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World Journal of Gastroenterology 2014年第12期20卷 3312-3319页

作者： Janne S Suominen Hanna Lampela Pivi Heikkil Jouko Lohi Hannu Jalanko Mikko P Pakarinen Department of Pediatric Surgery Pediatric Liver and Gut Research GroupChildren’s HospitalUniversity of Helsinki Department of Pathology HUSLABHelsinki University Central Hospital Department of Paediatrics Children’s HospitalHelsinki University Central Hospital

AIM:To study the relation between collagen 1,α-smooth muscle actin(α-SMA)and CD34 expression and the most essential portoenterostomy(PE)outcomes.METHODS:Liver specimens were obtained at PE from33 biliary atresia(BA)patients for immunohistochemical analysis of collagen 1,α-SMA and CD34.Liver biopsies from 35 organ donors were used as controls.Expression patterns were related to clinical data including age at PE,serum total and conjugated bilirubin concentration at the time of PE and during follow-up,incidence of esophageal varices in follow-up upper gastrointestinal endoscopies,and native liver survival as well as to detailed histopathological findings.RESULTS:Collagen 1(16.4%vs 4.5%,Pneovascularization was frequent as CD34-positive microvessels were observed in over half of the hepatic lobules.In controls,the CD34-positive microvessels were rare as they were completely absent in 40%and were found in less than 5%of the hepatic lobules in the rest.The difference between BA patients and controls was significant(Pneovascularization are enhanced in BA,progress with increasing PE age and relate to native liver survival and

关键词： Biliary atresia Liver fibrosis neovascularization

TNFSF15 facilitates the differentiation of CD11b^(+) myeloid cells into vascular pericytes in tumors

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Cancer Biology & Medicine 2023年第11期20卷 869-884页

作者： Xiangxiang Gu Yipan Zhu Cancan Zhao Yixin Cao Jingying Wang Qiangzhe Zhang Luyuan Li State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy Nankai Universityand Haihe Laboratory of Cell EcosystemTianjin 300350China

Objective:Immature vasculature lacking pericyte coverage substantially contributes to tumor growth,drug resistance,and cancer cell dissemination.We previously demonstrated that tumor necrosis factor superfamily 15(TNFSF15)is a cytokine with important roles in modulating hematopoiesis and vascular homeostasis.The main purpose of this study was to explore whether TNFSF15 might promote freshly isolated myeloid cells to differentiate into CD11b^(+) cells and further into pericytes.Methods:A model of Lewis lung cancer was established in mice with red fluorescent bone marrow.After TNFSF15 treatment,CD11b^(+) myeloid cells and vascular pericytes in the tumors,and the co-localization of pericytes and vascular endothelial cells,were assessed.Additionally,CD11b^(+) cells were isolated from wild-type mice and treated with TNFSF15 to determine the effects on the differentiation of these cells.Results:We observed elevated percentages of bone marrow-derived CD11b^(+)myeloid cells and vascular pericytes in TNFSF15-treated tumors,and the latter cells co-localized with vascular endothelial cells.TNFSF15 protected against CD11b^(+)cell apoptosis and facilitated the differentiation of these cells into pericytes by down-regulating Wnt3a-VEGFR1 and up-regulating CD49e-FN signaling pathways.Conclusions:TNFSF15 facilitates the production of CD11b^(+) cells in the bone marrow and promotes the differentiation of these cells into pericytes,which may stabilize the tumor neovasculature.

关键词： TNFSF15 myeloid cell neovascularization CD11b^(+)cell pericyte

Idiopathic steno-occlusive disease with bilateral internal carotid artery occlusion:A Case Report

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World Journal of Clinical Cases 2023年第13期11卷 3076-3085页

作者： Sherifa Ahmed Hamed Hosam Abozaid Yousef Department of Neurology and Psychiatry Assiut UniversityFaculty of MedicineAssiut 71516AssiutEgypt Department of Radiology Assiut UniversityFaculty of MedicineAssiut 71516AssiutEgypt

