Objective: The main goal of the present study was to investigate the effect of iron supplementation on glucose transporter 4 expressions in adipose tissue and skeletal muscle in female rats during pregnancy. Methods: ...Objective: The main goal of the present study was to investigate the effect of iron supplementation on glucose transporter 4 expressions in adipose tissue and skeletal muscle in female rats during pregnancy. Methods: Twenty-four pregnant Sprague-Dawley rats were randomly divided into 2 groups: a control group with a standard diet (containing iron 150 mg/kg) and an iron-supplementation group with a high-iron diet (containing iron 700 mg/kg) from day 0 to day 21 of pregnancy. Intraperitoneal glucose tolerance test was performed on gestational day 19. On gestational day 21, all of the pregnant rats from each group were sacrificed. The mean neonatal weights were measured and samples of maternal intraabdominal adipose tissue and skeletal muscle were taken to measure the expression of Glucose Transporter 4 (GLUT4) mRNA and protein. Results: Glucose tolerance decreased significantly in the iron supplementation group compared to the control group. The mean neonatal weights in the iron supplementation group were higher than that in the control group. Levels of GLUT4 mRNA in the adipose tissue were reduced by the administrations of high-iron diet. The skeletal muscle GLUT4 mRNA levels were not changed significantly by iron supplementation. Expression of GLUT4 protein both in the adipose tissue and skeletal muscle reduced significantly. Conclusion: These results suggest that iron supplementation during pregnancy would increase neonatal weights and could decrease maternal glucose tolerance by interfering GLUT4 expression in adipose tissue and skeletal muscle of rats.展开更多
The tumor heterogeneity results in different clinical characteristics of tumor patients,so precise therapy is a popular treatment strategy clinically.Microsatellite instability(MSI)is found in 10%-15%of colorectal can...The tumor heterogeneity results in different clinical characteristics of tumor patients,so precise therapy is a popular treatment strategy clinically.Microsatellite instability(MSI)is found in 10%-15%of colorectal cancer(CRC)patients and exhibits different clinical outcomes than microsatellite stable(MSS)patients.Surprisingly,MSI patients have a better prognosis than patients with stable microsatellites.Msl patients exhibit clinical features that are not responsive to chemotherapy,however,Msl patients showed excellent responses to immunotherapy.'Although the subtype classification of MSI is beneficial to the clinical treatment of CRC patients,the mechanism of MSl remains unclear.展开更多
Metabolic reprogramming is a hallmark of cancer,including lung cancer.However,the exact underlying mechanism and therapeutic potential are largely unknown.Here we report that protein arginine methyltransferase 6(PRMT6...Metabolic reprogramming is a hallmark of cancer,including lung cancer.However,the exact underlying mechanism and therapeutic potential are largely unknown.Here we report that protein arginine methyltransferase 6(PRMT6)is highly expressed in lung cancer and is required for cell metabolism,tumorigenicity,and cisplatin response of lung cancer.PRMT6 regulated the oxidative pentose phosphate pathway(PPP)flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phosphogluconate dehydrogenase(6PGD)and a-enolase(ENO1).Furthermore,PRMT6 methylated R324 of 6PGD to enhancing its activity;while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate(2-PG)binding to ENO1,respectively.Lastly,targeting PRMT6 blocked the oxidative PPP flux,glycolysis pathway,and tumor growth,as well as enhanced the antitumor effects of cisplatin in lung cancer.Together,this study demonstrates that PRMT6 acts as a posttranslational modification(PTM)regulator of glucose metabolism,which leads to the pathogenesis of lung cancer.It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.展开更多
Huangjiu is known for its unique aroma,primarily attributed to its high concentration ofβ-phenylethanol(ranging from 40 to 130 mg/L).Phenylalanine aminotransferase Aro9p and phenylpyruvate decarboxylase Aro10p are ke...Huangjiu is known for its unique aroma,primarily attributed to its high concentration ofβ-phenylethanol(ranging from 40 to 130 mg/L).Phenylalanine aminotransferase Aro9p and phenylpyruvate decarboxylase Aro10p are key enzymes in theβ-phenylethanol synthetic pathway of Saccharomyces cerevisiae^(HJ).This study examined the enzymatic properties of these two enzymes derived from S.cerevisiae^(HJ)and^(S288C).After substrate docking,Aro9p^(HJ)(-24.05 kJ/mol)and Aro10p^(HJ)(-14.33 kJ/mol)exhibited lower binding free energies compared to Aro9p^(S288C)(-21.93 kJ/mol)and Aro10p^(S288C)(-12.84 kJ/mol).ARO9 and ARO10 genes were heterologously expressed in E.coli BL21.Aro9p,which was purified via affinity chromatography,showed inhibition by L-phenylalanine(L-PHE),but the reaction rate Vmax(Aro9p^(HJ):23.89μmol⋅(min·g)^(-1)>Aro9p^(S288C):21.3μmol⋅(min·g)^(-1))and inhibition constant Ki values(Aro9p^(HJ):0.28 mol L^(-1)>Aro9p^(S288C)0.26 mol L^(-1))indicated that Aro9p from S.cerevisiae^(HJ)was more tolerant to substrate stress during Huangjiu fermentation.In the presence of the same substrate phenylpyruvate(PPY),Aro10p^(HJ)exhibited a stronger affinity than Aro10p^(S288C).Furthermore,Aro9p^(HJ)and Aro10p^(HJ)were slightly more tolerant to the final metabolitesβ-phenylethanol and ethanol,respectively,compared to those from^(S288C).The study suggests that the mutations in Aro9p^(HJ)and Aro10p^(HJ)may contribute to the increasedβ-phenylethanol concentration in Huangjiu.This is the first study investigating enzyme tolerance mechanisms in terms of substrate and product,providing a theoretical basis for the regulation of theβ-phenylethanol metabolic pathway.展开更多
