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Rationale for the use of multifunctional drugs as neuroprotective agents for glaucoma

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Neural Regeneration Research 2012年第4期7卷 313-318页

作者： Jiahua Fang fagang jiang Jingbo Li Yanhua Zhu Department of Ophthalmology Jingzhou First Hospital Yangtze University Jingzhou 434000 Hubei Province China Department of Ophthalmology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 Hubei Province China

Glaucoma, the leading cause globally of irreversible blindness, is a neurodegenerative disease characterized by progressive retinal ganglion cell death. To date, no drug has been shown to prevent the retinal ganglion cell loss associated with glaucoma. Multiple mechanisms lead to ganglion cell death in glaucoma, suggesting that a neuroprotectant that has a single mode of action, like memantine, would have a limited positive effect at slowing down ganglion cell death. Conversely simultaneously targeting several factors may be the best therapeutic approach to improve outcomes Multifunctional drugs are fast gaining acceptance as a strategy for the treatment of complex disorders of the central nervous system, such as Parkinson＇s disease, Alzheimer＇s disease and other progressive neurodegenerative diseases. In this paper, we review the current literature on multifunctional drugs and propose a rationale for the use of multifunctional drugs in glaucomatous optic neuropathy.

关键词： multifunctional drugs glaucoma neuroprotection neurodegenerative disease retinal ganglion cells reviews

A Study of Toxicity of 5-Fluorouracil on Bovine Trabecular Meshwork Cells in Vitro

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2001年第1期21卷 82-85页

作者：姜发纲吕源淑魏厚仁 Department of Ophthalmology Xiehe Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030

In order to explore whether the conventional use of 5 fluorouracil (5 Fu) had any toxic effects on trabecular meshwork cells, bovine trabecular meshwork cells were cultured in vitro and exposed to 5 Fu at different concentrations. The cellular morphology, ultrastructure, mortality and phagocytosis were studied under light microscopy, transmission electron microscopy and methods of Wright's stain. It was found that the toxic effects of 5 Fu on the cells were in a dose dependent mode. 1×10 -1 mg/ml of 5 Fu caused a large part of cells rounded up, while 1×10 -3 mg/ml of the drug only a rough appearance of the cell surface. Exposure to 1×10 -2 mg/ml of 5 Fu made mitochrone swollen and rough endoplasmic reticulum enlarged, with the cell mortality being 50.5 %. The latex microspheres engulfed in cytoplasm in cells receiving 1×10 -1 and 1×10 -2 mg/ml of 5 Fu were significantly decreased as compared with those in the control group ( P <0.01). It was concluded that the safe concentration of 5 Fu on bovine trabecular meshwork cells was 1×10 -3 mg/ml and the conventional dosage of 5 Fu in clinical practice would not cause injury to trabecular meshwork cells.

关键词： fluorouracil trabecular meshwork cell glaucoma toxicity

Secretions from hypochlorous acid-treated tumor cells delivered in a melittin hydrogel potentiate cancer immunotherapy

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Bioactive Materials 2022年第3期7卷 541-553页

作者： Yuhan Zhou Ting Ye Chengzhi Ye Chao Wan Siyue Yuan Yushuai Liu Tianyu Li fagang jiang Jonathan F.Lovell Honglin Jin Jing Chen Cancer Center Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022PR China Department of Pediatrics Renmin Hospital of Wuhan UniversityWuhan430060PR China Department of Ophthalmology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022PR China Department of Biomedical Engineering University at BuffaloState University of New York.BuffaloNew York14260USA College of Biomedicine and Health and College of Life Science and Technology Huazhong Agricultural UniversityWuhan430070China

Autologous tumor cells and cell-derived secretions(CDS)can induce antitumor immune *** conditions in which cells are cultured and treated impact CDS,and cellular insults alter their composition and *** this study,we generated CDS from tumor cells exposed to normal culture conditions,hypoxia,cisplatin,radiotherapy,photodynamic therapy,or hypochlorous acid(HOCl).In vitro HOCl-CDS showed the strongest stimulatory effects on dendritic cells and macrophages compared to CDS generated by hypoxia,cisplatin,radiotherapy or photodynamic *** improve HOCl-CDS activity at the tumor site,we loaded HOCl-CDS into a melittin-encapsulated hydrogel *** injected intratumorally,the HOCl-CDS hydrogel promoted tumor cell death,cytotoxic T lymphocyte infiltration,and tumor-associated macrophage reprogramming towards an M1 *** hydrogel inhibited tumor growth and prolonged the survival of mice bearing B16-F10 ***,hydrogel-delivered HOCl-CDS augmented the antitumor effects of immune checkpoint *** results underscore the importance of the CDS generation method and delivery approach for improving cancer immunotherapy.

