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Protective effect of thodioloside and bone marrow mesenchymal stem cells infected with HIF-1-expressing adenovirus on acute spinal cord injury

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Neural Regeneration Research 2020年第4期15卷 690-696页

作者： Xiao-Qin Ha Bo Yang Huai-Jing Hou xiao-Ling Cai Wan-Yuan Xiong Xu-Pan Wei Lanzhou University Second Hospital LanzhouGansu ProvinceChina Department of Clinical Laboratory Lanzhou General Hospital of Lanzhou Military Area CommandLanzhouGansu ProvinceChina School of Clinical Medicine Gansu University of Traditional Chinese MedicineLanzhouGansu ProvinceChina School of Life Science and Engineering Lanzhou University of TechnologyLanzhouGansu ProvinceChina

Rhodioloside has been shown to protect cells from hypoxia injury,and bone marrow mesenchymal stem cells have a good effect on tissue repair.To study the effects of rhodioloside and bone marrow mesenchymal stem cells on spinal cord injury,a rat model of spinal cord injury was established using the Infinite Horizons method.After establishing the model,the rats were randomly divided into five groups.Rats in the control group were intragastrically injected with phosphate buffered saline(PBS)(5μL).PBS was injected at 6 equidistant points around 5 mm from the injury site and at a depth of 5 mm.Rats in the rhodioloside group were intragastrically injected with rhodioloside(5 g/kg)and intramuscularly injected with PBS.Rats in the mesenchymal stem cell(MSC)group were intramuscularly injected with PBS and intramuscularly with MSCs(8×10^6/mL in a 50-μL cell suspension).Rats in the Ad-HIF-MSC group were intragastrically injected with PBS and intramuscularly injected with HIF-1 adenovirus-infected MSCs.Rats in the rhodioloside+Ad-HIF-MSC group were intramuscularly injected with MSCs infected with the HIF-1 adenovirus and intragastrically injected with rhodioloside.One week after treatment,exercise recovery was evaluated with a modified combined behavioral score scale.Hematoxylin-eosin staining and Pischingert’s methylene blue staining were used to detect any histological or pathological changes in spinal cord tissue.Levels of adenovirus IX and Sry mRNA were detected by real-time quantitative polymerase chain reaction and used to determine the number of adenovirus and mesenchymal stem cells that were transfected into the spinal cord.Immunohistochemical staining was applied to detect HIF-1 protein levels in the spinal cord.The results showed that:(1)compared with the other groups,the rhodioloside+Ad-HIF-MSC group exhibited the highest combined behavioral score(P<0.05),the most recovered tissue,and the greatest number of neurons,as indicated by Pischingert’s methylene blue staining.(2)Compared with the PBS group,HIF-1 protein ex

关键词： acute spinal cord injury adenovirus adenovirus gene IX bone marrow mesenchymal stem cells combined behavioral score scale HIF-1α nerve regeneration nerve repair Rhodiola rosea Sry

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Potential of Sestrin2 in the prevention and treatment of chronic diseases

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Journal of hainan Medical University 2021年第16期27卷 64-67页

作者： Ping Li Xiao-Qin Ha Institute of Nutrition and Food Hygiene School of Public HealthLanzhou UniversityLanzhou 730000China The 940th Hospital of the Chinese People's Liberation Army Joint Service Support Lanzhou730050China Gansu Provincial Key Laboratory of Stem Cell and Gene Medicine Lanzhou 730050China

The prevalence and lethality of chronic non-communicable diseases are constantly rising,becoming a global public health problem.The occurrence and development of chronic diseases are closely related to the generation of excessive free radicals and active oxygen in the body,and anti-oxidation will become an effective treatment.Sestrin2 protein,as a new stress protein found in mammals in recent years,has unique advantages in antioxidants,and is expected to become an effective biomarker and therapeutic target for chronic diseases.The following is a review of the regulatory role and mechanism of sestrin2 in chronic diseases in order to provide a reference for the research of other scholars.

