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Chinese Journal of Chemistry 2021年第9期39卷 2386-2390页

作者： Yan-Lan Liu guang-hui he Ye Liu Xiao-Bing Lu State Key Laboratory of Fine Chemicals Dalian University of TechnologyDalianLiaoning 116024China

Enan tioselective resoluti on copolymerization of racemic internal epoxides with carb on dioxide(CO_(2))is a challe nging issue because of their poor reactivity and complicated regio/***,we describe the first enantioselective resolution copolymeriza-tion of racemic aromatic 2,3-disubstituted c/s-epoxides and CO_(2) using enantiopure dinuclear cobalt(lll)complexes as catalyst under mild conditions,affordi ng the corresp on ding polycarbonates with completely alter nating structure and good enantioselectivity in the range of 70% to 97%*** isotactic polycarb on ate from/3-methylstyre ne oxide is a typical semicrystalli ne material,possessi ng a melting point of 241℃;while other isotactic-enriched copolymers from 2,3-disubstituted c/s-epoxides bearing a substitute group on the aromatic ring are amorphous,having glass transition temperatures between 86℃ and 124℃.Interestingly,the copolymer selectivity is correlated well with the Hammett substituent constant,and the highest polymer selectivity of 98%was found in the system using the epoxides bearing an electron-donating group on the benzene ring.

关键词： Asymmetric catalysis Internal c/s-epoxides Carbon dioxide fixation Polymerization Hammett constant

Protective effect of human umbilical cord mesenchymal stem cell-derived exosomes on rat retinal neurons in hyperglycemia through the brain-derived neurotrophic factor/TrkB pathway

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International Journal of Ophthalmology(English edition) 2021年第11期14卷 1683-1689页

作者： Xiang Gao guang-hui he Xiao-Tian Zhang Song Chen College of Medicine Nankai UniversityTianjin 300071China Tianjin Eye Hospital Tianjin 300020China Clinical College of Ophthalmology Tianjin Medical UniversityTianjin 300020China Ophthalmic Center of Xinjiang Production and Construction Corps Hospital Urumqi 830002Xinjiang Uygur Autonomous RegionChina

AIM:To explore whether human umbilical cord mesenchymal stem cell(hUCMSC)-derived exosomes(hUCMSC-Exos)protect rat retinal neurons in high-glucose(HG)conditions by activating the brain-derived neurotrophic factor(BDNF)-Trk B ***:h UCMSC-Exos were collected with differential ultracentrifugation methods and observed by transmission electron ***-linked immunosorbent assays(ELISAs)was used to quantify BDNF in hUCMSC-Exos,and Western blot was used to identify surface markers of *** retinal neurons were divided into 4 ***,cell viability,cell apoptosis,and TrkB protein expression were measured in retinal ***:hUCMSCs and isolated hUCMSC-Exos were successfully *** hUCMSC-Exos showed a diameter of 30 to 150 nm and had a phospholipid bimolecular membrane structure,as observed by transmission electron *** showed the BDNF concentration of hUCMSCs-Exos was 2483.16±***-Exos effectively reduced the apoptosis of retinal neuron rate and improved neuron survival rate,meanwhile,the results of immunofluorescence verified the fluorescence intensity of TrKB in neurons *** all above effects were reduced by treated hUCMSCs-Exos with BDNF ***-Exos effectively reduced the apoptosis rate of retinal neurons by activating the BDNF-TrkB pathway in a HG ***:In the HG environment,hUCMSC-Exos could carry BDNF into rat retinal neurons,inhibiting neuronal apoptosis by activating the BDNF-TrkB pathway.

关键词： human umbilical cord mesenchymal stem cells exosomes diabetic retin opathy retinal n euro ns BDNF-TrkB pathway

Transfection with CXCR4 potentiates homing of mesenchymal stem cells in vitro and therapy of diabetic retinopathy in vivo

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International Journal of Ophthalmology(English edition) 2018年第5期11卷 766-772页

作者： Jian Wang Wei Zhang guang-hui he Bin Wu Song Chen Tianjin Eye Hospital Tianjin Key Lab of Ophthalmology and Visual ScienceTianjin Eye InstituteClinical College of Ophthalmology Tianjin Medical University

