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ages对糖尿病大鼠骨质疏松的作用机制

中国老年学杂志 2011年第10期31卷 1808-1811页

作者：薛昊罡冷冰马恩元蒋维海崔双单广宇苗婷婷北华大学第一临床医院骨外科吉林吉林132011

目的探讨ages对骨质疏松症的作用机制。方法取SD大鼠腹腔内注射STZ诱导建立糖尿病骨质疏松动物模型,观察ages血清学、骨密度、骨组织中BMP-2基因、骨密度及骨代谢的变化。结果糖尿病大鼠BMD、生物力学指标、骨组织形态计量学反映成骨活... 详细信息

目的探讨ages对骨质疏松症的作用机制。方法取SD大鼠腹腔内注射STZ诱导建立糖尿病骨质疏松动物模型,观察ages血清学、骨密度、骨组织中BMP-2基因、骨密度及骨代谢的变化。结果糖尿病大鼠BMD、生物力学指标、骨组织形态计量学反映成骨活性的参数均降低,ages水平较正常对照组明显升高(Pages与BMP-2 mRNA和蛋白表达呈显著负相关,相关系数分别为-0.715(Pages含量显著增高,与BMP-2 mRNA和蛋白表达呈显著负相关,ages和BMP-2均参与了糖尿病骨质疏松的发生发展。

关键词： ages BMP-2 糖尿病骨质疏松

Georgia and Europe in the Early Middle ages

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Journal of Literature and Art Studies 2018年第12期8卷 1702-1712页

作者： Bejan Javakhia Ilia State Univeristy TbilisiGeorgia

The article deals with relations of Georgia to Europe in the late antique period and the early Middle ages.The analyses rests on the Byzantium and the Western European,as well as on Georgian written sources:historical chronicles,hagiographic texts and other information,reflecting political relations of the Iberia and Lazika—those-days kingdoms,located on the territory of Georgia—to the Western European and Byzantine space.The offered analysis will concentrate on the shared characteristics of European space in the Middle ages and will compare them to the general tendencies of development of Georgia in the same period.This enables to draw conclusion that Georgia was the part of the unified Christian space of the early Middle ages.

关键词： Georgia Europe Middle ages late antique

基于伏毒理论研究糖尿病大鼠皮肤溃疡难愈机制

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辽宁中医杂志 2023年第8期50卷 225-229,I0006页

作者：王双勋李大勇辽宁中医药大学辽宁沈阳110847 辽宁中医药大学附属医院辽宁沈阳110032

目的观察正常大鼠和糖尿病大鼠皮肤溃疡愈合过程中肉芽组织晚期糖基化终末产物(ages)、晚期糖基化终末产物受体(RAGE),Kelch样环氧氯丙烷相关蛋白-1(Keap1)/核因子E2相关因子(Nrf2)通路和Wnt/β-连环蛋白(β-catenin)通路的变化,以研究... 详细信息

目的观察正常大鼠和糖尿病大鼠皮肤溃疡愈合过程中肉芽组织晚期糖基化终末产物(ages)、晚期糖基化终末产物受体(RAGE),Kelch样环氧氯丙烷相关蛋白-1(Keap1)/核因子E2相关因子(Nrf2)通路和Wnt/β-连环蛋白(β-catenin)通路的变化,以研究糖尿病皮肤溃疡难愈的机制。方法Wistar雄性大鼠采用链脲佐菌素腹腔注射结合喂食高脂高糖饲料方法造糖尿病模型。28 d后,正常对照组和糖尿病组造背部皮肤溃疡模型。分别在第7、14天取溃疡肉芽组织。采用苏木素-伊红(HE)染色法检测肉芽组织病理变化;酶联免疫吸附测定(ELISA)法检测肉芽组织ages、RAGE、Wnt1、β-catenin、糖原合成酶激-3β(GSK-3β)蛋白含量;蛋白质印迹法(Western blot)法检测肉芽组织Keap1、Nrf2蛋白表达;逆转录-聚合酶链反应(RT-PCR)法检测肉芽组织RAGE、Keap1、Nrf2、Wnt1、β-catenin、GSK-3βmRNA表达水平。结果相比于正常对照组,糖尿病组大鼠肉芽组织中炎症细胞较多,成纤维细胞、胶原纤维和毛细血管数量较少。第7天的Wnt1、β-catenin蛋白含量均数上有差异,但无统计学意义(P>0.05),第14天的Wnt1、β-catenin蛋白含量低(Pages、RAGE、Keap1、GSK-3β蛋白和mRNA含量较高(Pages在组织中的沉积,可能抑制了Keap1/Nrf2通路和Wnt/β-catenin通路,这可能是导致了糖尿病大鼠皮肤溃疡难愈合的原因之一。

