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Aim To explore the effect of chrysin on chondrocyte autophagy in rat chondrocyte osteoarthritis model induced by lipopolysaccharide and its mechanism. Methods Normal articular cartilage cells of 10 SPF SD rats were isolated and cultured in vitro, and the autophagy of rat chondrocytes was induced by LPS. The experiment was divided into blank control group, LPS group, chrysin (CHR) group and LPS + CHR group, the activity of cells in each group was detected by CCK-8 method, the mitochondrial membrane potential of cells in each group was detected by Rhodaminel23, and the protein expression of PI3K, AKT, p-PI3K, p-AKT, Beclin-1 and LC3 II in cells of each group was detected by reactive oxygen species, Western blot method of DCFH-DA. Results Chrysin could inhibit the autophagy induced by LPS, especially when the concentration of chrysin was 10 mmol · L
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Objective:To explore the characteristics of cognitive function in patients with early onset and adult onset schizophrenia.Methods:In this cross-sectional study, 546 patients with schizophrenia who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-Ⅳ) were selected.Among them, 62 cases were defined as early onset schizophrenia (EOS, age of onset＜18 years) and 175 patients were defined as adult onset schizophrenia (AOS, age of onset≥25 years).Patients underwent clinical assessments with the Positive and Negative Symptom Scale (PANSS) and the Personal and Social Performance Scale (PSP), and comprehensive neuropsychological assessments.Results:The EOS patients got lower scores in motor function-PEGDOM T score [ (26±12) vs. (30±11), P＜0.01], working memory-average T score of PASAT and WMSSP[ (34±12) vs. (38±10), P＜0.05]and executive function (inhibition) -Stroop T score [ (35±12) vs. (39±10), P＜0.05]than AOS patients.No differences were fund in processing speed, verbal memory and learning, visual memory and learning (Ps＞0.05) between the two groups.Conclusion:It suggests that the EOS patients have worse motor function, working memory and inhibition.
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Objective To evaluate the expression profile of succinate dehydrogenase (SDH)B and SDHC in pheochromocytoma (PCC) and paraganglioma(PGL) (collectively abbreviated as PPGL), and their value in the early diagnosis of malignancy. Methods SDHB and SDHC immunohistochemistry were performed on 140 tumor specimens from 126 PPGL patients (PCC n＝62, PGL n＝61, PCC+PGL n＝3). Results (1) Germline mutation status of 67 patients were determined, of which, identifying 37(55.2%) patients with germline mutation: 2 (3.0%) SDHA, 18 ( 26. 9%) SDHB, 2 ( 3. 0%) SDHC, 5 ( 7. 5%) SDHD, 2 ( 3. 0%) VHL, 7 ( 10. 4%) RET, and 1(1.5%) NF1; and 30 (44.8%) individuals without known mutation. (2) Among 30 PPGLs from 27 patients with SDH-related (SDHx) mutations, 96.7%(29/30) stained negative for SDHB, 76.7%(23/30) stained negative for SDHC, while only 28.6%(14/49) and 18.4%(9/49) stained negative for SDHB and SDHC respectively in the 49 PPGLs without SDHx mutation (P<0.05). (3) The sensitivity of the SDH immunostaining in detecting the presence of germline SDHx mutation was 96.7%for SDHB and 76.7%for SDHC, while the specificity was 71.4%for SDHB and 81.6% for SDHC. ( 4 ) Among PPGLs without SDHB expression, 22. 9% were malignant. This percentage is significantly higher than that in PPGLs with preserved SDHB expression (3.8%, P<0.05). Conclusion SDHB and SDHC immunohistochemistry may serve as post-surgical screening tools to predict the presence of germline SDHx mutation in PPGLs. Negative SDHB expression calls for intense follow-up to rule out malignancy.
