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The role of corneal endothelium in macular corneal dystrophy development and recurrence

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Science China(Life Sciences) 2024年第2期67卷 332-344页

作者： Bi-Ning Zhang Benxiang Qi Chunxiao Dong Bin Zhang Jun Cheng Xin Wang Suxia Li Xiaoyun Zhuang Shijiu Chen Haoyun Duan Dewei Li Sujie Zhu Guoyun Li yihai cao Qingjun Zhou Lixin Xie Eye Institute of Shandong First Medical University Qingdao Eye Hospital of Shandong First Medical UniversityQingdao 266071China State Key Laboratory Cultivation Base Shandong Provincial Key Laboratory of OphthalmologyQingdao 266071China School of Ophthalmology Shandong First Medical UniversityQingdao 250021China Department of Medicine Qingdao UniversityQingdao 266071China Eye Institute of Shandong First Medical University Eye Hospital of Shandong First Medical University(Shandong Eye Hospital)Jinan 250021China Department of Ophthalmology School of Clinical MedicineWeifang Medical UniversityWeifang 261072China Institute of Translational Medicine College of MedicineQingdao UniversityQingdao 266071China Key Laboratory of Marine Drugs of Ministry of Education Shandong Provincial Key Laboratory of Glycoscience and GlycotechnologySchool of Medicine and PharmacyOcean University of ChinaQingdao 266071China Laboratory for Marine Drugs and Bioproducts Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266071China Department of Microbiology Tumor and Cell BiologyBiomedicumKarolinska InstitutetStockholm 17177Sweden

Macular corneal dystrophy(MCD)is a progressive,bilateral stromal dystrophic disease that arises from mutations in carbohydrate sulfotransferase 6(CHST6).Corneal transplantation is the ultimate therapeutic solution for MCD ***,postoperative recurrence remains a significant *** conducted a retrospective review of a clinical cohort comprising 102 MCD patients with 124 eyes that underwent either penetrating keratoplasty(PKP)or deep anterior lamellar keratoplasty(DALK).Our results revealed that the recurrence rate was nearly three times higher in the DALK group(39.13%,9/23 eyes)compared with the PKP group(10.89%,11/101 eyes),suggesting that surgical replacement of the corneal endothelium for treating MCD is advisable to prevent postoperative *** experimental data confirmed the robust m RNA and protein expression of CHST6 in human corneal endothelium and the rodent homolog CHST5 in mouse *** knockdown of wild-type Chst5 in mouse corneal endothelium(AC^(siChst5)),but not in the corneal stroma,induced experimental MCD with similar extracellular matrix synthesis impairments and corneal thinning as observed in MCD *** carrying Chst5 point mutation also recapitulated clinical phenotypes of MCD,along with corneal endothelial *** injection of wild-type Chst5 rescued the corneal impairments in AC^(siChst5)mice and retarded the disease progression in Chst5 mutant ***,our study provides new mechanistic insights and therapeutic approaches for MCD treatment by highlighting the role of corneal endothelium in MCD development.

关键词： macular corneal dystrophy recurrence corneal endothelium keratan sulfate penetrating keratoplasty

Blood vessels in fat tissues and vasculature-derived signals in controlling lipid metabolism and metabolic disease

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Chinese Medical Journal 2022年第22期135卷 2647-2652页

作者： yihai cao Department of Microbiology Tumor and Cell BiologyKarolinska Institute17165 StockholmSweden Hong Kong Centre for Cerebro-Cardiovascular Health Engineering Hong KongChina

Metabolic disorders,including endocrine disorders,obesity,diabetes,cerebrocardiovascular disease,and even cancer,are the most common and lethal diseases with the leading all-cause mortality around the globe.[1]For example,according to the World Health Organization,type 2 diabetes mellitus(T2DM)as a chronic disease owing to insulin resistance became the ninth leading cause of death with 1.5 million deaths in 2019.[2]Currently,there are approximately 422 million people worldwide suffering from diabetes,with the majority living in low-and middle-income countries.[3]High T2DM prevalence has been associated with obesity and lifestyle factors such as lack of physical exercise,although genetic factors are linked to a subpopulation of T2DM patients.

关键词： Blood metabolism obesity

Future options of anti-angiogenic cancer therapy

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Chinese Journal of Cancer 2016年第2期35卷 88-96页

作者： yihai cao Department of Microbiology Tumor and Cell BiologyKarolinska Institute Department of Medical and Health Sciences Linkoping University Department of Cardiovascular Sciences University of Leicester and NIHR Leicester Cardiovascular Biomedical Research UnitGlenfield Hospital

In human patients,drugs that block tumor vessel growth are widely used to treat a variety of cancer *** rigorous phase 3 clinical trials have demonstrated significant survival benefits;however,the addition of an anti-angiogenic component to conventional therapeutic modalities has generally produced modest survival benefits for cancer ***,it is unclear why these clinically available drugs targeting the same angiogenic pathways produce dissimilar effects in preclinical models and human *** this article,we discuss possible mechanisms of various anti-angiogenic drugs and the future development of optimized treatment regimens.

