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ObjectiveTo investigate the mechanism of Xuefu Zhuyu capsules against atherosclerosis via regulating polarization of macrophages based on Notch1/jagged canonical Notch ligand 1(Jagged1)/Hes family BHLH transcription factor 1(Hes1) signaling pathway. MethodThe mouse models with atherosclerosis were prepared by feeding the mice with an ApoE-/- high-fat diet for four weeks, and they were randomly divided into the model group, Xuefu Zhuyu capsule group, and atorvastatin group. C57BL/6 mice were fed as a normal group. The Xuefu Zhuyu capsule group was intragastrically given Xuefu Zhuyu capsules (0.728 g·kg-1·d-1), and the atorvastatin group was intragastrically given atorvastatin tablet (6.07 mg·kg-1·d-1). The normal group and the model group were given equal volume of the deionized water by intragastric administration, and the intervention lasted for 12 weeks. Aortic plaque morphology was observed by hematoxylin-eosin (HE) staining, and aortic plaque area and lipid deposition were observed by oil red O staining. The positive expression levels of CD86 and CD206 in aortic tissue were detected by immunohistochemistry, and serum levels of tumor necrosis factor (TNF)-α, interleukin(IL)-1β, transforming growth factor (TGF)-β1, and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). The relative mRNA expressions of inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1), Notch1, Jagged1, and Hes1 in aortic tissue were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The relative protein expression of iNOS, Arg-1, Notch1, Jagged1, and Hes1 in aortic tissue was detected by Western blot. ResultCompared with the normal group, the model group had significant aortic plaque and lipid deposition, and the expression levels of pro-inflammatory cytokines TNF-α and IL-1β were increased (P<0.01). The expression level of anti-inflammatory cytokine TGF-β1 showed a downward trend, but the difference was not statistically significant. The mRNA and protein expressions of iNOS were increased (P<0.01). The protein expression of Arg-1 was decreased (P<0.01), and the mRNA expression of related pathway molecule Jagged1, as well as the protein expressions of Notch1, Jagged1, and Hes1 were increased in the model group (P<0.05, P<0.01). Compared with those in the model group, the plaque area and lipid deposition had a decreasing trend in the Xuefu Zhuyu capsule group, and the expressions of TNF-α and IL-1β showed a downward trend. The expression of TGF-β1 was increased (P<0.05), and the expression of macrophage marker CD86 was decreased. The mRNA and protein expressions of iNOS were decreased (P<0.01). The mRNA and protein expressions of Arg-1 were increased (P<0.05, P<0.01). Furthermore, the mRNA and protein expressions of Notch1, Jagged1, and Hes1 were decreased (P<0.01). ConclusionXuefu Zhuyu capsules can reduce aortic plaque area and lipid deposition in mice with atherosclerosis, alleviate inflammation, inhibit M1 macrophages, and promote the expression of M2 macrophages, and the mechanism may be related to the regulation of Notch1/Jagged1/Hes1 signaling pathway.
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Poria is an important medicine for inducing diuresis to drain dampness from the middle energizer. However, the specific effective components and the potential mechanism of Poria remain largely unknown. To identify the effective components and the mechanism of Poria water extract (PWE) to treat dampness stagnancy due to spleen deficiency syndrome (DSSD), a rat model of DSSD was established through weight-loaded forced swimming, intragastric ice-water stimulation, humid living environment, and alternate-day fasting for 21 days. After 14 days of treatment with PWE, the results indicated that PWE increased fecal moisture percentage, urine output, D-xylose level and weight; amylase, albumin, and total protein levels; and the swimming time of rats with DSSD to different extents. Eleven highly related components were screened out using the spectrum-effect relationship and LC-MS. Mechanistic studies revealed that PWE significantly increased the expression of serum motilin (MTL), gastrin (GAS), ADCY5/6, p-PKAα/β/γ cat, and phosphorylated cAMP-response element binding protein in the stomach, and AQP3 expression in the colon. Moreover, it decreased the levels of serum ADH, the expression of AQP3 and AQP4 in the stomach, AQP1 and AQP3 in the duodenum, and AQP4 in the colon. PWE induced diuresis to drain dampness in rats with DSSD. Eleven main effective components were identified in PWE. They exerted therapeutic effect by regulating the AC-cAMP-AQP signaling pathway in the stomach, MTL and GAS levels in the serum, AQP1 and AQP3 expression in the duodenum, and AQP3 and AQP4 expression in the colon.
