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Objective:To investigate the role and mechanism of long non-coding RNA GAS5 in the targeted regulation of miR-29, miR-96, and miR-208 in promoting insulin secretion of pancreatic β-cells.Methods:Q-PCR was used to detect the expression of miR-29, miR-96, and miR-208 in sera of 122 healthy subjects and 88 type 2 diabetic patients; and so of long non-coding RNA GAS5 and miR-208 in the rat islet cell tumor strain ins-1832/13. Effects of silencing and overexpressing GAS5 on insulin secretion of islet β-cells by lentiviral vector construction were observed. Bioinformatics was used to predict that GAS5 had complementary binding sites with miR-29, miR-96, and miR-208, which was further verified by luciferase reporting system. GAS5 siRNA was co-transfected with miR-29, miR-96, and miR-208 inhibitors, and the effect of GAS5 on insulin receptor (INSR), insulin receptor substrate (irs-1) and PI3K levels was detected by the above method, so as to reveal the effect of GAS5 on insulin secretion in islet cells.Results:The expression of GAS5 in serum of T2DM patients was lower than that of healthy control group ( t=4.632, P<0.01), and expression of miR-29, miR-96, and miR-208 were higher than those of healthy control group ( t were 7.832, 9.164, and 12.359, all P<0.01). GAS5 level was negatively correlated with miR-29, miR-96, and miR-208 ( r were -0.50, -0.47, and -0.70, respectively). GAS5 expression was significantly decreased in serum of type 2 diabetic patients compared with that of in healthy subjects. Overexpression of GAS5 by lentivirus resulted in increased glucose-stimulated insulin secretion and increased insulin concentration compared to negative control. In contrast, knockdown of GAS5 led to significant reduction of glucose-stimulated insulin secretion and insulin concentration. GAS5 levels were negatively correlated with miR-29, miR-96, and miR-208 in serum samples of type-2 diabetes patients. GAS5 can negatively regulate the expression of miR-96, miR-29, and miR-208. By bioinformatics tools, we screened miR-29, miR-96 and miR-208 as targets of GAS5, and their interaction was validated with dual luciferase reporter gene assay. shGAS5 significantly decreased the expressions of INSR, IRS-1 and PI3K( P were 0.022, 0.038, and 0.009), while overexpressed GAS5 significantly upregulated the expressions of INSR, IRS-1 and PI3K at both mRNA and protein levels( P were 0.024, 0.045, and 0.016). Conclusion:GAS5 could stimulate insulin secretion of islet cell through its inhibitry regulationor of expressions of miR-29, miR-96, and miR-208, therely up-regulating INSR, IRS-1, and PI3K that may be the potential targets of these miRNAs, and stimulate insulin secretion of islet cells.
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To evaluate the relationship between atherosclerosis and hemodynamic of coronary artery in mice detecting by ultrasound bio‐microscopy flow imaging . Methods Double 14 20‐week‐old LDL‐R‐/‐and C57BL/6 male mice were selected ,and randomly divided into two groups in each genotype according to weight . Each two groups were fed to 28 weeks or 36 weeks age respectively with west diet . Coronary artery hemodynamics in these mice were assessed in vivo by Vevo ?2100 ultrasound imaging system ,then the intima‐media thickness( IM T ) of aorta in histopathology were analyzed . T he differences of coronary artery hemodynamic parameters such as maximum velocity ( Vmax ) ,mean velocity ( Vmean) and velocity time integral ( V T I) were compared between mice of different genotypes of the same week and mice of different weeks of the same genotype . And the relationship between coronary artery hemodynamic in ultrasound and aortic IM T in histopathology were analyzed . Results ① All coronary hemodynamic parameters in LDL‐R‐/‐ mice were significantly lower than those of wild‐type mice except the Vmax between two 28‐week‐old genotypes group at the same weeks of age of different genotypes ( all P ＜0 .05) . But there was no significant difference in coronary artery hemodynamic parameters between mice of the same genotype at different weeks of age( P ＞0 .05) . ②T he histopathological measurements of aortic IM T in LDL‐R‐/‐mice were significantly higher than those of wild type mice ( all P ＜ 0 .05 ) ,and those of 36‐week‐old mice were significantly higher than those of 28‐week‐old mice ( all P ＜ 0 .05 ) . ③ All coronary hemodynamic parameters such as Vmax ,Vmean and V TI were negatively correlated with pathological measurements of aortic IM T ( r ＝ －0 .532 , －0 .423 , －0 .524 ; all P ＜ 0 .05 ) . Conclusions The parameters of coronary artery hemodynamics obtained by ultrasound bio‐microscopy are well correlated with the pathological results of atherosclerosis . Ultrasound bio‐microscopic flow imaging can be used as a new method to evaluate the degree of atherosclerosis in mice by detecting the hemodynamic parameters of coronary artery .