关键词： Sestrin2 SESN2 Chronic non-communicable diseases Oxidative stress Review

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Effect of endothelial progenitor cells in neovascularization and their application in tumor therapy

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Chinese Medical Journal 2010年第17期123卷 2454-2460页

作者： DONG Fang ha xiao-qin Medical Experiment Center Lanzhou Military Command General Hospital of the People's Liberation Army Key Laboratory of Stem Cell and Gene Medicine of Gansu Province Lanzhou Gansu 730050 China

Objective To review the effect of endothelial progenitor cells in neovascularization as well as their application to the therapy of tumors.Data sources The data used in this review were mainly from PubMed for relevant English language articles published from 1997 to 2009. The search term was ＂endothelial progenitor cells＂.Study selection Articles regarding the role of endothelial progenitor cells in neovascularization and their application to the therapy of tumors were selected.Results Endothelial progenitor cells isolated from bone marrow, umbilical cord blood and peripheral blood can proliferate, mobilize and differentiate into mature endothelial cells. Experiments suggest endothelial progenitor cells take part in forming the tumor vascular through a variety of mechanisms related to vascular endothelial growth factor, matrix metalloproteinases, chemokine stromal cell-derived factor 1 and its receptor C-X-C receptor-4, erythropoietin, Notchsignal pathway and so on. Evidence demonstrates that the number and function change of endothelial progenitor cells in peripheral blood can be used as a biomarker of the response of cancer patients to anti-tumor therapy and predict the prognosis and recurrence. In addition, irradiation temporarily increased endothelial cells number and decreased the endothelial progenitor cell counts in animal models. Meanwhile, in preclinical experiments, therapeutic gene-modified endothelial progenitor cells have been approved to attenuate tumor growth and offer a novel strategy for cell therapy and gene therapy of cancer.Conclusions Endothelial progenitor cells play a particular role in neovascularization and have attractively potential prognostic and therapeutic applications to malignant tumors. However, a series of problems, such as the definitive biomarkers of endothelial progenitor cells, their interrelationship with radiotherapy and their application in cell therapy and gene therapy of tumors, need further investigation.

关键词： endothelial progenitor cells pathological neovascularization tumor therapy

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Research status of association between serum minerals and complications of type 2 diabetes

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Journal of hainan Medical University 2020年第19期26卷 77-80页

作者： Ping Li Jie Li hai-Xia Li Xiao-Qin Ha Institute of Nutrition and Food Hygiene School of Public HealthLanzhou UniversityLanzhou 730000China The 940th Hospital of the Chinese People's Liberation Army Joint Service Support Lanzhou 730050China

As a chronic metabolic disease,type 2 diabetes mellitus is prone to various microvascular and macrovascular complications.As a micronutrient,minerals have a small amount of body demand,but they are essential to the body's metabolism and play an important role in the occurrence of diabetes complication.This review summarizes the relationship between serum calcium,magnesium,iron,copper,and zinc and the complications of type 2 diabetes mellitus.It provides references for related scholars,and also provide favorable basis for early diagnosis,nutrition management with prevention and treatment of complications of type 2 diabetes.

关键词： Type 2 diabetes mellitus Minerals Trace elements Review

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Keratinocyte growth factor gene therapy ameliorates ulcerative colitis in rats

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World Journal of Gastroenterology 2011年第21期17卷 2632-2640页

作者： Chun-Jie Liu Ji-De Jin Tong-De Lv Zu-Ze Wu Xiao-Qin Ha Department of Pharmaceutical Engineering School of Chemical Engineering and Technology Yianjin University Tianjin 300072 China Department of Experimental Hematology Beijing Institute of Radiation Medicine Beijing 100850 China Center for Medical Experiment General Hospital of Lanzhou Military Command Key Laboratory of Stem Cell and Gene Medicine in Gansu Lanzhou 730050 Gansu Province China

AIM:To investigate the effect of keratinocyte growth factor(KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model.METHODS:The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 mL 5%(v/v) acetic acid.Twenty-four hours after exposed to acetic acid,rats were divided into three experimental groups:control group,attenuated Salmonella typhimurium Ty21a strain(SP) group and SP strain carrying human KGF gene(SPK) group,and they were separately administered orally with 10% NaHCO3,SP or SPK.Animals were sacrificed and colonic tissues were harvested respectively on day 3,5,7 and 10 after administration.Weights of rats,colonic weight/length ratio and stool score were evaluated.Histological changes of colonic tissues were examined by hematoxylin and eosin(HE) staining method.The expression of KGF,KGF receptor(KGFR) and TNF-α were measured either by enzyme-linked immunosorbent assay or Western blotting.Immunohistochemistry was used to detect the cellular localization of KGFR and Ki67.In addition,superoxide dismutase(SOD) activity and malondialdehyde(MDA) contents in the homogenate were measured.RESULTS:Body weight and colonic weight/length ratio were declined in SPK group compared with SP and control groups(body weight:272.78 ± 17.92 g vs 243.72 ± 14.02 g and 240.68 ± 12.63 g,P hanges of damaged colon were improved in SPK group as well.After administration of SPK strain,KGF expression increased markedly from the 3rd d,and remained at a high level till the 10th d.Furthermore,KGFR expression and Ki67 expression elevated,whereas TNF-α expression was inhibited in SPK group.In the group administered with SPK,SOD activity increased significantly(d 5:26.18 ± 5.84 vs 18.12 ± 3.30 and 18.79 ± 4.74 U/mg,P < 0.01;d 7:35.48 ± 3.35 vs 22.57 ± 3.44 and 21.69 ± 3.94 U/mg,P < 0.01;d 10:46.10 ± 6.23 vs 25.35 ± 4.76 and 27.82 ± 6.42 U/mg,P < 0.01) and MDA contents decreased according