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Objective To evaluate the value of captopril challenge test (CCT) in the diagnosis of primary aldosteronism (PA).Methods A total of 674 patients [(45.0±13.7) years, men 341, women 333] admitted to Peking Union Medical College Hospital from 2000 to 2015 were analyzed.Among them, 222 subjects were with essential hypertension (EH), 28 were with pheochromocytoma (PHEO), 246 were with idiopathic hyperaldosteronism (IHA) and 178 were with aldosterone producing adenoma (APA).All patients received CCT.24 h urine sodium was measured in partial patients.Plasma renin activity (PRA), aldosterone (ALD) were detected.Results Compared with EH [PRA: before 0.5(0.2,0.9) μg·L-1·h-1, after 0.8(0.4,1.5) μg·L-1·h-1;ALD: before (393±122) pmol/L, after (360±97) pmol/L] and PHEO [PRA: before 0.3(0.1,0.9) μg·L-1·h-1, after 0.4(0.1,1.6) μg·L-1·h-1;ALD: before (396±108) pmol/L, after (374±114) pmol/L], lower levels of PRA and higher levels of ALD before and after CCT were observed in PA patients [PRA: before 0.1 (0.1,0.2) μg·L-1·h-1, after 0.1 (0.1,0.2) μg·L-1·h-1;ALD: before (468±216) pmol/L;after (457±199) pmol/L].After CCT, the suppression rate of ALD [2.8% (-8.8%,15.4%) vs 6.6% (-4.3%, 17.6%)] and increasing rate of PRA [0(0,50%) vs 50%(0, 200%)] in PA patients were lower than those in EH patients.The ALD/PRA ratio (ARR) were higher in PA than that in EH or PHEO patients.In the EH subjects, ALD levels of seated posture were higher than those of recumbent posture both before and after receiving captopril, but with no changes in ARR after CCT.No significant differences in ALD and ARR (before and after receiving captopril) were observed between seated and recumbent position in the PA group.The ARR after CCT tended to decrease in EH subjects with elevated urine-sodium compared with those with normal urine-sodium.No changes could be viewed in ALD and PRA levels between normal urine-sodium and elevated urine-sodium groups among APA, IHA and EH patients either before or after CCT.Among patients with APA, the ALD levels before CCT and the ARR after CCT were lower in the patients with AngiotensionⅡ(AngⅡ) reactive than those without.A ROC curve analysis suggested that the optimal cutoff value was 46.2 (ALD unit:ng/dl;PRA unit:μg·L-1·h-1) for ARR after challenge in diagnosing PA, with the sensitivity of 88.7% and specificity of 84.8%.Conclusions ARR after 25 mg captopril had high sensitivity and specificity in diagnosis of PA with the cutoff of 46.2.Seated CCT could replace recumbent CCT as a more confirmatory test.The PRA increasing rate should be taken into consideration when diagnosis of PA.
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Objective@#To assess the association of the FSHR Thr307Ala-Asn680Ser gene polymorphism with male infertility.@*METHODS@#We searched Pubmed, EMBASE, Web of Science, CNKI, and WANFANG databases for literature on the correlation of the FSHR Thr307Ala-Asn680Ser gene polymorphism with male infertility published from 2005 to the present time. According to the inclusion criteria, we included 12 epidemiological case-control studies and subjected them to a comprehensive analysis with the Stata11.0 software.@*RESULTS@#A total of 2 893 male infertility patients and 3 312 controls were involved in the 12 studies. The Thr307Ala (rs6165) gene polymorphism was shown to be a risk factor for male infertility among the three comparison models (homozygous comparison model, hybrid comparison model and dominant comparison model), with the pooled odds ratios (OR) of 1.26 (95% CI: 1.03－1.54, P = 0.023), 1.18 (95% CI: 1.03－1.36, P = 0.018), and 1.20 (95% CI: 1.05－1.37, P = 0.006), respectively. And the Asn680Ser(rs6166) polymorphism was a risk factor for male infertility in the homozygous comparison and recessive comparison models, with the pooled ORs of 1.24, (95% CI: 1.05－1.45, P = 0.009) and 1.20 (95% CI: 1.04－1.39, P = 0.013), respectively. Layered meta-analysis showed that in the homozygous comparison model, the Thr307Ala-Asn680Ser polymorphism is a risk factor for male infertility in the white population, with the OR of 1.37 (95% CI: 1.03－1.82, P = 0.003) and 1.21 (95% CI: 1.00－1.47, P = 0.048), respectively.@*CONCLUSIONS@#In the homozygous model (GG vs AA), the FSHRThr307Ala-Asn680Ser gene polymorphism might be a protective factor against male infertility.
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Humans , Male , Case-Control Studies , Follicle Stimulating Hormone, Human , Genetics , Homozygote , Infertility, Male , Genetics , Polymorphism, Genetic , Risk FactorsABSTRACT
Objective To realize leap-forward development in hospital informatization with the cloud hospital construction in Xiamen Third Hospital taken as an example.Methods The concept of Health Medical Cloud in Xiamen was introduced,and the advantages,risks,establishment of safety protection unit,difficulty and etc were analyzed during the cloud hospital construction.Results The cloud hospital enhanced hospital efficiency and medical service greatly,and the objectives were fulfilled for the cloud hospital.Conclusion The cloud hospital saves the costs for construction,running and maintenance,shortens the period for system construction,enhances hospital informatization.