BACKGROUND Moyamoya disease(MMD)is a rare cause of acute stroke and transient ischemic attacks in children.We described clinical,diagnostic features and follow-ups of a young child with acute stroke.CASE SUMMARY We report a 4-year-old girl with left hemiparesis after an acute ischemic stroke.Her history was also significant for repeated left or right focal motor seizures,generalized tonic-clonic convulsions and transient ischemic attacks.Her magnetic resonance imaging and computed tomography(CT)of the brain and magnetic resonance angiography,CT angiography and venography on the cerebral vessels revealed evidence of bilateral fronto-parietal ischemic infarctions,occlusion of the right and left internal carotid arteries started at its bifurcation and non-visualization of right and left anterior and middle cerebral arteries.There was evidence of progression in angiography manifested as development of collaterals from the basal perforating vessels,increase in the extent of large intracranial arterial stenosis/occlusion and extensive collateral circulation with predominance from the posterior circulation.Physical and neurological evaluation and comprehensive laboratory investigations excluded an obvious comorbid disease or risk factor for the child’s condition.The diagnosis of MMD was highly suggested as a cause of the child’s steno-occlusive condition.She was treated symptomatically with levetiracetam,an antiepileptic medication.Aspirin was prescribed for secondary prevention.Her clinical manifestations were improved during the three years of follow-up.Revascularization surgery was postponed.CONCLUSION Up to our knowledge,this is the first report for MMD in a child in our country.The clinical improvement and the stabilization of the child’s condition over the 3 years of follow-up could be attributed to the rapid and extensive recruitment of collaterals and absence of risk factors or comorbidities.Revascularization surgery is highly recommended.

关键词： Steno-occlusive disease Moyamoya disease Internal carotid artery Collateral circulation neovascularization Case report

Effects of Interferon Alpha 2b on VEGFR-2, VEGFA, MAPK-1 and ERK-1 Gene Expression in Corneal neovascularization Models

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Open Journal of Ophthalmology 2018年第2期8卷 97-105页

作者： Mujdat Karabulut Harun Cakmak Gokay Bozkurt Sinem Karabulut Department of Ophthalmology Faculty of Medicine Sitki Kocman University Mugla Turkey Department of Ophthalmology Faculty of Medicine Adnan Menderes University Aydin Turkey Department of Medical Genetic Faculty of Medicine Adnan Menderes University Aydin Turkey

AIM: To investigate effects of interferon alpha 2b on vascular endothelial growth factor receptor-2 (VEGFR-2), vascular endothelial growth factor-A (VEGFA), mitogen activated protein kinase-1 (MAPK-1) and extracellular signal regulated kinase (ERK 1) gene expression in corneal neovascularization (CNV) modelsbyreal time polymerase chain reaction (PCR). METHODS: Thirty Wistar-Albino male rats were divided into three groups of ten rats each, and two corneas were obtained from each rat. CNV was induced by application of silver nitrate. In the first group one million IU/ml, in the second group three million IU/ml interferon-alfa 2b and in the third (control) group isotonic saline was applied to both eyes two times a day for two weeks. Rats were sacrificed by cervical dislocation and corneas were used for real time polymerase chain reaction. RESULTS: MAPK-1 gene expression levels were significantly higher in both first and second groups compared to the control group (p = 0.014 and p = 0.008, respectively). VEGFR-2 gene expression levels were found to be significantly higher in the second group than the control group (p = 0.028). VEGFA gene expression levels were also significantly higher in the second group than the control group, and there was no difference between the control and first group and between first and second groups (p > 0.05). ERK gene expression levels did not differ among all groups (p = 0.545). CONCLUSION: At the end of the study, it was shown that interferon-alfa 2b does not inhibit VEGFR-2, VEGFA, MAPK-1 or ERK 1 gene expression in CNV models despite its known anti-VEGF activities.