关键词： Angiogenesis, Cancer therapy, Anti-angiogenesis, Vascular endothelial growth factor, Biomarker

Treatment of acute pulmonary edema by blocking VEGF-induced vascular leakage

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Emergency and Critical Care Medicine 2021年第1期1卷 2-5页

作者： yihai cao Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholmSweden

Pulmonary edema induces local and systemic hypoxia in lungs and other tissues and organs,entailing the development of acute respiratory distress syndrome(ARDS).Hypoxia triggers a myriad of pathological responses,including angiogenesis and hyperpermeability of blood vessels in the lung and other *** endothelial growth factor,also named vascular permeability factor(VPF),is one of the key hypoxia-targeted *** is probably the most potent VPF in the *** this article,I will discuss the possibilities and mechanistic insights of blocking the VEGF signaling pathway for treating acute pulmonary *** particular,anti-VEGF drugs for treating Covid-19-induced pulmonary edema will be discussed.

关键词： Acute respiratory distress syndrome Anti-VEGF therapy Hypoxia Pulmonary edema Vascular endothelial growth factor

A facile and general method for synthesis of antibiotic-free protein-based hydrogel:Wound dressing for the eradication of drug-resistant bacteria and biofilms

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Bioactive Materials 2022年第12期7卷 446-458页

作者： Jiang Ouyang Qingyue Bu Na Tao Mingkai Chen Haijun Liu Jun Zhou Jinggong Liu Bo Deng Na Kong Xingcai Zhang Tianfeng Chen yihai cao Wei Tao The First Affiliated Hospital Department of ChemistryJinan UniversityGuangzhou510632China Center for Nanomedicine and Department of Anesthesiology Brigham and Women’s HospitalHarvard Medical SchoolBostonMA02115USA John A.Paulson School of Engineering and Applied Sciences Harvard UniversityCambridgeMA02138USA College of Chemistry and Chemical Engineering Central South UniversityChangshaHunan410083China The Second Affiliated Hospital of Guangzhou University of Chinese Medicine Guangdong Provincial Academy of Chinese Medical SciencesGuangzhou510006China Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholm17177Sweden

Antibacterial protein hydrogels are receiving increasing attention in the aspect of bacteria-infected-wound healing. However, bacterial drug resistance and biofilm infections lead to hard healing of wounds, thus the construction of biological agents that can overcome these issues is essential. Here, a simple and universal method to construct antibiotic-free protein hydrogel with excellent biocompatibility and superior antibacterial activity against drug-resistant bacteria and biofilms was developed. The green industrial microbicide tetrakis (hydroxymethyl) phosphonium sulfate (THPS) as cross-linking agent can be quickly cross-linked with model protein bovine serum albumin (BSA) to form antibacterial hydrogel through simple mixing without any other initiators, subsequently promoting drug-resistance bacteria-infected wound healing. This simple gelatinization strategy allows at least ten different proteins to form hydrogels (e.g. BSA, human serum albumin (HSA), egg albumin, chymotrypsin, trypsin, lysozyme, transferrin, myohemoglobin, hemoglobin, and phycocyanin) under the same conditions, showing prominent universality. Furthermore, drug-resistance bacteria and biofilm could be efficiently destroyed by the representative BSA hydrogel (B-Hydrogel) with antibacterial activity, overcoming biofilm-induced bacterial resistance. The in vivo study demonstrated that the B-Hydrogel as wound dressing can promote reepithelization to accelerate the healing of methicillin-resistant staphylococcus aureus (MRSA)-infected skin wounds without inducing significant side-effect. This readily accessible antibiotic-free protein-based hydrogel not only opens an avenue to provide a facile, feasible and general gelation strategy, but also exhibits promising application in hospital and community MRSA disinfection and treatment.