AIM：To investigate the effect of the overexpression of C-X-C chemokine receptor type 4（CXCR4） on homing of mesenchymal stem cells（MSCs） in vitro and therapeutic effects of diabetic retinopathy（DR） in ***：MSCs were infected by lentivirus constructed with *** expression of CXCR4 was examined by immunofluorescence,Western blot,and quantitative polymerase chain ***4-overexpressing MSCs were cultured in vitro to evaluate their chemotaxis,migration,and apoptotic ***4-overexpressing MSCs were intravitreally injected to observe and compare their effects in a mouse model of *** histological structure of DR in rats was inspected by hematoxylin and eosin *** expression of rhodopsin,neuron-specific enolase（NSE）,and inflammatory cytokines interleukin（IL）-6 and tumor necrosis factor（TNF）-α was examined by Western blot and immunohistochemical ***：The transduction of MSCs by lentivirus was effective,and the transduced MSCs had high expression levels of CXCR4 gene and *** migration activities were observed in CXCR4-overexpressing ***,reduced retinal damage,upregulation of rhodopsin and NSE protein,and downregulation of inflammatory cytokines IL-6 and TNF-α were observed in CXCR4-overexpressing MSCs in ***：The homing of MSCs can be enhanced by upregulating CXCR4 levels,possibly improving histological structures of ***4-overexpressing MSCs can be a novel strategy for treating DR.

关键词： chemokine receptor type 4 diabetic retinopathy mesenchymal stem cells transplantation

Protective effects of umbilical cord mesenchymal stem cell exosomes in a diabetic rat model through live retinal imaging

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International Journal of Ophthalmology(English edition) 2021年第12期14卷 1828-1833页

作者： Yan Fu Xiang Gao guang-hui he Song Chen Zhao-hui Gu Yue-Ling Zhang Li-Ying Li College of Medicine Nankai UniversityTianjin 300071China Department of Ophthalmology Baoding No.1 Central HospitalBaoding 071000Hebei ProvinceChina Tianjin Eye Hospital Tianjin 300020China Clinical College of Ophthalmology Tianjin Medical UniversityTianjin 300020China Ophthalmic Center of Xinjiang Production and Construction Corps Hospital Urumqi 830002Xinjiang Uygur Autonomous RegionChina

AIM:To assess the protective effect of human umbilical cord mesenchymal stem cell exosomes(hucMSC-Exs)in a diabetic rat model by using a variety of retinal ***:hucMSCs were subjected to differential ultracentrifugation for the collection of exosomes,and transmission electron microscopy(TEM),nanoparticle tracking analysis(NTA)using a NanoSight analysis system and Western blotting(WB)were used to analyze the expression of surface marker proteins such as CD63,CD9 and ***(STZ)was injected into the intraperitoneal cavity to establish a diabetic *** were divided into a normal group,diabetic group and hucMSC-Ex *** fluorescein angiography(FFA),optical coherence tomography(OCT)and other live imaging methods were used to observe the fundus of the ***,the eyeballs of rats from each group were collected for hematoxylin-eosin(he)staining to further analyze the retinal ***:Through TEM,NTA and WB,we successfully isolated *** FFA and OCT confirmed that hucMSC-Exs effectively prevented early retinal vascular damage and thickening of the ***,he staining of rat retinal sections revealed that exosomes effectively alleviated retinal structure disruption caused by ***:hucMSC-Exs have a protective effect on the retina in diabetic rat through FFA,OCT and he staining.

关键词： human umbilical cord mesenchymal stem cells exosomes diabetic retinopathy fundus fluorescein angiography optical coherence tomography rat

Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept:a quantitative analysis based on 4D label-free technique

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 676-685页

作者： Ting-Ting Feng Xiang Gao An-Ran Liang Bo-Wen Zhao guang-hui he Song Chen Clinical College of Ophthalmology Tianjin Medical UniversityTianjin 300070China Tianjin Key Laboratory of Ophthalmology and Visual Science Tianjin Eye InstituteTianjin Eye HospitalTianjin 300020China Key Laboratory of Ophthalmology Anyang Eye HospitalAnyang 455000Henan ProvinceChina Department of Ophthalmology Jining No.1 People’s HospitalJining 272011Shandong ProvinceChina

