目的探索黄芪-莪术配伍对乳腺癌的抑制作用及其机制。方法用浸泡法、水煎法提取黄芪、莪术的有效成分,并制备灌胃液。采用裸鼠皮下注射1.8×10^(6)个MDA-MB-231细胞的方法构建人乳腺癌细胞系裸鼠移植瘤模型。待裸鼠成瘤80 mm 3左右...目的探索黄芪-莪术配伍对乳腺癌的抑制作用及其机制。方法用浸泡法、水煎法提取黄芪、莪术的有效成分,并制备灌胃液。采用裸鼠皮下注射1.8×10^(6)个MDA-MB-231细胞的方法构建人乳腺癌细胞系裸鼠移植瘤模型。待裸鼠成瘤80 mm 3左右,开始分为6组:模型组(生理盐水)、黄芪组(黄芪0.4 g/ml)、莪术组(莪术0.4 g/ml)、黄芪莪术2∶1组、黄芪莪术1∶1组、黄芪莪术1∶2组。然后用灌胃针对小鼠进行灌胃给药处理,每日给药一次,连续给药4周。处死后游标卡尺测量肿瘤的大小,用HE染色法检测肿瘤细胞排列情况和病理学特征,用TUNEL检测细胞凋亡的情况,用RT-PCR检测PI3K、Akt1、Akt2、PTEN基因的表达情况,用Western blot检测各组p-Akt、PTEN蛋白的表达水平。结果黄芪莪术2∶1组的乳腺肿瘤明显小于模型组和药物单独作用组(P<0.05),并且肿瘤细胞排列更疏松、坏死更严重,肿瘤细胞凋亡数目最多。RT-PCR和Western blot结果显示黄芪莪术2∶1组PI3K、Akt1、Akt2基因表达水平显著低于模型组和药物单独作用组,PTEN蛋白表达水平显著高于模型组和药物单独作用组(P<0.05)。结论黄芪-莪术配伍对乳腺癌有明显的抑制作用,可能是通过抑制PI3K、Akt1、Akt2基因的表达并促进PTEN基因的表达实现的。展开更多
AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis C virus(HCV) core protein in Hep G2 cells.METHODS: HCV genotype 1b core protein was cloned and expressed in Hep G2 cell...AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis C virus(HCV) core protein in Hep G2 cells.METHODS: HCV genotype 1b core protein was cloned and expressed in Hep G2 cells. The cholesterol content was determined after transfection. The expression of sterol regulatory element binding protein 2(SREBP2) and the rate-limiting enzyme in cholesterol synthesis(HMGCR) was measured by quantitative real-time PCR and immunoblotting after transfection. The effects of core protein on the SREBP2 promoter and 3'-untranslated region were analyzed by luciferase assay. We used different target predictive algorithms, micro RNA(mi RNA) mimics/inhibitors, and site-directed mutation to identify a putative target of a particular mi RNA.RESULTS: HCV core protein expression in Hep G2 cells increased the total intracellular cholesterol level(4.05 ± 0.17 vs 6.47 ± 0.68, P = 0.001), and this increase corresponded to an increase in SREBP2 and HMGCR m RNA levels(P = 0.009 and 0.037, respectively) and protein expression. The molecular mechanism studyrevealed that the HCV core protein increased the expression of SREBP2 by enhancing its promoter activity(P = 0.004). In addition, mi R-185-5p expression was tightly regulated by the HCV core protein(P = 0.041). Moreover, overexpression of mi R-185-5p repressed the SREBP2 m RNA level(P = 0.022) and protein expression. In contrast, inhibition of mi R-185-5p caused upregulation of SREBP2 protein expression. mi R-185-5p was involved in the regulation of SREBP2 expression by HCV core protein. CONCLUSION: HCV core protein disturbs the cholesterol homeostasis in Hep G2 cells via the SREBP2 pathway; mi R-185-5p is involved in the regulation of SREBP2 by the core protein.展开更多
AIM: To investigate the effect of leptin on the angiogenesis of RF/6 A cells(monkey retinal choroidal endothelial cells) in vitro and test the cellular signaling in the mechanism.METHODS: RF/6 A cells were cultured in...AIM: To investigate the effect of leptin on the angiogenesis of RF/6 A cells(monkey retinal choroidal endothelial cells) in vitro and test the cellular signaling in the mechanism.METHODS: RF/6 A cells were cultured in vitro and randomly divided into four groups: normal control, with leptin at 50, 100, 200 ng/m L for cell counting kit-8(CCK8). RF/6 A cell proliferation and migration were examined by Transwell assays, while RF/6 A cell tube formation by Matrigel assay. JAK2, p-JAK2, STAT3, and p-STAT3 protein expression was measured by Western blotting. Cells were then divided into the following treatment groups: control, 100 ng/m L leptin and AG-490(100 ng/m L leptin+10 μmol/L AG-490) for examinations of RF/6 A cellular behaviour again. Analysis of differences was carried out using one-way ANOVA and least significant difference(LSD).RESULTS: RF/6 A cell proliferation, migration and cell tube formation were promoted significantly by leptin in a dose-dependent manner(P<0.05). Western blotting showed that leptin up-regulated p-JAK2 and p-STAT3 expression levels. Treatment with the JAK/STAT pathway inhibitor, AG-490, decreased leptin-induced p-JAK2 and p-STAT3 expression, and inhibited cell proliferation, migration and cell tube formation induced by leptin(P<0.05). CONCLUSION: Leptin can promote RF/6 A cell angiogenesis in vitro via activation of the JAK2/STAT3 signaling pathway.展开更多
