ABSTRACT
ObjectiveTo investigate the effect and mechanism of Mori Folium extract on the glucose and lipid metabolism disorders in the liver of rats with type 2 diabetes mellitus （T2DM） through the phosphatidylinositol 3-kinase/protein kinase B/peroxisome proliferation-activated receptor α/carnitine palmitoyl transferase-1 （PI3K/Akt/PPARα/CPT-1） signaling pathway. MethodThe T2DM model was induced by the high-fat diet combined with the intraperitoneal injection of streptozotocin （STZ）. The model rats were randomly divided into a model group， a metformin （0.2 g·kg-1） group， and a Mori Folium water extract （4.0 g·kg-1） group according to blood glucose and body weight. In the 8-week administration， fasting blood glucose was measured at the same time every week. The histomorphological and fat changes in the rat liver were observed by hematoxylin-eosin （HE） staining and oil red O staining. The levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） in the serum were measured by biochemical methods. Western blot （WB） was used to quantitatively detect the protein expression of p-PI3K，PI3K，p-Akt，Akt，PPARα，and CPT-1 in the rat liver. ResultAfter 8-week administration， the blood glucose of rats was higher in the model group than that in the control group （P<0.01）， and lower in the Mori Folium water extract group than that in the model group （P<0.01）. The results of HE staining showed that the liver tissue structure of the control group was complete， and the hepatocytes were arranged radially around the central vein， while the hepatocyte injury in the model group was obvious. Compared with the model group， the Mori Folium water extract group showed improved vacuolar degeneration and no lesions such as small bile duct hyperplasia. Oil red O staining showed that there was no obvious steatosis and necrosis in the hepatocytes of rats in the control group， and no lipid droplets in the hepatocytes were observed， while the model group showed increased lipid droplets. Mori Folium significantly reduced the lipid droplets in the liver. Biochemical analysis showed that the levels of TC， TG， LDL-C， AST， and ALT in the model group were significantly higher than those in control group （P<0.01）. The levels of TC， TG， LDL-C， AST， and ALT in the Mori Folium water extract group were significantly lower than those in the model group （P<0.05，P<0.01）. WB showed that the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 in the model group were lower than those in the control group （P<0.01）. Mori Folium water extract could increase the protein expression of p-PI3K/PI3K， p-Akt/Akt， PPARα， and CPT-1 （P<0.05 or P<0.01）. ConclusionThe hypoglycemic mechanism of Mori Folium water extract may be related to the regulation of the PI3K/Akt/PPARα/CPT-1 signaling pathway.
ABSTRACT
Objective • To establish the Fbxo22 knockout mouse model and study the biological function of FBXO22. Methods • The Fbxo22 knockout mice were generated by CRISPR-Cas9 technology. The number, appearance, weight of different embryos and mice were measured. Meanwhile, the food intake and survival of Fbxo22-/- mice were analyzed. Results • Although the Fbxo22-/- embryos were present at approximately Mendelian ratios on embryonic day 17.5/18.5, most of them died within 48 hours of birth. Furthermore, those surviving Fbxo22-/- mice showed reduced body size and food intake and decreased life span. Conclusion • FBXO22 is an important, albeit not essential, protein for early postnatal survival and normal development.
ABSTRACT
Objective · To establish the Fbxo22 knockout mouse model and study the biological function of FBXO22. Methods · The Fbxo22 knockout mice were generated by CRISPR-Cas9 technology. The number, appearance, weight of different embryos and mice were measured. Meanwhile, the food intake and survival of Fbxo22-/- mice were analyzed. Results · Although the Fbxo22-/- embryos were present at approximately Mendelian ratios on embryonic day 17.5/18.5, most of them died within 48 hours of birth. Furthermore, those surviving Fbxo22-/- mice showed reduced body size and food intake and decreased life span. Conclusion · FBXO22 is an important, albeit not essential, protein for early postnatal survival and normal development.
ABSTRACT
<p><b>OBJECTIVE</b>Increased cAMP response element modulator α (CREMα) in T cells plays an essential role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of this study was to investigate the mechanisms that elevates CREMα expression in SLE.</p><p><b>METHODS</b>CD4T cells from 5 healthy volunteers and 5 SLE patients were isolated for analysis of histone H3 lysine 27 trimethylation (H3K27me3) enrichment in different gene promoters using chromatin immunoprecipitation (ChIP) microarray. The levels of H3K27me3, H3K27 demethylases Jumonji domain containing 3 (JMJD3) and ubiquitously transcribed X (UTX), and H3K27 methyltransferase enhancer of zeste homolog 2 (EZH2) within the CREMα promoter were subsequently tested by ChIP and real?time PCR in CD4T cells from 30 normal controls and 30 SLE patients; CREMα mRNA level was also determined by real?time RT?PCR.</p><p><b>RESULTS</b>Analysis of ChIP microarray data identified that H3K27me3 enrichment at the CREMα promoter in CD4T cells from SLE patients was 0.23 times that of the normal control subjects. The results of ChIP and real?time PCR confirmed a marked decrease of H3K27me3 enrichment at the CREMα promoter in CD4T cells from SLE patients (P<0.001). The level of H3K27me3 at the promoter was negatively correlated with CREMα mRNA level in CD4T cells from SLE patients (P<0.001). In addition, a sharp increase was observed in JMJD3 binding at the CREMα promoter region in CD4T cells from SLE patients (P<0.001), and it was negatively correlated with H3K27me3 enrichment (P<0.001) and positively correlated with CREMα mRNA level (P<0.001). There were no significant changes in UTX (P=0.172) or EZH2 (P=0.281) binding at the CREMα promoter region in CD4T cells from SLE patients as compared to normal controls.</p><p><b>CONCLUSION</b>Increased JMJD3 binding down-regulates H3K27me3 enrichment at the CREMα promoter in CD4T cells of SLE patients to stimulate CREMα overexpression and result in the development of SLE.</p>