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Animals , Rats , Poria , Spleen , Albumins , Chromatography, Liquid , Cyclic AMP Response Element-Binding ProteinABSTRACT
OBJECTIVE To investigate the effect and mechanism of Poria cocos polysaccharides on the regulation of blood glucose in type 2 diabetes mellitus (T2DM)model rats by phosphatidylinositol 3-kinase(PI3K)/protein kinase B (Akt)/forked box transcription factor O 1(FoxO1)pathway. METHODS SD rats were randomly divided into blank control group (no modeling ,no administration),model group (modeling,no administration ),metformin group (modeling,200 mg/kg)and P. cocos polysaccharide low-dose,medium-dose and high-dose groups (modeling,100,200,400 mg/kg),8 in each group. Except for blank control group , other groups were given high fat diet combined with streptozotocin to construct the model of T 2DM rats. At the same time , administration groups were given relevant dose of medicine intragastrically ,and blank control group and model group were given constant volume of water intragastrically ,once a day ,for consecutive 42 days. During the experiment ,general condition and bodyweight of rats were observed every day ;fasting blood glucose (FBG)of rats were collected ,and oral glucose tolerance test were conducted and area under curve (AUC)was calculated the day before last administration. After last medication ,the heart ,liver, kidney organ index were calculated ;the levels of HbA 1c,TC,TG,MDA,SOD,GSH-Px and hepatic glycogen content were detected. HE staining was used to observe the pathological changes of liver and pancreatic tissue ,and the pathological grade score was calculated. Western blot assay was used to detect the protein expressions of p-PI 3K,p-Akt,p-FoxO1, PEPCK and G 6Pase in liver tissues. RESULTS Compared with blank control group ,the rats of model group suffered cc1965@163.com from polydipsia ,polyphagia and polyuria ;the body weight , the levels of SOD and GSH-Px ,the protein expressions of p-PI 3K,p-Akt and p-FoxO 1 were significantly decreased (P<0.05);liver and kidney organ index ,blood glucose level at 0,0.5 and 2 hours after intragastric administration of glucose solution ,AUC, FBG,HbA1c,serum levels of MDA ,TC,TG and hepatic glycogen content ,liver and pancreatic pathological grade score ,the protein expressions of PEPCK and G 6Pase were all increased significantly (P<0.05). Compared with model group ,the general condition of rats in P. cocos polysaccharide groups were all improved ,and all of above indicators had been reversed to varying degrees. CONCLUSIONS P. cocos polysaccharide can downregulate protein expressions of PEPCK and G 6Pase which are key enzymes of gluconeogenesis ,inhibit hepatic gluconeogenesis ,effectively decrease blood glucose levels and regulate glucolipid metabolism in T 2DM model rats by weakening oxidative stress and upregulating PI 3K/Akt/FoxO1 pathway.
