Aim： To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods： Forty-eight male Sprague-Dawley rats were randomly divided into four groups： group A, normal rats...Aim： To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods： Forty-eight male Sprague-Dawley rats were randomly divided into four groups： group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone （T） undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T （FT） and dihydrotestosterone （DHT） were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score （VESS） was computed. Results： Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups （P 〈 0.01）; DHT concentrations of group D rats were significantly decreased （P 〈 0.01 ） when compared with those of groups A and C. Rats in groups B and D rats （with low androgen levels） had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion： These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.展开更多
To investigate the effects of hypoxic exercise training on microRNA （miRNA） expression and the role of miRNA expression in regulating lipid metabolism, 20 dietary-induced obese SD rats were divided into a normoxic s...To investigate the effects of hypoxic exercise training on microRNA （miRNA） expression and the role of miRNA expression in regulating lipid metabolism, 20 dietary-induced obese SD rats were divided into a normoxic sedentary group （N, n=10） and a hypoxic exercise training group （H, n=10）. After four weeks, measurements were taken of body weight, body length, fat mass, serum lipid concentration, miRNAs differentially expressed in rat liver, and gene and protein expression levels of perexisome proliferator activated receptor a （PPARα）, fatty acid synthetase （FAS）, and carnitine palmitoyl transferase 1A （CPTIA） in rat liver. Body weight, Lee＇s index, fat mass, fat/weight ratio, and serum levels of total cholesterol （TC） and high density lipoprotein cholesterol （HDL-C） were all significantly lower in the H group than in the N group （P〈0.01）. Six miRNAs expressed significantly differently in the liver （P〈0.05）. Specifically, expression levels of miR-378b were significantly lower in the H group than in the N group （P〈0.05）. Compared with the normoxic sedentary group, hypoxic exercise training resulted in a lower ratio of FAS mRNA to CPTIA mRNA （P〈0.05）, as well as lower CPT1A protein levels （P〈0.01）, while a higher ratio of FAS to CPT1A protein levels （P〈0.01） was observed. In conclusion, hypoxic training may elevate the resistance of high fat diet induced obesity in rats by reducing the expression of miR-378b, and decrease the fatty acid mitochondrial oxidation in obese rat livers by decreasing the protein expression of CPTIA and increasing the protein expression ratio of FAS/CPTIA.展开更多
Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and n...Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.展开更多
Background:Non-communicable chronic diseases have become the leading causes of disease burden worldwide.The trends and burden of“metabolic associated fatty liver disease”(MAFLD)are unknown.We aimed to investigate th...Background:Non-communicable chronic diseases have become the leading causes of disease burden worldwide.The trends and burden of“metabolic associated fatty liver disease”(MAFLD)are unknown.We aimed to investigate the cardiovascular and renal burdens in adults with MAFLD and non-alcoholic fatty liver disease(NAFLD).Methods:Nationally representative data were analyzed including data from 19,617 non-pregnant adults aged≥20years from the cross-sectional US National Health and Nutrition Examination Survey periods,1999 to 2002,2003 to 2006,2007 to 2010,and 2011 to 2016.MAFLD was defined by the presence of hepatic steatosis plus general overweight/obesity,type 2 diabetes mellitus,or evidence of metabolic dysregulation.Results:The prevalence of MAFLD increased from 28.4%(95% confidence interval 26.3–30.6)in 1999 to 2002 to 35.8%(33.8–37.9)in 2011 to 2016.In 2011 to 2016,among adults with MAFLD,49.0%(45.8–52.2)had hypertension,57.8%(55.2–60.4)had dyslipidemia,26.4%(23.9–28.9)had diabetes mellitus,88.7%(87.0–80.1)had central obesity,and 18.5%(16.3–20.8)were current smokers.The 10-year cardiovascular risk ranged from 10.5%to 13.1%;19.7%(17.6–21.9)had chronic kidney diseases(CKDs).Throughthe fourperiods,adults withMAFLD showedanincrease in obesity;increase intreatment to lower bloodpressure(BP),lipids,and hemoglobin A1c;and increase in goal achievements for BP and lipids but not in goal achievement for glycemic control in diabetes mellitus.Patients showed a decreasing 10-year cardiovascular risk over time but no change in the prevalence of CKDs,myocardial infarction,or stroke.Generally,although participants with NAFLD and those with MAFLD had a comparable prevalence of cardiovascular disease and CKD,the prevalence of MAFLD was significantly higher than that of NAFLD.Conclusions:From 1999 to 2016,cardiovascular and renal risks and diseases have become highly prevalent in adults with MAFLD.The absolute cardiorenal burden may be greater for MAFLD than for NAFLD.These data call for early identification and 展开更多