关键词： Corneal neovascularization Vascular Endothelial Growth Factor Interferon-Alfa2b Real Time Polymerase Chain Reaction

Inhibitory Actions of Tetrandrine on Tumor Necrosis Factor α-Induced NF-κB Activation in neovascularization of Cultured Choroidal Explants

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Chinese Medicine 2010年第3期1卷 75-83页

作者： Minoru Kikuchi Shusuke Kamimura Masaaki Nomura Tatsuo Takahashi Nobuyoshi Hagino Shinjiro Kobayashi 不详

Tetrandrine (1 μM), a bis-benzylisoquinoline alkaloid isolated from Stephania tetrandra S Moore, signifi-cantly decreased tumor necrosis factor alpha (TNFα;10 ng/ml)-induced increase in the number of micro vessels that budded from cultured rat choroidal explants. Tetrandrine also decreased the TNFα-induced in-crease in the number of cells composing the microvessels. Ammonium pyrrolidine dithiocarbamate (APDC;0.1-0.3 μM), an inhibitor of nuclear factor-κB (NF-κB), decreased the TNFα-induced increase in the number of microvessels in a concentration-dependent manner. TNFα increased the phosphorylation and degradation of inhibitor of NF-κB (IκBα), as well as increasing the DNA-binding activity of NF-κB in choroidal explants. TNF? induced an increase of vascular endothelial growth factor (VEGF)-A mRNA, but not VEGF-C mRNA or VEGF-D mRNA. TNFα-induced angiogenic action was inhibited by treatment of VEGF-A antibody in cultured choroidal capillaries. Tetrandrine inhibited the TNFα-induced increases of phosphorylation and degradation of IκBα, and reduced the TNFα-induced increase of DNA-binding activity of NF-κB in chor-oidal explants. In conclusion, tetrandrine inhibits TNFα-induced activation of NF-κB in the choroidal capil-laries via inhibition of TNFα-induced phosphorylation of IκBα.

关键词： Choroidal neovascularization Anti-angiogenesis Tetrandrine Tumor Necrosis Factor α NF-κB Activity Phosphorylation of IκBα

冒险在类型 2 糖尿病 mellitus 与糖尿病的 retinopathy 的网膜的 neovascularization 联系的因素

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International Journal of Ophthalmology(English edition) 2011年第2期4卷 182-185页

作者： Ze-Long Zhong Mei Han and Song Chen Clinical College of Ophthalmology Tianjin Medical University Tianjin Eye Hospital Tianjin 300020 China

·AIM:To evaluate the risk factors associated with retinal neovascularization of diabetic retinopathy in northern Chinese Han patients with type 2 diabetes mellitus (T2DM).·METHODS:The clinical characteristics of 200 patients with proliferative diabetic retinopathy (PDR) and 100 age-matched healthy individuals were compared.The univariate and multivariate logistic regression analysis were performed in the patients with PDR.·RESULTS:Fasting blood glucose (FBG),triglyceride (TG),total cholesterol (TC),blood urea nitrogen (BUN),uric acid (UA),white blood cell count (WBC),absolute neutrophil count,hematocrit (HCT) and mean platelet volume (MPV) and mean platelet volume (MPV) were all significantly higher in patients with PDR than in the control group (Pneovascularization of DR were duration of diabetes mellitus (OR=1.112;P =0.000),BUN (OR=1.277;P =0.000),smoking (OR=3.967;P=0.000) and MPV(OR=2.472;P =0.000).On the other hand,panretinal photocoagulation was associated with reduced risk of retinal neovascularization (OR=0.983;P =0.000).·CONCLUSION:Preventing and controlling T2DM in terms of risk factors,including duration of diabetes,BUN,smoking and MPV,might offer novel approaches to prevent or delay the onset of retinal neovascularization in patients with PDR.·

关键词： diabetic retinopathy diabetes mellitus,type 2 retinal neovascularization risk factors

The Notch signaling pathway in retinal dysplasia and retina vascular homeostasis

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Journal of Genetics and Genomics 2010年第9期37卷 573-582页

作者： Minhua Zheng Zifeng Zhang Xingcheng Zhao Yuqiang Ding Hua Han Department of Medical Genetics and Developmental Biology Fourth Military Medical University Xi'an 710032 China Department of Ophthalmology Xifing Hospital Fourth Military Medical University Xi' an 710032 China Department of Anatomy and Neurobiology Tongji University School of Medicine Shanghai 200092 China

