Microbial metabolites and heart failure: Friends or enemies?

Heart failure (HF), a global health issue characterized by structural or functional cardiac dysfunction, which was found to be associated with the gut microbiome recently. Although multiple studies suggested that the gut microbiome may have an impact on the development of cardiovascular diseases, the underlying mechanism of the gut microbiome in HF remains unclear. The study of metabolites from gut microbiota influenced by dietary nutrition uptake suggested that gut microbiota may affect the process of HF. However, on the basis of the microbiota's complicated roles and their interactions with metabolites, studies of microbial metabolites in HF had rarely been described so far. In this review, we focused on dietary nutrition-related factors that were involved in the development and progression of HF, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and bile acids (BAs), to summarize their advances and several potential targets in HF. From a therapeutic standpoint, we discussed microbial metabolites as a potential strategy and their applications in HF as well.

Minimally invasive right infra-axillary thoracotomy for transaortic septal myectomy.

Extended left ventricular septal myectomy remains the gold standard for the treatment of hypertrophic obstructive cardiomyopathy (HOCM) with refractory symptoms. On the basis of traditional modified transaortic Morrow myectomy, we innovatively performed a minimally invasive, video-assisted single-port thoracotomy through the right infra-axillary region. Our procedure can provide good visualization of the left ventricular outflow tract and hypertrophic ventricular septum for accurate resection. It also ensures optimal exposure of the mitral valve in the presence of complex mitral subvalvular structures.

MiR-96-5p is an oncogene in lung adenocarcinoma and facilitates tumor progression through ARHGAP6 downregulation.

Accumulating investigations illustrated that miRNA acts as a key regulator in tumor progression, whereas regulatory role of miR-96-5p in lung adenocarcinoma (LUAD) is warranted. Thus, we sought to probe mechanism of miR-96-5p in this disease. Through bioinformatics analysis, miR-96-5p level in normal tissue and LUAD tissue in TCGA database were obtained. Meanwhile, mRNA expression dataset was analyzed to obtain downregulated mRNAs binding to miR-96-5p. qRT-PCR assessed miR-96-5p and ARHGAP6 mRNA in LUAD. Western blot assessed protein level of ARHGAP6 in LUAD. Dual-luciferase reporter gene detection verified targeting relationship of miR-96-5p and ARHGAP6. Biological functional experiments such as CCK-8, colony formation, scratch healing, and Transwell assessed cell proliferation, migration, and invasion. MiR-96-5p was overexpressed, which fostered LUAD cell proliferation, migration, and invasion. ARHGAP6 was downregulated in LUAD and targeted by miR-96-5p. ARHGAP6 upregulation prominently restored promotion of miR-96-5p on cell progression. MiR-96-5p could stimulate LUAD progression through targeting ARHGAP6. This study generates a novel direction and lays a theoretical basis for targeted therapy.

Protective effect of trichostatin A on CD19+CD5+CD1dhigh regulatory B cells in heart transplantation.

Heart transplantation is widely used for the treatment of several heart diseases. Regulatory B cells (Breg cells) serve a critical role in immune tolerance. However, the role of Breg cells in immune tolerance in the context of allogeneic heart transplantation remains poorly understood. The present study aimed to explore the effect of histone deacetylase (HDAC) inhibitor trichostatin A (TSA)­regulated Breg on the regulation of immune tolerance in heart transplantation. By constructing anallogeneic heart transplantation mouse model, and performing flow cytometry, reverse transcription­quantitative PCR, western blotting and carboxyfluorescein succinimidyl esterstaining assays, TSA­regulated Breg cells and their effects on immune tolerance in heart transplantation were evaluated. The results demonstrated that TSA increased the frequency of CD19+CD5+CD1dhigh Breg cells both in vitro and in vivo. Moreover, TSA treatment increased the frequency of IL­10 and TGF­ß­producing CD19+CD5+CD1dhigh Breg cells, and IL­10 and TGF­ß levels in vitro and in vivo. TSA administration significantly prolonged the survival rate in a heart transplant experiment model. In addition, the IL­10 inhibitor ammonium trichloro(dioxoethylene­o,o')tellurate partially reduced the survival rate and the percentages of CD19+CD5+CD1dhigh Breg cells in mice receiving heart allografts. In contrast, anti­CD20 treatment significantly decreased the survival rate in these mice. Collectively, the present findings suggested that TSA may induce immune tolerance following heart transplantation by regulating CD19+CD5+CD1dhigh Breg cells. These results provide a theoretical basis for the prevention of immunological rejection in cardiac transplantation.

Causes and predictors of readmission after transcatheter aortic valve implantation : A meta-analysis and systematic review.

BACKGROUND: Since readmission rate is an important clinical index to determine the quality of inpatient care and hospital performance, the aim of this study was to explain the causes and predictors of readmission following transcatheter aortic valve implantation (TAVI) at short-term and mid-term follow-up. METHODS AND RESULTS: A systematic review and meta-analysis of all published articles from Embase, Pubmed/MEDLINE, and Ovid was carried out. In all, 10 studies including 52,702 patients were identified. The pooled estimate for the overall event rate was 0.15, and cardiovascular causes were the main reason for 30-day readmission (0.42, 95% confidence interval [CI]: 0.39-0.45). In addition, the pooled incidence of 1­year readmission was 0.31, and cardiovascular events were still the main cause (0.41, 95% CI: 0.33-0.48). Patients with major and life-threatening bleeding, new permanent pacemaker implantation, and clinical heart failure were associated with a high risk for early readmission after TAVI. Moreover, an advanced (≥3) New York Heart Association classification, acute kidney injury, paravalvular leak, mitral regurgitation (≥ moderate), and major bleeding predicted unfavorable outcome to 1­year readmission. Female gender and transfemoral TAVI was associated with a lower risk for unplanned rehospitalization. CONCLUSIONS: This meta-analysis found cardiovascular factors to be the main causes for both 30-day and 1­year rehospitalization. Heart failure represented the most common cardiovascular event at both short-term and mid-term follow-up. Several baseline characteristics and procedure-related factors were deemed unfavorable predictors of readmission. Importantly, transfemoral access and female gender were associated with a lower risk of readmission.

Effect of miR-744 on Ameliorating Heart Allograft Rejection in BALB/c Mice Via Regulation of TNFRSF4 Expression in Regulatory T Cells.

CD134 (TNFRSF4) is a member of the TNFR superfamily, which is specifically expressed on T cells. Previous studies have shown that blocking of CD134L-CD134 interaction reduces the percentage of activated T cells and prevents effector T cell-mediated graft rejection in heart transplantation. However, the role of microRNA-regulated inhibition of the CD134 signal in cardiac transplantation of T-regulatory (Treg) cells is not clear. In this study, we found microRNA 744 (miR-744) agomir administration enhanced the expression levels of miR-744 in CD4+CD25+ Treg cells from heart transplantation mice. Moreover, miR-744 agomir administration significantly enhanced the expression levels of CD62L and Ki67 in CD4+CD25+ Treg cells from heart transplantation mice and further enhanced immunosuppressive function of Treg cells following coculture with CD4+CD25- T cells for different ratios. In addition, miR-744 agomir treatment significantly prolonged survival time and reduced rejection response of heart allografts in vivo, which are involved in downregulation of TNFRSF4 expression. These results provided a novel molecular mechanism of ameliorating heart allograft rejection in Treg cells, which could be used in the treatment of heart allograft rejection clinically.

miR-21 promotes non-small cell lung cancer cells growth by regulating fatty acid metabolism.

BACKGROUND: Lung cancer is one of the most common malignant tumors worldwide. CD36 is a receptor for fatty acids and plays an important role in regulating fatty acid metabolism, which is closely related to tumorigenesis and development. The regulation of miR-21 and its role in tumorigenesis have been extensively studied in recent years. However, the relationship between miR-21 and CD36 regulated fatty acid metabolism in human non-small cell lung cancer remains unknown. METHODS: In this study, lentivirus transfection, qRT-PCR, cell migration, immunofluorescence, and western blot were used to examine the relationship between miR-21 and CD36 regulated fatty acid metabolism and the regulation role of miR-21 in human non-small cell lung cancer. RESULTS: This study demonstrated that up-regulation of miR-21 promoted cell migration and cell growth in human non-small cell lung cancer cells. Moreover, the intracellular contents of lipids including cellular content of phospholipids, neutral lipids content, cellular content of triglycerides were significantly increased following miR-21 mimic treatment compared with control, and the levels of key lipid metabolic enzymes FASN, ACC1 and FABP5 were obviously enhanced in human non-small cell lung cancer cells. Furthermore, down-regulation of CD36 suppressed miR-21 regulated cell growth, migration and intracellular contents of lipids in human non-small cell lung cancer cells, which suggested that miR-21 promoted cell growth and migration of human non-small cell lung cancer cells through CD36 mediated fatty acid metabolism. Inhibition of miR-21 was revealed to inhibit cell growth, migration, intracellular contents of lipids, and CD36 protein expression level in human non-small cell lung cancer cells. In addition, PPARGC1B was a direct target of miR-21, and down-regulation of PPARGC1B reversed the inhibition of CD36 expression induced by miR-21 inhibitor. CONCLUSIONS: These results explored the mechanism of miR-21 promoted non-small cell lung cancer and might provide a novel therapeutic method in treating non-small cell lung cancer in clinic.

Effect of miR-21 on Apoptosis in Lung Cancer Cell Through Inhibiting the PI3K/ Akt/NF-κB Signaling Pathway in Vitro and in Vivo.