In order to quickly detect the rancidification of Huangjiu in pottery jars,this study developed a fast detection method based on the principle of electrical conductivity changes caused by microbial contamination.The c...In order to quickly detect the rancidification of Huangjiu in pottery jars,this study developed a fast detection method based on the principle of electrical conductivity changes caused by microbial contamination.The change in total acid in Huangjiu was positively correlated with the increase of electrical conductivity.This method was applied to an online monitoring system for Huangjiu storage in stainless steel tanks.When the electrical conductivity exceeds the normal fluctuation range(mean+3 standard deviations)of previous data,the monitoring system recognizes microbial contamination.By optimizing the conductivity-temperature compensation coefficient and conductivity statistical method,the standard deviation of the method was reduced and the sensitivity of microbial pollution monitoring was improved.The ranges of conductivity and compensation coefficient of common types of Huangjiu were estimated.Interference in conductivity measurements due to environmental factors was minimised through the synchronous comparison of conductivity data for multiple tanks of Huangjiu.The standard deviation,which indicates the fluctuation range of the system,decreased from 143 to 2μS/cm.The monitoring system was then applied in Huangjiu storage tanks with capacities of 60 t and 300 t.Through the comparison of conductivity data change,the abnormal signals caused by microbial contamination during the storage of Huangjiu were found over time.Meanwhile,through offline detection of total acid in Huangjiu,the effectiveness of microbial contamination online detection was verified.展开更多
文摘Objective: The main goal of the present study was to investigate the effect of iron supplementation on glucose transporter 4 expressions in adipose tissue and skeletal muscle in female rats during pregnancy. Methods: Twenty-four pregnant Sprague-Dawley rats were randomly divided into 2 groups: a control group with a standard diet (containing iron 150 mg/kg) and an iron-supplementation group with a high-iron diet (containing iron 700 mg/kg) from day 0 to day 21 of pregnancy. Intraperitoneal glucose tolerance test was performed on gestational day 19. On gestational day 21, all of the pregnant rats from each group were sacrificed. The mean neonatal weights were measured and samples of maternal intraabdominal adipose tissue and skeletal muscle were taken to measure the expression of Glucose Transporter 4 (GLUT4) mRNA and protein. Results: Glucose tolerance decreased significantly in the iron supplementation group compared to the control group. The mean neonatal weights in the iron supplementation group were higher than that in the control group. Levels of GLUT4 mRNA in the adipose tissue were reduced by the administrations of high-iron diet. The skeletal muscle GLUT4 mRNA levels were not changed significantly by iron supplementation. Expression of GLUT4 protein both in the adipose tissue and skeletal muscle reduced significantly. Conclusion: These results suggest that iron supplementation during pregnancy would increase neonatal weights and could decrease maternal glucose tolerance by interfering GLUT4 expression in adipose tissue and skeletal muscle of rats.
基金supported by grants from National Nature Science Foundation of China(No.81973356,81902826 and 82273963)Natural Science Foundation of Tianjin(No.21JCZDJC00060 and 21JCYBJC00180)the Fundamental Research Funds for the Central Universities of Nankai University(No.ZB22010404,3206054,91923101,63213082,and 92122017).
文摘The tumor heterogeneity results in different clinical characteristics of tumor patients,so precise therapy is a popular treatment strategy clinically.Microsatellite instability(MSI)is found in 10%-15%of colorectal cancer(CRC)patients and exhibits different clinical outcomes than microsatellite stable(MSS)patients.Surprisingly,MSI patients have a better prognosis than patients with stable microsatellites.Msl patients exhibit clinical features that are not responsive to chemotherapy,however,Msl patients showed excellent responses to immunotherapy.'Although the subtype classification of MSI is beneficial to the clinical treatment of CRC patients,the mechanism of MSl remains unclear.
