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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.
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OBJECTIVE@#To evaluate the efficacy and safety of tacrolimus in the treatment of children with myasthenia gravis (MG).@*METHODS@#A total of 28 children with MG were treated with tacrolimus. MG-Activities of Daily Living (MG-ADL) scale was used to assess clinical outcome and safety after 1, 3, 6, 9, and 12 months of treatment.@*RESULTS@#After tacrolimus treatment, the MG-ADL score at 1, 3, 6, 9 and 12 months was lower than that at baseline (P<0.05), and the MG-ADL score showed a gradually decreasing trend. The response rates to tacrolimus treatment at 1, 3, 6, 9, and 12 months were 59%, 81%, 84%, 88%, and 88% respectively. At 6, 9, 12, and 18 months of treatment, 4, 13, 14, and 15 children respectively were withdrawn from prednisone. No recurrence was observed during treatment. Major adverse reactions/events were asymptomatic reduction in blood magnesium in 5 children and positive urine occult blood in 1 child, which turned negative without special treatment, and tacrolimus was not stopped due to such adverse reactions/events. One child was withdrawn from tacrolimus due to recurrent vomiting. According to CYP3A5 genotypes, all of the patients were divided into two groups: slow metabolic type (n=19) and non-slow metabolic type (fast metabolic type + intermediate type; n=9). The non-slow metabolism group received a higher dose of tacrolimus, but had a lower trough concentration of tacrolimus than the slow metabolism group (P<0.05). The slow metabolism group had a higher response rates to tacrolimus treatment than the non-slow metabolism group (P<0.05).@*CONCLUSIONS@#Tacrolimus appears to be effective and safe in the treatment of children with MG and is thus an option for immunosuppressive therapy. CYP3A5 genotyping has a certain guiding significance for determining the dosage of tacrolimus.
Subject(s)
Child , Humans , Activities of Daily Living , Immunosuppressive Agents , Myasthenia Gravis , Drug Therapy , Neoplasm Recurrence, Local , Tacrolimus , Therapeutic UsesABSTRACT
<p><b>BACKGROUND</b>Nucleolin (NCL) is the most abundant RNA-binding protein in the cell nucleolus and plays an important role in chromatin stability, ribosome assembly, ribosomal RNA maturation, ribosomal DNA transcription, nucleocytoplasmic transport, and regulation of RNA stability and translation efficiency. In addition to its anti-apoptotic properties, the underlying mechanisms associated with NCL-related roles in different cellular processes remain unclear. In this study, the effect of NCL on microRNA (miRNA) expression was evaluated by generating transgenic mice with myocardial overexpression of NCL and by analyzing microarrays of mature and precursor miRNAs from mice.</p><p><b>METHODS</b>Using microinjection of alpha-MyHc clone 26-NCL plasmids, we generated transgenic mice with myocardial overexpression of NCL firstly, and then mature and precursor miRNAs expression profiles were analyzed in NCL transgenic mice (n = 3) and wild-type (WT) mice (n = 3) by miRNA microarrays. Statistical Package for the Social Sciences version 16.0 software (SPSS, Inc., Chicago, IL, USA) was used to perform Student's t-test, and statistical significance was determined at P < 0.05.</p><p><b>RESULTS</b>Several miRNAs were found to be differentially expressed, of which 11 were upregulated and 4 were downregulated in transgenic mice with myocardial overexpression of NCL compared to those in WT mice. Several differentially expressed miRNAs were subsequently confirmed and quantified by real-time quantitative reverse transcription-polymerase chain reaction. Bioinformatics analysis was used for the prediction of miRNA targets. Furthermore, in vitro experiments showed that NCL regulated miR-21 expression following hydrogen peroxide preconditioning.</p><p><b>CONCLUSIONS</b>Myocardial-protection mechanisms exerted by NCL might be mediated by the miRNAs identified in this study.</p>
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Background Primary conjunctival lymphoid hyperplasia exhibit atypical clinical symptoms and easy to cause misdiagnosis and mistreatment.Understanding the clinical characteristics of primary conjunctival lymphoid hyperplasia is of an important clinical significance.Objective This study was to analyze the clinical characteristics and therapeutic outcome of patients with primary conjunctival lymphoid hyperplasia.Methods The medical records of 20 patients with primary conjunctival lymphoid hyperplasia who was treated in Beijing Tongren Hospital from January 2012 to December 2014 were retrospectively analyed.The age,symptoms,therapy,prognosis,histopathological features and immonochemistry results were reviewed,and the treating approach targeting to different types of conjunctival lymphoid hyperplasia was evaluated.The fellow-up duration was 1-2 years.Results Age of the patients ranged from 27 to 83 years old.The lesions were classified as benign lymphocytic hyperplasia,atypical lymphoid hyperplasia and lymphoma.Majority of lesions located in fornix conjunctiva tissue (90％).Follicle-like appearance was seen in the benign lymphocytic hyperplasia,and pink elavation was exhibited at the bulbar conjunctiva in the atypical lymphoid hyperplasia.A diffuse salmon fish like appearance in conjunctiva was the primary feature of conjunctival lymphoma.Histopathological examination showed that conjunctival benign lymphocytic hyperplasia had follicle-like tissue in lesions,atypical lymphoid hyperplasia exhibited diffuse lymphocyte filtration,and conjunctival lymphoma appeared monocyte filtration.The 3 tpyes of lesions also could be differentiated by immunochemistry.The medicine was applied in the eyes with benign lymphocytic hyperplasia,and the combination of resection of lesions with conjunctival tissue or amniotic membrane transplantation was used for the atypical lymphoid hyperplasia or lymphoma eyes.No recurrence of the lesions was found during fellow-up duration.Conclusions The clinical manifestations of conjunctival lymphoid hyperplasia lesions are varied,and it is easy to be confused with chronic ocular surface diseases.Pathology and immunochemistry are helpful for the differential diagnosis.The treating regimen is dependent on the lesion type.Most patients have a favorable prognosis with treatment.
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OBJECTIVE:To establish a method for content determination of eucalyptol in Chimonanthus Zhejiangensis. METH-ODS:GC was conducted with Zebron ZB-WAX capillary column with temperature programmed;FID detector was used with the temperature of 250 ℃;the volume temperature was 220 ℃ and the carrier gas was nitrogen with high purity. RESULTS:Eucalyp-tol had a good linear relationship in the range of 0.017 69-1.415 mg/ml(r=0.999 1);the RSDs of precisions,stability and reproduc-ibility tests were no more than 1.87%and the average recovery was 99.72%(RSD=0.65%,n=6).There were big differences in dif-ferent areas of the same month and the maximum was more than one time (1.064%-0.450%);there were also big differences in the same area of different months(0.633%-1.064%). CONCLUSIONS:The method is simple,accurate,fast and reproducible and suitable for the quality control of Chimonanthus Zhejiangensis.