BACKGROUND/AIMS: Lung cancer is one of the most common malignancies in the world. Apoptosis-stimulating protein of p53 (ASPP2), a tumorigenesis related protein, plays a critical role in the initiation and development of various types of cancers. However, the effect of ASPP2 on lung cancer remains unknown. The purpose of this study aims to investigate the mechanism of ASPP2 regulated by miR-21 in lung cancer in vitro and in vivo. METHODS: In the study, migration and invasion assays, apoptosis assay, caspase activity assay, TUNEL staining, real time PCR and western blot were used to investigate the mechanism of ASPP2 regulated by miR-21 in lung cancer in vitro and in vivo. RESULTS: We demonstrated that the miR-21 inhibitor induced apoptosis through inhibiting the PI3K/Akt/NF-κB signaling pathway in non-small cell lung carcinoma (NSCLC). Moreover, ASPP2 was directly targeted by miR-21 in NSCLC cells. Down-regulation of miR-21 suppressed cell migration and invasion, as well as the EMT signaling pathway in NSCLC cells. Furthermore, the miR-21 inhibitor induced cell apoptosis via the caspase dependent pathway in NSCLC cells. The miR-21 inhibitor enhanced caspase-3, 8, 9 activity in NSCLC cells. In addition, the caspase inhibitor significantly reduced the apoptosis induced by the miR-21 inhibitor in NSCLC cells. CONCLUSIONS: Our results revealed that the miR-21 inhibitor could induce apoptosis through inhibiting the PI3K/Akt/NF-κB signaling pathway in human NSCLC cells, and might serve as a therapeutic strategy to treat NSCLC.

Rare association of two cardiovascular malformations successfully corrected in a single surgery: a case report.

BACKGROUND: Partial anomalous pulmonary venous connection (PAPVC) without an atrial septal defect (ASD) associated with coarctation of the aortic arch is a rare congenital cardiac anomaly. This rare combination is only described in a few studies; none report the correction of these two malformations in a single surgery. CASE PRESENTATION: A 5-year-old girl was admitted to our hospital because the echocardiography revealed coarctation of the aortic arch; this diagnosis was confirmed by computed tomography (CT), which also showed her left superior pulmonary vein draining into the vertical vein without ASD (Fig. 1). She exhibited no special clinical symptoms. Her upper-limb blood pressure was approximately 110/90 mmHg, whereas her lower-limb blood pressure was approximately 75/50 mmHg. CONCLUSIONS: We surgically repaired the case of PAPVC to the vertical vein with aortic coarctation, in which the two cardiovascular malformations were corrected in a single surgery without cardiopulmonary bypass.

The effects of low-molecular-weight heparin on lung and pulmonary artery injuries in acute pulmonary embolism rat model via platelet-derived growth factor-ß.

OBJECTIVE: To evaluate the effects of anticoagulant agent (low-molecular-weight heparin, LMWH) on the pulmonary artery intima hyperplasia of rats with acute pulmonary embolism (APE) by assaying platelet-derived growth factor-ß (PDGF-ß). METHODS: A total of 90 Sprague-Dawley rats were randomly assigned into the sham, APE, and LMWH groups with 30 rats in each group. The APE rat models were established by injecting autologous blood clots via external jugular veins. In each group, six mice were sacrificed at the 1st day (D1), 4th day (D4), 7th day (D7), 14th day (D14), and 28th (D28) subsequent to the induction of APE to collect the lungs. Right ventricle pressure (RVP) and mean pulmonary arterial pressure (mPAP) were measured. Western blot and RT-PCR analyses were used to assess PDGF-ß expression at various time points. In addition, changes in lung pathology were evaluated using hematoxylin and eosin (H&E) staining and electron microscope. RESULTS: The overall success rate of establishing APE rat models was 85.7% (60/70). There was no difference in mPAP between the sham group and the APE group at the D1, D4, D7, and D14. However, at the D28, mPAP in the APE group was significantly higher than that in the sham group. There was no difference among the three groups regarding RVP. PDGF-ß expression were decreased in the LMWH group at all time points compared with the sham and APE groups (P < 0.01). Furthermore, pulmonary embolism, alveolar wall necrosis and hemorrhage, and inflammation were significantly attenuated in the LMWH group compared with the sham and APE groups subsequent to the induction of APE. CONCLUSION: LMWH attenuates lung and pulmonary artery injuries and improves prognosis. Decreased PDGF-ß in the lungs may be the important factor in the effects observed.

Right ventricular outflow tract obstruction caused by right ventricular fibroma in a 5-month-old infant: a case report.

BACKGROUND: Cardiac fibroma is rarely encountered in children, and even more rare in neonates. We herein report a case of a 5-month-old female with severe right ventricular outflow tract obstruction caused by a large right ventricle fibroma that was successfully surgically resected. CASE PRESENTATION: This report describes the case of a 5-month-old female infant with a large mass measuring 26 × 22 mm in the right ventricle cured successfully with surgery. Physical examination revealed a harsh S1 sound and a grade IV systolic murmur on the left sternal border. Surgical resection was indicated due to severe right ventricular outflow tract obstruction and further follow-up evaluation was uneventful. CONCLUSION: The surgical procedure to excise such a large cardiac fibroma in a 5-month-old infant is feasible and safe.