关键词： Cancer immunotherapy Hydrogel Melittin Anti-PD-1 Cell-derived secretions

Identification of Graves’ophthalmology by laser-induced breakdown spectroscopy combined with machine learning method

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Frontiers of Optoelectronics 2021年第3期14卷 321-328页

作者： Jingjing LI Feng CHEN Guangqian HUANG Siyu ZHANG Weiliang WANG Yun TANG Yanwu CHU Jian YAO Lianbo GUO fagang jiang Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhan 430074China Department of Ophthalmology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China School of Remote Sensing and Information Engineering Wuhan UniversityWuhan 430079China

Diagnosis of the Graves’ophthalmology remains a significant *** identified between Graves’ophthalmology tissues and healthy controls by using laser-induced breakdown spectroscopy(LIBS)combined with machine learning *** this work,the paraffin-embedded samples of the Graves’ophthalmology were prepared for LIBS spectra *** metallic elements(Na,K,Al,Ca),non-metallic element(O)and molecular bands((C-N),(C-O))were selected for diagnosing Graves’*** selected spectral lines were inputted into the supervised classification methods including linear discriminant analysis(LDA),support vector machine(SVM),k-nearest neighbor(ANN),and generalized regression neural network(GRNN),*** results showed that the predicted accuracy rates of LDA,SVM,ANN,GRNN were 76.33%,96.28%,96.56%,and 96.33%,*** sensitivity of four models were 75.89%,93.78%,96.78%,and 96.67%,*** specificity of four models were 76.78%,98.78%,96.33%,and 96.00%,*** demonstrated that LIBS assisted with a nonlinear model can be used to identify Graves’ophthalmopathy with a higher rate of *** ANN had the best performance by comparing the three nonlinear ***,LIBS combined with machine learning method can be an effective way to discriminate Graves’ophthalmology.

关键词： Graves’ophthalmology laser-induced breakdown spectroscopy(LIBS) linear discriminant analysis(LDA) support vector machine(SVM) k-nearest neighbor(kNN) generalized regression neural network(GRNN)

金丝桃素对兔慢性高眼压视网膜谷氨酸含量的影响

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眼科研究 2007年第5期25卷 370-372页

作者：李双姜发纲华中科技大学同济医学院附属协和医院眼科武汉在读硕士研究生430022

目的研究蛋白激酶C(PKC)特异性抑制剂金丝桃素(hypericin)对兔慢性高眼压视网膜谷氨酸含量的影响。方法取29只成年家兔,后房内注射α-糜蛋白酶,建立兔慢性高眼压模型,以眼压≥30mmHg为造模成功。造模成功兔眼10d后玻璃体内分别注入0.1m... 详细信息

目的研究蛋白激酶C(PKC)特异性抑制剂金丝桃素(hypericin)对兔慢性高眼压视网膜谷氨酸含量的影响。方法取29只成年家兔,后房内注射α-糜蛋白酶,建立兔慢性高眼压模型,以眼压≥30mmHg为造模成功。造模成功兔眼10d后玻璃体内分别注入0.1ml金丝桃素或生理盐水。另用3只正常兔作空白对照。用高效液相色谱法测定不同时间点的视网膜谷氨酸含量。结果正常兔视网膜谷氨酸含量为(1.71×10-5±0.23×10-5)mmol/g,慢性高眼压兔视网膜谷氨酸含量比正常兔显著升高(P<0.05)。慢性高眼压兔金丝桃素处理4d后视网膜谷氨酸含量为(8.53×10-5±1.06×10-5)mmol/g,同期生理盐水处理后为(11.31×10-5±0.10×10-5)mmol/g,二者差异有统计学意义(P<0.05)。结论慢性高眼压兔视网膜谷氨酸含量显著升高,可能与视网膜神经节细胞的损伤有关。金丝桃素玻璃体腔注射能显著降低兔慢性高眼压模型视网膜谷氨酸含量。

关键词：谷氨酸金丝桃素慢性高眼压视网膜神经节细胞

A Novel Targeting Drug Delivery System Based on Self-Assembled Peptide Hydrogel

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Journal of Biomaterials and Nanobiotechnology 2011年第5期2卷 622-625页

作者： Liang Liang Jun Yang Qinghua Li Ming Huo fagang jiang Xiaoding Xu Xianzheng Zhang 不详

In the last two decades, 5-fluorouracil (5-FU) is widely used in clinical practice to inhibit the fibroblasts to proliferate and improve the success rate of glaucoma-filtering surgery, but 5-FU has many toxic effects to normal ocular tissues. The self-assembled peptide hydrogels may serve as a new class of biomaterials for applications including tissue engineering and drug delivery. How to deliver 5-FU quickly and precisely to the target sites of ocular tissue by a self-assembled peptide hydrogel remains unexplored. RGD (arginine-glycine-aspartic acid) sequence is cell attachment site in extracellular matrix (ECM). Thus, If the self-assembled peptide hydrogel containing the RGD sequence that act as a specific attachment site for the proliferated fibroblasts adhesion could be designed, after integrated 5-FU, a novel targeting drug delivery system will be put into practice in the future.

