Objective:To determine the relationship between insulin resistance and related variables(serum testosterone,interleukin(IL-6)and leptin level)in obese and non-obese healthy subjects.Methods:Community-based crosssectio...Objective:To determine the relationship between insulin resistance and related variables(serum testosterone,interleukin(IL-6)and leptin level)in obese and non-obese healthy subjects.Methods:Community-based crosssectional,analytic study was undertaken in 60 subjects for each obese group(BMI≥30.0 kg/m2)and non-obese group(BMI 18.5 to 24.9 kg/m2)(age;18-45 years)residing in Magway Township from December 2016 to December 2017.Serum insulin,testosterone,IL-6 and leptin levels were measured by enzyme linked immunoassay,and serum fasting glucose was measured by glucose oxidase method.Insulin sensitivity was calculated by HOMA formula(Homeostatic Model Assessment).Results:HOMA-IR,serum leptin and IL-6 level were significantly higher in obese group while serum testosterone level was significantly lower in obese group.There was a significantly correlation between HOMA-IR with leptin(r=0.306,p=0.001),IL-6(r=0.237,p=0.009)and testosterone(r=-0.209,p=0.02).Moreover,serum leptin was significantly and positively correlated with IL-6(r=0.391,p<0.001)while serum testosterone was significantly and negatively correlated with leptin(r=-0.408,p<0.001),and IL-6(r=-0.34,p<0.001).Conclusions:Obese men are more likely to have low testosterone,high inflammatory markers leptin and Il-6,which were associated with decreased insulin sensitivity.展开更多
C-type lysozyme genes （Lyzls） belong to the class of lysozymes and are highly expressed in the testis and epididymis. The members Lyzl4 and Spaca3 have been reported to play a role in sperm-egg binding and fertilisa...C-type lysozyme genes （Lyzls） belong to the class of lysozymes and are highly expressed in the testis and epididymis. The members Lyzl4 and Spaca3 have been reported to play a role in sperm-egg binding and fertilisation in mice. However, the function of the remaining two mouse c-type lysozyme genes, Lyzll and Lyzl6, is still not clear. In the present study, we analysed the tissue expression and androgen-dependent expression of mouse c-type lysozyme genes and the possible contribution of human recombinant LYZL6 （rLYZL6） to immunity. The expression of Lyzlswas detected by RT-PCR, Western blots, immunohistochemistry and immunofluorescence. The bacteriolytic activity of rLYZL6 was analysed by a colony-forming assay. In mice, the expression of Lyzlgenes was mainly in the testis and epididymis in a developmentally regulated manner and androgen- or testicular factor-regulated manner. Immunodetection revealed the presence of LYZL6 protein in primary spermatocytes and round spermatids of the testis and on the post-acrosomal area and midpiece of mature epididymal spermatozoa. The rLYZL6 protein exhibited antibacterial activity. From the results, Lyzls may play a role in mitochondrial function of spermatozoa and LYZL6 may contribute to the innate immunity of the male genital tract.展开更多
Objective： We have continued previous work in which we demonstrated that #117 and #372 amino acids contributed to the high activities of human CYP2A13 in catalyzing 4-methylnitrosamino-1-（3-pyridyl）-1-butanone（NNK...Objective： We have continued previous work in which we demonstrated that #117 and #372 amino acids contributed to the high activities of human CYP2A13 in catalyzing 4-methylnitrosamino-1-（3-pyridyl）-1-butanone（NNK） and aflatoxin BI（AFB1） carcinogenic activation. The present study was designed to identify other potential amino acid residues that contribute to the different catalytic characteristics of two CYP2A enzymes, CYP2A6 and CYP2A13, in nicotine metabolism and provide insights of the substrate and related amino acid residues interactions. Methods： A series of reciprocally substituted mutants of CYP2A6lle^300→ Phe, CYP2A6Gly^301aAla, CYP2A6Ser^369 → Gly, CYP2A13Phe^300→ Ile, CYP2A13Ala^301 → Gly and CYP2A13Gly^369 → Set were generated by site-directed mutagenesis/baculovirus-Sf9 insect cells expression. Comparative kinetic analysis of nicotine 5＇hydroxylatin by wild type and mutant CYP2A proteins was performed. Results：All amino acid residue substitutions at 300, 301 and 369 caused significant kinetic property changes in nicotine metabolism. While CYP2A6Ile^300→ Phe and CYP2A6Gly^301→Ala mutations had notable catalytic efficiency increases compared to that for the wild type CYP2A6, CYP2A13Phe^300→Ile and CYP2A13Ala^301→Gly replacement introduced remarkable catalytic efficiency decreases. In addition, all these catalytic efficiency alterations were caused by Vmax variations rather than Km changes. Substitution of #369 residue significantly affected both Km and Vmax values. CYP2A6Ser^369 → Gly increase the catalytic efficiency via a significant Km decrease versus Vmax enhancement, while the opposite effects were seen with CYP2A13Gly^369 → Ser. Conclusion：#300, #301 and #369 residues in human CYP2A6/13 play important roles in nicotine 5＇ -oxidation. Switching #300 or #301 residues did not affect the CYP2A protein affinities toward nicotine, although these amino acids are located in the active center. Set369 to Gly substitution indirectly affected nicotine binding by creating more space and conformational flexibility for the nearby residues, such as Leu^370 which is crucial for many hydroxylations.展开更多
Hydroxylsqualamine was synthesized stereoselectively in 13 steps and 19% overall yield from methyl hyo-deoxycholanate by using stereospecific epoxidation and asymmetric isopropylation as key steps.