关键词：糖尿病皮肤溃疡 ages RAGE Keap1/Nrf2通路 Wnt/β-catenin通路

ages诱导软骨细胞凋亡和影响细胞外基质变化的研究

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南京医科大学学报（自然科学版） 2014年第12期34卷 1649-1653页

作者：席勇王树金李云龙夏炎任永信南京医科大学第一附属医院骨科江苏南京210029 丹阳市人民医院骨科江苏丹阳212300

目的 :明确晚期糖基化终末产物(advanced glycation end products,ages)诱导小鼠关节软骨细胞凋亡情况和影响细胞外基质变化。方法:体外分离培养小鼠软骨关节细胞,给予不同浓度ages共培养后,分别于24 h和48 h时间点观察细胞凋亡情况;通... 详细信息

目的 :明确晚期糖基化终末产物(advanced glycation end products,ages)诱导小鼠关节软骨细胞凋亡情况和影响细胞外基质变化。方法:体外分离培养小鼠软骨关节细胞,给予不同浓度ages共培养后,分别于24 h和48 h时间点观察细胞凋亡情况;通过Western blot方法检测Ⅰ型胶原、MMP-3、MMP-9以及p53蛋白的表达情况。结果:不同浓度ages处理软骨细胞24 h后,与对照组比较,细胞凋亡率出现升高(Pages组细胞凋亡率明显升高(Pages浓度和培养时间增加,软骨细胞的凋亡率也增加。200 mg/L的浓度ages处理软骨细胞48 h后,Ⅰ型胶原蛋白的表达显著下降(Pages处理软骨细胞48 h后,p53、MMP-3、MMP-9的表达显著高于对照组和BSA组(Pages能诱导小鼠软骨细胞凋亡,并刺激软骨细胞p53、MMP-3、MMP-9表达增多,降低Ⅰ型胶原蛋白表达。

关键词：骨性关节炎 ages 细胞凋亡细胞外基质

Fluorescent advanced glycation end-products (ages) detected by spectro-photofluorimetry, as a screening tool to detect diabetic microvascular complications

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Journal of Diabetes Mellitus 2012年第2期2卷 221-226页

作者： Maria Pia de la Maza Fernando Garrido Nadia Escalante Laura Leiva Gladys Barrera Sylvia Schnitzler Mario Zanolli Juan Verdaguer Sandra Hirsch Natallia Jara Daniel Bunout Institute of Nutrition & Food Technology University of Chile Santiago Chile

BACKGROUND: Advanced glycation end-products (ages) are one of the mechanisms related to diabetic vascular complications. However, since ages are multiple and heterogeneous moieties, there is no universally accepted method to measure them for clinical purposes. The aim of this work was to study the utility of a simple fluorimetric assay as predictor of complications. METHODS: Blood samples from 102 type 2 diabetic patients were obtained to assess glucose, glycosylated haemoglobin, creatinine, lipoproteins and C Reactive Protein (CRP), fluorescent ages by spectrophotofluorimetry and non-fluorescent ages by measurement of N(ε)-carboxymethyl-Lysine (CML) using an ELISA kit in a subsample of 82 patients. Urinary fluorescent ages, albumin and creatinine were also measured in a morning urine sample. Microvascular complications were studied by ophthalmologic examination, albuminuria and peripheral nerve conduction velocity. RESULTS: Patients without microvascular complications had significantly lower levels of both serum and urinary ages. CML was associated with retinopathy. Multiple regression analysis confirmed that ages, length of diabetes and glycosylated haemoglobin were all variables associated with diabetic complications, in this sample. CONCLUSIONS: A simple fluorimetric assay to measure low molecular weight fluorescent ages, and CML could be employed as screening tools to predict diabetic complications, at a primary care setting. ages should probably be considered as another therapeutic target in diabetes management.

