Retracted: MicroRNA-208b Alleviates Post-Infarction Myocardial Fibrosis in a Rat Model by Inhibiting GATA4.

The laboratory methods and results cannot be replicated and the western blot images in Figures 3 and 4 are not original. Reference: Chaoyuan Zhou, Qintao Cui, Guobao Su, Xiaoliang Guo, Xiaochen Liu, Jie Zhang. MicroRNA-208b Alleviates Post-Infarction Myocardial Fibrosis in a Rat Model by Inhibiting GATA4. Med Sci Monit, 2016; 22: 1808-1816. DOI: 10.12659/MSM.896428.

Change and clinical significance of serum cortisol, BNP, and PGE-2 levels in premature infants with patent ductus arteriosus.

BACKGROUND: To analyze the change and clinical significance of cortisol, B-type brain natriuretic peptide (BNP), and prostacyclin-2 (PGE-2) levels in premature infants with patent ductus arteriosus (PDA). METHODS: A total of 67 cases of premature infants admitted to our hospital from January 2018 to April 2020 were included, all of whom developed PDA (PDA group). According to the presence or absence of symptoms, they were divided into the symptomatic group (28 cases) and the asymptomatic group (39 cases). In addition, 62 premature infants without PDA who were born in our hospital during the same period were selected as the control group. The expression levels of cortisol, BNP, and PGE-2 in infants in different groups and between infants with symptoms and without symptoms were analyzed, along with the risk factors leading to PDA in preterm infants. The value of cortisol, BNP, and PGE-2 in the diagnosis of PDA in premature infants was also analyzed. RESULTS: Compared with the control group, cortisol in the PDA group was significantly decreased (P<0.05), while the levels of BNP and PGE-2 were significantly increased (P<0.05). The cortisol level in the asymptomatic group was significantly higher than that in the symptomatic group, while the levels of BNP and PGE-2 were opposite, and the differences were statistically significant (P<0.05). Logistic regression analysis showed that birth weight <1,200 g, decreased cortisol, increased BNP, and increased PGE-2 were independent risk factors leading to PDA in preterm infants, and the differences were statistically significant (P<0.05). Receiver operating characteristic (ROC) curve showed that the sensitivity and specificity of cortisol+BNP+PGE-2 in the diagnosis of PDA in premature infants were 75.60% and 73.10%, respectively. The area under the curve (AUC) value was 0.759 (95% CI: 0.611-0.859), which was significantly higher than the AUC values of the 3 tests alone (P<0.05). CONCLUSIONS: The expression of cortisol decreased in premature infants with PDA, while the levels of BNP and PGE-2 significantly increased. Dynamic detection of the changes in these levels can provide an important reference for the early diagnosis of PDA and for the assessment of disease progression.

[Knockout of PTEN improves cardiac function and inhibits NLRP3-mediated cardiomyocyte pyroptosis in rats with myocardial ischemia-reperfusion].

Objective To investigate the effects of phosphate and tension homology deleted on chromsome ten (PTEN) knockout on rat heart function and pyroptosis of cardiomyocytes mediated by NLR family pyrin domain containing 3 (NLRP3). Methods Rat models of myocardial ischemia/reperfusion (I/R) injury were established. The rats were divided into sham operation group (wild-type healthy rats), wild-type I/R group (wild-type healthy rats treated with myocardial I/R), and I/R group (PTEN KO rats treated with myocardial I/R). PTEN mRNA level was detected by reverse transcription PCR, and myocardial pathological damage was observed by HE staining. Heart rate (HR) and left ventricular wall thickness (LVWT) were measured by echocardiography, and left ventricular systolic blood pressure (LVSP), left ventricular ejection fraction (LVEF), and fraction shortening (FS) were recorded by BL-420F bioassay system. Serum creatine kinase isoenzyme (CK-MB), myoglobin (Mb) and cardiac troponin I (cTnI) were detected by ELISA. Western blot analysis was used to detect the protein expression of NLRP3, embryonic lethal, abnormal vision, Drosophila-like 1 (ELAVL1), caspase-1 (caspase-1), and IL-1ß in heart tissues. Immunohistochemical staining was performed to detect the content of caspase-1 in cardiac tissues. Apoptosis of myocardial tissue was observed with TUNEL staining. Results Compared with the sham operation group, PTEN mRNA and protein levels in the wild-type I/R group significantly increased, HR, LVSP, LVEF, FS, and LVWT went down significantly, and serum CK-MB, Mb, and cTnI levels significantly increased, and NLRP3, ELAVL1, caspase-1, and IL-1ß protein expression levels went up significantly. After PTEN was knocked out, PTEN mRNA and protein levels were significantly reduced, the pathological damage of cardiomyocytes was alleviated, and HR, LVSP, LVEF, FS, and LVWT were significantly elevated, and serum CK-MB, Mb, and cTnI levels were significantly inhibited. NLRP3, ELAVL1, caspase-1, and IL-1ß protein levels and the number of apoptotic cardiomyocytes were significantly reduced after PTEN knockout. Conclusion Knockout of PTEN can alleviate the pathological damage of myocardium and inhibit nlrp3-mediated apoptosis of cardiomyocytes, indicating that knockout of PTEN can alleviate myocardial I/R damage.