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Objective To realize leap-forward development in hospital informatization with the cloud hospital construction in Xiamen Third Hospital taken as an example.Methods The concept of Health Medical Cloud in Xiamen was introduced,and the advantages,risks,establishment of safety protection unit,difficulty and etc were analyzed during the cloud hospital construction.Results The cloud hospital enhanced hospital efficiency and medical service greatly,and the objectives were fulfilled for the cloud hospital.Conclusion The cloud hospital saves the costs for construction,running and maintenance,shortens the period for system construction,enhances hospital informatization.
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<p><b>OBJECTIVE</b>To compare the roles of alisma and gliclazide in the treatment of diabetes in Goto-Kakizaki (GK) rats.</p><p><b>METHODS</b>GK rats were randomly divided into alisma group, gliclazide group, and blank group, and Wistar rats were used as the normal group. After two weeks of treatment, body weight, food intake,fasting glucose, impaired glucose tolerance, and other indicators were measured.</p><p><b>RESULTS</b>The body weight increased after the treatment in the normal group,blank group,and gliclazide group [(241.3 ± 7.0)g vs.(263.5 ± 11.1)g, (242.8 ± 7.1)g vs.(267.9 ± 16.8)g, (243.9 ± 12.2)g vs.(277.9 ± 9.8)g, P<0.05] but decreased in alisma group [(244.6 ± 9.2)g vs.(227.9 ± 13.7)g, P<0.05]. The food intake showed no significant change before and after administration among different groups(P>0.05). Fasting glucose was significantly lower in normal group than in control group,alisma group,and gliclazide group [(4.8 ± 0.2) mmol/L vs.(8.2 ± 1.4) mmol/L,(8.1 ± 0.6) mmol/L, (8.1 ± 0.9)mmol/L, P<0.05] one week after drug administration; it was not significantly different among blank group,alisma group,and gliclazide group before drug administration (P>0.05); however, it significantly decreased in alisma group and gliclazide group two weeks after administration [(6.9 ± 0.7) mmol/L vs.(8.1 ± 0.6) mmol/L; (5.8 ± 0.5) mmol/L vs.(8.1 ± 0.9) mmol/L, P<0.05]; compared with the blank group, the fasting glucose was significantly lower in the alisma group and gliclazide group,and it was also significantly different between these two groups [(6.9 ± 0.7) mmol/L vs.(8.8 ± 0.6) mmol/L,(5.8 ± 0.5)mmol/L vs.(8.8 ± 0.6)mmol/L, (6.9 ± 0.7) mmol/L vs.(5.8 ± 0.5)mmol/L, P<0.05]. Compared with the normal group,glucose tolerance was abnormal in blank group,alisma group,and gliclazide group;after two weeks of treatment,glucose tolerance was significantly improved in alisma group (P<0.05); compared with the pretreatment level and that in the blank group,the glucose tolerance in gliclazide group showed no significant difference (P> 0.05).</p><p><b>CONCLUSIONS</b>Both alisma and gliclazide monotherapy is effective in lowering fasting blood glucose. As a single-target drug,gliclazide has stronger effecacy in lowering fasting glucose. However, alisma, as a mixture, can also control weight and improve glucose intolerance.</p>
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Animals , Rats , Alisma , Blood Glucose , Body Weight , Diabetes Mellitus, Experimental , Gliclazide , Rats, WistarABSTRACT
Aim To study targeting capability of anti-CD19 (Fab)-LDMto CD19 +B lymphoma cells in vi-vo and in vitro.Methods Flow cytometry was em-ployed to determine the affinity of Cy5 labeled anti-CD19 (Fab)-LDP to human lymphoma Raji cells.And the optical imaging system was used to analyze the dis-tribution of Cy5-anti-CD19 (Fab )-LDP in lymphoma-transplanted xenograft nude mice in vivo.Results The results of flow cytometry demonstrated that Cy5-an-ti-CD19(Fab)-LDP had remarkable affinity with lym-phoma Raji cells;Raji lymphoma xenograft model was established successfully in nude mice and in vivo fluo-rescence imaging analysis indicated that the antibody-drug conjugates could specially be localized in the tar-get tumor.Conclusion The experiments in vivo and vitro confirm that anti-CD19 (Fab)-LDP has remarka-ble affinity to targeting CD19 +lymphoma cells,and the antibody drugs anti-CD19 (Fab )-LDP have the probability to be new drugs for the treatment of malig-nant lymphoma.
