Effect of iron supplementation on glucose transporter 4 expression in adipose tissue and skeletal muscle of pregnant rats

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.

The dysfunctional Wnt pathway down-regulates MLH1/SET expression and promotes microsatellite instability and immunotherapy response in colorectal cancer

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.

胎儿胆囊发育异常的研究进展

胆囊发育异常虽少见,但可合并染色体异常和/或并发胆道闭锁和囊性纤维化等严重并发症。常规中孕期胎儿超声筛查时,胆囊发育异常未被充分重视,但产前发现对生后及时诊治具有重要意义。现综述胎儿胆囊发育异常的研究进展,包括胆囊重复、胆囊内回声物质和胆石症、异位胆囊、胆囊增大、囊性纤维化的临床特征及围产儿预后,总结胆囊未显示的类型、发病率、临床特征、产前诊断和围产儿预后,以期提高对胆囊发育异常产前筛查的重视。

PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism

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.

Enzymatic properties and inhibition tolerance analysis of key enzymes inβ-phenylethanol anabolic pathway of Saccharomyces cerevisiae HJ

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.

Development of a monitoring system for Huangjiu storage based on electrical conductivity

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.