MicroRNA-208b Alleviates Post-Infarction Myocardial Fibrosis in a Rat Model by Inhibiting GATA4.

BACKGROUND Myocardial infarction affects the health of many people. Post-infarction myocardial fibrosis has attracted much attention, but details of the mechanism remain elusive. In this study, the role of microRNA-208b (miR-208b) in modulating post-infarction myocardial fibrosis and the related mechanism were investigated. MATERIAL AND METHODS A rat model of myocardial infarction induced by ligating the left anterior descending artery was used to analyze the expression and roles of miR-208b by overexpression with the lentivirus vector of pre-miR-208b. Myocardial function was assessed and the expression of fibrosis-related factors type I collagen (COL1) and ACTA2 (alias αSMA) was detected. Myocardial fibroblasts isolated from newborn rats were transfected with luciferase reporter vectors containing wild-type or mutant Gata4 3' UTR to verify the relationship between Gata4 and miR-208b. We then transfected the specific small interference RNA of Gata4 to detect changes in COL1 and ACTA2. RESULTS miR-208b was down-regulated in hearts of model rats (P<0.01). Overexpressing miR-208b improved myocardial functions, such as reducing the infarction area (P<0.05) and promoting LVEF and LVFS (P<0.01), and inhibited COL1 and ACTA2 (P<0.01). Luciferase reporter assay proved Gata4 to be the direct target of miR-208b, with the target sequence in the 3'UTR. Inhibiting GATA4 resulted in the down-regulation of COL1 and ACTA2, suggesting that the role of miR-208b was achieved via regulating GATA4. CONCLUSIONS This study demonstrates the protective function of miR-208b via GATA4 in post-infarction myocardial fibrosis, providing a potential therapeutic target for treating myocardial fibrosis.

Sildenafil improves the function of endothelial cells in patients suffering from congenital heart disease with pulmonary hypertension.

Aim of this study was to investigate the potential effects of sildenafil on the function of endothelial cells from patients with congenital heart disease with pulmonary hypertension (CHDPH). Patients who are diagnosed as CHD with PH (n=30) or without PH (n=30), and 30 healthy persons (control) were enrolled in this study. The 30 CHDPH cases were separated into two groups, one was given aspirin while the other received aspirin and sildenafil. An ELISA assay was used to detect the biological indexes for endothelial cells. Furthermore, 24 male New Zealand white rabbits were used to construct the CHDPH model. The signal pathway-related protein expression was analyzed using RT-PCR and western blotting. Compared to that in healthy people, levels for flowmediated dilatation (FDM), NO, and adiponectin (APN) were significantly decreased while endothelin (ET-1) was significantly increased in CHD patients, while their levels were drastically changed in CHDPH patients (P<0.01). Besides, no significant differences for expression levels including FDM, APN, NO, and ET-1 was observed in CHDPH patients receiving aspirin. But the levels for FDM, APN, NO, and ET-1 were significantly changed in CHDPH patients after treatment with sildenafil for 3 months (P<0.01). The mRNA and protein levels for JNK1/2, MAPK, and NF-κB were significantly increased in CHDPH rabbits compared to the control (P<0.01), but their levels were significantly suppressed by the sildenafil application compared to the CHDPH group (P<0.01). Taken together, our study suggested that sildenafil may play a protective role on endothelial function via suppressing the JNK and NF-κB signal pathways in CHDPH patients.

Brain­derived neurotrophic factor gene polymorphisms are associated with coronary artery disease­related depression and antidepressant response.

Depression is a well­established risk factor for cardiac morbidity and mortality in patients with coronary artery disease (CAD). Previous studies have demonstrated that the level of brain­derived neurotrophic factor (BDNF) is decreased in depressed patients and this depletion may be reversed by antidepressants. Several recent studies have suggested that BDNF is involved in the pathogenesis of CAD. The aim of the present study was to investigate the possible association between seven single nucleotide polymorphisms (SNPs) of the BDNF gene (SNPs; rs16917204, rs6265, rs7103873, rs16917237, rs56164415, rs13306221 and rs10767664) and coronary artery disease­related depression (CAD­D). In the present study, 616 CAD patients without depression (CAD­nD) and 155 patients with CAD­D were recruited, and the response to an eight week sertraline antidepressant treatment regimen was also evaluated. The results demonstrated that a significant association existed between the SNP rs6265, located in exon 4 of the BDNF gene, and CAD­D [χ2=9.634, P=0.002, odds ratio (OR)=1.486, 95% confidence interval (CI)=1.156­1.910]. Another potential association was observed for rs13306221 (χ2=5.194, P=0.023, OR=2.139, 95% CI=1.096­4.175) in the promoter region of the BDNF gene. Strong linkage disequilibrium was observed in block 1 (rs16917204, rs6265; D'>0.9). However, there was no evidence of a significant linkage disequilibrium between the seven SNPs in our sample population. Additionally, carriers of the A allele of rs6265 exhibited improved responses to the sertraline treatment (χ2=8.942, P=0.003, OR=2.136, 95% CI=1.293­3.528). To the best of our knowledge, these results demonstrate, for the first time, the presence of a significant association between BDNF rs6265 and CAD­D, the identification of which may facilitate early diagnosis of CAD­D in the future.