关键词： Drug Delivery System Self-Assembly Filtering Surgery

Effects of Hydrostatic Pressure on Cultured Bovine Trabecular Meshwork Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 1999年第4期19卷 319-322,327页

作者：姜发纲魏厚仁吕源淑周元清张缨 Department of Ophthalmology Xiehe Hospital Tongji Medical University Wuhan 430022

In order to explore the effects of pressure on trabecular meshwork cells, bovine trabecular meshwork cells were cultured in vitro and subjected to different levels of hydrostatic pressure. The cellular morphology, ultrastructure and phagocytosis were studied with inverted phase-contrast microscopy, light microscopy and transmission electron microscopy, etc. It was found that the cells subjected to 2. 0 kPa or 2. 67 kPa for 48 h had no remarkable difference as compared with the controls in terms of parameters observed. Those under 4. 0 kPa for 24 h showed slight changes in structure and a mild decrease in phagocytic function. The damage appeared more severe if the pressure was higher or lasted longer. From the above we conclude that trabecular meshwork cells can only bear pressure below a certain level. They may be destroyed structurally or impaired functionally by pressure over this level.

关键词： trabecular meshwork cells pressure glaucoma

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卵巢切除术后性激素的改变对兔眼压的影响

临床眼科杂志 2005年第6期13卷 549-551页

作者：许畅姜发纲华中科技大学同济医学院附属协和医院眼科武汉430022

目的观察卵巢切除术后血清性激素水平的改变对兔眼压的影响。方法采用随机分组法,将20只新西兰大耳雌兔分为实验组10只和对照组10只,前者经腹部切除卵巢,后者仅打开腹腔不处理卵巢。免疫化学发光法检测兔血清雌激素、孕激素、睾酮水平,... 详细信息

目的观察卵巢切除术后血清性激素水平的改变对兔眼压的影响。方法采用随机分组法,将20只新西兰大耳雌兔分为实验组10只和对照组10只,前者经腹部切除卵巢,后者仅打开腹腔不处理卵巢。免疫化学发光法检测兔血清雌激素、孕激素、睾酮水平,用Schoitz眼压计采用双砝码对读(矫正球壁硬度)测量兔的眼压。结果实验组兔卵巢切除术后,血清雌激素、孕激素水平下降,睾酮上升。同时术后眼压升高,4周后恢复正常。相关性分析显示眼压升高与血清雌孕激素水平改变有关,与血清睾酮无关。结论兔卵巢切除术后,血清雌激素、孕激素水平下降伴兔眼压升高,性激素与眼压之间的联系可能有重要的病理生理意义。

关键词：卵巢切除术雌激素孕激素睾酮眼压

层粘连蛋白对人视网膜母细胞瘤株基质金属蛋白酶-2和基质金属蛋白酶-9的影响

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眼视光学杂志 2007年第3期9卷 188-191页

作者：龙华姜发纲华中科技大学同济医学院附属协和医院眼科湖北武汉430022

目的研究层粘连蛋白(laminin,LN)对人视网膜母细胞瘤株(Hxo-Rb44)基质金属蛋白酶-2(matrix metallopro-teinase,MMP-2)和基质金属蛋白酶-9(matrix metalloproteinase,MMP-9)及其mRNA表达的影响。方法在体外培养的人视网膜母细胞瘤细胞株(Hxo-Rb44)内分别加入含0μg/ml、5μg/ml、10μg/ml、20μg/mlLN的无血清RPMI-1640培养基,培养24h后,分别利用免疫组化SP染色法和PT-PCR检测每个实验组Hxo-Rb44表达MMP-2,MMP-9及其mRNA的含量,统计学方法比较不同实验组Hxo-Rb44表达MMP-2,MMP-9及其mRNA的差异。结果视网膜母细胞瘤细胞经LN刺激后,细胞内MMP-2和MMP-9及其mRNA表达均增加,免疫组化结果显示5μg/ml、10μg/ml、20μg/mlLN处理组MMP-2和MMP-9的染色灰度值分别是178.1±11.7和167.0±15.7、147.9±13.4和140.3±12.0、114.4±13.6和104.0±10.6,和对照组相比,差异有显著性(P<0.05),且LN浓度越高,其表达越强。5μ/ml、10!g/ml、20!g/mlLN处理组的MMP-2/β-actin、MMP-9/β-actin灰度值比值分别是0.181±0.016和0.254±0.023、0.201±0.021和0.287±0.020、0.243±0.019和0.320±0.022,与对照组相比,差异均有显著性(P<0.05),且随着LN浓度增高而增高,呈明显的量效关系。结论LN可诱导视网膜母细胞瘤细胞中表达的MMP-2和MMP-9及其mRNA增加,并呈剂量依赖型。提示LN对视网膜母细胞瘤的侵袭和转移可能具有促进作用。

关键词：视网膜母细胞瘤基质金属蛋白酶类层粘连蛋白