AIM: The GFAP was traditionally considered to be a biomarker for neural gila (mainly astrocytes and nonmyelinating Schwann cells). Genetically, a 2.2-kb human GFAP promoter has been successfully used to target astr...AIM: The GFAP was traditionally considered to be a biomarker for neural gila (mainly astrocytes and nonmyelinating Schwann cells). Genetically, a 2.2-kb human GFAP promoter has been successfully used to target astrocytes in vitro and in vivo. More recently, GFAP was also established as one of the several makers for identifying hepatic stellate cells (HSC). In this project, possible application of the same 2.2-kb human GFAP promoter for targeting HSC was investigated. METHODS: The GFAP-lacZ transgene was transfected into various cell lines (HSC, hepatocyte, and other nonHSC cell types). The transgene expression specificity was determined by X-gal staining of the β-galactosidase activity. And the responsiveness of the transgene was tested with a typical pro-fibrotic cytokine TGF-β1. The expression of endogenous GFAP gene was assessed by real-time RT-PCR, providing a reference for the transgene expression. RESULTS: The results demonstrated for the first time that the 2.2 kb hGFAP promoter was not only capable of directing HSC-specific expression, but also responding to a known pro-fibrogenic cytokine TGF-β1 by upregulation in a doseand time-dependent manner, similar to the endogenous GFAP. CONCLUSION: In conclusion, these findings suggested novel utilities for using the GFAP promoter to specifically manipulate HSC for therapeutic purpose.展开更多
In animal societies, some stressful events can lead to higher levels of physiological stress. Such stressors, like social rank, also predict an increased vulnerability to an array of diseases. However, the physiologic...In animal societies, some stressful events can lead to higher levels of physiological stress. Such stressors, like social rank, also predict an increased vulnerability to an array of diseases. However, the physiological relationship between social rank and stress varies between different species, as well as within groups of a single species. For example, dominant individuals are more socially stressed at times, while at other times it is the subordinate ones who experience this stress. Together, these variations make it difficult to assess disease vulnerability as connected to social interactions. In order to learn more about how physiological rank relationships vary between groups of a single species, cortisol measurements from hair samples were used to evaluate the effects of dominance rank on long-term stress levels in despotic and less stringent female rhesus macaque hierarchal groups. In despotic groups, cortisol levels were found not to be correlated with social rank, but a negative correlation was found between social rank and cortisol levels in less stringent hierarchies. Low ranking monkeys in less stringent groups secreted elevated levels of cortisol compared to higher ranking animals. These data suggest that variations in the strictness of the dominance hierarchy are determining factors in rank related stress physiology. The further consideration of nonhuman primate social system diversity and the linear degree of their hierarchies may allow for the development of valid rank-related stress models that will help increase our understanding and guide the development of new therapeutics for diseases related to human socioeconomic status.展开更多
Human activities significantly alter ecosystems and their services; however, quantifying the impact of human activities on ecosystems has been a great challenge in ecosystem management. We used the Universal Soil Loss...Human activities significantly alter ecosystems and their services; however, quantifying the impact of human activities on ecosystems has been a great challenge in ecosystem management. We used the Universal Soil Loss Equation and county-level socioeconomic data to assess the changes in the ecosystem service of soil conservation between 2000 and 2010, and to analyze its spatial characteristics and driving factors in the southwestern China. The results showed that cropland in the southwestern China decreased by 3.74%, while urban land, forest, and grassland areas increased by 46.78%, 0.86%, and 1.12%, respectively. The soil conservation increased by 1.88 × 10^(11) kg, with deterioration only in some local areas. The improved and the degraded areas accounted for 6.41% and 2.44% of the total land area, respectively. Implementation of the Sloping Land Conversion Program and urbanization explained 57.80% and 23.90% of the variation in the soil conservation change, respectively, and were found to be the main factors enhancing soil conservation. The 2008 Wenchuan earthquake was one of the factors that led to the degradation of soil conservation. Furthermore, industrial adjustment, by increasing shares of Industry and Service and reducing those of Agriculture, has also promoted soil conservation. Our results quantitatively showed and emphasized the contributions to soil conservation improvement made by implementing ecological restoration programs and promoting urbanization. Consequently, these results provide basic information to improve our understanding of the effects of ecological restoration programs, and help guide future sustainable urban development and regional industrial restructuring.展开更多