The retina is one of the most essential elements of vision pathway in vertebrate. The dysplasia of retina cause congenital blindness or vision disability in individuals, and the misbalance in adult retinal vascular homeostasis leads to neo adults, such as diabetic retinopathy or age-related macular degeneration. Many developmental signaling pathways are involved in the process of retinal development and vascular homeostasis. Among them, Notch signaling pathway has long been studied, and Notch signaling-interfered mouse models show both neural retina dysplasia and vascular abnormality. In this review, we discuss the roles of Notch signaling in the maintenance of retinal progenitor cells, specification of retinal neurons and glial cells, and the sustaining of retina vascular homeostasis, especially from the aspects of conditional knockout mouse models. The potential of Notch signal manipulation may provide a powerful cell fate- and neovascularization-controUing tool that could have important applications in treatment of retinal diseases.

关键词： Notch signaling retinal dysplasia vascular homeostasis neovascularization knockout mice

In vivo longitudinal and multimodal imaging of hypoxia-inducible factor 1a and angiogenesis in breast cancer

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Chinese Medical Journal 2020年第2期133卷 205-211页

作者： He-Wen Tang Hai-Liang Feng Ming Wang Qing-Li Zhu Yu-Qin Liu Yu-Xin Jiang Department of Ultrasound Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Cell Resource Center Institute of Basic Medical ScienceChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Background:Angiogenesis and hypoxia-inducible factor 1a(HIF-1a)play major roles in solid tumors.This study aimed to establish a longitudinal and multimodal imaging model for in vivo evaluation of HIF1a and angiogenesis in breast cancer.Methods:By transfection of a 5 hypoxia-responsive element(HRE)/green fluorescent protein(GFP)plasmid,the cell line Ca761-hregfp was established,which emitted green fluorescence triggered by HIF-1a under hypoxia.The cells were subjected to CoCl2-simulated hypoxia to confirm the imaging strategy.We grew Ca761-hre-gfp cells in the left rear flanks of twelve 615 mice.Experiments were conducted on days 4,9,15,and 19.For in vivo analysis,Ca761-hre-gfp subcutaneous allografted tumors were imaged in vivo using contrast-enhanced ultrasound(CEUS)and fluorescence imaging(FLI)during tumor development.The tumor size,CEUS peak intensity,and FLI photons were measured to evaluate tumor growth,angiogenesis,and HIF-1a activity,respectively.After each experiment,three mice were randomly sacrificed and tumor specimens were collected to examine HIF-1a activity and the microvessel density(MVD).Results:In vitro,both green fluorescence and HIF-1a expression were detected in Ca761-hre-gfp cells treated with CoCl2,indicating the suitability of the cells to detect HIF-1a activity.In vivo,HIF-1a activity first increased and then decreased,which was significantly correlated with angiogenic changes(r=0.803,P=0.005).These changes were confirmed by immunohistochemical staining of HIF-1a and MVD.Conclusions:The findings validated the Ca761-hre-gfp murine allograft model for reliable evaluation of HIF-1a activity and angiogenesis longitudinally using both molecular and pre-clinical non-invasive imaging modalities.The cell line may be useful for studies of anti-HIF pathway therapies.

关键词： Breast cancer Hypoxia-inducible factor 1 Pathological neovascularization Ultrasonography Fluorescence imaging

Human umbilical cord-derived endothelial progenitor cells promote growth cytokines-mediated neorevascularization in rat myocardial infarction

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Chinese Medical Journal 2009年第5期122卷 548-555页

作者： HU Cheng-heng LI Zhi-ming DU Zhi-min ZHANG Ai-xia YANG Da-ya WU Gui-fu Division of Cardiology First Affiliated Hospital and Key Laboratory on Assisted Circulation Ministry of Health of China Sun Yat-sen University Guangzhou Guangdong 510080 China