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Prenatal lead exposure could not only affect various organ systems of the mother, but also provide a plumbeous environment for the fetus and newborns, and may affect the fetus in a number of detrimental ways. The aim of this study was to adequately determine the interaction between these factors and risky behaviors such as smoking. Data from Nanjing Maternity and Child Health Care Hospital survey during the years of 2006-2011 were used [n = 4400] to evaluate the effections of age, parity, body mass index [BMI], race/ethnicity, pregnancy, iron [Fe] storage status and smoking status on the consumption of the levels of blood cadmium [Cd] and lead [Pb] of females aged 16-35 yr old. The blood samples were sent to determine blood lead / cadmium concentration by the Inductively Coupled Plasma Mass Spectrometry [ICP-MS]. STATA 12.1 software [www.stata.com] was used to fit regression models for each of the two metals. For both of the two metals, age was positively while BMI was negatively associated with the levels of these metals in blood. Smokers showed statistically significantly higher levels of Cd and Pb [P=0.007], while irrespective of race/ethnicity and Fe storage status as compared to nonsmokers. Novel to this study, pregnancy was found to be associated with significantly lower levels of Cd and Pb, while irrespective of race/ethnicity and Fe storage status as compared to non-pregnant females. It is conceivable that pregnancy could thus accelerate clearance of these metals in the blood
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The expression profile in the mouse hepatitis B virus X (HBx)-transfected model was investigated in order to lay a foundation for further study on the implication of cytokines expression in hepatitis B virus (HBV) infection. Hydrodynamic injection method via the tail vein was used to establish the animal HBx-transfected model. By using microassay, the differential expression of gene in each group was analyzed, which was further confirmed by using real-time PCR and semi-quantitative PCR. Most of chemokine genes such as Ccl2, Ccl5, Ccl9, MIG and IP-10 were up-regulated in the HBx-transfected mouse model versus the control mice, which was coincided with the microarray results. Western blotting and immunohistochemistry were applied to detect the expression of MIG and IP-10 in the liver tissues. Simultaneously, ELISA was adopted to measure the content of IFN-γ in the liver tissues. DNA microassay revealed that the expression of 611 genes changed in HBx-transfected mice as compared with that in pCMV-tag2B-transfected mice, and most of the screened chemokines were up-regulated (including MIG and IP-10). Additionally, IFN-γ protein levels were increased by 20.7% (P<0.05) in pCMV-tag2B-HBx-transfected mice as compared with the untreated mice. IFN-γ protein levels were reduced by 53.9% (P<0.05) in pCMV-tag2B-transfected mice as compared with the untreated mice, which was consistent with the up-regulation of MIG and IP-10. It was suggested HBx transfection could induce the expression of MIG and IP-10 in the liver tissues, which might play the roles in HBV-related liver immunity and cytokines-mediated antiviral effect.
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The expression profile in the mouse hepatitis B virus X (HBx)-transfected model was investigated in order to lay a foundation for further study on the implication of cytokines expression in hepatitis B virus (HBV) infection. Hydrodynamic injection method via the tail vein was used to establish the animal HBx-transfected model. By using microassay, the differential expression of gene in each group was analyzed, which was further confirmed by using real-time PCR and semi-quantitative PCR. Most of chemokine genes such as Ccl2, Ccl5, Ccl9, MIG and IP-10 were up-regulated in the HBx-transfected mouse model versus the control mice, which was coincided with the microarray results. Western blotting and immunohistochemistry were applied to detect the expression of MIG and IP-10 in the liver tissues. Simultaneously, ELISA was adopted to measure the content of IFN-γ in the liver tissues. DNA microassay revealed that the expression of 611 genes changed in HBx-transfected mice as compared with that in pCMV-tag2B-transfected mice, and most of the screened chemokines were up-regulated (including MIG and IP-10). Additionally, IFN-γ protein levels were increased by 20.7% (P<0.05) in pCMV-tag2B-HBx-transfected mice as compared with the untreated mice. IFN-γ protein levels were reduced by 53.9% (P<0.05) in pCMV-tag2B-transfected mice as compared with the untreated mice, which was consistent with the up-regulation of MIG and IP-10. It was suggested HBx transfection could induce the expression of MIG and IP-10 in the liver tissues, which might play the roles in HBV-related liver immunity and cytokines-mediated antiviral effect.