关键词： THPS Protein hydrogel Bacterial resistance Anti-Biofilm Wound dressing

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棕色脂肪激活对机体正常和异常造血的影响

中国细胞生物学学报 2024年第6期46卷 1081-1089页

作者：成天然邵雅刘欢赵红菲赵梓含姜珊张诗悦孙露王彤许元富曹义海中国医学科学院血液病医院(中国医学科学院血液学研究所) 北京协和医学院血液与健康全国重点实验室国家血液系统疾病临床医学研究中心细胞生态海河实验室天津300020 天津医学健康研究院天津300020 西安交通大学第一附属医院检验科西安710061 瑞典卡罗林斯卡学院微生物和肿瘤生物学系索尔纳17165

激活棕色脂肪组织(BAT)可以抑制实体肿瘤生长,然而其对正常或异常造血细胞的影响仍然不清楚。因此,该研究采用β3-肾上腺素受体激动剂米拉贝隆分别激活野生型和白血病小鼠BAT,观察和分析其对正常造血细胞以及白血病细胞的影响。通过流... 详细信息

激活棕色脂肪组织(BAT)可以抑制实体肿瘤生长,然而其对正常或异常造血细胞的影响仍然不清楚。因此,该研究采用β3-肾上腺素受体激动剂米拉贝隆分别激活野生型和白血病小鼠BAT,观察和分析其对正常造血细胞以及白血病细胞的影响。通过流式分析了不同时间点米拉贝隆治疗组和对照组小鼠骨髓、脾脏、肝脏和外周血中白血病细胞的比例,以及骨髓中造血干/祖及成熟细胞的比例、数目、细胞周期、凋亡和集落形成能力;验证了脂肪组织的激活程度;通过手术移除BAT来检测米拉贝隆激活BAT在白血病中的作用。研究结果显示,米拉贝隆治疗组显著激活了BAT,减少了急性白血病小鼠的骨髓、脾脏、肝脏和外周血中白血病细胞的比例,延长了小鼠生存期。米拉贝隆对正常C57小鼠的成熟免疫细胞和骨髓造血干/祖细胞的比例和数量没有明显影响,但在白血病小鼠中治疗组骨髓中各类成熟免疫细胞的比例和绝对数均显著高于对照组,造血干/祖细胞的比例和绝对数均显著增加,细胞凋亡减少,集落形成能力增强。手术切除BAT阻断了米拉贝隆介导的抗白血病作用。研究结果表明,通过米拉贝隆预给药可以激活棕色脂肪组织,抑制白血病细胞的增殖,促进白血病小鼠正常造血干/祖细胞的增殖分化和存活,延长小鼠生存期,为今后白血病的临床治疗提供了一种新的策略。

关键词：造血干/祖细胞棕色脂肪组织米拉贝隆能量代谢白血病

Perivascular localized cells commit erythropoiesis in PDGF-B-expressing solid tumors

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Cancer Communications 2023年第6期43卷 637-660页

作者： Kayoko Hosaka Chenchen Wang Shiyue Zhang Xue Lv Takahiro Seki Yin Zhang Xu Jing Jieyu Wu Qiqiao Du Xingkang He Yulong Fan Xuan Li Makoto Kondo Masahito Yoshihara Hong Qian Lihong Shi Ping Zhu Yuanfu Xu Yunlong Yang Tao Cheng yihai cao Department of Microbiology Tumor and Cell BiologyKarolinska InstituteStockholmSweden State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjinP.R.China Tianjin Institutes of Health Science TianjinP.R.China School of Pharmacology Binzhou Medical UniversityYantaiShandongP.R.China Department of Clinical Laboratory the Second Hospital of Shandong UniversityJinanShandongP.R.China Department of Gastroenterology Sir Run Run Shaw HospitalZhejiang University Medical SchoolHangzhouZhejiangP.R.China Center for Hematology and Regenerative Medicine Department of MedicineKarolinska InstituteKarolinska University HospitalStockholmSweden Department of Biosciences and Nutrition Karolinska InstituteHuddingeSweden Department of Cellular and Genetic Medicine School of Basic Medical SciencesFudan UniversityShanghaiP.R.China

Background:Tumors possess incessant growth features,and expansion of their masses demands sufficient oxygen supply by red blood cells(RBCs).In adult mammals,the bone marrow(BM)is the main organ regulating hematopoiesis with dedicated *** than BM,extramedullary hematopoiesis is discovered in various pathophysiological ***,whether tumors can contribute to hematopoiesis is completely *** evidence shows that,in the tumor microenvironment(TME),perivascular localized cells retain progenitor cell properties and can differentiate into other ***,we sought to better understand whether and how perivascular localized pericytes in tumors manipulate ***:To test if vascular cells can differentiate into RBCs,genome-wide expression profiling was performed using mouse-derived *** tracing of perivascular localized cells employing NG2-CreERT2:R26R-tdTomato mouse strain was used to validate the findings in ***-activated cell sorting(FACS),single-cell sequencing,and colony formation assays were applied for biological *** production of erythroid differentiationspecific cytokine,erythropoietin(EPO),in TME was checked using quantitative polymerase chain reaction(qPCR),enzyme-linked immunosorbent assay(ELISA,magnetic-activated cell sorting and *** investigate BM function in tumor erythropoiesis,BM transplantation mouse models were ***:Genome-wide expression profiling showed that in response to plateletderived growth factor subunit B(PDGF-B),neural/glial antigen 2(NG2)+perivascular localized cells exhibited hematopoietic stem and progenitor-like features and underwent differentiation towards the erythroid ***-B simultaneously targeted cancer-associated fibroblasts to produce high levels of EPO,a crucial hormone that necessitates *** analysis using genetic tracing of NG2+cells in tumors defined the perivascular localized cell-derived sub