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Objective@#To investigate the effects of acylated ghrelin and des-acylated ghrelin on skeletal muscle atrophy in elderly mice.@*Methods@#Eighteen-month-old wild type(WT)mice and ghrelin-/- mice were selected to perform body composition analysis and wheel-running test under conditions of feeding versus fasting.The gene expressions of myogenic regulatory factors including muscle differentiation factor MyoD, myogenin, atrogin-1, muscle-specific RING finger protein 1(muRF-1), and insulin growth factor 1(IGF-1)in mice gastrocnemius muscle were detected by realtime polymerase chain reaction(PCR).@*Results@#The locomotor activity during the wheel-running test were significantly lower in elderly ghrelin-/- mice than in elderly WT mice(3 929±263 times/h vs.5359±601 times/h, t=4.87, P<0.05). The gene expressions of MyoD, myogenin, atrogin-1, muRF-1 and IGF-1 had no significant difference between the two groups(P>0.05). After 48 h fasting, the decrements of body weight, fat and muscle weight were more in ghrelin-/- mice than in WT mice(P<0.05). In fasting old ghrelin-/- mice, the gene expressions of MyoD and myogenin were increased(improved)(t=232.00 and 121.00, P<0.05), and the gene expressions of atrogin-1 and muRF-1 were decreased(improved)(t=30.40 and 54.00, P<0.05)after treatment with both acylated ghrelin and desacylated ghrelin.@*Conclusions@#The acylated ghrelin and desacylated ghrelin may play protective roles in age-related muscle atrophy.
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Objective To investigate the effects of acylated ghrelin and des-acylated ghrelin on skeletal muscle atrophy in elderly mice.Methods Eighteen-month-old wild type (WT)mice and ghrelin-/-mice were selected to perform body composition analysis and wheel-running test under conditions of feeding versus fasting.The gene expressions of myogenic regulatory factors including muscle differentiation factor MyoD,myogenin,atrogin-1,muscle-specific RING finger protein 1 (muRF-1),and insulin growth factor 1 (IGF-1) in mice gastrocnemius muscle were detected by realtime polymerase chain reaction (PCR).Results The locomotor activity during the wheel-running test were significantly lower in elderly ghrelin-/-mice than in elderly WT mice (3 929 ± 263 times/h vs.5359± 601 times/h,t =4.87,P < 0.05).The gene expressions of MyoD,myogenin,atrogin-1,muRF-1 and IGF-1 had no significant difference between the two groups (P > 0.05).After 48 h fasting,the decrements of body weight,fat and muscle weight were more in ghrelin-/-mice than in WT mice(P<0.05).In fasting old ghrelin-/-mice,the gene expressions of MyoD and myogenin were increased(improved) (t =232.00 and 121.00,P < 0.05),and the gene expressions of atrogin-1 and muRF-1 were decreased(improved) (t =30.40 and 54.00,P<0.05)after treatment with both acylated ghrelin and desacylated ghrelin.Conclusions The acylated ghrelin and desacylated ghrelin may play protective roles in age-related muscle atrophy.
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Endometriosis (EM) is one of the most common gynaecological disorder affecting women in their reproductive age. Mechanisms involved in the pathogenesis of EM remains poorly understood, however inflammatory responses have been reported to be significantly involved. The efficacy of 6-shogaol on proliferation of endometriotic lesions and inflammatory pathways in experimentally-induced EM model was explored in this study. EM was stimulated in Sprague-Dawley rats by implantation of autologous endometrium onto the peritoneum abdominal wall. Separate groups were treated with 6-shogaol (50, 100 or 150 mg/kg b.wt/day) via oral gavage for one month period. Gestrinone (GTN) group received GTN (0.5 mg/kg/day) as positive control. Five weeks after implantation, the spherical volume of ecto-uterine tissues was determined. Treatment with 6-shogaol significantly reduced the implant size. Histological analysis reported atrophy and regression of the lesions. 6-shogaol administration effectively down-regulated NF-κB signaling, VEGF and VEGFR-2 (Flk-1) expression in the endometriotic lesions. Excess production of IL-1β and IL-6 (pro-inflammatory cytokines), PGE2 and nitric oxide (NO) were reduced. Overall, the results of the study reveal the efficacy of 6-shogaol against endometriosis via effectively suppressing proliferation of the lesions and modulating angiogenesis and COX-2/NF-κB-mediated inflammatory cascades.