AIM:To identify different metabolites,proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy(PDR)and resistance to anti-vascular endothelial growth factor(VEGF)drugs,and to provide biomarkers for the diagnosis and treatment of ***:Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry(LC-MS/MS)analyses based on 4D label-free *** differentially expressed proteins(DEPs),Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway representation and protein interactions were ***:A total of 12 samples were *** proteomics results showed that a total of 58 proteins were identified as DEPs,of which 47 proteins were up-regulated and 11 proteins were *** found that C1q and tumor necrosis factor related protein 5(C1QTNF5),Clusterin(CLU),tissue inhibitor of metal protease 1(TIMP1)and signal regulatory protein alpha(SIRPα)can all be specifically regulated after aflibercept *** functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by *** addition,protein-protein interaction(PPI)network evaluation revealed that TIMP1 plays a central role in neural *** addition,CD47/SIRPαmay become a key target to resolve anti-VEGF drug resistance in ***:Proteomic analysis is an approach of choice to explore the molecular mechanisms of *** data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept,among which C1QTNF5,CLU,TIMP1 and SIRPαmay become targets for future treatment of PDR and resolution of anti-VEGF resistance.

关键词： vitreous proliferative diabetic retinopathy proteome 4D label-free

Mesenchymal stem cells-derived exosomes ameliorate blue light stimulation in retinal pigment epithelium cells and retinal laser injury by VEGF-dependent mechanism

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International Journal of Ophthalmology(English edition) 2018年第4期11卷 559-566页

作者： guang-hui he Wei Zhang Ying-Xue Ma Jing Yang Li Chen Jian Song Song Chen Tianjin Eye Hospital Tianjin Key Lab of Ophthalmologyand Visual ScienceTianjin Eye InstituteClinical College of OphthalmologyTianjin Medical UniversityTianjin 300020China

AIM： To observe the effect of exosomes derived from human umbilical cord blood mesenchymal stem cells（h UCMSCs） on the expression of vascular endothelial growth factor-A（VEGF-A） in blue light injured human retinal pigment epithelial（RPE） cells and laser-induced choroidal neovascularization（CNV） in ***： Exosomes were isolated from h UCMSCs and characterized by transmission electron microscope and Western blot. MSCs-derived exosomes were cultured with RPE cells exposed to blue light. The m RNA and protein expression of VEGF-A were determined by real time-polymerase chain reaction（PCR） and Western blot, respectively. Immunofluorescence assay was used for the detection of the expression level of VEGF-A. We injected different doses of MSCs-derived exosomes intravitreally to observe and compare their effects in a mouse model of laserinduced retinal injury. The histological structure of CNV in rats was inspected by hematoxylin-eosin（he） staining and fundus fluorescein angiography. The expression of VEGF-A was detected by ***： Exosomes exhibited the typical characteristic morphology（cup-shaped） and size（diameter between 50 and 150 nm）. The exosomes marker, CD63, and h UCMSCs marker, CD90, showed a robust presence. In vitro, MSCsderived exosomes downregulated the m RNA（Exo-L： t=6.485, 7.959, 9.286; Exo-M： t=7.517, 10.170, 13.413; Exo-H： t=10.317, 12.234, 14.592, P〈0.05） and protein（Exo-L： t=2.945, 4.477, 6.657; Exo-M： t=4.713, 6.421, 8.836; Exo-H：t=6.539, 12.194, 12.783; P〈0.05） expression of VEGF-A in RPE cells after blue light stimulation. In vivo, we found that the MSCs-derived exosomes reduced damage, distinctly downregulated VEGF-A（Exo-H： t=0.957, 1.382; P〈0.05）, and gradually improved the histological structures of CNV for a better visual function（Exo-L： 0.346, Exo-M： 3.382, Exo-H： 8.571; P〈0.05）. CONCLUSION： MSCs-derived exosomes ameliorate blue light stimulation in RPE cells and laser-induced retinal injury via downregulation of VEGF

关键词： exosome human umbilical cord mesenchymal stem cell retinal pigment epithelial cell choroidal neovascularization vascular endothelial growth factor

Efficacy of internal limiting membrane peeling for diabetic macular edema after preoperative anti-vascular endothelial growth factor injection

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International Journal of Ophthalmology(English edition) 2020年第11期13卷 1758-1764页