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Animals , Male , Mice , Chemokine CXCL10 , Allergy and Immunology , Chemokine CXCL9 , Allergy and Immunology , Cytokines , Allergy and Immunology , DNA, Viral , Genetics , Hepatitis B , Genetics , Allergy and Immunology , Virology , Hepatitis B virus , Genetics , Allergy and Immunology , Mice, Inbred C57BL , Mice, Transgenic , Trans-Activators , Genetics , Transfection , MethodsABSTRACT
The aim of the present study was to investigate the effects of adiponectin (APN) on the expression of T-cadherin in cultured Sprague-Dawley (SD) rat cardiomyocytes injured by hypoxia/reoxygenation (H/R). Primary myocardial cells from neonatal rats were obtained by enzymatic digestion. The cells were divided into control group, H/R group and H/R+APN (3, 10, 20 and 30 μg/mL) groups. The H/R group was incubated in anoxic environment (anoxic solution saturated with high concentration N2) for 3 h, and then in the reoxygenation environment (the reoxygenation solution saturated with pure oxygen) for 1 h. The H/R+APN group was pretreated with different concentrations of APN for 24 h prior to the initiation of H/R. The content of lactate dehydrogenase (LDH) was measured by chemistry chromatometry. Cellular apoptosis was analyzed by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The expression of T-cadherin was detected by RT-PCR and Western blotting. The results showed that, compared with control group, the apoptotic rate and release of LDH were significantly increased in the H/R group, whereas the expressions of T-cad mRNA and protein were decreased. Pretreating with APN significantly and dose-dependently decreased apoptotic rate and LDH release, and up-regulated T-cad mRNA and protein level in rat neonatal cardiomyocytes under H/R conditions. These results suggest that APN may protect cardiomyocytes against H/R-induced injury by up-regulating H/R-decreased T-cad expression.
Subject(s)
Animals , Rats , Adiponectin , Pharmacology , Apoptosis , Cadherins , Metabolism , Cell Hypoxia , L-Lactate Dehydrogenase , Metabolism , Myocytes, Cardiac , Metabolism , Pathology , Oxygen , Rats, Sprague-Dawley , Up-RegulationABSTRACT
The present study was to investigate the effect of glucagon like peptide-1 (GLP-1) on high glucose-induced oxidative stress of cardiomyocytes and the possible role of the PI3K-Akt signal path in this process in the neonatal SD rats. With enzymatic digestion and immunofluorescence identification, cardiomyocytes after 72-96 h of primary culture were used in experiment. The cells were divided into 5 groups: normal control group, high glucose group, high glucose + GLP-1 group, high glucose + GLP-1 + LY294002 group and high osmolarity control group. The content of MDA was detected by TBA colouration method. The content of SOD was detected by xanthine oxidase method. The change of NADPH P47phox subunit mRNA quantity was detected by PCR gel electrophoresis. The level of ROS was detected by flow cytometry, and was also observed by fluorescence microscope. The DNA ladder was examined by agarose gel electrophoresis, and the cell apoptosis was determined by Annexin-V-FITC/PI flow cytometry, and the phosphorylation of Akt was determined by Western blotting. Compared with those in the normal control group, in the high glucose group, the cells grew poorly, and the beating rate was significantly lower (P < 0.05); The apoptotic rate was significantly increased (P < 0.05); The MDA content was increased (P < 0.05); It showed the typical DNA ladder, which is the characteristic of apoptosis; The SOD activity was decreased (P < 0.05); The level of intracellular ROS increased (P < 0.05); And the expression of NADPH P47phox subunit mRNA was increased; However the phosphorylation level of Akt was decreased. Pretreatment with GLP-1 improved the above-mentioned parameters and decreased the expression of NADPH P47phox subunit mRNA (P < 0.05). However, compared with the high glucose + GLP-1 group, LY294002, an inhibitor of PI3K-Akt signal path, attenuated the protective effect of GLP-1 in the high glucose + GLP-1 + LY294002 group. It is suggested that GLP-1 plays a protective role in the high glucose-induced injury and apoptosis of cardiomyocytes, and the PI3K-Akt signal path is involved in this process.