Subject(s)
Female , Humans , Abdominal Wall , Atrophy , Dinoprostone , Endometriosis , Endometrium , Gestrinone , In Vitro Techniques , Interleukin-6 , Nitric Oxide , Peritoneum , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor Receptor-2ABSTRACT
Objective To explore the prospective monitoring and control methods for missing reporting of health-care-associated infection(HAI)cases,analyze its implementation efficacy,provide basis for formulating targeted strategy for monitoring missing report of HAI.Methods From January 2016 to June 2017,the quality control circle (QCC)method was used to prospectively monitor HAI cases in hospitalized patients,missing reporting of HAI was controlled.Results "Information system intelligence screening+mobile messaging alerts+ HAI supervision"trinity monitoring model for avoid missing reporting of HAI cases was established,after the first round of PDCA(plan, do,check,action)cycle,missing reporting rate of HAI decreased from 79.16% before QCC to 59.75% after QCC, difference was statistically significant (χ2=208.821,P=0.000).Compared with missing reporting rate of HAI af-ter the first round of PDCA,missing reporting rate of HAI after the second round of PDCA dropped to 26.18%, difference was statistically significant (χ2=200.075,P=0.002).Conclusion Active prospective prevention and control before missing reporting of HAI can effectively avoid missing reporting of HAI cases.
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Objective To explore the influence of the protection motivation theory (PMT) on the self-nursing ability of high-risk diabetic foot (DF) patients. Methods The outpatients in our hospital were selected with high-risk DF between January 2013 and May 2014, randomly divided into the control group and PMT group, 52 cases in each group. Guided under the protection motivation theory, PMT group received a six-month health education and management; and the control group accepted conventional health education of diabetes. Before and after the intervention, some observation indexes of the two groups respectively were evaluated including the ability of diabetic foot self-nursing, foot condition, fasting blood sugar, 2 h postprandial blood glucose. Result After six months, the scores of the self-care ability of diabetic foot and foot condition from the patients of PMT group were higher than that of PMT group before the intervention and that of control group after intervention (P<0.05). Conclusion PMT can help patients with high-risk DF enhance their foot self-care ability, improve their foot condition, control their blood sugar, and prevent the DF onset.
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We investigated the distribution characteristics of Yersinia enterocolitica in Ningxia ,China .In accordance with the requirements of the National Yersinia enterocolitica Disease Monitoring Scheme ,Y .enterocolitica were isolated from differ‐ent kinds of specimens collected in Ningxia in 2008 to 2013 .Then they were serotyped and detected for virulence gene and ana‐lyzed the pulsed‐field gel electrophoresis (PFGE) in Chinese CDC .It was found that 173 strains were isolated from various types of 9 643 specimens ,and the detection rate was 1 .79% .There were statistical differences among detection rates in differ‐ent years and in different specimens (P<0 .01) .Pathogenic serotypes O∶3 and O∶9 carried ail gene and ystA gene were de‐tected from specimens of pigs and diarrhea patient .Non‐pathogenic serotypes O∶5 and O∶8 and non‐typeable strains didn't carry ail gene and ystA gene ,and also can't be detected from swine ,cattle ,sheep ,chickens and dogs .In conclusion ,Y .en‐terocolitica was widely distributed in Ningxia and pigs were the dominant animal host .In all pathogenic serotypes ,the highest proportion was O∶3 following by O∶9 .It was no time and regional difference in the distribution of that in Ningxia ,China .
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Objective This study was to analyze the causes of the complications of ultrasound -guided percutaneous renal bi-opsy in children . Methods We retrospectively analyzed the complications of ultrasound-guided percutaneous renal biopsy in 236 children along with the age, sex, sample length, times of puncture, and types of disease of the patients .We used the binary Logistic regression model to analyze the influences of various factors on the post -biopsy complications . Results After renal biopsy , 22 (9.3%) of the patients experienced various degrees of but no severe complications .The incidence of complications was significantly correlated with the sample length (P<0.05), but not with the age, sex, sample length, times of puncture, and types of disease of the patients. Conclusion Ultrasound-guided percutaneous renal biopsy is an effective diagnostic method for children , with a high suc-cess rate and a low incidence of complications .And the incidence of complications can be reduced by improving the skills of puncturing and accuracy of ultrasound positioning .