作者： Jing Guo Xue Bi Shan-Na Chen Song Chen guang-hui he Bin Wu Wei Zhang Jian Wang Clinical College of Ophthalmology Tianjin Medical UniversityTianjin 300070China Tianjin Eye Hospital Tianjin Eye InstituteTianjin Key Lab of Ophthalmology and Visual ScienceTianjin 300020China Department of Ophthalmology Guangdong Hospital of Traditional Chinese MedicineGuangzhou 510120Guangdong ProvinceChina Xiamen Kehong Eye Hospital Xiamen 361000Fujian ProvinceChina

AIM:To explore the efficacy of minimally invasive vitrectomy(MIV)with or without internal limiting membrane(ILM)peeling on the treatment of diabetic macular edema(DME)in proliferative diabetic retinopathy(PDR)combining with preoperative anti-vascular endothelial growth factor(anti-VEGF)***:Totally 132 eyes(132 patients)diagnosed PDR with DME were included between June 2015 and June 2018 in Tianjin Eye *** single MIV treatment group included 68 eyes and the MIV combined with ILM peeling group included 64 ***-VEGF drugs were injected intravitreally 1wk before the operation and the period of follow-up was 1 to ***-corrected visual acuity(BCVA),central retinal thickness(CRT),total macular volume(TMV),macular edema(ME)severity,intraocular pressure(IOP),and complications were *** factors of visual acuity following ILM peeling were ***:The BCVA was higher than preoperative values at 1,3,6,and 12mo after surgery in both groups(all Phe BCVA of the combined group was significantly higher than that of the MIV only group(0.52±0.23 v/s 0.64±0.29 IogMAR,P=0.011 in 6mo;0.41±0.25\/s 0.52±0.25 IogMAR,P=0.008 in 12mo).Mean CRT values postoperative were significantly lower than preoperative values in both groups from the 1^(st) month(lmo 397.65±106.18 vs 451.94±118.88 μm in MIV only group;388.88±108.68 v/s 464.36±111.53 μm in combined group;both Phe two groups were statistically significant at 3,6,and 12mo(P=0.004,0.003,0.00 respectively).The TMV was decreased from the 3^(rd) month in the single treatment group(3mo 11.14±1.66 vs 12.20±2.09 mm^(3),Phe proportion of eyes with edema that had CRT more than 350μm was significantly lower than before surgery(13.24%vs 77.94%in MIV only group;1.56%vs 81.25%in combined group;both Phere was no significant difference in the recurrence incidence of macular epiretinal membrane,ME,transien

关键词： proliferative diabetic retinopathy macular edema vitreous macular traction internal limiting membrane minimally invasive vitrectomy anti-vascular endothelial growth factor

Mesenchymal stem cell-derived exosomes inhibit the VEGF-A expression in human retinal vascular endothelial cells induced by high glucose

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International Journal of Ophthalmology(English edition) 2021年第12期14卷 1820-1827页

作者： guang-hui he Ying-Xue Ma Meng Dong Song Chen Yu-Chuan Wang Xiang Gao Bin Wu Jian Wang Jun-Hua Wang Clinical College of Ophthalmology Tianjin Medical UniversityTianjin 300070China Tianjin Eye Hospital Tianjin Eye InstituteTianjin Key Lab of Ophthalmology and Visual ScienceTianjin 300020China Ophthalmic Center of Xinjiang Production and Construction Corps Hospital Urumqi 830002Xinjiang Uygur Autonomous RegionChina Medical College of NanKai University Tianjin 300000China