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Objective To explore the value of layer-specific strain in assessment of left ventricular function in patients with heterozygous familial hypercholesterolemia (HeFH) with normal left ventricular ejection fraction (LVEF).Methods Thirty-four patients with diagnosed HeFH and underwent transthoracic echocardiography were included as HeFH group,while 29 healthy volunteers were taken as control group.EchoPAC software was used to obtain endocardial longitudinal strain (LSendo),myocardial longitudinal strain (LSmyo) and epicardial longitudinal strain (LSepi) of the epicardial,and then statistical analysis was performed.Results LSendo and LSmyo in HeFH group were significantly lower than those in control group (P＜0.001).LSendo and LSmyo were negatively correlated with total cholesterol and low density lipoprotein cholesterol (all P＜0.05).Conclusion Layer-specific strain of left ventricular is of great value in assessing early myocardial damage in patients with HeFH.
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ObjectiveAnalyze the mechanism of traditional Chinese medicine Salvia miltiorrhiza in treating coronary heart disease (CHD).MethodsThe animal experiment using actual research, namely the selection of rat isolated heart perfusion model, rat model of myocardial ischemia and ventricular tachycardia in rabbits model, then the effects of different animal groups in hemodynamics, coronary flow, serum superoxide dismutase (SOD) content, malondialdehyde (MDA) the results of the content.ResultsAfter treatment, the content of SOD was significantly increased and the content of MDA was significantly decreased in the treatment group, and the difference between the two groups was statistically significant (P<0.05).ConclusionTraditional chinese medicine Salvia miltiorrhiza has significant effect on the treatment of coronary heart disease, which is beneficial to the recovery of patients' condition, and is worthy of clinical application.
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BACKGROUND:Autologous conditioned serum (ACS) is a new and safe biological therapy method mainly used for osteoarthritis, rheumatoid arthritis and other similar diseases. OBJECTIVE:To explore the purification method and cytokine profile of ACS. METHODS:Blood obtained equipment (containing 3 mm of glass beads) was used to collect peripheral blood samples that were mixed uniformly and then placed in a 37℃ thermostatic incubator for 24 hours, finally filtered to obtain ACS. The quantitative determination of interleukin (IL)-1Ra, IL-6, IL-8, and IL-1β was conducted, and the 36 kinds of cytokines were semi-quantitatively detected by cytokine antibody array. RESULTS AND CONCLUSION: The levels of various cytokines in ACS were obviously increased, among which, IL-1Ra level (important for alleviating osteoarthritis) was increased from 140.25 ng/L to 1125 ng/L(increased by above 8 times); IL-6 level was increased from 389.5 ng/L to 2802 ng/L; IL-8 level was not detected firstly and finally increased to 2822 ng/L. Cytokine antibody array results showed that at least 10 kinds of cytokines in ACS were changed, and most of cytokines were on a rise, and few in decline. These results indicate that the ACS contains IL-1Ra and a variety of cytokines, and some chemokines in the ACS recruit more immune cells to the inflammation sites and accelerate the inflammatory process, further exerting therapeutic effects.
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Aim To evaluate the inhibitive effects of celastrol on LDL oxidation and HAEC cell oxidative damage. Methods The Cu2+-induced LDL oxidation model was employed to evaluate celastrol inhibitive effect on LDL oxidation in vitro, the oxidative reaction kinetic curves were determined, and the AUC, lag time,TBARS value were assayed. The AAPH-induced HAEC damaging cellular model was employed to evalu-ate the effect of celastrol on oxidative cellular damage. The safe dose of celastrol on normal cells was deter-mined by MTT method, and the effects of celastrol on HAEC oxidative damage were evaluated at the range of this safe dose. The LDH leakage,ROS level,SOD and GPX enzymatic activity,Nrf2 and HO-1 mRNA expres-sion were determined. Results At the dose range of 100 nmol · L-1 to 1 μmol · L-1 , celastrol effectively extended the lag time of LDL oxidative process induced by Cu2+, reduced the AUC of oxidative reaction kinet-ic curve and reduced the generation of lipid peroxide in the LDL oxidative process. In the cellular experiment, celastrol effectively reduced the LDH leakage induced by AAPH, increased the integrity of cell membrane and nucleus, enhanced the antioxidative enzyme activi-ties of cellular SOD,GPX and increased the expressions of Nrf2,HO-1 mRNA, celastrol also maintained the in-tegrity of cellular structure. Conlusion Celastrol can effectively inhibit LDL oxidation induced by Cu2+, and can inhibit HAEC cell oxidative damage induced by AAPH at the dose range of 100 to 400 nmol·L-1 .