Lignin is a major component of plant cell walls and is essential for plant growth and development. Lignin biosynthesis is controlled by a hierarchical regulatory network involving multiple transcription factors. In th...Lignin is a major component of plant cell walls and is essential for plant growth and development. Lignin biosynthesis is controlled by a hierarchical regulatory network involving multiple transcription factors. In this study, we showed that the gene encoding an APETALA 2/ethylene-responsive element binding factor(AP2/ERF) transcription factor, PagERF81,from poplar 84 K(Populus alba × P. glandulosa) is highly expressed in expanding secondary xylem cells. Two independent homozygous Pagerf81 mutant lines created by gene editing, produced significantly more but smaller vessel cells and longer fiber cells with more lignin in cell walls, while PagERF81 overexpression lines had less lignin,compared to non-transgenic controls. Transcriptome and reverse transcription quantitative PCR data revealed that multiple lignin biosynthesis genes including Cinnamoyl CoA reductase 1(PagCCR1),Cinnamyl alcohol dehydrogenase 6(PagCAD6), and 4-Coumarate-CoA ligase-like 9(Pag4CLL9) were upregulated in Pagerf81 mutants, but down-regulated in PagERF81 overexpression lines. In addition, a transient transactivation assay revealed that PagERF81 repressed the transcription of these three genes.Furthermore, yeast one hybrid and electrophoretic mobility shift assays showed that PagERF81 directly bound to a GCC sequence in the PagCCR1 promoter. No known vessel or fiber cell differentiation related genes were differentially expressed, so the smaller vessel cells and longer fiber cells observed in the Pagerf81 lines might be caused by abnormal lignin deposition in the secondary cell walls. This study provides insight into the regulation of lignin biosynthesis, and a molecular tool to engineer wood with high lignin content, which would contribute to the lignin-related chemical industry and carbon sequestration.展开更多
Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T...Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)patients.Methods A total of 4670 T2D patients from seven communities in Shanghai,China were enrolled.The anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were measured.Results The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased.Next,the population was divided into two groups:abdominal obesity and non-abdominal obesity groups.After adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity group.There was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity group.In the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p levels.In the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity.The 25(OH)D influenced C-p in part by influencing glucagon.The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.展开更多
Objective: To explore the molecular-level mechanism on the hematopoiesis effect of Angelicae sinensis Radix(ASR) with systems-based interactome analysis. Methods: This systems-based interactome analysis was designed t...Objective: To explore the molecular-level mechanism on the hematopoiesis effect of Angelicae sinensis Radix(ASR) with systems-based interactome analysis. Methods: This systems-based interactome analysis was designed to enforce the workflow of "ASR(herb)→compound→target protein→internal protein actions→ending regulated protein for hematopoiesis". This workflow was deployed with restrictions on regulated proteins expresses in bone marrow and anemia disease and futher validated with experiments. Results: The hematopoiesis mechanism of ASR might be accomplished through regulating pathways of cell proliferation towards hemopoiesis with cross-talking agents of spleen tyrosine kinase(SYK), Janus kinase 2(JAK2), and interleukin-2-inducible T-cell kinase(ITK). The hematopoietic function of ASR was also validated by colonyforming assay performed on mice bone marrow cells. As a result, SYK, JAK2 and ITK were activated. Conclusion: This study provides a new approach to systematically study and predict the therapeutic mechanism for ASR based on interactome analysis towards biological process with experimental validations.展开更多
OBJECTIVE Gastric cancer is one of the most common malignant tumors,and the incidence rate is the highest in all kinds of tumors in China.However,it remains unclear that how signifi.cantly gastric cells are dependent ...OBJECTIVE Gastric cancer is one of the most common malignant tumors,and the incidence rate is the highest in all kinds of tumors in China.However,it remains unclear that how signifi.cantly gastric cells are dependent on glycolysis,and which type of gastric cells are sensitive to glycolysis inhibition.In this study,several kind of gastric cancer cell lines were used as the research object,and the metabolic characteristics of different cell lines were systematically analyzed to provide theoretical support for the accurate treatment of gastric cancer.METHODS We examined the energy metabolism of four gastric cancer cell lines(MGC-803,SGC-7901,HGC-27 and BGC-823) by using glycolysis inhibitor,2-deoxy-D-glucose(2-DG) and inhibitor of oxidative phosphorylation,oligomycin.Oxygen consumption rates(OCR) and L-lactate were also measured with an XF96 Analyzer(Seahorse Biosciences) to deter.mine the significance of metabolism of oxidative phosphorylation and aerobic glycolysisin gastric cells.In addition,western blot was used to detect the contribution of AMP-activated protein kinase(AMPK),and anti-apoptotic proteins(Bcl-2 and survivin) to clarify the mechanism of death or survival of gastric cancer cells treated by 2-DG or oligomycin.RESULTS In this study,it was shown that the growth of gastric cell lines were suppressed by 2-DG.However,the sensitivity to 2-DG was quite different among cell lines:IC 50 of 2-DG was from 3.28 mmol·L^(-1)(MGC-803) to 15.57 mmol·L^(-1)(BGC-823).MGC-803 was relatively sensitive to 2-DG(IC 50:3.28 mmol·L^(-1)),consumed more glucose and produced more lactate(waste product of glycolysis) than the three other cell lines.Consequently,MGC-803 could be more dependent on glycolysis than other cell lines,which was further confirmed by the fact that glucose(+) FCS(-) medium showed more growth and survival than glucose(-) FCS(+) medium.Alternatively,BGC-823,most resistant to 2-DG(IC50:15.57 mmol · L-1),was most sensitive to oligomycin,and showed more growth and survival in glucose(-) FCS(+) medium than 展开更多
Wood is produced by the accumulation of secondary xylem via proliferation and differentiation of the cambium cells in woody plants. Identifying the regulators involved in this process remains a challenging task. In th...Wood is produced by the accumulation of secondary xylem via proliferation and differentiation of the cambium cells in woody plants. Identifying the regulators involved in this process remains a challenging task. In this study, we isolated Pag SAG101 a,the homolog of Arabidopsis thaliana SAG101, from a hybrid poplar(Populus alba × Populus glandulosa)clone 84 K and investigated its role in secondary xylem development. Pag SAG101 a was expressed predominantly in lignified stems and localized in thenucleus. Compared with non-transgenic 84 K plants,transgenic plants overexpressing Pag SAG101 a displayed increased plant height, internode number,stem diameter, xylem width, and secondary cell wall thickness, while opposite phenotypes were observed for Pag SAG101 a knock-out plants.Transcriptome analyses revealed that differentially expressed genes were enriched for those controlling cambium cell division activity and subsequent secondary cell wall deposition during xylem formation.In addition, the tandem CCCH zinc finger protein Pag C3 H17, which positively regulates secondary xylem width and secondary wall thickening in poplar, could bind to the promoter of Pag SAG101 a and mediate the regulation of xylem differentiation.Our results support that Pag SAG101 a, downstream of Pag C3 H17, functions in wood development.展开更多
基金Acknowledgment This study was support by Natural Science Foundation of Shanghai, China （No. 06ZR14137）.
文摘Aim： To investigate the relationship between low androgen level and ultrastructure of vascular endothelium. Methods： Forty-eight male Sprague-Dawley rats were randomly divided into four groups： group A, normal rats with sham castration; group B, castrated rats; group C, castrated rats given testosterone （T） undecanoate; and group D, intact rats treated with 5α-reductase inhibitor. After 10 weeks of treatment or castration, rats in different groups were killed and serum T, free T （FT） and dihydrotestosterone （DHT） were measured. The aortic endothelia were scanned under electron microcopy and the Vascular Endothelium Structure Score （VESS） was computed. Results： Serum T and FT concentrations of rats in group B were significantly lower than those of the other three groups （P 〈 0.01）; DHT concentrations of group D rats were significantly decreased （P 〈 0.01 ） when compared with those of groups A and C. Rats in groups B and D rats （with low androgen levels） had obvious damage to their endothelial surfaces, which appeared crimpled, rough, adhesive and ruptured, and had high destruction of VESS. Conclusion： These results suggest that low concentrations of T and DHT are associated with ultrastructural damage of the aortic endothelia in male rats.
基金Project supported by the Science Foundation for the Youth of China Institute of Sport Science （CISS） （No. 13-19）
文摘To investigate the effects of hypoxic exercise training on microRNA （miRNA） expression and the role of miRNA expression in regulating lipid metabolism, 20 dietary-induced obese SD rats were divided into a normoxic sedentary group （N, n=10） and a hypoxic exercise training group （H, n=10）. After four weeks, measurements were taken of body weight, body length, fat mass, serum lipid concentration, miRNAs differentially expressed in rat liver, and gene and protein expression levels of perexisome proliferator activated receptor a （PPARα）, fatty acid synthetase （FAS）, and carnitine palmitoyl transferase 1A （CPTIA） in rat liver. Body weight, Lee＇s index, fat mass, fat/weight ratio, and serum levels of total cholesterol （TC） and high density lipoprotein cholesterol （HDL-C） were all significantly lower in the H group than in the N group （P〈0.01）. Six miRNAs expressed significantly differently in the liver （P〈0.05）. Specifically, expression levels of miR-378b were significantly lower in the H group than in the N group （P〈0.05）. Compared with the normoxic sedentary group, hypoxic exercise training resulted in a lower ratio of FAS mRNA to CPTIA mRNA （P〈0.05）, as well as lower CPT1A protein levels （P〈0.01）, while a higher ratio of FAS to CPT1A protein levels （P〈0.01） was observed. In conclusion, hypoxic training may elevate the resistance of high fat diet induced obesity in rats by reducing the expression of miR-378b, and decrease the fatty acid mitochondrial oxidation in obese rat livers by decreasing the protein expression of CPTIA and increasing the protein expression ratio of FAS/CPTIA.
基金grants from the National Natural Science Foundation of China(No.81270885,No.81570726 and No.81600609)Shanghai Jiao Tong University School of Medicine(2014)+4 种基金the Ministry of Science and Technology in China(No.2012CB524906)the Science and Technology Commission of Shanghai Municipality(No.14495810700 and No.16410723200)Three-year Action Plan for Public Health System Construction in Shanghai by Shanghai Municipal Commission of Health and Family Planning(2015-2017)Clinical Potential Subject Construction of Shanghai Jiao Tong University School of Medicine(2014),Shanghai Municipal Health Bureau of China(No.20124262)Seed Founding of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine(No.JYZZ032).
文摘Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas.We aimed to investigate the association between euthyroid hormones and islet betacell function in general population and non-treated type 2 diabetes mellitus(T2DM)patients.A total of 5089 euthyroid participants(including 4601 general population and 488 non-treated T2DM patients)were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016.Anthropometric indices,biochemical parameters,and thyroid hormones were measured.Compared with general population,non-treated T2DM patients exhibited higher total thyroxine(TT4)and free thyroxine(FT4)levels but lower ratio of free triiodothyronine(T3):T4(P<0.01).HOMA-βhad prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age,body mass index(BMI)and smoking.When analyzed by quartiles of FT4 or free T3:T4,there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups.Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients,which was independent of age,BMI,smoking,hypertension and lipid profiles.FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects.Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.
基金supported by the National Natural Science Foundation of China(No.91857117)the Science and Technology Commission of Shanghai Municipality(Nos.19140902400,18410722300).