关键词： Advanced Glycation End-Products ages Microangiopathy Microvascular Complications

Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies

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World Journal of Hepatology 2014年第12期6卷 880-893页

作者： Masayoshi Takeuchi Jun-ichi Takino Akiko Sakasai-Sakai Takanobu Takata Tadashi Ueda Mikihiro Tsutsumi Hideyuki Hyogo Sho-ichi Yamagishi Department of Advanced Medicine Medical Research Institute Kanazawa Medical University Uchinadamachi Ishikawa 920-0293 Japan Laboratory of Biochemistry Faculty of Pharmaceutical Sciences Hiroshima International University Kure Hiroshima 737-0112 Japan Department of Hepatology Kanazawa Medical University Uchinada-machi Ishikawa 920-0293 Japan Department of Gastroenterology and Metabolism Hiroshima University Hospital Hiroshima 734-8551 Japan Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications Kurume University School of Medicine Kurume Fukuoka 830-0011 Japan

Non-alcoholic fatty liver disease(NAFLD)is a major cause of liver disease around the world.It includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis(NASH)and can lead to fibrosis,cirrhosis,liver failure,and/or hepatocellular carcinoma.NAFLD is also associated with other medical conditions such as obesity,diabetes mellitus(DM),metabolic syn-drome,hypertension,insulin resistance,hyperlipidemia,and cardiovascular disease(CVD).In diabetes,chronic hyperglycemia contributes to the development of both macro-and microvascular conditions through a variety of metabolic pathways.Thus,it can cause a variety of metabolic and hemodynamic conditions,including upregulated advanced glycation end-products(ages)synthesis.In our previous study,the most abundant type of toxic ages(TAGE);i.e.,glyceraldehyde-derived ages,were found to make a significant contribution to the pathogenesis of DM-induced angiopathy.Furthermore,accumulating evidence suggests that the binding of TAGE with their receptor(RAGE)induces oxidative damage,promotes inflammation,and causes changes in intracellular signaling and the expression levels of certain genes in various cell populations including hepatocytes and hepatic stellate cells.All of these effects could facilitate the pathogenesis of hypertension,cancer,diabetic vascular complications,CVD,dementia,and NASH.Thus,inhibiting TAGE synthesis,preventing TAGE from binding to RAGE,and downregulating RAGE expression and/or the expression of associated effector molecules all have potential as therapeutic strategies against NASH.Here,we examine the contributions of RAGE and TAGE to various conditions and novel treatments that target them in order to prevent the development and/or progression of NASH.

关键词： alcoholic NASH glycation ages fructose pathogenesis inhibiting stellate microvascular obesity

The Issue of Genealogy of Armenians, Georgians and Other Caucasian Nations in the Historiography of the Middle ages

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Journal of Literature and Art Studies 2017年第2期7卷 207-225页