关键词：溃疡性结肠炎角质细胞生长因子大鼠模型基因疗法酶联免疫吸附试验减毒沙门氏菌 SOD活性超氧化物歧化酶

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Human Papillomavirus 16E6 Oncogene Mutation in Cervical Cancer

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Chinese Journal of Cancer Research 2009年第2期21卷 97-101页

作者： Feng Sun Xiao-Qin Ha Tong-de Lv Chuan-ping Xing Bin Liu xiao-zhe Cao Department of Pathology The Second People＇s Hospital of Zhuhai Zhuhai 519020 China Department of General Laboratory Department of Pathology Lanzhou General Hospital of PLALanzhou 730050 China

Objective： Cervical cancer （CC） is the second most common type of cancer in women worldwide, after breast cancer. High-risk human papillomaviruses （HR-HPVs） are considered to be the major causes of cervical cancer. HPV16 is the most common type of HR-HPVs and HPV16 E6 gene is one of the major oncogenes. Specific mutations are considered as dangerous factors causing CC. This study was designed to find mutations of HPV16 E6 and the relationship between the mutations and the happening of CC. Methods： The tissue DNA was extracted from 15 biopsies of CC. Part of HPV16 E6 gene （nucleotide 201-523） was amplified by polymerase chain reaction （PCR） from the CC tissue DNA. The PCR fragments were sequenced and analyzed. Results： The result of PCR showed that the positive rate of HPV16 E6 was 93.33% （14/13）. After sequencing ana analyzing, in the 13 out of 14 PCR fragments, 4 maintained prototype （30.77%）, 8 had a same 350G mutation （61.54%）, and 1 had a 249G mutation （7.69%）. Conclusion： This study suggest that there is a high infection rate of HPV in cervical cancer and most of the HPV16 E6 gene has mutations. Those mutations may have an association with the development of cervical cancer.

关键词： Cervical cancer Human papUlomavirus E6 gene Mutation

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Effects of hepatocyte growth factor-mediated activation of Dll4-Notch-Hey2 signaling pathway

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Chinese Medical Journal 2011年第1期124卷 127-131页

作者： GAO Yu-fang ha xiao-qin LU Tong-de haN Juan-ping Experimental Center of Medicine Lanzhou General Hospital Lanzhou Command People's Liberation Army Lanzhou Gansu 730050 China Department of Laboratory Diagnosis Central Hospital ofXianyang Xianyang Shaanxi 712000 China

Background Hepatocyte growth factor （HGF） treats ischemic disease by promoting arteriogenesis, however, its mechanism of action is not known. The notch signaling pathway plays an important role in neovascularization. The relationship between the proliferation and migration ability of artery endothelial cells and the Dll4-Notch-Hey2 signaling pathway in the process of arteriogenesis was investigated as a mechanism of action of HGE Methods Based on the prophase study cells and supernatant were harvested at the indicated time after human femoral artery endothelial cells （HFAECs） were infected with adenovirus-HGF （Ad-HGF） at 200 pfu/cell. Cells were analyzed for HGF expression and Notch1, DII4 and Hey2 expression by ELISA and reverse transcription-PCR （RT-PCR）. The changes in the proliferation and migration ability of HFAECs were observed by M-I-I- and Transwell migration experiments Ad-GFP-infected HFAECs were used as control. Results Compared with the control group the Ad-HGF group＇s HGF expression was not increased with time, and the induction by HGF of Notch1, DII4 and Hey2 gene transcription was not enhanced with an increase of HGF. The proliferation ability of Ad-HGF-transduced HFAECs was enhanced and their migration ability was also enhanced in the presence of HGF. Conclusions Through activating the DII4-Notch-Hey2 signaling pathway, HGF indirectly promotes the proliferation and migration ability of cells, so that offspring artery branches are formed.