关键词： cancer hematopoiesis PDGF-B perivascular localized cell stem cell tumor vasculature

Tumor-derived insulin-like growth factor-binding protein-1 contributes to resistance of hepatocellular carcinoma to tyrosine kinase inhibitors

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Cancer Communications 2023年第4期43卷 415-434页

作者： Hiroyuki Suzuki Hideki Iwamoto Takahiro Seki Toru Nakamura Atsutaka Masuda Takahiko Sakaue Toshimitsu Tanaka Yasuko Imamura Takashi Niizeki Masahito Nakano Shigeo Shimose Tomotake Shirono Yu Noda Naoki Kamachi Miwa Sakai Kazutoyo Morita Masamichi Nakayama Tomoharu Yoshizumi Ryoko Kuromatsu Hirohisa Yano yihai cao Hironori Koga Takuji Torimura Division of Gastroenterology Department of MedicineKurume University School of MedicineKurume CityFukuokaJapan Liver Cancer Research Division Research Center for Innovative Cancer TherapyKurume UniversityKurume CityFukuokaJapan Iwamoto Internal Medicine Clinic Kitakyushu CityFukuokaJapan Department of Microbiology Tumor and Cell biologyKarolinska InstitutetStockholmSweden Department of Surgery and Science Graduate School of Medical ScienceKyushu UniversityFukuoka CityFukuokaJapan Department of Pathology Kurume University School of MedicineKurume CityFukuokaJapan

Background:Antiangiogenic tyrosine kinase inhibitors(TKIs)provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma(HCC).However,patients with HCC often develop resistance toward antiangiogenic TKIs,and the underlying mechanisms are not *** aim of this study was to determine the mechanisms underlying antiangiogenic TKI resistance in ***:We used an unbiased proteomic approach to define proteins that were responsible for the resistance to antiangiogenic TKIs in HCC *** evaluated the prognosis,therapeutic response,and serum insulin-like growth factor-binding protein-1(IGFBP-1)levels of 31 lenvatinib-treated HCC *** on the array of results,a retrospective clinical study and preclinical experiments using mouse and human hepatoma cells were ***,in vivo genetic and pharmacological gain-and loss-of-function experiments were ***:In the patient cohort,IGFBP-1 was identified as the signaling molecule with the highest expression that was inversely associated with overall ***,antiangiogenic TKI treatment markedly elevated tumor IGFBP-1 levels via the hypoxia-hypoxia inducible factor ***-1 stimulated angiogenesis through activation of the integrinα5β1-focal adhesion kinase ***,loss of IGFBP-1 and integrinα5β1 by genetic and pharmacological approaches re-sensitized HCC to lenvatinib ***:Together,our data shed light onmechanisms underlying acquired resistance of HCC to antiangiogenic *** TKIs induced an increase of tumor IGFBP-1,which promoted angiogenesis through activating the IGFBP-1-integrinα5β1 *** data bolster the application of a new therapeutic concept by combining antiangiogenic TKIs with IGFBP-1 inhibitors.

关键词： hepatocellular carcinoma hypoxia IGFBP-1 lenvatinib molecular targeting resistance tyrosine kinase inhibitors

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血管生成在疾病治疗中的应用与展望

山东大学学报（医学版） 2021年第9期59卷 9-14页

作者：曹义海瑞典卡罗林斯卡医学院微生物和肿瘤、细胞生物学系瑞典斯德哥尔摩17165

血管生成与新生参与了许多疾病的发生、演变和进展,包括最常见和致命性心血管疾病、癌症、糖尿病、炎症及眼科疾病等。促进或抑制血管生成已经成为上述疾病的重要治疗策略。截至撰写本文时,许多靶向血管生成的药物已经获得了不同国家食... 详细信息

血管生成与新生参与了许多疾病的发生、演变和进展,包括最常见和致命性心血管疾病、癌症、糖尿病、炎症及眼科疾病等。促进或抑制血管生成已经成为上述疾病的重要治疗策略。截至撰写本文时,许多靶向血管生成的药物已经获得了不同国家食品药品监督管理局的批准,用于治疗恶性疾病和眼科疾病。本文将介绍血管生成参与疾病进展的机制、靶向血管生成的新型治疗策略及其在临床应用中的挑战与展望。

关键词：血管生成肿瘤眼科疾病心脑血管疾病代谢性疾病新型冠状病毒肺炎