Background Cell-based vascular therapies of endothelial progenitor cells （EPCs） mediated neovascularization is still a novel but promising approach for the treatment of ischemic disease. The present study was designed to investigate the therapeutic potentials of human umbilical cord blood-derived EPCs （hUCB-EPCs） in rat with acute myocardial infarction. Methods Human umbilical cord blood （hUCB） mononuclear cells were isolated using density gradient centrifugation from the fresh human umbilical cord in healthy delivery woman, and cultured in M199 medium for 7 days. The EPCs were identified by double-positive staining with 1,1＇-dioctadecyl-3,3,3＇,3＇-tetramethylindocarbocyanine percholorate-labeled acetylated low-density lipoprotein （DiI-Ac-LDL） and fluorescein isothiocyanate-conjugated Ulex europaeus lectin （FITC-UEA-I）. The rat acute myocardial infarction model was established by the ligation of the left anterior descending artery. The hUCB-EPCs were intramyocardially injected into the peri-infarct area. Four weeks later, left ventricular function was assessed by a pressure-volume catheter. The average capillary density （CAD） was evaluated by anti-VIII immunohistochemistry staining to reflect the development of neovascularization at the peri-infarct area. The graft cells were identified by double immunofluorescence staining with human nuclear antigen （HNA） and CD31 antibody, representing human origin of EPCs and vascular endothelium, respectively. Expressions of cytokines, proliferating cell nuclear angigen （PCNA）, platelet endothelial cell adhesion molecule （PECAM） and vascular endothelial growth factor （VEGF） were detected to investigate the underlying mechanisms of cell differentiation and revascularization. Results The donor EPCs were detectable and integrated into the host myocardium as confirmed by double-positive immunofluorescence staining with HNA and CD31. And the anti-VIII staining demonstrated a higher degree of microvessel formation in EPCs transplanted rats, associated with a significant improvement

关键词： human umbilical cord blood endothelial progenitor cells acute myocardial infarction neovascularization

Lichong decoction inhibits micro-angiogenesis by reducing the expressions of hypoxia inducible factor-1αand vascular endothelial growth factor in hysteromyoma mouse model

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Journal of Traditional Chinese Medicine 2020年第6期40卷 928-937页

作者： Wang Wenna Zhang Wufang Li Donghua Qian Ruiya Zhu Lijuan Liu Yu Chen Chao School of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China Gynecology department The fourth ward of Beijing Obstetrics and Gynecology HospitalCapital Medical University Beijing Maternaland ChildBeijing 100006China

OBJECTIVE:To investigate the efficacy of Lichong decoction(LD)from Traditional Chinese Medicine,on micro-angiogenesis in a mouse model of hysteromyoma.METHODS:A mouse model of hysteromyoma was developed by orthotopic intrauterine injection of primary human myoma cells isolated from patients from the Beijing Obstetrics and Gynecology Hospital into CB-17 Scid mice.Mice were administered high-dose LD,low-dose LD,mifepristone or water(control)daily by gavage for 4 weeks.Uterine diameter and coefficient(uterine weight/body weight)were measured.Uterine morphology was assessed by light microscopy(hematoxylin and eosin)and transmission electron microscopy.Serum levels of estradiol,progesterone,follicle-stimulating hormone and luteinizing hormone(LH)were measured by enzyme-linked immunosorbent assay.Uterine protein expression of hypoxia inducible factor(HIF)-1α,CD31 and proliferating cell nuclear antigen(PCNA)was detected by immunohistochemistry.VEGF and HIF-1αm RNAs were quantified by RT-PCR.RESULTS:High-dose LD,low-dose LD and mifepristone reduced uterine diameter and coefficient,and attenuated the morphologic abnormalities associated with hysteromyoma.High-dose LD,low-dose LD and mifepristone inhibited hysteromyoma-induced micro-angiogenesis,as evidenced by a decrease in the number of new microvessels co-immunostaining for CD31 and PCNA(P<0.01).High-dose LD and mifepristone lowered serum levels of estradiol,progesterone and LH(P<0.05).High-dose LD,low-dose LD and mifepristone down-regulated HIF-1αm RNA and protein expressions and VEGF m RNA expression(P<0.01).CONCLUSION:The inhibition of hysteromyoma by LD may involve reductions in HIF-1αand VEGF expression and suppression of micro-angiogenesis.

关键词： Leiomyoma neovascularization pathologic Hypoxia-inducible factor-1α Vascular endothelial growth factors Lichong decoction