Objectives.To study the expression of TNF α mRNA and the effect of somatostatin on the expression of TNF α mRNA in multiorgans of rats with acute hemorrhagic necrotic pancreatitis(AHNP). Methods.AHNP in the rat was ...Objectives.To study the expression of TNF α mRNA and the effect of somatostatin on the expression of TNF α mRNA in multiorgans of rats with acute hemorrhagic necrotic pancreatitis(AHNP). Methods.AHNP in the rat was induced by retrograde injection of 5% sodium taurocholate into the bile-pancreatic duct. Somatostatin octapeptide (SS-OP) (2μg/kg)was injected into the femoral vein imme- diately in rats of the treatment group after inductive AHNP. Rats of the sham operative group received in- jection of saline. Sixty animals of the AHNP and sham operative groups at the designated time(0. 2h, 0. 5 h, 2h, 4h, 8h, after the operation,six animals at each time point)and tweleve animals of treatment group at 4h after the operation were sacrificed for samples of pancreas, liver and lung. The expressions of TNF α mRNA within the pancreas, liver and lung were established by RT-PCR. Results. TNF α mRNA became detectable in the pancreas as early as 0. 2h after inductive AHNP, while it was undetectable in other organs until 0. 5h. Expression of TNF α mRNA in each tissue increased continuously and reached a peak at 4h,demonstrating a significant difference compared with that at 0. 5h and 8h. Expressions of TNF α mRNA from pancreas, liver and lung were decreased 50-80% in the treat- ment group, the pancreatic necrosis was also attenuated dramatically. Conclusion. TNF α mRNA was detectable in pancreas,liver and lung tissues at the early stage of AH- NP.SS-OP can significantly inhibit the expression of TNF α mRNA and attenuate the pancreatic necrosis. We feel that this may be an important mechanism of SS-OP in the treatment of AHNP.展开更多
White adipocytes play important roles in many physiological processes, including energy storage, endocrine signaling, and inflammatory responses. Understanding the molecular mechanisms of adipocyte formation (adipoge...White adipocytes play important roles in many physiological processes, including energy storage, endocrine signaling, and inflammatory responses. Understanding the molecular mechanisms of adipocyte formation (adipogenesis) provides insights into therapeutic approaches against obesity and its related diseases. Many transcriptional Factors and epigenetic enzymes are known to regulate adipogenesis; however, whether histone variants play a role in this process is unknown. Here we found that macroH2A1.1 (mH2A1.1), a variant of histone H2A, was upregulated during adipocyte differentiation in 3T3-L1 ceils and in the white adipose tissue of obese mice. Ablation of mH2A1.1 activated Wnt/β-catenin signaling pathway, while overexpression of mH2A1.1 showed opposite effects. We farther found that mH2A1.1 regulated Wnt/β-catenin signaling pathway by cooperating with EZH2, a histone H3K27 methyltrans- ferase, thus led to accumulation of H3K27me2 and H3K27me3 on the promoters of Wnt genes. Mutations in the macro-domain, mH2A1.1G224E, and mH2A1.1G314E, not only impaired adipogenesis, but also impaired the binding ability of mH2A1.1 to EZH2 and the enrichments of H3K27me2 and H3K27me3 on the promoters of Wnt genes. Together, our study reveals a novel regulatory role of mH2A1.1 in adipogenesis and obesity, which provides new insights in white fat development.展开更多
基金Supported by the Biomedical Research Councilthe Institute of Bioengineering and Nanotechnology,the Republic of Singapore
文摘AIM: The GFAP was traditionally considered to be a biomarker for neural gila (mainly astrocytes and nonmyelinating Schwann cells). Genetically, a 2.2-kb human GFAP promoter has been successfully used to target astrocytes in vitro and in vivo. More recently, GFAP was also established as one of the several makers for identifying hepatic stellate cells (HSC). In this project, possible application of the same 2.2-kb human GFAP promoter for targeting HSC was investigated. METHODS: The GFAP-lacZ transgene was transfected into various cell lines (HSC, hepatocyte, and other nonHSC cell types). The transgene expression specificity was determined by X-gal staining of the β-galactosidase activity. And the responsiveness of the transgene was tested with a typical pro-fibrotic cytokine TGF-β1. The expression of endogenous GFAP gene was assessed by real-time RT-PCR, providing a reference for the transgene expression. RESULTS: The results demonstrated for the first time that the 2.2 kb hGFAP promoter was not only capable of directing HSC-specific expression, but also responding to a known pro-fibrogenic cytokine TGF-β1 by upregulation in a doseand time-dependent manner, similar to the endogenous GFAP. CONCLUSION: In conclusion, these findings suggested novel utilities for using the GFAP promoter to specifically manipulate HSC for therapeutic purpose.
基金funded by the National Science Foundation of China (NSFC 31271167, and 31070963)the 973 program (2007CB947703 and 2011CB707800)the Key Program of the Chinese Academy of Sciences, China (KSCX2-EW-R-13)
文摘In animal societies, some stressful events can lead to higher levels of physiological stress. Such stressors, like social rank, also predict an increased vulnerability to an array of diseases. However, the physiological relationship between social rank and stress varies between different species, as well as within groups of a single species. For example, dominant individuals are more socially stressed at times, while at other times it is the subordinate ones who experience this stress. Together, these variations make it difficult to assess disease vulnerability as connected to social interactions. In order to learn more about how physiological rank relationships vary between groups of a single species, cortisol measurements from hair samples were used to evaluate the effects of dominance rank on long-term stress levels in despotic and less stringent female rhesus macaque hierarchal groups. In despotic groups, cortisol levels were found not to be correlated with social rank, but a negative correlation was found between social rank and cortisol levels in less stringent hierarchies. Low ranking monkeys in less stringent groups secreted elevated levels of cortisol compared to higher ranking animals. These data suggest that variations in the strictness of the dominance hierarchy are determining factors in rank related stress physiology. The further consideration of nonhuman primate social system diversity and the linear degree of their hierarchies may allow for the development of valid rank-related stress models that will help increase our understanding and guide the development of new therapeutics for diseases related to human socioeconomic status.