The Yanchang Formation Chang 7 oil-bearing layer of the Ordos Basin is important in China for producing shale oil.The present-day in situ stress state is of practical implications for the exploration and development o...The Yanchang Formation Chang 7 oil-bearing layer of the Ordos Basin is important in China for producing shale oil.The present-day in situ stress state is of practical implications for the exploration and development of shale oil;however,few studies are focused on stress distributions within the Chang 7 reservoir.In this study,the present-day in situ stress distribution within the Chang 7 reservoir was predicted using the combined spring model based on well logs and measured stress data.The results indicate that stress magnitudes increase with burial depth within the Chang 7 reservoir.Overall,the horizontal maximum principal stress(SHmax),horizontal minimum principal stress(Shmin) and vertical stress(Sv) follow the relationship of Sv≥SHmax>Shmin,indicating a dominant normal faulting stress regime within the Chang 7 reservoir of Ordos Basin.Laterally,high stress values are mainly distributed in the northwestern parts of the studied region,while low stress values are found in the southeastern parts.Factors influencing stress distributions are also analyzed.Stress magnitudes within the Chang 7 reservoir show a positive linear relationship with burial depth.A larger value of Young's modulus results in higher stress magnitudes,and the differential horizontal stress becomes higher when the rock Young's modulus grows larger.展开更多
The South Tianshan Orogen and adjacent regions of Central Asia are located in the southwestern part of the Central Asian Orogenic Belt.The formation of South Tianshan Orogen was a diachronous,scissors-like process,whi...The South Tianshan Orogen and adjacent regions of Central Asia are located in the southwestern part of the Central Asian Orogenic Belt.The formation of South Tianshan Orogen was a diachronous,scissors-like process,which took place during the Palaeozoic,and its western segment was accepted as a site of the fnal collision between the Tarim Craton and the North Asian continent,which occurred in the late Palaeozoic.However,the post-collisional tectonic evolution of the South Tianshan Orogen and adjacent regions remains debatable.Based on previous studies and recent geochronogical data,we suggest that the fnal collision between the Tarim Craton and the North Asian continent occurred during the late Carboniferous.Therefore,the Permian was a period of intracontinental environment in the southern Tianshan and adjacent regions.We propose that an earlier,small-scale intraplate orogenic stage occurred in late Permian to Triassic time,which was the frst intraplate process in the South Tianshan Orogen and adjacent regions.The later largescale and well-known Neogene to Quaternary intraplate orogeny was induced by the collision between the India subcontinent and the Eurasian plate.The paper presents a new evolutionary model for the South Tianshan Orogen and adjacent regions,which includes seven stages:(I)late Ordovicianeearly Silurian opening of the South Tianshan Ocean;(II)middle Silurianemiddle Devonian subduction of the South Tianshan Ocean beneath an active margin of the North Asian continent;(III)late Devonianelate Carboniferous closure of the South Tianshan Ocean and collision between the Kazakhstan-Yili and Tarim continental blocks;(IV)early Permian post-collisional magmatism and rifting;(V)late PermianeTriassic the frst intraplate orogeny;(VI)JurassicePalaeogene tectonic stagnation and(VII)NeoceneeQuaternary intraplate orogeny.展开更多