Subject(s)
Animals , Female , Male , Rats , Animals, Newborn , Apoptosis , Cells, Cultured , Glucagon-Like Peptide 1 , Pharmacology , Glucose , Pharmacology , Myocytes, Cardiac , Cell Biology , Pathology , Oxidative Stress , Phosphatidylinositol 3-Kinases , Metabolism , Protective Agents , Pharmacology , Proto-Oncogene Proteins c-akt , Metabolism , Rats, Sprague-Dawley , Signal TransductionABSTRACT
<p><b>OBJECTIVE</b>To examine the expression of tumor necrosis factor in placenta of pregnant rats with chronic periodontitis.</p><p><b>METHODS</b>Twenty Wistar female rats were randomly divided into two groups, control (n = 8) and experimental group (n = 12). The periodontitis model was established in the experimental group. The females and males in the two groups got together four weeks later. Nineteen days after pregnancy all rats were executed and placenta collected. The delivery time and neonatal birth weight were recorded and the pathological changes of periodontal tissue observed. Tumor necrosis factor (TNF) expression was examined in placenta by real-time quantitative polymerase chain reaction analysis.</p><p><b>RESULTS</b>The animal model of chronic periodontitis was successfully established. Experimental group delivered 30 offspring and the control group 56 offspring. The average number of pups born alive per litter in experimental group (4.1 ± 2.2) was significantly lower than that in control group (9.2 ± 2.2), P < 0.05. The birth weight of pups in experimental group [(5.01 ± 0.43) g] was significantly lower than that in the control group [(5.79 ± 0.53) g], P < 0.05. The relative quantitative expression of TNF was (1.807 ± 0.265) in experimental group the and (1.003 ± 0.021) in the control group (P = 0.001).</p><p><b>CONCLUSIONS</b>Chronic periodontitis may be related to preterm low birth weight.</p>
Subject(s)
Animals , Female , Pregnancy , Rats , Aggregatibacter actinomycetemcomitans , Animals, Newborn , Birth Weight , Chronic Periodontitis , Metabolism , Microbiology , Disease Models, Animal , Fusobacterium nucleatum , Placenta , Metabolism , Porphyromonas gingivalis , Pregnancy Complications, Infectious , Metabolism , Microbiology , Prevotella intermedia , Random Allocation , Rats, Wistar , Tumor Necrosis Factor-alpha , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of RNA interference (RNAi) targeting angiotensin II Type 1 receptor (ATlR) and angiotensin-converting enzyme (ACE) on blood pressure and myocardial remodeling in spontaneous hypertensive rats (SHRs).</p><p><b>METHODS</b>Saline (control), adenovirus (Ad5) and recombinant adenoviral vectors (Ad5-ACE-shRNA, Ad5-AT1R-shRNA and Ad5-ACE-AT1R-shRNA expressing ACE, AT1R, ACE and AT1R gene-specific shRNA, respectively) were randomly administered by caudal intravasation to SHRs (n = 12 each group) at day 1 and 17. Normotensive Wistar-Kyoto rats (WKY) served as normal controls. Systolic blood pressure (SBP) of the caudal artery was measured daily. Expression of ACE and AT1R at mRNA levels in ventricle and aorta were evaluated by fluorescence quantitative PCR. Angiotension II serum concentration was measured by ELISA at day 3 (n = 6 each group). The ratio of left ventricular to body weight (LVW/BW) and myocardial collagen content were measured, myocardial ultrastructure observed under transmission electron microscope at the study end.</p><p><b>RESULTS</b>The caudal artery pressure of saline and Ad5 group was equally increased by about 26 mm Hg(1 mm Hg = 0.133 kPa) compared to baseline (both P < 0.05). Ad5-ACE-shRNA, Ad5-AT1R-shRNA and Ad5-ACE-AT1R-shRNA injection significantly reduced SBP (-24 mm Hg, -22 mm Hg and -26 mm Hg respectively, all P < 0.05 vs. baseline) and the antihypertensive effect could last at least 15 days post each injection. SBP was not affected by saline and Ad5 injections. ACE and AT1 mRNA expressions at ventricle and aorta were significantly decreased in Ad5-ACE-shRNA, Ad5-ACE-AT1R-shRNA and Ad5-AT1R-shRNA, Ad5-ACE-AT1R-shRNA treated SHRs compared to those in saline and Ad5 groups (all P < 0.05) and was comparable to that in WKY group (P > 0.05). The LVW/BW ratio [(2.22 +/- 0.18) microg/mg, (2.23 +/- 0.19) microg/mg, (2.17 +/- 0.16) microg/mg] and myocardial collagen content [(1.291 +/- 0.019) microg/mg, (1.298 +/- 0.019) microg/mg, (1.276 +/- 0.019) microg/mg] in Ad5-ACE-shRNA, Ad5-AT1R-shRNA and Ad5-ACE-AT1R-shRNA treated SHRs were also significantly lower than those in saline treated [(3.23 +/- 0.13) microg/mg and(1.683 +/- 0.013) microg/mg, both P < 0.05] and Ad5 treated SHRs [(3.25 +/- 0.12) microg/mg and(1.693 +/- 0.013) microg/mg, both P < 0.05], but still higher than those of WKY group [(2.06 +/- 0.12) microg/mg and (1.258 +/- 0.019) microg/mg, both P < 0.05]. Myocardial ultrastructure was also significantly improved in all SHRs underwent RNAi treatments compared to saline and Ad5 treated SHRs.</p><p><b>CONCLUSION</b>RNAi targeting ACE and AT1R gene significantly inhibited myocardial and aortic ACE and AT1R mRNA expressions and resulted in prolonged antihypertensive effects and myocardial ultrastructure improvements in SHRsl. The RNAi technology may be a potential new strategy of gene therapy for hypertension.</p>