文摘Objective:To determine the relationship between insulin resistance and related variables(serum testosterone,interleukin(IL-6)and leptin level)in obese and non-obese healthy subjects.Methods:Community-based crosssectional,analytic study was undertaken in 60 subjects for each obese group(BMI≥30.0 kg/m2)and non-obese group(BMI 18.5 to 24.9 kg/m2)(age;18-45 years)residing in Magway Township from December 2016 to December 2017.Serum insulin,testosterone,IL-6 and leptin levels were measured by enzyme linked immunoassay,and serum fasting glucose was measured by glucose oxidase method.Insulin sensitivity was calculated by HOMA formula(Homeostatic Model Assessment).Results:HOMA-IR,serum leptin and IL-6 level were significantly higher in obese group while serum testosterone level was significantly lower in obese group.There was a significantly correlation between HOMA-IR with leptin(r=0.306,p=0.001),IL-6(r=0.237,p=0.009)and testosterone(r=-0.209,p=0.02).Moreover,serum leptin was significantly and positively correlated with IL-6(r=0.391,p<0.001)while serum testosterone was significantly and negatively correlated with leptin(r=-0.408,p<0.001),and IL-6(r=-0.34,p<0.001).Conclusions:Obese men are more likely to have low testosterone,high inflammatory markers leptin and Il-6,which were associated with decreased insulin sensitivity.
基金This research was financially supported by the grants from the National Natural Science Foundation of China （No. 31071262） and the Shandong Science and Technology Department （No. 032050102）.
文摘C-type lysozyme genes （Lyzls） belong to the class of lysozymes and are highly expressed in the testis and epididymis. The members Lyzl4 and Spaca3 have been reported to play a role in sperm-egg binding and fertilisation in mice. However, the function of the remaining two mouse c-type lysozyme genes, Lyzll and Lyzl6, is still not clear. In the present study, we analysed the tissue expression and androgen-dependent expression of mouse c-type lysozyme genes and the possible contribution of human recombinant LYZL6 （rLYZL6） to immunity. The expression of Lyzlswas detected by RT-PCR, Western blots, immunohistochemistry and immunofluorescence. The bacteriolytic activity of rLYZL6 was analysed by a colony-forming assay. In mice, the expression of Lyzlgenes was mainly in the testis and epididymis in a developmentally regulated manner and androgen- or testicular factor-regulated manner. Immunodetection revealed the presence of LYZL6 protein in primary spermatocytes and round spermatids of the testis and on the post-acrosomal area and midpiece of mature epididymal spermatozoa. The rLYZL6 protein exhibited antibacterial activity. From the results, Lyzls may play a role in mitochondrial function of spermatozoa and LYZL6 may contribute to the innate immunity of the male genital tract.
文摘Objective： We have continued previous work in which we demonstrated that #117 and #372 amino acids contributed to the high activities of human CYP2A13 in catalyzing 4-methylnitrosamino-1-（3-pyridyl）-1-butanone（NNK） and aflatoxin BI（AFB1） carcinogenic activation. The present study was designed to identify other potential amino acid residues that contribute to the different catalytic characteristics of two CYP2A enzymes, CYP2A6 and CYP2A13, in nicotine metabolism and provide insights of the substrate and related amino acid residues interactions. Methods： A series of reciprocally substituted mutants of CYP2A6lle^300→ Phe, CYP2A6Gly^301aAla, CYP2A6Ser^369 → Gly, CYP2A13Phe^300→ Ile, CYP2A13Ala^301 → Gly and CYP2A13Gly^369 → Set were generated by site-directed mutagenesis/baculovirus-Sf9 insect cells expression. Comparative kinetic analysis of nicotine 5＇hydroxylatin by wild type and mutant CYP2A proteins was performed. Results：All amino acid residue substitutions at 300, 301 and 369 caused significant kinetic property changes in nicotine metabolism. While CYP2A6Ile^300→ Phe and CYP2A6Gly^301→Ala mutations had notable catalytic efficiency increases compared to that for the wild type CYP2A6, CYP2A13Phe^300→Ile and CYP2A13Ala^301→Gly replacement introduced remarkable catalytic efficiency decreases. In addition, all these catalytic efficiency alterations were caused by Vmax variations rather than Km changes. Substitution of #369 residue significantly affected both Km and Vmax values. CYP2A6Ser^369 → Gly increase the catalytic efficiency via a significant Km decrease versus Vmax enhancement, while the opposite effects were seen with CYP2A13Gly^369 → Ser. Conclusion：#300, #301 and #369 residues in human CYP2A6/13 play important roles in nicotine 5＇ -oxidation. Switching #300 or #301 residues did not affect the CYP2A protein affinities toward nicotine, although these amino acids are located in the active center. Set369 to Gly substitution indirectly affected nicotine binding by creating more space and conformational flexibility for the nearby residues, such as Leu^370 which is crucial for many hydroxylations.
基金the National Natural Science Foundation of China (No. 20272068).
文摘Hydroxylsqualamine was synthesized stereoselectively in 13 steps and 19% overall yield from methyl hyo-deoxycholanate by using stereospecific epoxidation and asymmetric isopropylation as key steps.