基金Supported by Medical Specialty Development Projects of Beijing Municipal Administration of Hospitals,No.ZYLX201402Ministry of Education of The People’s Republic of China,No.20121107110012+1 种基金Beijing Municipal Commission of Education,No.11320016Collaborative Innovation Center of Infectious Diseases and Beijing Key Laboratory of Emerging Infectious Diseases,Beijing,China
文摘AIM: To investigate the molecular mechanism for regulation of cholesterol metabolism by hepatitis C virus(HCV) core protein in Hep G2 cells.METHODS: HCV genotype 1b core protein was cloned and expressed in Hep G2 cells. The cholesterol content was determined after transfection. The expression of sterol regulatory element binding protein 2(SREBP2) and the rate-limiting enzyme in cholesterol synthesis(HMGCR) was measured by quantitative real-time PCR and immunoblotting after transfection. The effects of core protein on the SREBP2 promoter and 3'-untranslated region were analyzed by luciferase assay. We used different target predictive algorithms, micro RNA(mi RNA) mimics/inhibitors, and site-directed mutation to identify a putative target of a particular mi RNA.RESULTS: HCV core protein expression in Hep G2 cells increased the total intracellular cholesterol level(4.05 ± 0.17 vs 6.47 ± 0.68, P = 0.001), and this increase corresponded to an increase in SREBP2 and HMGCR m RNA levels(P = 0.009 and 0.037, respectively) and protein expression. The molecular mechanism studyrevealed that the HCV core protein increased the expression of SREBP2 by enhancing its promoter activity(P = 0.004). In addition, mi R-185-5p expression was tightly regulated by the HCV core protein(P = 0.041). Moreover, overexpression of mi R-185-5p repressed the SREBP2 m RNA level(P = 0.022) and protein expression. In contrast, inhibition of mi R-185-5p caused upregulation of SREBP2 protein expression. mi R-185-5p was involved in the regulation of SREBP2 expression by HCV core protein. CONCLUSION: HCV core protein disturbs the cholesterol homeostasis in Hep G2 cells via the SREBP2 pathway; mi R-185-5p is involved in the regulation of SREBP2 by the core protein.
基金Supported by the Matching Funds of the National Natural Science Foundation of China(No.XYFYPT-2020-01)the Natural Science Foundation of Shaanxi Province(No.2020JM-685+2 种基金No.2021JM-547)the Fundamental Research Funds for the Central Universities(No.1191329116)the Foundation of Xi’an Health Committee(No.2020MS07)。
文摘AIM: To investigate the effect of leptin on the angiogenesis of RF/6 A cells(monkey retinal choroidal endothelial cells) in vitro and test the cellular signaling in the mechanism.METHODS: RF/6 A cells were cultured in vitro and randomly divided into four groups: normal control, with leptin at 50, 100, 200 ng/m L for cell counting kit-8(CCK8). RF/6 A cell proliferation and migration were examined by Transwell assays, while RF/6 A cell tube formation by Matrigel assay. JAK2, p-JAK2, STAT3, and p-STAT3 protein expression was measured by Western blotting. Cells were then divided into the following treatment groups: control, 100 ng/m L leptin and AG-490(100 ng/m L leptin+10 μmol/L AG-490) for examinations of RF/6 A cellular behaviour again. Analysis of differences was carried out using one-way ANOVA and least significant difference(LSD).RESULTS: RF/6 A cell proliferation, migration and cell tube formation were promoted significantly by leptin in a dose-dependent manner(P<0.05). Western blotting showed that leptin up-regulated p-JAK2 and p-STAT3 expression levels. Treatment with the JAK/STAT pathway inhibitor, AG-490, decreased leptin-induced p-JAK2 and p-STAT3 expression, and inhibited cell proliferation, migration and cell tube formation induced by leptin(P<0.05). CONCLUSION: Leptin can promote RF/6 A cell angiogenesis in vitro via activation of the JAK2/STAT3 signaling pathway.
