Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide and macrophage polarization plays an important role in its pathogenesis.However,which molecule regulates macrophage polarizatio...Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide and macrophage polarization plays an important role in its pathogenesis.However,which molecule regulates macrophage polarization in NAFLD remains unclear.Herein,we showed NAFLD mice exhibited increased 17β-hydroxysteroid dehydrogenase type 7(17β-HSD7)expression in hepatic macrophages concomitantly with elevated M1 polarization.Single-cell RNA sequencing on hepatic non-parenchymal cells isolated from wild-type littermates and macrophage-17β-HSD7 knockout mice fed with high fat diet(HFD)for 6 weeks revealed that lipid metabolism pathways were notably changed.Furthermore,17β-HSD7 deficiency in macrophages attenuated HFD-induced hepatic steatosis,insulin resistance and liver injury.Mechanistically,17β-HSD7 triggered NLRP3 inflammasome activation by increasing free cholesterol content,thereby promoting M1 polarization of macrophages and the secretion of pro-inflammatory cytokines.In addition,to help demonstrate that 17β-HSD7 is a potential drug target for NAFLD,fenretinide was screened out from an FDA-approved drug library based on its 17β-HSD7 dehydrogenase inhibitory activity.Fenretinide dose-dependently abrogated macrophage polarization and pro-inflammatory cytokines production,and subsequently inhibited fat deposition in hepatocytes co-cultured with macrophages.In conclusion,our findings suggest that blockade of 17β-HSD7 signaling by fenretinide would be a drug repurposing strategy for NAFLD treatment.展开更多
Objective: To seek a new biochemical index for diagnosis of coronary heart disease (CHD) of shen-Yang deficiency syndrom (CHD-SYD). Methods: Sixty-one patients with CHD were divided into 3 groups according to their TC...Objective: To seek a new biochemical index for diagnosis of coronary heart disease (CHD) of shen-Yang deficiency syndrom (CHD-SYD). Methods: Sixty-one patients with CHD were divided into 3 groups according to their TCM Syndrome type, 10 patients in the group without Xin-Qi deficiency (Group A), 25 in the group with Xin-Qi deficiency but without Shen-Yang deficiency (Group B) and 26 in the group both with Xin-Qi deficiency and Shen-Yang deficiency (Group C). Levels of 17-hydroxy-corticoste-roid in urine (urinary 17-OHCS) per 24 hrs, and serum level of high density lipoprotein cholesterol (HDL-C) and high density lipoprotein phospholipid (HDL-PL) in them were determined in synchrostep and compared with those in the control group of 23 healthy aged persons, urinary 17-OHCS per 24 hrs was taken as the diagnostic standard to screen a new index for diagnosis of Shen-Yang deficiency Syndrome, and preliminary appraisal to the index was made. Results: Serum HDL-PL in the CHD-SYD patients( Group C) was 616+157 mg/L, which was obviously lower than that in the patients of Group A and B. With low HDL-PL(<650 mg/L) used as the index to diagnose CHD-SYD, the sensitivity was 73%, the specificity 86% and the accuracy 80%. Conclusion: HDL-PL <650 mg/L could be adopted as an index for CHD-SYD diagnosis, which is simple and practical.展开更多
基金supported by the National Nature Science Foundation of China(Nos.82173872 and 81872663)。
文摘Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide and macrophage polarization plays an important role in its pathogenesis.However,which molecule regulates macrophage polarization in NAFLD remains unclear.Herein,we showed NAFLD mice exhibited increased 17β-hydroxysteroid dehydrogenase type 7(17β-HSD7)expression in hepatic macrophages concomitantly with elevated M1 polarization.Single-cell RNA sequencing on hepatic non-parenchymal cells isolated from wild-type littermates and macrophage-17β-HSD7 knockout mice fed with high fat diet(HFD)for 6 weeks revealed that lipid metabolism pathways were notably changed.Furthermore,17β-HSD7 deficiency in macrophages attenuated HFD-induced hepatic steatosis,insulin resistance and liver injury.Mechanistically,17β-HSD7 triggered NLRP3 inflammasome activation by increasing free cholesterol content,thereby promoting M1 polarization of macrophages and the secretion of pro-inflammatory cytokines.In addition,to help demonstrate that 17β-HSD7 is a potential drug target for NAFLD,fenretinide was screened out from an FDA-approved drug library based on its 17β-HSD7 dehydrogenase inhibitory activity.Fenretinide dose-dependently abrogated macrophage polarization and pro-inflammatory cytokines production,and subsequently inhibited fat deposition in hepatocytes co-cultured with macrophages.In conclusion,our findings suggest that blockade of 17β-HSD7 signaling by fenretinide would be a drug repurposing strategy for NAFLD treatment.
文摘Objective: To seek a new biochemical index for diagnosis of coronary heart disease (CHD) of shen-Yang deficiency syndrom (CHD-SYD). Methods: Sixty-one patients with CHD were divided into 3 groups according to their TCM Syndrome type, 10 patients in the group without Xin-Qi deficiency (Group A), 25 in the group with Xin-Qi deficiency but without Shen-Yang deficiency (Group B) and 26 in the group both with Xin-Qi deficiency and Shen-Yang deficiency (Group C). Levels of 17-hydroxy-corticoste-roid in urine (urinary 17-OHCS) per 24 hrs, and serum level of high density lipoprotein cholesterol (HDL-C) and high density lipoprotein phospholipid (HDL-PL) in them were determined in synchrostep and compared with those in the control group of 23 healthy aged persons, urinary 17-OHCS per 24 hrs was taken as the diagnostic standard to screen a new index for diagnosis of Shen-Yang deficiency Syndrome, and preliminary appraisal to the index was made. Results: Serum HDL-PL in the CHD-SYD patients( Group C) was 616+157 mg/L, which was obviously lower than that in the patients of Group A and B. With low HDL-PL(<650 mg/L) used as the index to diagnose CHD-SYD, the sensitivity was 73%, the specificity 86% and the accuracy 80%. Conclusion: HDL-PL <650 mg/L could be adopted as an index for CHD-SYD diagnosis, which is simple and practical.