Subject(s)
Animals , Male , Rats , Blood Pressure , Gene Silencing , Heart Rate , Hypertension , Genetics , Peptidyl-Dipeptidase A , Genetics , Metabolism , RNA Interference , Rats, Inbred SHR , Rats, Inbred WKY , Receptor, Angiotensin, Type 1 , Genetics , Metabolism , Ventricular RemodelingABSTRACT
The aim of the present study is to investigate the effects of adiponectin (APN) on hypoxia/reoxygenation (H/R) injury in cultured cardiomyocytes. Primary cardiomyocytes were obtained from neonatal rats by enzymatic digestion method and identified by immunofluorescent technique. Primary cells cultured for 72 h were used in experiment and divided into 5 groups randomly: Control group, H/R group, H/R+APN group, H/R+APN+adenine 9-beta-D-arabinfuranoside (AraA, AMPK inhibitor) group, and H/R+AraA group. The cardiocyte morphology and beating rate were observed under inverted microscope. The DNA ladder was examined by agarose gel electrophoresis, and the cell apoptosis was determined by flow cytometry. Moreover, the malondialchehyche (MDA) content in myocardial cells and the superoxide dismutase (SOD) activity in the supernatant were measured using kits, the fluorescence intensity of intracellular Ca2+ was observed by laser scanning confocal microscope, and the phosphorylation of AMPK was determined by Western blotting. Compared with control group, H/R group showed increased apoptotic rate, oxidative stress level, intracellular Ca2+ concentration and phosphorylation level of AMPK (P<0.05), while significant ameliorations in the above indices were seen in H/R+APN group. On the contrast, AraA attenuated the protective effect of APN and decreased the phosphorylation of AMPK. These results suggest that adiponectin can protect cardiomyocytes from H/R-induced oxidative stress and apoptosis through AMPK pathway.
Subject(s)
Animals , Female , Male , Rats , AMP-Activated Protein Kinases , Metabolism , Adiponectin , Pharmacology , Animals, Newborn , Apoptosis , Calcium , Metabolism , Cardiotonic Agents , Pharmacology , Cell Hypoxia , Cells, Cultured , Myocardial Reperfusion Injury , Myocytes, Cardiac , Cell Biology , Oxidative Stress , Rats, Sprague-Dawley , Signal TransductionABSTRACT
<p><b>BACKGROUND</b>Chronic heart failure (CHF) and diabetes mellitus portend high morbidity and mortality because of an interrelated pathophysiologic process. This large cohort study aimed to analyze the prevalence, clinical characteristics and long-term outcome of patients with CHF and diabetes.</p><p><b>METHODS</b>A total of 1119 patients with NYHA functional class II - IV and left ventricular ejection fraction (LVEF) < 45% between January 1995 and May 2009 were recruited. Clinical variables, biochemical and echocardiographic measurements were retrospectively reviewed, and composite major cardiac events (MCE) including death, heart transplantation, and refractory heart failure requiring multiple hospitalizations were recorded.</p><p><b>RESULTS</b>The prevalence of CHF with diabetes was progressively increased with time (16.9% in 1995 - 1999; 20.4% in 2000 - 2004, and 29.1% in 2005 - 2009) and age (18.5% in < 60 years, 26.6% in 60 - 80 years, and 26.6% in > 80 years). Compared with CHF patients without diabetes, those with diabetes had worse cardiac function, more abnormal biochemical changes, and higher mortality. Treatment with glucose-lowering agents significantly improved LVEF and decreased MCE. An elevated serum HbA1c level was associated with large left ventricular end-systolic diameter (P < 0.05), decreased LVEF (P < 0.01) and reduced survival (P < 0.05). Multivariable Logistic regression analysis revealed that after adjustment for confounding factors, NYHA functional class (OR 2.65, 95%CI 1.14 - 6.16, P = 0.024) and HbA1c level >or= 7% (OR 2.78, 95%CI 1.00 - 7.68, P = 0.049) were independent risk factors for adverse outcomes in CHF patients with diabetes.</p><p><b>CONCLUSIONS</b>Prevalence of CHF with diabetes was increasing during past decades, and patients with CHF and diabetes had worse clinical profiles and prognosis. Aggressive anti-CHF and diabetes therapies are needed to improve overall outcomes for these patients.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Diabetes Complications , Epidemiology , Diabetes Mellitus , Drug Therapy , Epidemiology , Glycated Hemoglobin , Heart Failure , Drug Therapy , Epidemiology , Multivariate Analysis , Prevalence , Ventricular Function, LeftABSTRACT