文摘Background:Non-communicable chronic diseases have become the leading causes of disease burden worldwide.The trends and burden of“metabolic associated fatty liver disease”(MAFLD)are unknown.We aimed to investigate the cardiovascular and renal burdens in adults with MAFLD and non-alcoholic fatty liver disease(NAFLD).Methods:Nationally representative data were analyzed including data from 19,617 non-pregnant adults aged≥20years from the cross-sectional US National Health and Nutrition Examination Survey periods,1999 to 2002,2003 to 2006,2007 to 2010,and 2011 to 2016.MAFLD was defined by the presence of hepatic steatosis plus general overweight/obesity,type 2 diabetes mellitus,or evidence of metabolic dysregulation.Results:The prevalence of MAFLD increased from 28.4%(95% confidence interval 26.3–30.6)in 1999 to 2002 to 35.8%(33.8–37.9)in 2011 to 2016.In 2011 to 2016,among adults with MAFLD,49.0%(45.8–52.2)had hypertension,57.8%(55.2–60.4)had dyslipidemia,26.4%(23.9–28.9)had diabetes mellitus,88.7%(87.0–80.1)had central obesity,and 18.5%(16.3–20.8)were current smokers.The 10-year cardiovascular risk ranged from 10.5%to 13.1%;19.7%(17.6–21.9)had chronic kidney diseases(CKDs).Throughthe fourperiods,adults withMAFLD showedanincrease in obesity;increase intreatment to lower bloodpressure(BP),lipids,and hemoglobin A1c;and increase in goal achievements for BP and lipids but not in goal achievement for glycemic control in diabetes mellitus.Patients showed a decreasing 10-year cardiovascular risk over time but no change in the prevalence of CKDs,myocardial infarction,or stroke.Generally,although participants with NAFLD and those with MAFLD had a comparable prevalence of cardiovascular disease and CKD,the prevalence of MAFLD was significantly higher than that of NAFLD.Conclusions:From 1999 to 2016,cardiovascular and renal risks and diseases have become highly prevalent in adults with MAFLD.The absolute cardiorenal burden may be greater for MAFLD than for NAFLD.These data call for early identification and
基金supported by the National Key Scientific Research Project of China (2021YFD2200205)the Ten-Thousand Talents Program of China to Meng-Zhu Lu。
文摘Lignin is a major component of plant cell walls and is essential for plant growth and development. Lignin biosynthesis is controlled by a hierarchical regulatory network involving multiple transcription factors. In this study, we showed that the gene encoding an APETALA 2/ethylene-responsive element binding factor(AP2/ERF) transcription factor, PagERF81,from poplar 84 K(Populus alba × P. glandulosa) is highly expressed in expanding secondary xylem cells. Two independent homozygous Pagerf81 mutant lines created by gene editing, produced significantly more but smaller vessel cells and longer fiber cells with more lignin in cell walls, while PagERF81 overexpression lines had less lignin,compared to non-transgenic controls. Transcriptome and reverse transcription quantitative PCR data revealed that multiple lignin biosynthesis genes including Cinnamoyl CoA reductase 1(PagCCR1),Cinnamyl alcohol dehydrogenase 6(PagCAD6), and 4-Coumarate-CoA ligase-like 9(Pag4CLL9) were upregulated in Pagerf81 mutants, but down-regulated in PagERF81 overexpression lines. In addition, a transient transactivation assay revealed that PagERF81 repressed the transcription of these three genes.Furthermore, yeast one hybrid and electrophoretic mobility shift assays showed that PagERF81 directly bound to a GCC sequence in the PagCCR1 promoter. No known vessel or fiber cell differentiation related genes were differentially expressed, so the smaller vessel cells and longer fiber cells observed in the Pagerf81 lines might be caused by abnormal lignin deposition in the secondary cell walls. This study provides insight into the regulation of lignin biosynthesis, and a molecular tool to engineer wood with high lignin content, which would contribute to the lignin-related chemical industry and carbon sequestration.
基金supported by the National Natural Science Foundation of China(No.82120108008,No.91857117)the Project of Biobank(No.YBKA201909)from Shanghai Ninth People’s Hospital,Shanghai Jiaotong University School of Medicinea grant from Shanghai Jiaotong University School of Medicine(No.19XJ11007).
文摘Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)patients.Methods A total of 4670 T2D patients from seven communities in Shanghai,China were enrolled.The anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were measured.Results The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased.Next,the population was divided into two groups:abdominal obesity and non-abdominal obesity groups.After adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity group.There was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity group.In the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p levels.In the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity.The 25(OH)D influenced C-p in part by influencing glucagon.The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.