AIM:To determine the effect of exosomes derived from human umbilical cord blood mesenchymal stem cells(hUCMSCs)on the expression of vascular endothelial growth factor A(VEGF-A)in human retinal vascular endothelial cells(HRECs).METHODS:Exosomes were isolated from hUCMSCs using cryogenic ultracentrifugation and characterized by transmission electron microscopy,Western blotting and nanoparticle tracking *** were randomly divided into a normal control group(group A),a high glucose model group(group B),a high glucose group with 25μg/mL(group C),50μg/mL(group D),and 100μg/mL exosomes(group E).Twenty-four hours after coculture,the cell proliferation rate was detected using flow cytometry,and the VEGF-A level was detected using *** coculture 8,16,and 24h,the expression levels of VEGF-A in each group were detected using PCR and Western ***:The characteristic morphology(membrane structured vesicles)and size(diameter between 50 and 200 nm)were observed under transmission electron *** average diameter of 122.7 nm was discovered by nanoparticle tracking analysis(NTA).The exosomal markers CD9,CD63,and HSP70 were strongly *** proliferation rate of the cells in group B increased after 24h of *** analyses revealed that the upregulation of VEGF-A expression in HRECs stimulated by high glucose could be downregulated by cocultured hUCMSC-derived exosomes(F=39.03,Phe upregulation of VEGF-A protein(group C:F=7.96;group D:F=17.29;group E:F=11.89;8h:F=9.45;16h:F=12.86;24h:F=42.28,P<0.05)and mRNA(group C:F=4.137;group D:F=13.64;group E:F=22.19;8h:F=7.253;16h:F=16.98;24h:F=22.62,P<0.05)in HRECs stimulated by high glucose was downregulated by cocultured hUCMSC-derived exosomes(P<0.05).CONCLUSION:hUCMSC-derived exosomes downregulate VEGF-A expression in HRECs stimulated by high glucose in time and concentration dependent manner.

关键词： mesenchymal stem cells exosomes retinal vascular endothelial cells vascular endothelial growth factor A coculture

Protective effect of LIF-huM SCs on the retina of diabetic model rats

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International Journal of Ophthalmology(English edition) 2021年第10期14卷 1508-1517页

作者： Shan-Na Chen Zhi-Gang Xu Ying-Xue Ma Song Chen guang-hui he Mei Han Xiang Gao Jun-Hua Wang Bin Wu Jian Wang Clinical College of Ophthalmology Tianjin Medical UniversityTianjin 300070China Tianjin Eye Hospital Tianjin Eye InstituteTianjin Key Lab of Ophthalmology and Visual ScienceTianjin 300020China Xiamen Kehong Eye Hospital Xiamen 361000Fujian ProvinceChina Department of Ophthalmology Baoan Central HospitalShenzhen 518000China Department of Ophthalmology Tianjin First Central HospitalTianjin 300192China Department of Vitreous and Retinopathy Tianjin Eye HospitalTianjin Eye InstituteTianjin Key Lab of Ophthalmology and Visual ScienceTianjin 300020China Department of Ophthalmology Tianjin Eye HospitalTianjin Eye InstituteTianjin Key Lab of Ophthalmology and Visual ScienceTianjin 300020China Studying for a Doctor of Medicine Degree from Nankai University Tianjin 300000China

AIM:To investigate the protective effect of human umbilical cord mesenchymal stem cells(hUCMSCs)modified by the LIF gene on the retinal function of diabetic model rats and preliminarily explore the possible ***:A stably transfected cell line of hUCMSCs overexpressing leukemia inhibitory factor(LIF)was *** was verified by fluorescent quantitative polymerase chain reaction(qPCR).Forty-eight adult Sprague-Dawley rats were randomly divided into a normal control group(group A),streptozotocin-induced diabetic control group(group B),diabetic rats at 3mo injected with empty vector-transfected hUCMSCs(group C)or injected with LIF-hUCMSCs(group D).Four weeks after the intravitreal injection,analyses in all groups included retinal function using flash electroretinogram(F-ERG),retinal blood vessel examination of retinal flat mounts perfused with fluorescein isothiocyanate-dextran(FITCdextran),and retinal structure examination of sections using hematoxylin and eosin *** levels of adiponectin(APN),high-sensitivity C-reactive protein(hsCRP),and neurotrophin-4(NT-4)in each group was detected using immunohistochemistry,PCR,Western blotting,and ELISA,***:A stable transgenic cell line of LIF-hUCMSCs was constructed.F-ERG and FITC-dextran examinations revealed no abnormalities of retinal structure and function in group A,severe damage of the retinal blood vessels and function in group B,and improved retinal structure and function in group C and especially group ***,ELISA,and Western blot analyses revealed progressively higher APN and NT-4 expression levels in groups B,C,and D than in group ***-CRP expression was significantly higher in group B than in groups A,C,and D,and was significantly higher in group C than in group D(Phe retina of diabetic rats by upregulating APN and NT-4 expression and downregulating hs-CRP expression in the retina.

关键词： leukemia inhibitory factor human umbilical cord mesenchymal stem cells diabetic retinopathy diabetic rats adiponectin high-sensitivity C-reactive protein neurotrophin-4

Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu guang-hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis