Spatiotemporal expression of histone acetyltransferases, p300 and CBP, in developing embryonic hearts

Histone acetyltransferases (HATs), p300 and cAMP response element binding protein (CREB)-binding protein (CBP) are two structurally related transcriptional co-activators that activate expression of many eukaryotic genes involved in cellular growth and signaling, muscle differentiation and embryogenesis. However, whether these proteins play important and different roles in mouse cardiogenesis is not clear. Here, we investigate the protein distributions and mRNA expression of the two HATs in embryonic and adult mouse heart during normal heart development by using immunohistochemical and RT-PCR techniques. The data from immunohistochemical experiments revealed that p300 was extensively present in nearly every region of the hearts from embryonic stages to the adulthood. However, no CBP expression was detected in embryonic hearts at day E7.5. CBP expression appeared at the later stages, and the distribution of CBP was less than that of p300. In the developmental hearts after E10.5, both for p300 and CBP, the mRNA expression levels reached a peak on day E10.5, and then were gradually decreased afterwards. These results reveal that both p300 and CBP are related to embryonic heart development. The dynamic expression patterns of these two enzymes during mouse heart development indicate that they may play an important role on heart development. However, there is a difference in spatiotemporal expression patterns between these two enzymes during heart development. The expression of p300 is earlier and more predominate, suggesting that p300 may play a more important role in embryonic heart development especially during cardiac precursor cell induction and interventricular septum formation

A Case of Pediatric Heart Failure Caused by Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery: Case Report and Literature Review

A female patient aged 3 months and 10 days was admitted to the cardiology department because of symptoms of heart failure. According to the echocardiography results, the patient received a diagnosis of primary endocardial fibroelastosis and was treated with γ-globulin, prednisone, digoxin, and diuretics. Coronary computed tomographic angiography and coronary angiography were performed as there was no improvement after 2 months of treatment. Finally, the patient received a diagnosis of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). ALCAPA is a rare congenital heart defect that can cause severe heart failure during infancy, and is easily misdiagnosed clinically. In this report, we show the process of misdiagnosis of the case and consult the relevant literature, hoping to improve the understanding and early diagnosis of ALCAPA. </p

The {332}<113> Twinning Behavior of a Ti-15Mo Medical Alloy during Cyclic Deformation and Its Effect on Microstructure and Performance

In this study, the microstructural evolution of a Ti-15Mo medical alloy was investigated, when the in situ cyclic tensile strain had 2% amplitude and the tension–compression cyclic deformation had 1%, 2%, and 3% amplitude. The Vickers hardness and wear resistance of the alloy were also optimized due to the grain-refining effect after cyclic deformation and annealing. The twinning-induced plasticity (TWIP) was considered the main deformation mechanism of the Ti-15Mo alloy during the tensile–compressive cycle deformation with suitable strain amplitude. The {332} twins and boundaries were the main contributors to the grain refinement. The optimal microstructure, hardness, and wear resistance were obtained in the alloy deformed by tension–compression cyclic strain with a 3% strain amplitude. The wear resistance of the annealed alloy in Hank’s solution was excellent in contrast to the original Ti-15Mo alloy due to its reasonable microstructure and hardness. It is clear that abundant twins were formed and retained in the coarse grains of the original alloy after cyclic deformation and annealing, which provided the expected refined grains and performance

Image_1_Health-related quality of life in children with congenital heart disease following interventional closure versus minimally invasive closure.TIF

IntroductionThe presence of atrial septal defect (ASD) or ventricular septal defect (VSD) significantly affects children’s quality of life and, if not treated adequately, can contribute to increased mortality. In this study, we evaluated and compared the health-related quality of life (HRQL) of children who underwent treatment using either minimally invasive closure (MIC) or interventional closure (IC).Materials and methodsIn this observational and comparative study 199 children (2 to 4.5 years of age) underwent closure treatment for simple ASD or VSD at the Children’s Hospital of Chongqing Medical University between February 2021 and September 2021. Of these, 116 were treated with IC and 83 with MIC. Both preoperative and postoperative HRQL scores were assessed using the PedsQLTM3.0 Cardiac Module and the children were followed up at 3 and 6 months after surgery.ResultsThe two groups did not differ significantly in terms of demographics, baseline clinical characteristics, or pre-operative data. The duration of anesthesia (45 mins vs. 109 mins), procedures (25 mins vs. 48 mins), and length of postoperative hospital stay (4.32 days vs. 6.87 days) in the IC group were significantly less than in the MIC group (P ConclusionThe health-related quality of life in children with ASD and VSD improved continuously regardless of IC or MIC intervention. However, IC led to better HRQL in the early postoperative stage.</p

Islet-1 may function as an assistant factor for histone acetylation and regulation of cardiac development-related transcription factor Mef2c expression.

OBJECTIVE:Islet-1 is an important transcription factor for cardiac development through mediating extensive interactions between DNA and proteins. The present study was to investigate the role of Islet-1 in regulating the expression of cardiac development-related transcription factors and mechanism. METHODS AND RESULTS:The expression of Islet-1 and histone acetylases (HATs) subtype p300 was determined in newborn mouse hearts and mouse embryonic hearts at different development stages using Western blot. The expression of Islet-1 and cardiac development-related transcription factors Mef2c, GATA4 and Tbx5 as well as histone H3 acetylation level were determined in cardiac progenitor cells with and without transfection of Islet-1 interference RNA (RNAi) in lentivirus using PCR and Western blot. Islet-1 peak expression occurred on day E14.5 in mouse embryonic heart, and was present in the promoter regions of Mef2c, GATA4 and Tbx5 that were precipitated with p300 antibody. When Islet-1 was inhibited with specific RNAi in cardiac progenitor cells, the expression of Mef2c and Tbx5, but not GATA4, was significantly suppressed along with selective reduction in histone H3 acetylation in the promoter region of Mef2c, but not GATA4 and Tbx5. The level of Mef2c DNA, not GATA4 and Tbx5, in the complex associated with p300 was significantly decreased in the cells with Islet-1 knockdown. CONCLUSIONS:These data suggested that Islet-1 might function as an assistant factor that was involved in the regulation of histone acetylation and Mef2c expression via assisting p300 on specifically targeting the promoter of Mef2c

Effect of Pyrolysis Conditions on the Performance of Co–Doped MOF–Derived Carbon Catalysts for Oxygen Reduction Reaction

MOF–derived porous carbon is a type of promising catalyst to replace expensive Pt–based catalysts for oxygen reduction reaction (ORR). The catalytic activity for ORR depends closely on pyrolysis conditions. In this work, a Co–doped ZIF–8 material was chosen as a research object. The effect of pyrolysis conditions (temperature, heating rate, two–step heating) on the ORR performance of ZIF–derived carbon catalysts was systematically studied. The Co–ZIF–8 catalyst carbonized at 900 °C exhibits better ORR catalytic activity than that carbonized at 800 °C and 1000 °C. Moreover, a low heating rate can enhance catalytic activity. Two–step pyrolysis is proven to be an effective way to improve the performance of catalysts. Reducing the heating rate in the low–temperature stage is more beneficial to the ORR performance, compared to the heating rate in the high–temperature stage. The results show that the Co–ZIF–8 catalyst exhibits the best performance when the precursor was heated to 350 °C at 2 °C/min, and then heated to 900 °C at 5 °C/min. The optimum Co–ZIF–8 catalyst shows a half–wave potential of 0.82 V and a current density of 5.2 mA·cm−2 in 0.1 M KOH solution. It also exhibits high content of defects and good graphitization. TEM mapping shows that Co and N atoms are highly dispersed in the polyhedral carbon skeleton. However, two–step pyrolysis has no significant effect on the stability of the catalyst

The Microstructure, Mechanical Properties, and Corrosion Resistance of a Novel Extruded Titanium Alloy

Titanium alloys are widely used in marine engineering and other industries. To broaden their application, a novel (α + β) titanium alloy Ti−6Al−3Mo−2Zr−2Fe was studied in this work. A tube with an outer diameter of 60mm, inner diameter of 38 mm, and length of 500 mm was produced by ingot metallurgy and hot extrusion. The microstructure, mechanical properties, and corrosion resistance of the tube were systematically analyzed. The as−extruded Ti−6Al−3Mo−2Zr−2Fe alloy exhibited a typical duplex microstructure. EBSD observation showed that a strong 10 1¯0>//RD fiber texture of an α phase with a close−packed hexagonal structure was formed in the radial direction. The transformation temperature Tβ was determined to be 880–890 °C. A duplex microstructure with fine α platelets was obtained when the alloy was solution−treated at 850 °C for 1 h and underwent an aging treatment at 550 °C for 6 h. The room−temperature tensile strength and elongation of the aged alloy reached 1081.5 MPa and 6.5%, respectively. The corrosion resistance was tested by open circuit potential and a potentiodynamic polarization curve. The results show that the corrosion resistance of the Ti−6Al−3Mo−2Zr−2Fe alloy was better than that of the commonly used TC4 alloy in both a 3.5% NaCl solution and an acidic solution

Differentiation of mesenchymal stem cells into cardiomyocytes is regulated by miRNA-1-2 via WNT signaling pathway

Abstract Background Bone marrow derived stem cells (BMSCs) have the potential to differentiate into cardiomyocytes, but the rate of differentiation is low and the mechanism of differentiation is unclear completely. Here, we aimed to investigate the role of miR1-2 in differentiation of mouse BMSCs into cardiomyocyte-like cells and reveal the involved signaling pathways in the procedure. Methods Mouse BMSCs were treated with miR1-2 and 5-azacytine (5-aza). The expression of cardiac cell markers: NKx2.5, cTnI and GATA4 in BMSCs were examined by qPCR. The apoptosis rate was detected by flow cytometry and the activity of the Wnt/β-catenin signaling pathway was evaluated by measuring the upstream protein of this signaling pathway. Results After over-expression of miR1-2 in mouse BMSCs, the apoptosis rate was significantly lower than the 5-aza group, while the expressions of cardiac-specific genes: such as Nkx2.5, cTnI and GATA4 were significantly increased compared to the control group and the 5-aza group. Meanwhile, over-expression of miR1-2 in mouse BMSCs enhanced the expression of wnt11, JNK, β-catenin and TCF in the Wnt/β-catenin signaling pathway. Use of LGK-974, an inhibitor of Wnt/β-catenin signaling pathway, significantly reduced the expression of cardiac-specific genes and partially blocked the role of the miR1-2. Conclusion Over-expression of miR1-2 in mouse BMSCs can induce them toward promoted cardiomyocyte differentiation via the activation of the Wnt/β-catenin signaling pathway. Compared to 5-aza, miR1-2 can induce differentiation of BMSCs into cardiomyocytes more effectively with a less cytotoxicity

MicroRNA-7 as a potential therapeutic target for aberrant NF-κB-driven distant metastasis of gastric cancer

Abstract Background Dysregulated miR-7 and aberrant NF-κB activation were reported in various human cancers. However, the expression profile, clinical relevance and dysregulated mechanism of miR-7 and NF-κB RelA/p65 in human gastric cancers (GC) metastasis remain largely unknown. This study is to investigate the expression profile, clinical relevance and dysregulated mechanism of miR-7 and NF-κB RelA/p65 in GC and to explore the potential therapeutic effect of miR-7 to GC distant metastasis. Methods TCGA STAD and NCBI GEO database were used to investigate the expression profile of miR-7 and NF-κB RelA/p65 and clinical relevance. Lentivirus-mediated gene delivery was applied to explore the therapeutic effect of miR-7 in GC. Real-time PCR, FACS, IHC, IF, reporter gene assay, IP, pre-miRNA-7 processing and binding assays were performed. Results Low miR-7 correlated with high RelA/p65 in GC with a clinical relevance that low miR-7 and high RelA/p65 as prognostic indicators of poor survival outcome of GC patients. Moreover, an impaired pre-miR-7 processing caused by dysregulated Dicer1 expression is associated with downregulated miR-7 in GC cells. Functionally, delivery of miR-7 displays therapeutic effects to GC lung and liver metastasis by alleviating hemangiogenesis, lymphangiogenesis as well as inflammation cells infiltration. Mechanistically, miR-7 suppresses NF-κB transcriptional activity and its downstream metastasis-related molecules Vimentin, ICAM-1, VCAM-1, MMP-2, MMP-9 and VEGF by reducing p65 and p-p65-ser536 expression. Pharmacologic prevention of NF-κB activator LPS obviously restored miR-7-suppressed NF-κB transcriptional activation and significantly reverted miR-7-inhibited cell migration and invasion. Conclusions Our data suggest loss of miR-7 in GC promotes p65-mediated aberrant NF-κB activation, facilitating GC metastasis and ultimately resulting in the worse clinical outcome. Thus, miR-7 may act as novel prognostic biomarker and potential therapeutic target for aberrant NF-κB-driven GC distant metastasis

Acetylation level of histone H3 in cardiac progenitor cells after inhibiting Islet-1 expression.

<p>Western blotting analysis showed that detectable level of histone H3 acetylation was present in cardiac progenitor cells, and was not significantly changed when Islet-1 expression was inhibited (A, <i>p</i>>0.05, n=3). However, the DNA quantity of Mef2c in the promoter region immunoprecipitated with acH3 antibody was significantly decreased in the cells transfected with Islet-1 RNAi as compared with the controls, while no difference was observed in the DNA quantity of GATA4 and Tbx5 in the cells (B). *<i>p</i><0.05, n=3. </p