文摘Objective: To explore the molecular-level mechanism on the hematopoiesis effect of Angelicae sinensis Radix(ASR) with systems-based interactome analysis. Methods: This systems-based interactome analysis was designed to enforce the workflow of "ASR(herb)→compound→target protein→internal protein actions→ending regulated protein for hematopoiesis". This workflow was deployed with restrictions on regulated proteins expresses in bone marrow and anemia disease and futher validated with experiments. Results: The hematopoiesis mechanism of ASR might be accomplished through regulating pathways of cell proliferation towards hemopoiesis with cross-talking agents of spleen tyrosine kinase(SYK), Janus kinase 2(JAK2), and interleukin-2-inducible T-cell kinase(ITK). The hematopoietic function of ASR was also validated by colonyforming assay performed on mice bone marrow cells. As a result, SYK, JAK2 and ITK were activated. Conclusion: This study provides a new approach to systematically study and predict the therapeutic mechanism for ASR based on interactome analysis towards biological process with experimental validations.
基金supported by National Natural Science Foundation of China(81502952)
文摘OBJECTIVE Gastric cancer is one of the most common malignant tumors,and the incidence rate is the highest in all kinds of tumors in China.However,it remains unclear that how signifi.cantly gastric cells are dependent on glycolysis,and which type of gastric cells are sensitive to glycolysis inhibition.In this study,several kind of gastric cancer cell lines were used as the research object,and the metabolic characteristics of different cell lines were systematically analyzed to provide theoretical support for the accurate treatment of gastric cancer.METHODS We examined the energy metabolism of four gastric cancer cell lines(MGC-803,SGC-7901,HGC-27 and BGC-823) by using glycolysis inhibitor,2-deoxy-D-glucose(2-DG) and inhibitor of oxidative phosphorylation,oligomycin.Oxygen consumption rates(OCR) and L-lactate were also measured with an XF96 Analyzer(Seahorse Biosciences) to deter.mine the significance of metabolism of oxidative phosphorylation and aerobic glycolysisin gastric cells.In addition,western blot was used to detect the contribution of AMP-activated protein kinase(AMPK),and anti-apoptotic proteins(Bcl-2 and survivin) to clarify the mechanism of death or survival of gastric cancer cells treated by 2-DG or oligomycin.RESULTS In this study,it was shown that the growth of gastric cell lines were suppressed by 2-DG.However,the sensitivity to 2-DG was quite different among cell lines:IC 50 of 2-DG was from 3.28 mmol·L^(-1)(MGC-803) to 15.57 mmol·L^(-1)(BGC-823).MGC-803 was relatively sensitive to 2-DG(IC 50:3.28 mmol·L^(-1)),consumed more glucose and produced more lactate(waste product of glycolysis) than the three other cell lines.Consequently,MGC-803 could be more dependent on glycolysis than other cell lines,which was further confirmed by the fact that glucose(+) FCS(-) medium showed more growth and survival than glucose(-) FCS(+) medium.Alternatively,BGC-823,most resistant to 2-DG(IC50:15.57 mmol · L-1),was most sensitive to oligomycin,and showed more growth and survival in glucose(-) FCS(+) medium than
基金supported by the Fundamental Research Funds of CAF(CAFYBB2017ZY001)the Ten-thousand Talents Program of China to Meng-Zhu Lu。
文摘Wood is produced by the accumulation of secondary xylem via proliferation and differentiation of the cambium cells in woody plants. Identifying the regulators involved in this process remains a challenging task. In this study, we isolated Pag SAG101 a,the homolog of Arabidopsis thaliana SAG101, from a hybrid poplar(Populus alba × Populus glandulosa)clone 84 K and investigated its role in secondary xylem development. Pag SAG101 a was expressed predominantly in lignified stems and localized in thenucleus. Compared with non-transgenic 84 K plants,transgenic plants overexpressing Pag SAG101 a displayed increased plant height, internode number,stem diameter, xylem width, and secondary cell wall thickness, while opposite phenotypes were observed for Pag SAG101 a knock-out plants.Transcriptome analyses revealed that differentially expressed genes were enriched for those controlling cambium cell division activity and subsequent secondary cell wall deposition during xylem formation.In addition, the tandem CCCH zinc finger protein Pag C3 H17, which positively regulates secondary xylem width and secondary wall thickening in poplar, could bind to the promoter of Pag SAG101 a and mediate the regulation of xylem differentiation.Our results support that Pag SAG101 a, downstream of Pag C3 H17, functions in wood development.