基金Under the auspices of National Key Technology Research and Development Program of China(No.2011BAC09B08)Special Issue of National Remote Sensing Survey and Assessment of Eco-Environment Change between 2000 and 2010(No.STSN-04-01)
文摘Human activities significantly alter ecosystems and their services; however, quantifying the impact of human activities on ecosystems has been a great challenge in ecosystem management. We used the Universal Soil Loss Equation and county-level socioeconomic data to assess the changes in the ecosystem service of soil conservation between 2000 and 2010, and to analyze its spatial characteristics and driving factors in the southwestern China. The results showed that cropland in the southwestern China decreased by 3.74%, while urban land, forest, and grassland areas increased by 46.78%, 0.86%, and 1.12%, respectively. The soil conservation increased by 1.88 × 10^(11) kg, with deterioration only in some local areas. The improved and the degraded areas accounted for 6.41% and 2.44% of the total land area, respectively. Implementation of the Sloping Land Conversion Program and urbanization explained 57.80% and 23.90% of the variation in the soil conservation change, respectively, and were found to be the main factors enhancing soil conservation. The 2008 Wenchuan earthquake was one of the factors that led to the degradation of soil conservation. Furthermore, industrial adjustment, by increasing shares of Industry and Service and reducing those of Agriculture, has also promoted soil conservation. Our results quantitatively showed and emphasized the contributions to soil conservation improvement made by implementing ecological restoration programs and promoting urbanization. Consequently, these results provide basic information to improve our understanding of the effects of ecological restoration programs, and help guide future sustainable urban development and regional industrial restructuring.
文摘Objectives.To study the expression of TNF α mRNA and the effect of somatostatin on the expression of TNF α mRNA in multiorgans of rats with acute hemorrhagic necrotic pancreatitis(AHNP). Methods.AHNP in the rat was induced by retrograde injection of 5% sodium taurocholate into the bile-pancreatic duct. Somatostatin octapeptide (SS-OP) (2μg/kg)was injected into the femoral vein imme- diately in rats of the treatment group after inductive AHNP. Rats of the sham operative group received in- jection of saline. Sixty animals of the AHNP and sham operative groups at the designated time(0. 2h, 0. 5 h, 2h, 4h, 8h, after the operation,six animals at each time point)and tweleve animals of treatment group at 4h after the operation were sacrificed for samples of pancreas, liver and lung. The expressions of TNF α mRNA within the pancreas, liver and lung were established by RT-PCR. Results. TNF α mRNA became detectable in the pancreas as early as 0. 2h after inductive AHNP, while it was undetectable in other organs until 0. 5h. Expression of TNF α mRNA in each tissue increased continuously and reached a peak at 4h,demonstrating a significant difference compared with that at 0. 5h and 8h. Expressions of TNF α mRNA from pancreas, liver and lung were decreased 50-80% in the treat- ment group, the pancreatic necrosis was also attenuated dramatically. Conclusion. TNF α mRNA was detectable in pancreas,liver and lung tissues at the early stage of AH- NP.SS-OP can significantly inhibit the expression of TNF α mRNA and attenuate the pancreatic necrosis. We feel that this may be an important mechanism of SS-OP in the treatment of AHNP.
基金This work was supported by the National Natural Science Foundation of China (31471208, 31671195, and 31271370), the Natural Science Foundation of Hubei Province (2016CFA012), the Fundamental Research Funds for the Central Universities, Integrated Innovative Team for Major Human Diseases of Tongji Medical College, and the Front Youth Program, Huazhong University of Science and Technology.
文摘White adipocytes play important roles in many physiological processes, including energy storage, endocrine signaling, and inflammatory responses. Understanding the molecular mechanisms of adipocyte formation (adipogenesis) provides insights into therapeutic approaches against obesity and its related diseases. Many transcriptional Factors and epigenetic enzymes are known to regulate adipogenesis; however, whether histone variants play a role in this process is unknown. Here we found that macroH2A1.1 (mH2A1.1), a variant of histone H2A, was upregulated during adipocyte differentiation in 3T3-L1 ceils and in the white adipose tissue of obese mice. Ablation of mH2A1.1 activated Wnt/β-catenin signaling pathway, while overexpression of mH2A1.1 showed opposite effects. We farther found that mH2A1.1 regulated Wnt/β-catenin signaling pathway by cooperating with EZH2, a histone H3K27 methyltrans- ferase, thus led to accumulation of H3K27me2 and H3K27me3 on the promoters of Wnt genes. Mutations in the macro-domain, mH2A1.1G224E, and mH2A1.1G314E, not only impaired adipogenesis, but also impaired the binding ability of mH2A1.1 to EZH2 and the enrichments of H3K27me2 and H3K27me3 on the promoters of Wnt genes. Together, our study reveals a novel regulatory role of mH2A1.1 in adipogenesis and obesity, which provides new insights in white fat development.