基金supported by grants from the Natural Science Foundation of Tianjin(21JCZDJC00060,China)the National Nature Science Foundation of China(81973356,91957120,81902826,and 81672781)+4 种基金the Fundamental Research Funds for the Central Universities of Nankai University(3206054,91923101,63213082 and 92122017,China)the State Key Laboratory of Drug Research(SIMM2105KF-08,China)the National Key R&D Program of China(No.2018YFC2002000)the Innovative S&T Projects for Young Researchers of Tianjin Academy of Agricultural Science(grant No.201918,China)the Natural Science Foundation of Tianjin(19JCYBJC29600 and 21JCYBJC00180,China)。
文摘Metabolic reprogramming is a hallmark of cancer,including lung cancer.However,the exact underlying mechanism and therapeutic potential are largely unknown.Here we report that protein arginine methyltransferase 6(PRMT6)is highly expressed in lung cancer and is required for cell metabolism,tumorigenicity,and cisplatin response of lung cancer.PRMT6 regulated the oxidative pentose phosphate pathway(PPP)flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phosphogluconate dehydrogenase(6PGD)and a-enolase(ENO1).Furthermore,PRMT6 methylated R324 of 6PGD to enhancing its activity;while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate(2-PG)binding to ENO1,respectively.Lastly,targeting PRMT6 blocked the oxidative PPP flux,glycolysis pathway,and tumor growth,as well as enhanced the antitumor effects of cisplatin in lung cancer.Together,this study demonstrates that PRMT6 acts as a posttranslational modification(PTM)regulator of glucose metabolism,which leads to the pathogenesis of lung cancer.It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.
基金supported by the National Natural Science Foundation of China(32072205,22138004)Shaoxing Science and Technology Plan Project(2022B43001).
文摘Huangjiu is known for its unique aroma,primarily attributed to its high concentration ofβ-phenylethanol(ranging from 40 to 130 mg/L).Phenylalanine aminotransferase Aro9p and phenylpyruvate decarboxylase Aro10p are key enzymes in theβ-phenylethanol synthetic pathway of Saccharomyces cerevisiae^(HJ).This study examined the enzymatic properties of these two enzymes derived from S.cerevisiae^(HJ)and^(S288C).After substrate docking,Aro9p^(HJ)(-24.05 kJ/mol)and Aro10p^(HJ)(-14.33 kJ/mol)exhibited lower binding free energies compared to Aro9p^(S288C)(-21.93 kJ/mol)and Aro10p^(S288C)(-12.84 kJ/mol).ARO9 and ARO10 genes were heterologously expressed in E.coli BL21.Aro9p,which was purified via affinity chromatography,showed inhibition by L-phenylalanine(L-PHE),but the reaction rate Vmax(Aro9p^(HJ):23.89μmol⋅(min·g)^(-1)>Aro9p^(S288C):21.3μmol⋅(min·g)^(-1))and inhibition constant Ki values(Aro9p^(HJ):0.28 mol L^(-1)>Aro9p^(S288C)0.26 mol L^(-1))indicated that Aro9p from S.cerevisiae^(HJ)was more tolerant to substrate stress during Huangjiu fermentation.In the presence of the same substrate phenylpyruvate(PPY),Aro10p^(HJ)exhibited a stronger affinity than Aro10p^(S288C).Furthermore,Aro9p^(HJ)and Aro10p^(HJ)were slightly more tolerant to the final metabolitesβ-phenylethanol and ethanol,respectively,compared to those from^(S288C).The study suggests that the mutations in Aro9p^(HJ)and Aro10p^(HJ)may contribute to the increasedβ-phenylethanol concentration in Huangjiu.This is the first study investigating enzyme tolerance mechanisms in terms of substrate and product,providing a theoretical basis for the regulation of theβ-phenylethanol metabolic pathway.
基金supported by the National Natural Science Foundation of China(Nos.32072205 and 22138004)the first phase of the connotation construction of the 14th Five-Year Plan of Tibetan medicine(No.2021ZYYGH008),China.
文摘In order to quickly detect the rancidification of Huangjiu in pottery jars,this study developed a fast detection method based on the principle of electrical conductivity changes caused by microbial contamination.The change in total acid in Huangjiu was positively correlated with the increase of electrical conductivity.This method was applied to an online monitoring system for Huangjiu storage in stainless steel tanks.When the electrical conductivity exceeds the normal fluctuation range(mean+3 standard deviations)of previous data,the monitoring system recognizes microbial contamination.By optimizing the conductivity-temperature compensation coefficient and conductivity statistical method,the standard deviation of the method was reduced and the sensitivity of microbial pollution monitoring was improved.The ranges of conductivity and compensation coefficient of common types of Huangjiu were estimated.Interference in conductivity measurements due to environmental factors was minimised through the synchronous comparison of conductivity data for multiple tanks of Huangjiu.The standard deviation,which indicates the fluctuation range of the system,decreased from 143 to 2μS/cm.The monitoring system was then applied in Huangjiu storage tanks with capacities of 60 t and 300 t.Through the comparison of conductivity data change,the abnormal signals caused by microbial contamination during the storage of Huangjiu were found over time.Meanwhile,through offline detection of total acid in Huangjiu,the effectiveness of microbial contamination online detection was verified.