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This study reviews a case of mitochondrial respiratory chain complex I deficiency due to the 10191T>C mutation in mitochondrial ND3 gene. The previously healthy boy progressively presented with blepharoptosis, weakness, epilepsy and motor regression at age 6 years. Elevated blood lactate and pyruvate were observed. Brain magnetic resonance imaging showed symmetrical lesions in the basal ganglia. Leigh syndrome was thus confirmed. The protein from the mitochondria and genomic DNA of the boy and his parents was collected from peripheral blood leucocytes for the activity test for mitochondrial complex I to V and genetic analysis. The results showed the activity of complex I (33.1 nmol /min in 1 milligram mitochondrial protein) was lower than normal reference value (44.0±5.4 nmol /min in 1 milligram mitochondrial protein). The ratio of complex I to citrate synthase (19.8%) was also lower than normal reference value (48%±11%). The activities of complexes II to V were normal. 10191T>C mutation in ND3 gene of mitochondria was identified in the boy. 10191T>C mutation and complex I deficiency were not detected in his parents. At present, he is 16 years old, and of normal intelligence with spastic paralysis in both lower extremities after treatment. It is concluded that a Chinese boy with isolated complex I deficiency due to 10191T>C mutation in ND3 gene was firstly diagnosed by peripheral leukocytes mitochondrial respiratory chain enzyme assay and gene analysis. This study can provide clinical data for the nosogenesis of Leigh syndrome.
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Adolescent , Humans , Male , Brain , Pathology , Electron Transport Complex I , Genetics , Leigh Disease , Genetics , Magnetic Resonance Imaging , Mitochondrial Diseases , Genetics , MutationABSTRACT
The role of dopamine D3 receptors playing in drug dependence has attracted a lot of attention.Pharmacological experiments suggest that dopamine D3 receptors be involved in mechanism of drug addiction and affect the movement and behavior of rodents. Dopamine D3 receptor gene is considered as a candidate gene related to dopaminergic system dysfunction including schizophrenic disorders and essential tremor.
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<p><b>OBJECTIVE</b>To construct the recombinant adenovirus expression vector of a short hairpin RNA (shRNA) targeting phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene for gene therapy of ischemic cerebral injury.</p><p><b>METHODS</b>The U6 expression promoter and shRNA of pGenesil-1-shRNA, which was constructed and identified in our previous experiment, were subcloned to pAdTrack shuttle plasmid. The product pAdTrack-U6-shRNA was linearized by PmeI for homologous recombination with pAdEasy-1 in pAdEasy-1 competence bacteria. The positive clone was identified by enzyme digestion, PCR analysis and DNA sequence analysis. After linearization by PacI, the recombinant adenovirus DNA shuttle plasmid pAdEasy-U6-shRNA was transfected into 293 cells for packaging and amplification of Ad-U6-shRNA, which was further identified by PCR analysis and DNA sequence analysis. Western blotting was used to detect the expression of PTEN protein in the hippocampal neurons infected with the adenovirus.</p><p><b>RESULTS</b>The pAdTrack-U6-shRNA and pAd-U6-shRNA plasmids had been successfully constructed as verified by PCR analysis, enzyme digestion and DNA sequence analysis. PCR analysis and DNA sequence analysis confirmed successful packaging of the recombinant adenovirus Ad-U6-shRNA in 293 cells. PTEN protein expression decreased significantly in the hippocampal neurons after infection by the recombinant virus.</p><p><b>CONCLUSION</b>We have successfully constructed the recombinant adenovirus Ad-U6-shRNA targeting PTEN gene, which provides a basis for investigating the role of PTEN in neuroprotection after cerebral ischemic injury using RNA interference.</p>