关键词： hepatocyte growth factor genetic transcription cell migration,＂ cell proliferation

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Sestrin2在2型糖尿病血栓形成中的作用

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中国生物制品学杂志 2021年第12期34卷 1520-1523,1528页

作者：李萍(综述) 哈小琴(审校) 兰州大学公共卫生学院营养与食品卫生研究所甘肃兰州730000 中国人民解放军联勤保障部队第九四〇医院检验科甘肃兰州730050 甘肃省干细胞与基因药物重点实验室甘肃兰州730050

2型糖尿病(type 2 diabetes,T2D)现已成为全球性的公共卫生问题,患者多处于血液高凝状态或血栓前状态。在T2D死亡患者中,约80%死于血栓事件。为提高糖尿病患者的生存寿命和质量,对于血栓的防治就显得极其重要。Sestrin2作为近年来发现... 详细信息

2型糖尿病(type 2 diabetes,T2D)现已成为全球性的公共卫生问题,患者多处于血液高凝状态或血栓前状态。在T2D死亡患者中,约80%死于血栓事件。为提高糖尿病患者的生存寿命和质量,对于血栓的防治就显得极其重要。Sestrin2作为近年来发现的新型高度保守的蛋白,具有突出的抗氧化能力,已成为多种疾病研究中的热点。同样在糖尿病血栓形成的各个环节中也有重要参与,具有潜在的抗血栓作用。但目前关于Sestrin2与糖尿病血栓形成关系的文章较少,相关的综述更是鲜有报道。因此,本文就Sestrin2在糖尿病血栓形成的关键环节发挥的作用作一综述,为其他学者的研究提供参考的同时,也为血栓的治疗提供新的思路和靶点。

关键词： Sestrin2 2型糖尿病血栓形成

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肠道微生物代谢产物参与动脉粥样硬化的研究进展

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中国生物制品学杂志 2022年第1期35卷 112-118,122页

作者：李海霞(综述) 魏静哈小琴(审校) 兰州大学公共卫生学院营养与食品卫生研究所甘肃兰州730000 人民解放军联勤保障部队第九四〇医院检验科甘肃兰州730050 甘肃中医药大学临床医学院甘肃兰州730030

肠道微生物群像一个内分泌器官,能产生多种生物活性代谢物,影响宿主的健康。近来研究发现,肠道微生物的代谢组成变化在肥胖、高血压、慢性心脏和肾脏疾病中起重要作用。多项研究表明,肠道微生物衍生的许多代谢物与动脉粥样硬化事件密切... 详细信息

肠道微生物群像一个内分泌器官,能产生多种生物活性代谢物,影响宿主的健康。近来研究发现,肠道微生物的代谢组成变化在肥胖、高血压、慢性心脏和肾脏疾病中起重要作用。多项研究表明,肠道微生物衍生的许多代谢物与动脉粥样硬化事件密切相关,如三甲胺N-氧化物(trimethylamine N-oxide,TMAO)、胆汁酸(bile acid)、短链脂肪酸(short-chain fatty acids,SCFAs)、尿毒症毒素(uremic toxins)以及多酚(polyphenols)等。虽然目前代谢组学的应用已对这些微生物代谢物进行了准确的表征和定量分析,但其作用机制尚不明确。本文对肠道微生物代谢产物在动脉粥样硬化发展中的作用作一综述,为预防或治疗动脉粥样硬化提供新的策略。

关键词：肠道微生物动脉粥样硬化三甲胺N-氧化物胆汁酸短链脂肪酸尿毒症毒素多酚

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胃肠缺血缺氧应激损伤修复的新策略:细胞因子联合基因治疗

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世界华人消化杂志 2017年第6期25卷 479-483页

作者：哈小琴兰州军区兰州总医院检验中心甘肃省兰州市730050

应激引发的胃肠缺血缺氧损伤是一种常见的消化系统疾病,应激导致胃肠损伤的机制复杂,临床上治疗手段多样,但治疗效果并不理想.随着人们对细胞因子研究的不断深入,许多与胃肠缺血缺氧损伤关系密切的细胞因子如肝细胞生长因子、低氧诱导... 详细信息

应激引发的胃肠缺血缺氧损伤是一种常见的消化系统疾病,应激导致胃肠损伤的机制复杂,临床上治疗手段多样,但治疗效果并不理想.随着人们对细胞因子研究的不断深入,许多与胃肠缺血缺氧损伤关系密切的细胞因子如肝细胞生长因子、低氧诱导因子及角质细胞生长因子等已被大量的研究,有关细胞因子介入疾病治疗的研究也越来越多,研究者将细胞因子构建到真核表达载体上制备成基因治疗药物,通过口服给损伤局部组织中转移细胞因子基因达到治疗目的.细胞因子联合基因治疗可能是一种安全、有效的胃肠缺血缺氧应激损伤修复的新策略,这将会为缺氧缺血性疾病的机制及治疗提供新的观点和方法,本文将对相关内容展开详细论述.

关键词：胃肠应激损伤细胞因子基因治疗

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