作者： Manana Sanadze The University of Georgia GeorgiaTbilisi

The paper shows that the story about the origin of Armenians, Georgians and other Caucasians from a common ancestor, namely, from Targamos (Togormah)—The Life of the Fore-Patriarchs and Ancestors of the Georgian Kings, which is represented in the introductory part of The Georgian Chronicles and is dated back to the end of the11th, is a compiled work that mainly contains, on the one hand, an old Georgian genealogical-geographical story about Tarshish’s son Kartlos (Iber) and his six brothers ( Egros, Movakan, Heros, Bardos, Lekan and Caucas)created at the end of the 6th c.-first half of the 8th c. based on Byzantine works, and on the other hand, a genealogical story created in old Armenian historiography about Targamos and his son Hayk that went through certain steps of development as well. In the process of synthesizing, Togormah (Targamos) and his son Hayk (Haos)were inserted between Tarsish and his son Kartlos (Iber), which violated the Biblical scheme as well as the structure of the sentence in which the insertion was made. The goal of developing the synthesized scheme was to bring evidence of the common origin of Georgians and Armenians, as long as quite a large number of Armenians,because of the incorporation of a large part of Armenian territories within Georgian borders, became citizens of Georgia. At the same time, the story also offers a justification in the eyes of the Muslim world for the claims of Georgia for Armenian territories. According to the newly-created synthesized scheme, Georgia was “the successor brother” of Armenia(Haos//Hayk) and considering the absence of Armenian states, i.e., “the elder brother”,Georgia was the only legal heir of Armenian territories.

关键词： Georgians Armenians Caucasians Middle ages genealogy

New Constraints from Pb-Evaporation Zircon ages of the Méiganga Amphibole-Biotite Gneiss, Central Cameroon, on Proterozoic Crustal Evolution

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International Journal of Geosciences 2011年第2期2卷 138-147页

作者： Ganwa Alembert Alexandre Siebel Wolfgang Shang Kongnyuy Cosmas Naimou Seguem Ekodeck Georges Emmanuel 不详

The amphibole biotite gneiss (ABGn) in the Méiganga area forms part of a meta volcano-sedimentary sequence of the Adamawa Yade domain (AYD), Central African Fold Belt (CAFB). This sequence shows affinity with immature sediments (greywackes, arkoses) with intercalation of mafic lavas or tuffs. New 207Pb/206Pb zircon evaporation ages for two ABGn samples range from 1887 - 2339 Ma and from 675 - 889 Ma, respectively. These ages and evidence from internal zircon structures indicate that igneous rocks of Archean to Paleoproterozoic and of early Neoproterozoic age contributed to the detritus of the sedimentary sequence. The deposition of detritus took place prior to 614 - 619 Ma which represent the syntectonic emplacement of the Méiganga metadiorite. Leucogranites north to the Méiganga area were generated by melting of crust identical to that which provided the source of the ABGn. The metasedimentary sequence investigated in this study is similar to that of the southern part of the AYD and in the Borborema Province, NE Brazil. The tectonic and geochronologic characteristics of the AYD in the Méiganga area support the idea that during the Proterozoic, Central Africa and NE Brazil were part of the same continental landmass.

关键词： Metasediment 207Pb/206Pb ages Crustal Evolution Adamawa Yade Domain Central African Fold Belt

Effects of Root Extracts from <i>Panax ginseng</i>C. A. Meyer (Araliaceae) of Different ages on K562 Cells

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American Journal of Plant Sciences 2013年第6期4卷 1291-1296页

作者： Xunan Lyu Yizhen Zhang Qing Mu Zhou Cheng Jiakuan Chen Wenju Zhang Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering Institute of Biodiversity Science School of Life Sciences Fudan University Shanghai China Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering Institute of Biodiversity Science School of Life Sciences Fudan University Shanghai China School of Life Science and Technology Tongji University Shanghai China. School of Pharmacy Fudan University Shanghai China

It is well accepted in China that elder ginsengs have more bioactivity and value than younger ones. However, there is little research about the comparison of beneficial effects of ginsengs with different ages. In this study, ginseng root extracts (GRE) were extracted from ginsengs of 5, 8, 12, 14, and 16 years old, respectively, using 55% ethanol and their effects on human leukemic K562 cells within 48 hours were tested by using Cell Counting Kit-8. The results show that there are significant increases in the cell viability of all the GRE groups compared with Control group within 32 hours. Furthermore, the growth curves of GRE groups were obviously distinct from each other. The cell viability of 5-year-old and 8-year-old GRE groups kept a rapid increase while that of 16-year-old GRE group showed a strong fluctuation within 28 hours. Our results demonstrate that root extracts from ginsengs of different ages contain different bioactivity constituents and have different effects on cell.

关键词： Panax ginseng Root Extracts ages K562 Cell Line