基金financial supports are from the National Natural Science Foundation of China (41702130 and 41971335)China Postdoctoral Science Foundation (2017T100419 and 2019M660269)Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)。
文摘The Yanchang Formation Chang 7 oil-bearing layer of the Ordos Basin is important in China for producing shale oil.The present-day in situ stress state is of practical implications for the exploration and development of shale oil;however,few studies are focused on stress distributions within the Chang 7 reservoir.In this study,the present-day in situ stress distribution within the Chang 7 reservoir was predicted using the combined spring model based on well logs and measured stress data.The results indicate that stress magnitudes increase with burial depth within the Chang 7 reservoir.Overall,the horizontal maximum principal stress(SHmax),horizontal minimum principal stress(Shmin) and vertical stress(Sv) follow the relationship of Sv≥SHmax>Shmin,indicating a dominant normal faulting stress regime within the Chang 7 reservoir of Ordos Basin.Laterally,high stress values are mainly distributed in the northwestern parts of the studied region,while low stress values are found in the southeastern parts.Factors influencing stress distributions are also analyzed.Stress magnitudes within the Chang 7 reservoir show a positive linear relationship with burial depth.A larger value of Young's modulus results in higher stress magnitudes,and the differential horizontal stress becomes higher when the rock Young's modulus grows larger.
基金supported by the National Natural Science Foundation of China (Grant Nos. 40772121, 40314141 and 40172066)China National Project No. 973 (2009CB219302)IGCP Project #592 "Continental construction in Central Asia" supported by UNESCO-IUGS
文摘The South Tianshan Orogen and adjacent regions of Central Asia are located in the southwestern part of the Central Asian Orogenic Belt.The formation of South Tianshan Orogen was a diachronous,scissors-like process,which took place during the Palaeozoic,and its western segment was accepted as a site of the fnal collision between the Tarim Craton and the North Asian continent,which occurred in the late Palaeozoic.However,the post-collisional tectonic evolution of the South Tianshan Orogen and adjacent regions remains debatable.Based on previous studies and recent geochronogical data,we suggest that the fnal collision between the Tarim Craton and the North Asian continent occurred during the late Carboniferous.Therefore,the Permian was a period of intracontinental environment in the southern Tianshan and adjacent regions.We propose that an earlier,small-scale intraplate orogenic stage occurred in late Permian to Triassic time,which was the frst intraplate process in the South Tianshan Orogen and adjacent regions.The later largescale and well-known Neogene to Quaternary intraplate orogeny was induced by the collision between the India subcontinent and the Eurasian plate.The paper presents a new evolutionary model for the South Tianshan Orogen and adjacent regions,which includes seven stages:(I)late Ordovicianeearly Silurian opening of the South Tianshan Ocean;(II)middle Silurianemiddle Devonian subduction of the South Tianshan Ocean beneath an active margin of the North Asian continent;(III)late Devonianelate Carboniferous closure of the South Tianshan Ocean and collision between the Kazakhstan-Yili and Tarim continental blocks;(IV)early Permian post-collisional magmatism and rifting;(V)late PermianeTriassic the frst intraplate orogeny;(VI)JurassicePalaeogene tectonic stagnation and(VII)NeoceneeQuaternary intraplate orogeny.
