DOI Listing
December 2016

Ethmoid osteoma as a culprit of orbital emphysema: a case report.

Medicine (Baltimore) 2015 May;94(18):e724

From the Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Orbital emphysema is generally recognized as a complication of orbital fractures involving any paranasal sinuses. The recognition about its etiology has extended beyond sole trauma, but few articles mentioned tumors to be a possible cause.In this case report, we present a patient with orbital emphysema associated with ethmoid osteoma without orbital cellulitis or trauma history. The patient developed sudden proptosis, eyelid swelling, and movement limitation of the left eye, peripheral diplopia, and left periorbital crepitus after a vigorous nose blowing.Complete surgical resection of ethmoid osteoma followed by repair of the orbital medial wall was performed with assistance of combined endoscopy and navigational techniques. Twelve-month follow-up showed no residual lesion or recurrence; the orbital medial wall was accurately repaired with good visual function and facial symmetry.Tumors should be considered for differential diagnosis of orbital emphysema, and combined endoscopy and navigational techniques may improve safety, accuracy, and effectiveness of orbital surgeries.
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http://dx.doi.org/10.1097/MD.0000000000000724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602527PMC
May 2015

Treatment of orbital blowout fracture using porous polyethylene with embedded titanium.

J Craniofac Surg 2015 Mar;26(2):569-72

From the Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

The study was performed to evaluate the effectiveness and safety of porous polyethylene with embedded titanium in the repair of orbital blowout fracture. The study was designed as a prospective case series. Patients who were diagnosed with orbital blowout fracture from May 2012 to March 2013 were included in the study. A composite material of porous polyethylene and titanium mesh was used. Orbital volumes before and after surgery were measured, and the results of diplopia and ocular movement were recorded. The occurrence of diplopia was grouped and compared according to the time interval between injury and surgery. The incidence of other complications was also recorded. A total of 26 patients were involved in the study. The minimal follow-up time was 12 months. All surgeries were performed uneventfully. The orbital volume significantly decreased after the surgery, and the remission rate and the elimination rate of diplopia in 12 months were 85.7% and 47.6%, respectively. Postoperative diplopia was correlated with the time interval between injury and surgery. One patient presented with undercorrection of enophthalmos, and another patient presented with acute aggravation of diplopia and exophthalmos after surgery, which was resolved with treatment. In conclusion, porous polyethylene with embedded titanium was effective and safe in the repair of orbital blowout fracture, and studies with more subjects and longer follow-up period are recommended in future studies.
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http://dx.doi.org/10.1097/SCS.0000000000001407DOI Listing
March 2015

Let-7b overexpression leads to increased radiosensitivity of uveal melanoma cells.

Melanoma Res 2015 Apr;25(2):119-26

aDepartment of Ophthalmology, Ninth People's Hospital bDepartment of Radiation Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Uveal melanoma (UM) is an intraocular malignant tumor in adults that is characterized by rapid progression and recurrence. Irradiation has become the primary therapy for UM patients who are not candidates for surgery. However, after large-dose fraction irradiation treatment, some patients undergo subsequent enucleation because of radiotherapy-related complications. This situation has raised concerns on how to optimize the effectiveness of radiation treatment. Recent investigations of microRNAs are changing our understanding of UM tumor biology and are helping to identify novel targets for radiotherapy. The radioresistant UM cell lines OM431 and OCM1 were selected and exposed to irradiation, and let-7b was found to be downregulated after exposure. We then confirmed that let-7b mimics could inhibit UM growth both in vitro and in vivo. More specifically, transfection with let-7b mimics markedly resensitized OCM1 and OM431 cells to irradiation by reducing the population of S-phase cells. Cyclin D1 plays a vital role in cell cycle arrest, which is induced by let-7b overexpression. Cyclin D1 is also a target of let-7b and its expression is suppressed by upregulation of let-7b. Collectively, our results indicate that let-7b overexpression can in turn downregulate cyclin D1 expression and enhance the radiosensitivity of UM through cell cycle arrest. Let-7b could serve as a marker for radiosensitivity and could enhance the therapeutic benefit of UM cell irradiation.
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http://dx.doi.org/10.1097/CMR.0000000000000140DOI Listing
April 2015
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