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Humans , Adenoviridae , Genetics , Metabolism , Genetic Vectors , Genetics , PTEN Phosphohydrolase , Genetics , RNA Interference , RNA, Small Interfering , Genetics , Recombinant Proteins , Genetics , Sequence Analysis, DNAABSTRACT
<p><b>BACKGROUND</b>Dyslipidaemia is a potential independent risk factor for cerebrovascular disease in patients with diabetes. The aim of this study was to investigate dyslipidaemia, treatment and control of dyslipidaemia among diabetic patients with ischemic stroke in a Chinese hospital.</p><p><b>METHODS</b>A total of 1046 type 2 diabetic patients were assigned to diabetes with (n = 522) and diabetes without stroke groups. The two groups were matched by gender, age and diabetes duration. Lipid and lipoprotein profile were measured. Serum level and control of lipids were assessed and classified according to American Diabetes Association (ADA) guidelines and an intensified low density lipoprotein-cholesterol (LDL-C) target recommended in Chinese dyslipidaemia control criteria.</p><p><b>RESULTS</b>Diabetic patients suffering stroke displayed not only poorly-controlled lipid and lipoprotein profiles, including the significantly lower proportion of patients achieving intensified LDL-C target of < 2.07 mmol/L (80 mg/dl), and high density lipoprotein-cholesterol (HDL-C) target (14.4% vs 21.0%, P = 0.005; 45.8% vs 51.9%, P = 0.048 respectively), but also less adherence to therapy prescribed for dyslipidaemia (30.8% vs 41.0%, P = 0.001), when compared with diabetic patients without stroke. For the diabetic women with stroke, situation of dyslipidaemia was worse, with significantly lower serum level of HDL-C and apoA1, higher LDL-C level and higher ratio of apoB/apoA1 when compared with diabetic counterparts without stroke.</p><p><b>CONCLUSIONS</b>Many diabetic patients with ischemic stroke remain uncontrolled for dyslipidaemia. Intensified LDL-C and overall lipid lowering clinical goals are potential precautions taken against ischemic stroke among diabetic patients in China.</p>
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Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , China , Diabetes Mellitus, Type 2 , Dyslipidemias , Epidemiology , Stroke , EpidemiologyABSTRACT
Leigh syndrome is a genetically heterogeneous disease caused by defects in enzymes involved in aerobic energy metabolism and the Krebs', cycle. Mitonchondrial complex I deficiency is a main cause of Leigh syndrome. In this study, a Chinese child with Leigh syndrome caused by 13513G>A mutation was reported. The proband was the first child of his parents. The previously healthy boy presented with generalized epilepsy at 12 years of age. When he visited Peking University First Hospital at 13 years of age, he had subacute loss of vision in two eyes and temporal defect of visual field in the left eye. He walked with a spastic gait. His blood lactate and pyruvate levels were elevated. Muscle biopsy showed mild lipid accumulation in muscle fiber. An electrocardiogram showed incomplete right bundle branch block. Brain magnetic resonance imaging showed bilateral, symmetrical lesions in the basal ganglia, supporting the diagnosis of Leigh syndrome. 13513G>A mutation was identified by gene analysis in the patient, which led to mitochondrial respiratory chain complex I deficiency. Multivitamins and L-carnitine were administered. At present, the patient is 16 years old and has progressive deterioration with significant muscle weakness and body weight loss. He is absent from school. He has no obvious retardation in intelligence. 13513G>A mutation was first identified by gene analysis in Chinese population with Leigh syndrome. This may be helpful in genetic counseling.
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Adolescent , Humans , Male , DNA, Mitochondrial , Genetics , Electron Transport Complex I , Leigh Disease , Genetics , MutationABSTRACT
The effect of rosiglitazone and advanced glycation end products (AGEs) on the expression of fractalkine in cultured human renal mesangial cells (HRMC) were investigated. Rosiglitazone inhibits the upregulation of fractalkine induced by AGEs in HRMC.