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Objective To evaluate the application of M-mode echocardiography and Doppler echocardiography in diagnosing complete atrioventricular block (CAVB) in fetus. Methods M-mode and Doppler echocardiography were used to screen the fetuses and bradycadia was established as CAVB in 10 cases. Atrial and ventricular rhythm was measured by M-mode echocardiography. Flow of mitral valve, left ventricular in-flow and out-flow tract, venous duct was measured by Doppler echocardiography. The characteristics and prognoses of CAVB fetus were compared and analyzed. Results CAVB was established as independence in rhythm of atrium and ventricle. The rhythm of atrium could be in normal range, while the rhythm of ventricle should be slower than normal. Enlarged chambers were observed in 6 cases, cardiac dysfunction in 5 cases, and pericardial effusion in 7 cases. Tricuspid regurgitation and mitral regurgitation existed in 5 and 1 case, respectively. All of the CAVB fetus in this study underwent abortions. Conclusions Fetal echocardiography is proven to be a useful tool to diagnose CAVB, which greatly influenced the cardiac function in fetuses. Clear diagnosis as early as possible is crucial to the treatment of CAVB fetus.
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<p><b>BACKGROUND</b>An zidovudine (AZT)-substitution regimen containing 24-week stavudine (d4T) followed by long-term AZT for HIV therapy is potential to trade off short-term AZT-related anemia and long-term risks associated with d4T in resource-limited settings. However, evidence is scarce. This study aims to assess the efficacy and safety of AZT-substitution regimen, aiming to find a regimen with better efficacy, less adverse events, and more affordability in resource-limited settings.</p><p><b>METHODS</b>This prospective, multicenter study enrolled 499 (190 on d4T regimen, 172 on AZT regimen, and 137 on AZT-substitution regimen) HIV-1-infected subjects who initiated combined antiretroviral therapy and attended follow-up visits over 96 weeks from 2009 to 2011. Lamivudine (3TC) and either nevirapine (NVP) or efavirenz (EFV) were the other two drugs in the antiretroviral regimens. Virologic and immunologic responses and adverse events were monitored at baseline and at weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96.</p><p><b>RESULTS</b>In terms of hematological adverse effects, AZT-substitution group had similar safety profiles to d4T group and was superior to AZT group. In comparison with AZT-substitution group, AZT group was associated with higher risk of developing anemia (adjusted hazard ratio (aHR) for anemia ≥ grade II, 8.44, 95% CI 1.81-39.46) and neutropenia (aHR for neutropenia ≥ grade II, 1.86, 95% CI 1.19-2.93). The prevalence of lipodystrophy in d4T group was 19.5%, while that in AZT-substitution group was zero. As to antiretroviral efficacy, these three groups showed no differences.</p><p><b>CONCLUSION</b>AZT-substitution regimen provides a relatively safe and effective first-line antiretroviral strategy in resource-limited settings.</p>
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Adult , Female , Humans , Male , Middle Aged , Anti-HIV Agents , Therapeutic Uses , HIV Infections , Drug Therapy , Prospective Studies , Stavudine , Therapeutic Uses , Zidovudine , Therapeutic UsesABSTRACT
Objective To observe the therapeutic efficacy and safety of the glucagon-like peptide-1 ( GLP-1 )analogue combined with isulin for treating obese or overweight type 2 diabetes.Methods 40 cases with obese or overweight type 2 diabetic patients( body mass index(BMI) ≥24) who have previously used human insulin,and experienced poor glycemic control( ≥7.5％ ) were selected.They were randomly divided into two groups.A group treated by GLP-1 analogue liraglutide plus insulin,and B group by continuous adjustment of insulin.12 weeks later,fasting blood glucose(FBG),2-hour plasma glucose (2hPG),hemoglobin A 1 C (HbA1c),body weight were observed and the incidence of hypoglycemia,insulin dosage were recorded.Results Weight and insulin dosage of group A was significantly lower than those of group B after treatment 12 week( t =2.738,2.865,all P ＜ 0.01 ).Numbers of hypoglycemia events were 6 in group A(30％ ),and 9 in group B(45％ ),but there was no statistical significance between the two groups ( P ＞ 0.05).Conclusion The addition of liraglutide to insulin in patients with obese or overweight type 2 diabetes is associated with reductions in weight and insulin dosage,without increase risk of hypoglycemia.This treatment proved effective and safe.