Objective：To investigate the neurocognition and function of social life among human immunodeficiency virus (HIV) positive subjects infected by plasma donation.Methods:Totally 203 HIV positive subjects infected by plasma donation were recruited.Neuropsychological (NP) battery tests including executive function,verbal fluency,learning,memory,fine motor skill,speed of information processing and working memory domains were performanced among these subjects,as well as the Activity of Daily Living Scale (ADLs).And 198 HIV negative plasma donors were matched in gender,age and years of schooling.The cut-off of Global Deficit Score (GDS) was 0.5.Results：The HIV positive subjects performanced worse in global cognitive function [(45.7±5.9 vs.(49.4±6.0),P<0.01]and 7 cognitive domains than those of HIV negative subjects.HIV and HCV infection interacted on aspect of fine motor skill (F=5.28,P<0.05).The impairment rate of the subjects in asymptomatic stage and AIDS were 29.2% and 43.0% respectively.The HIV positive subjects showed more decline of ADLs scores than that of HIV negative subjects [(0.49±1.32) vs.(0.14±0.75),P<0.01].Working months,individual and family's income of HIV positive subjects were also less than that of HIV negative subjects(P<0.01).The lowest CD4 count in NP-impaired group was lower than that in non-impaired group [(214.3±144.0) vs.(274.8±161.1),P=0.01].Subjects with NP impairment reported more decline of ADLs scores [(0.75±1.58) vs.(0.34±1.13),P<0.01] than those without NP impairment.The global cognitive function scores were correlated with decline of ADLs scores (r=-0.22,P<0.01).Conclusion：HIV positive subjects are impairment on aspect of 7 cognitive domains,and co-infection of HCV can lead to more fine motor skill impairment.The more progression of disease,the higher NP impairment ratio.HIV infected subjects show decline of ADL,poorer occupational function and economical status.The lowest CD4 count may be a predictor to NP impairment.NP impairment is a factor which influenced the activity of daily living and the income of individual and family.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the possible correlation between atherosclerosis and chronic periodontitis by establishing an animal model of chronic periodontitis and atherosclerosis in Wistar rat.</p><p><b>METHODS</b>Sixty male Wistar rats were divided into four groups: A (control group), B (chronic periodontitis group), C (atherosclerosis group), D (chronic periodontitis accompany with atherosclerosis group). Every group was accepted the corresponding treatment. Animals were sacrificed after 12 weeks. The periodontal index, levels of serum total cholesterol (TC) and low-density lipoprotein (LDL), the concentration of TNF-alpha and matrix metalloproteinase (MMP-3) were examined. The severity of chronic periodontitis and atherosclerosis was quantified by histopathology. The date were statistically analyzed.</p><p><b>RESULTS</b>Through detection of periodontal tissue of experimental teeth, serum and histopathology, animal models were successful. Histopathologic observation revealed:obvious inflammation of periodontal tissue was observed in group B and D. Attachment loss level in group B [(137.86 +/- 28.39) microm] and D [(162.36 +/- 22.69) microm] was higher than that in group A [(4.26 +/- 1.07) microm] and C [(68.07 +/- 18.25) microm] (P < 0.05), and that in group C was higher than group A (P < 0.05). Atherosclerotic lesions of abdominal aorta were formed in group C and D. The level of TC, LDL in group C and D was higher than that in group A and B (P < 0.05), and that in group D was higher than group C (P < 0.05). Animals in group B and D showed higher level of TNF-alpha, MMP-3 in serum than that in group A and C (P < 0.05). There was no correlation between the level of MMP-3 and TC (P = 0.971) or LDL (P = 0.604).</p><p><b>CONCLUSIONS</b>Chronic periodontitis may be a risk factor and contribute to the pathogenesis of atherosclerosis. MMP-3 may be an independent risk factor of atherosclerosis exclude TC and LDL.</p>